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    P1.12 - Small Cell Lung Cancer/NET (Not CME Accredited Session)

    • Type: Poster Viewing in the Exhibit Hall
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      P1.12-01 - A Single-Arm Multi-Center Phase II Study of Apatinib in Patients with ES-SCLC After Second/Third-Line Chemotherapy

      16:45 - 18:00  |  Presenting Author(s): Yun Fan  |  Author(s): Zhiyu Huang, Wenfeng Li, Yuping Li, Jun Chen, Yanjun Xu, Hongyang Lu, Xinmin Yu, Yu Jin Xu, Jing Qin, Ying Jin, Xiaoling Xu, Lei Gong, Fajun Xie, Na Han, Peng Zhang, Kaiyan Chen

      • Abstract

      Background

      The survival of patients (pts) with extensive-stage small-cell lung cancer (ES-SCLC) was poor. And the standard treatment strategies have not yet been established for those who failed from second/third-line chemotherapy. Apatinib, a vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitor, has been shown anti-cancer activity and manageable toxicities in several solid cancers.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      A single-arm multi-center phase II study was designed to determine the efficacy and safety of apatinib in pts with ES-SCLC after second/third-line chemotherapy (clinical trial information: NCT02945852). The inclusion criteria mainly included aged 18-75 years; pathologically confirmed SCLC; received chemotherapy with two or three regimens previously, including first-line platinum-based regimen. Pts were treated with afatinib 500 mg/day p.o. until tumor progression or lack of tolerability. One treatment cycle was 28 days long. The full analysis set included patients who received at least one cycle of treatment. Treatment interruptions or dose reductions were allowed when grade 3 hematologic or grade 2 nonhematologic toxicities occurred. The primary endpoint is progression-free survival(PFS); secondary endpoint includes the safety of afatinib, overall survival (OS), objective response rate (ORR) and disease control rate (DCR).

      4c3880bb027f159e801041b1021e88e8 Result

      As of Mar 2018, 40 pts from 3 institutions were recruited into the trial. Median age was 60 years, and 37 pts were male (92.5%). 17/40 (42.5%) pts experienced dose reduction or treatment interruptions. Followed up to Apr 26, 2018, the median during time of afatinib treatment was 80 days and 36 pts were eligible for assessing tumor responses. In the 36 pts, 8 (22.2%) pts achieved partial responses [PR], 20 (55.5%) pts achieved stable disease [SD] and 8 (22.2%) pts were assessed as progressive disease [PD]. The ORR was 22.2% (8 pts PR) and the DCR was 77.8% (8 pts PR, 20 pts SD). During the follow-up, a total of 25 pts died. The median PFS and OS was 86 days and 105 days, respectively. The most common adverse events were anemia (69.4%, 25/36), hand-foot syndrome (61.1%, 22/36), urine protein (55.6%, 20/36), hypertension (52.8%, 19/36) and fatigue (44.4%, 16/36). The related grade 3-4 toxicities included hypertension (47.2%, 17/36), hand-foot syndrome (5.6%, 2/36), Oral ulcer (5.6%, 2/36) and elevated aminotransferase (5.6%, 2/36).

      8eea62084ca7e541d918e823422bd82e Conclusion

      In this prospective phase II trial, apatinib showed encouraging durable response rates and survival in patients with ES-SCLC after second/third-line chemotherapy, with an acceptable safety profile.

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      P1.12-02 - Phase II Study of Amrubicin Monotherapy in Elderly or Poor-Risk Patients with Extensive Disease of Small Cell Lung Cancer

      16:45 - 18:00  |  Presenting Author(s): Satoshi Igawa  |  Author(s): Tomoya Fukui, Masayuki Shirasawa, Takahiro Ozawa, Hideyuki Sone, Seiichiro Kusuhara, Noriko Nishinarita, Yasuhiro Hiyoshi, Masaru Kubota, Hisashi Mitsufuji, Jiichiro Sasaki, Masato Katagiri, Katsuhiko Naoki

      • Abstract

      Background

      Previous study indicated that an optional anti-cancer drug for the treatment in pretreated patients with small-cell lung cancer (SCLC) is amrubicin. However, no prospective studies have evaluated amrubicin in chemo-naive elderly or poor-risk patients with SCLC. Therefore, this study aimed to evaluate the efficacy of amrubicin as first-line chemotherapy for elderly or poor-risk patients with extensive-disease SCLC (ES-SCLC).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Patients with chemotherapy-naive ES-SCLC received multiple cycles of 40 mg/m2 amrubicin for 3 consecutive days every 21 days. The primary endpoint was the overall response rate (ORR), and the secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety.

      4c3880bb027f159e801041b1021e88e8 Result

      Between March 2011 and August 2015, 36 patients were enrolled in this study. Each patient received a median of four treatment cycles (range, 1–6 cycles). ORR was 52.8% [95% confidence interval (CI), 37–69%]. The median PFS and OS periods were 5.0 months (95% CI, 3.4–6.6 months) and 9.4 months (95% CI, 5.2–13.6 months), respectively. Neutropenia was the most common grade 3 or 4 adverse event (69.4%), with febrile neutropenia developing in 13.9% of patients. No treatment-related death occurred. At the time of starting second-line chemotherapy, 19 of 22 patients (86%) had significantly improved or maintained their performance status (PS) relative to their PS at the time of starting amrubicin monotherapy as first-line chemotherapy (P = 0.027).

      8eea62084ca7e541d918e823422bd82e Conclusion

      The results of the present study suggest that amrubicin could be considered as a viable treatment option for chemotherapy-naive elderly or poor-risk patients with ES-SCLC.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      P1.12-03 - A Prospective Study of Apatinib in Advanced Small Cell Lung Cancer Patients Failed from Two or More Lines of Chemotherapy

      16:45 - 18:00  |  Presenting Author(s): Yutao Liu  |  Author(s): Xingsheng Hu, Shengyu Zhou, Junling Li, Peng Liu, Yan Wang, Xueyu Hao, Yuankai Shi, Jun Jiang

      • Abstract

      Background

      Small lung cancer (SCLC), a highly malignant neoplastic, chemoresponsive disease. For SCLC patients who with worsening status after second-line treatment, there is currently no affirmative and widely accepted chemotherapy regimen. Apatinib is a novel oral multi-target small-molecule TKI mainly targeting the intracellular ATP-binding domain of VEGFR-2, which has a significant effect of anti-angiogenesis to suppress the growth of tumors. This study evaluated the efficacy and safety of Apatinib in SCLC patients who failed from second- or further-line chemotherapy.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Data was collected from the files of patients treated with Apatinib 500mg qd who diagnosed with advanced SCLC and failed from second or more lines of chemotherapy. Efficacy assessed after one cycles (4 weeks), then every two cycles (8 weeks) once again. The primary endpoint was PFS and the tumor response was determined according to the RECIST 1.1. PFS were graphed by Kaplan-Meier curves of progression-free survival. AEs were also evaluated and toxicity grade was determined based on CTCAE 4.0.

      4c3880bb027f159e801041b1021e88e8 Result

      22 patients were enrolled from November 10, 2016 to April 18, 2018, the number of patients that can be evaluated is 19. One patients obtained partial response, and 15 obtained stable disease, representing a DCR of 84.11%. Median PFS was 140 days (95% confidence interval [CI] 94.84–185.16). Although only one patient showed PR, all the patients’ target lesions were reduced. A total of 46 AEs were reported during the trial, grade 3-4 AEs were hypertension (9.09%), leukopenia (4.55%) and proteinuria (4.55%) which most could be relieved by dose reduction. figure 1..jpg

      8eea62084ca7e541d918e823422bd82e Conclusion

      In conclusion, Apatinib has a certain therapeutic effect in patients with advanced SCLC (third- or further-line). To further investigate the role of Apatinib in advanced SCLC patients, large sample and additional clinical trials are needed.

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      P1.12-04 - A Ph3 Study of Niraparib as Maintenance Therapy in 1L Platinum Responsive Extensive Disease Small Cell Lung Cancer Patients

      16:45 - 18:00  |  Presenting Author(s): Shun Lu  |  Author(s): Liyan Jiang, Xinghao Ai, Junling Li, Xiaorong Dong, Dan Zhang, Qi Liu

      • Abstract

      Background

      Small cell lung cancer (SCLC) accounts for 15% of lung cancer, characterized by early dissemination and rapid development of chemo-resistant disease after platinum response (60-80%). Less than 2% of extensive disease SCLC (ED-SCLC) patients survive 5 years. The bi-allelic loss or inactivation of TP53 and RB1 is common in SCLC, the poly(ADP-ribose) polymerase-1 (PARP-1), a critical DNA damage repair enzyme, is highly expressed in SCLC, and SCLC is sensitive to platinum based chemotherapy, suggesting that the defect in DNA damage repair pathways plays an important role in SCLC. ZL2306/ Niraparib is a highly selective PARP-1/2 inhibitor which was exclusively licensed for development in China by Zai Laboratory from TESARO. In SCLC PDX model, niraparib demonstrated anti-tumor activities as monotherapy. In addition, niraparib demonstrated promising tumor growth inhibition in maintenance post platinum treatment in platinum sensitive SCLC PDX models. Clinically, in phase III NOVA study, niraparib demonstrated clear clinical benefit as maintenance treatment by significantly extending progression free survival in all platinum-sensitive recurrent ovarian cancer patients regardless gBRCA or HRD status which led to the approval by FDA and EMA in ovarian cancer. It is suggested that niraparib maintenance therapy could provide potential clinical benefit in platinum responsive SCLC. ZL-2306-005 is a randomized double-blind multi-center phase 3 study to evaluate the efficacy and safety of niraparib versus placebo as maintenance therapy in ED-SCLC patients who have had responses to platinum based chemotherapy.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Approximately 590 Chinese patients with histologically or cytologically confirmed ED-SCLC who have achieved either complete response or partial response to their platinum based chemotherapy to their newly diagnosed disease will be randomized (2:1) to 2 groups, receiving either ZL-2306 or placebo in ZL-2306-005 study. Patients need to complete 4 cycles of etoposide + cisplatin/ carboplatin. All patients will be stratified by gender, LDH level and history of prophylactic cranial irradiation. ZL-2306 will be started with 300mg PO QD for patients with a baseline body weight ≥77 kg and a baseline platelet count ≥150,000/μL, or 200 mg PO QD for patients with a baseline body weight <77 kg or a baseline platelet count <150,000/μL based on RADAR analysis in NOVA study. Patients will remain on treatment until disease progression or intolerable toxicity. The co-primary endpoints are PFS assessed by independent central radiologic review and OS; the secondary endpoints are PFS assessed by investigator, CFI, QoL, safety and tolerability.

      4c3880bb027f159e801041b1021e88e8 Result

      Section not applicable

      8eea62084ca7e541d918e823422bd82e Conclusion

      Section not applicable

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      P1.12-05 - Efficacy of Perioperative Chemotherapy for High-Grade Neuroendocrine Tumors

      16:45 - 18:00  |  Presenting Author(s): Hiroyuki Ogawa  |  Author(s): Yugo Tanaka, Yoshitaka Kitamura, Hiroki Tanaka, Yuuki Nishioka, Shinya Tane, Wataru Nishio, Yoshimasa Maniwa, Masahiro Yoshimura

      • Abstract

      Background

      Large-cell neuroendocrine carcinoma (LCNEC) and small-cell lung cancer (SCLC) are categorized as high-grade neuroendocrine tumors (HGNECs). There have been few studies to show the efficacy of perioperative chemotherapy for HGNEC as a single entity.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We retrospectively reviewed the medical records of patients who underwent tumor resection and were diagnosed with HGNECat Hyogo Cancer Center (Akashi, Japan) and Kobe University Hospital (Kobe, Japan)between January 2001 and December 2016. Overall survival (OS) was estimated by the Kaplan–Meier method. Multivariate analyses using a Cox proportional hazards model were performed to search for prognostic factors for HGNEC. Propensity score matching was performed to compare the OS between the treatment groups.

      4c3880bb027f159e801041b1021e88e8 Result

      We identified 197 patients who underwent surgery and who were diagnosed with HGNEC. Forty-three patients were excluded for the following reasons: pathological stage 4 or incomplete resection (n=25), synchronous multiple cancers (n=14), and insufficient medical records (n=5) We finally analyzed 153 HGNEC patients (LCNEC n=95, SCLC n=58). Seventy patients (LCNEC n=34, SCLC n=36) received perioperative chemotherapy. All of them received a platinum-based anticancer drug, and 80% received combined treatment with irinotecan or etoposide (n=56). The 5-year OS rates of the surgery plus chemotherapy and surgery alone groups were 75.5% and 34.7% (P<0.01), respectively. The HR for death in the surgery plus chemotherapy group was 0.34 (95% CI 0.20-0.56; P<0.01) in comparison to the surgery alone group. The multivariate analysis revealed that perioperative chemotherapy (HR 0.30, P<0.01), sublobar resection (HR 2.04, P=0.04), and lymph node metastasis (HR 3.54, P<0.01) were independently associated with survival. After adjustment for the patients’ background characteristics by propensity matching, the 5-year OS rates of the surgery plus chemotherapy group were significantly higher than those of the surgery alone group (78.7% and 32.9%; P < 0.01). The HR for death in the surgery plus chemotherapy group was 0.33 (95% CI 0.15-0.68; p<0.01) in comparison to the surgery alone group.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Surgical resection combined with perioperative chemotherapy was considered to be effective for HGNEC. Sublobar resection might increase the risk of death in HGNEC patients. Therefore if the general condition of the patient permits, perioperative chemotherapy should be performed, and the extent of resection in the treatment of HGNEC should be lobectomy or more.

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      P1.12-06 - Pulmonary Neuroendocrine (Carcinoid) Tumors: CommNETs/NANETS Endorsement and Update of the ENETs Best Practice Consensus

      16:45 - 18:00  |  Presenting Author(s): Simron Singh  |  Author(s): Emily K. Bergsland, Cynthia M. Card, Thomas A. Hope, Pamela L. Kunz, David T. Laidley, Ben Lawrence, Simone Leyden, Michael Michael, Lucy E. Modahl, Sten Myrehaug, Sukhmani Kaur Padda, Rodney F. Pommier, Robert A Ramirez, Michael Soulen, Jonathan Strosberg, Alia Thawer, Benjamin Wei, Bin Xu, Eva Segelov

      • Abstract

      Background

      The lung is the most common single site of origin of neuroendocrine cancers, and lung neuroendocrine tumor (LNET) incidence and prevalence is rising. There is a lack of both LNET-specific data and up to date clinical guidance. Management of LNETs often relies on extrapolation from other tumor sites. The Commonwealth Neuroendocrine Tumour Collaboration (CommNETS) and North American Neuroendocrine Tumor Society (NANETS) sought to consider current data and provide updated guidance on LNET diagnosis and management.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      The latest best practice consensus on LNETs was published by the European Neuroendocrine Tumor Society (ENETS) in 2015. A review of content and methods using the AGREE II Rigour of Development subscale (www.agreetrust.org) confirmed the quality of the ENETS initiative, providing a basis for endorsement and update. A systematic literature search was conducted and a 22 member, multidisciplinary CommNETS/NANETS expert panel endorsed or modified recommendations from a patient-centered perspective. All statements were graded using Oxford criteria (CEBM.net).

      4c3880bb027f159e801041b1021e88e8 Result

      A total of 230 studies were identified for consideration by the panel. Recommendations were modified or added to reflect clinical data not available in 2015. Out of the 52 ENETS statements, 40% were endorsed, 58% were modified or updated, one was removed and four were added. Themes identified in the consensus update include new statements, practice changing modifications, augmented grades of recommendation and statement refinements, each addressing specialties ranging from epidemiology, pathology and diagnosis to treatment and follow-up (Table 1). The importance of LNET directed research and patient-centered care throughout the treatment trajectory is also emphasized, along with directions for future research.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Ongoing collaboration is essential for future development of updated LNET clinical guidance and to direct research efforts in a patient-centered context. Our consensus update demonstrates international collaboration to develop guidance on clinical management of malignancies for which limited data are available.

      Table 1. Themes in CommNETS/NANETS Lung NET Consensus Update

      New statements

      Epidemiology

      Highlights marked increase in the incidence and prevalence of lung NETs

      Radiation Therapy

      Guidance on use of palliative EBRT for patients with symptomatic locally advanced or metastatic disease

      Medical Therapy

      Recommendation of pre-surgical prophylaxis with SSAs for patients with carcinoid syndrome

      Indicates lack of benefit of anti-angiogenics in lung NET

      Practice changing statement modifications

      Diagnosis

      Indicates limited clinical value of chromogranin A in lung NET diagnosis and disease state characterization

      Surgery

      Indicates that cytoreductive surgery of the liver may be expanded to patients with non-aggressive tumors, including those with more limited extra-hepatic disease

      Statements with augmented recommendations

      Surgery

      The grades of recommendation for complete anatomic resection and systematic nodal dissection for peripheral tumors and for preference of lung parenchymal-sparing surgery over pneumonectomy were each augmented to Grade B

      Medical Therapy

      The grades of recommendation for PRRT and mTOR inhibitors statements were augmented to Grades B and A, respectively

      Statement refinements

      Pathology

      Refined to reflect new standards for classification (WHO 2015) and staging (UICC/AJCC 8th edition)

      Tailored to highlight need for endobronchial biopsy or surgical resection for sufficient sampling to differentiate TC from AC

      Diagnosis

      Radiological imaging statements were modified to simplify guidance and clarify differences in requirements for diagnostic compared to liver imaging, and to guide application of various nuclear imaging techniques

      Bronchoscopy statements were simplified to highlight efficacy and safety of bronchoscopy

      Surgery

      Surgery for localized disease statements modified to reflect equivalence of sublobar resection and lobectomy, especially for typical carcinoid tumors

      Endobronchial resection statements were revised to reflect need to limit procedure to high risk patients or as a bridge to surgery

      Medical Therapy

      Follow-up statement was revised to better define and direct post-treatment surveillance for lung NETs patients who receive medical therapy

      AC; atypical carcinoid; EBRT, external beam radiotherapy; NET, neuroendocrine tumor; PRRT, peptide receptor radionuclide therapy; SSA; somatostatin analog; TC, typical carcinoid

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      P1.12-06a - Rovalpituzumab Tesirine Maintenance Therapy Following 1st Line Platinum‑Based Chemotherapy in Small Cell Lung Cancer

      16:45 - 18:00  |  Presenting Author(s): Philip Komarnitsky  |  Author(s): Ho-Jin Lee, Manan Shah, Shekman Wong, Sanja Gauthier, Juliann Dziubinski, Stacy Osbaugh, Fan Zhang

      • Abstract

      Background

      Small Cell Lung Cancer (SCLC) embodies 15-20% of lung cancers. Patients are staged with either limited or extensive disease (ED); the standard front-line treatment for the latter is chemotherapy with carbo- or cisplatin combined with etoposide or irinotecan. Response rates are high with limited duration. Recurrence may be attributable to chemo-resistant tumor initiating cells (TICs). Delta-like protein 3 (DLL3) is an inhibitory Notch receptor ligand identified as a novel target in SCLC TICs. DLL3 is highly expressed in SCLC but not normal tissue. Rovalpituzumab tesirine (Rova-T™) is an antibody-drug conjugate composed of a DLL3-targeting IgG1 monoclonal antibody tethered to a DNA cross-linking toxin. Rova-T has shown activity in recurrent/relapsed ED SCLC patients1. Given DLL3 expression in TICs, exploration of Rova-T front-line maintenance strategies in ED SCLC is warranted. The postulated mechanism of action of Rova-T and its clinical activity indicate potential to improve progression-free and overall survival in this setting.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      This is a Phase 3, randomized, double-blind, placebo-controlled, international study (NCT03033511, no patients enrolled yet as of 7 February 2017). Approximately 740 ED SCLC patients will be enrolled to include ~480 patients with high DLL3 expression. Eligibility: patients ≥ 18 years; histologically or cytologically confirmed ED SCLC with ongoing clinical benefit (complete/partial response or stable disease) after 4 cycles of 1st line platinum-based therapy; definitively treated CNS metastases allowed; > 3 but ≤ 9 wks between the administration of the last cycle of platinum-based chemotherapy and randomization; available tumor tissue for DLL3 expression testing; ECOG performance score 0-1. Patients will be randomly assigned 1:1 to receive 0.3 mg/kg Rova-T or placebo on Day 1 of each 6-wk cycle, omitting every 3rd cycle. Primary objectives: determine if Rova-T improves progression-free and overall survival. Secondary objectives: assess Rova-T antitumor activity by determining objective response rate, clinical benefit rate, duration of response, and changes in patient reported outcomes.

      1. Rudin et al., Lancet Oncol, 2016.

      4c3880bb027f159e801041b1021e88e8 Result

      Section not applicable

      8eea62084ca7e541d918e823422bd82e Conclusion

      Section not applicable

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      P1.12-06b - Rovalpituzumab Tesirine vs Topotecan in Patients with Advanced Small Cell Lung Cancer Following 1<sup>st</sup> Line Chemotherapy

      16:45 - 18:00  |  Presenting Author(s): Philip Komarnitsky  |  Author(s): Ho-Jin Lee, Manan Shah, Shekman Wong, Scott Gulbranson, Juliann Dziubinski, Laura Caffrey, Poonam Tanwani, Monica Motwani, Fan Zhang

      • Abstract

      Background

      Small cell lung cancer (SCLC) represents ~15% of lung cancers. Standard therapy most often consists of a platinum-based therapy + a second agent (etoposide). Initial response rates are high but not durable. Treatment for relapsed patients is limited, but includes topotecan. However, efficacy of topotecan is suboptimal and there is a high unmet need in this population. Delta-like protein 3 (DLL3) is an atypical Notch receptor family ligand identified as a target in SCLC and neuroendocrine carcinomas (NECs). DLL3 is highly expressed in SCLC and NECs but not normal tissue. Rovalpituzumab tesirine (Rova-T™) is an antibody-drug conjugate composed of a DLL3-targeting IgG1 monoclonal antibody tethered to a toxic DNA crosslinker. Rova-T has antitumor activity in relapsed SCLC patients, and was well-tolerated1. Thus, we are investigating Rova-T vs topotecan as a 2nd line therapy in advanced SCLC.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      This is a Phase 3, randomized, open-label, multicenter study (NCT03061812) to assess efficacy, safety, and tolerability of Rova-T vs topotecan. Approximately 411 patients will be enrolled and randomized 2:1 between 2 arms. Arm A regimen: 0.3 mg/kg Rova-T intravenous (IV) on Day 1 + 8 mg dexamethasone orally, twice daily on Day -1, 1 and 2 of a 42-day cycle; administered for 2 cycles with up to 2 additional cycles permitted. Arm B: 1.5 mg/m2 topotecan (or per local label) IV on Days 1-5 of each 21-day cycle; administered until disease progression. Patient eligibility: ≥ 18 years; confirmed, advanced/metastatic SCLC with first disease progression following frontline standard therapy; DLL3-high tumor expression; ECOG 0-1; no prior exposure to a pyrrolobenzodiazepine-based drug or topotecan, irinotecan, or other topoisomerase I inhibitor. Efficacy endpoints include progression free survival, overall survival, objective response rate, duration of response, and patient-reported outcomes.

      1. Rudin et al., Lancet Oncol, 2016.

      4c3880bb027f159e801041b1021e88e8 Result

      Section not applicable

      8eea62084ca7e541d918e823422bd82e Conclusion

      Section not applicable

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      P1.12-07 - Time to the End of Thoracic Radiotherapy Affects to Survival Outcomes Greater than Radiation Dose in Limited Stage Small Cell Lung Cancer

      16:45 - 18:00  |  Presenting Author(s): Sung-Ja Ahn  |  Author(s): Jae-Uk Jeong, Wan Jeon, Young-Chul Kim, In-Jae Oh, Cheol-Kyu Park, Mee Sun Yoon, Ju-Young Song, Taek-Keun Nam, Woong-Ki Chung

      • Abstract

      Background

      Early thoracic radiotherapy (TRT) concurrent with chemotherapy and radiation doses of 45 Gy given 1.5 Gy bid still has taken a seat as a standard treatment option for limited-stage small cell lung cancer (LS-SCLC). We aim to search the association between radiation parameters and survival outcomes in LS-SCLC patients who undertaken more than 45 Gy of TRT.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      One hundred and one patients with LS-SCLC who completed TRT between August 2005 and March 2014 were reviewed retrospectively. Median age was 64 years (43-80) and male to female was 88 vs. 13. Stage IIIA was 30 and IIIB was 55, respectively. TRT was performed using 3-dimensional conformal radiation therapy (3DCRT) and delivered using 2Gy single fraction per day in 73.2% of patients. The median dose TRT was 50 Gy (45-65), and all patients received concurrent chemoradiotherapy. PCI was combined in 56 (55.4%) patients.

      4c3880bb027f159e801041b1021e88e8 Result

      The median survival for all patients was 26.9 months. Local failure occurred in 41 patients (40.5%), and distant metastasis was noted in 54 patients (53.4%). The 3-year local control, progression-free survival (PFS), and overall survival (OS) rates were 52.0%, 29.5%, and 56.4%, respectively. On univariate analysis, the American Joint Committee on Cancer stage (p<0.001), timing of TRT (≤2 vs, >2 cycles, p=0.017), tumor response (CR vs. PR, p=0.015), the duration from the start date of chemotherapy to the end of TRT (SER) (≤70 vs >70 days, p=0.025), and PCI (p=0.003) were the significant predictors of OS and stage (p<0.001) and PCI (p=0.017) were the significant predictors in PFS. Multivariate analysis revealed that stage (hazard ratio [HR], 3.61; 95% CI, 2.15-6.07) was the only significant factor in PFS and stage (HR, 2.49; 95% CI, 1.56-3.98), SER (HR, 1.93; 95% CI, 1.22-3.07), PCI (HR, 0.52; 95% CI, 0.33-0.84), and tumor response (HR, 1.76; 95% CI, 1.12 – 2.77) were the significant predictors in OS. There was one fatal radiation pneumonitis. Grade 3 radiation pneumonitis and esophagitis was shown in 7 (6.9%) vs. 7 (6.9%) patients, respectively. Grade 3 and 4 leukopenia was shown in 30 (29.7%) vs. 11 (10.8%) patients and febrile neutropenia was 9 (8.9%) vs. 1 (0.9%) patients, respectively.

      8eea62084ca7e541d918e823422bd82e Conclusion

      SER less than 70 days was a significant predictors of OS in LS-SCLC patients who received more than 45 Gy of TRT concurrently with chemotherapy. We could not find any significant positive survival benefits of TRT dose or BED escalation in our patients groups.

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      P1.12-08 - The Effect of Cisplatin Versus Carboplatin on Cancer Outcomes for Small Cell Lung Cancer Patients in a Population-Based Cohort

      16:45 - 18:00  |  Presenting Author(s): David E Dawe  |  Author(s): Trevor Aquin, Shantanu Banerji, Oliver Bucher

      • Abstract

      Background

      Small cell lung cancer (SCLC) is associated with high rates of mortality and treatment involves chemotherapy. In non-small cell lung cancer, using cisplatin results in superior response and survival compared to carboplatin, but causes more toxicity. Little research regarding this drug choice in SCLC exists, but available studies suggest equivalent survival. Nevertheless, many oncologists continue to use cisplatin preferentially.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Using the population-based Manitoba Cancer Registry, we identified SCLC cases diagnosed from 2004 to 2013 in Manitoba and completed a retrospective chart review for those treated with chemotherapy. Demographics, tumour response, and treatment toxicity were compared between cisplatin and carboplatin treated groups. Overall survival (OS) and progression free survival (PFS) were evaluated using multivariate Cox proportional hazard methods. Likelihood of completing chemotherapy (at least 4 cycles) was assessed using multivariable logistic regression.

      4c3880bb027f159e801041b1021e88e8 Result

      Of the 531 patients identified, 139 (26.2%) received carboplatin and 392 (73.8%) received cisplatin as part of first line chemotherapy. More patients who received carboplatin had poor performance status (13.7% v 7.4%), elevated LDH (58.3% v 42.3%), and extensive stage disease (69.8% v 54.1%), all p<0.01. Unadjusted median OS was 224 v 322 days for carboplatin and cisplatin. Multivariable adjusted analysis for OS using cisplatin patients not completing treatment as the reference comparator showed hazard ratios for carboplatin completers – 0.65 (0.43-0.98), cisplatin completers – 0.69 (0.47-1.00), and carboplatin incompleters – 1.00 (0.64-1.55), p = 0.13. For PFS carboplatin completers – 1.07 (0.60-1.90), cisplatin completers – 0.83 (0.51-1.36), and carboplatin incompleters – 0.96 (0.64-1.46), p = 0.59. There was not significant difference between carboplatin and cisplatin in likelihood of completing chemotherapy, when adjusted for other patient characteristics - 0.75 (0.47-1.22), p=0.26 Those treated with carboplatin had significantly less neutropenia (57.6% v 74.7%), nephrotoxicity (2.9% v 13.5%), neurotoxicity (0.7% v 12.0%), and nausea/vomiting (28.1% v 42.6%) associated with treatment, all p<0.01.

      8eea62084ca7e541d918e823422bd82e Conclusion

      In a real world, population-based setting, carboplatin appears to be an equally effective treatment option for SCLC, facilitating equivalent survival while avoiding toxicity. Clinicians may wish to re-examine their preference for cisplatin.

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      P1.12-09 - The Effect of Site of First Chemotherapy on Small Cell Lung Cancer Patient Outcomes

      16:45 - 18:00  |  Presenting Author(s): David E Dawe  |  Author(s): Rebekah Rittberg, Trevor Aquin, Susan Green, Oliver Bucher, Shantanu Banerji

      • Abstract

      Background

      Small cell lung cancer (SCLC) ischaracterized by a rapid doubling time and high responsiveness to chemotherapy (CT) with a rapid relapse. Due to the sensitivity of SCLC to CT, it is one of the few malignancies treated in acutely ill patients admitted to hospital with a poor performance status (PS). However, there is little available information on the outcomes and toxicity experienced by patients with SCLC who require initial CT as an inpatient.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      A retrospective cohort study was conducted evaluating patients consecutively diagnosed with SCLC in Manitoba from 2004 to 2013 treated with platinum-doublet CT. Patient demographics, staging, treatment, CT toxicities, Eastern Cooperative Oncology Group(ECOG) PS, treatment response, and survival were collected using the Manitoba Cancer Registry and chart review. Outcomes of progression free survival (PFS) and overall survival (OS) were evaluated based on site of first CT (inpatient versus outpatient) and PS.

      4c3880bb027f159e801041b1021e88e8 Result

      530 patients received CT for SCLC with 82 patients (15%) receiving their first CT as an inpatient. Sixty-three percent of inpatients received the full CT course, compared to 81% of outpatients, (p=0.0006). Outpatients had a greater likelihood of responding to CT (p=0.0043). Neutropenia, febrile neutropenia, thrombocytopenia, nephrotoxicity and fatigue were all experienced less often by the inpatient cohort, (p<0.0001), (p=0.0040), (p<0.0001), (p<0.0001) and (0.0068). For inpatients, OS at 12, 24 and 60 months was 22%, 9% and 7%, versus outpatient OS of 43%, 20% and 9%, (each p<0.0001). Median PFS and OS were longer for outpatients, 212 versus 161 days, (p=0.0035) and 321 versus 192 days, (p=0.0003). Patients with poorer ECOG PS had shorter PFS and OS; with a median PFS for PS 0, 1-2, 3-4 of 316, 203 and 147 days, (p<0.0001) and median OS for PS 0, 1-2 and 3-4 of 498, 303 and 179 days, (p<0.0001). On multivariate analysis, ECOG PS was an independent predictor of outcome, (p=0.0005) while site of first CT was not significant when ECOG PS was included, (p=0.3494).

      8eea62084ca7e541d918e823422bd82e Conclusion

      Although SCLC patients initially treated as inpatients had shorter PFS and OS, some experienced long term survival, including a 7% five-year survival. CT toxicities were not more common for inpatients. This validates that administration of CT in hospital can be considered as these patients may have a meaningful long-term response to therapy if properly selected. As previously identified in the literature, this data demonstrated that patients with poorer ECOG PS have shorter PFS and OS.

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      P1.12-10 - Patterns of Curative Chemo-Radiotherapy Regimen and Impacts on the Outcome of Limited Stage SCLC in a Canadian Institution: 2010 – 2015 Diagnoses

      16:45 - 18:00  |  Presenting Author(s): Anifat A. Elegbede  |  Author(s): Michelle Dean, Gwyn Bebb

      • Abstract

      Background

      Curative intent chemotherapy and radiotherapy (ChemoRT) is the widely recommended treatment for limited stage (LS) small cell lung cancer (SCLC) follow by prophylactic cranial irradiation (PCI) in those who responded to the initial therapy. LS-SCLC is however characterized by high relapse rate with only about 20% surviving to 2 years. Our objective is to examine the characteristics, treatment patterns and overall survival of LS-SCLC for patients diagnosed within a 5-year period at the Tom Baker Cancer Centre, Canada, prior to wide adoption of emerging treatment options including surgery and immunotherapy in the curative and palliative settings respectively.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Using the Glans-Look Lung Research (GLR) database, we defined the clinical and demographic features of patients diagnosed with LS-SCLC from 2010 to 2015, determined the rate of systemic treatment uptake, and investigated the impact of PCI, curative intent, and palliative treatments on overall survival. We summarized our findings with descriptive statistics (including Fisher’s Exact test) and Kaplan Meier survival curves using SPSS. Statistical significance was set at p value < 0.05 and 95% confidence intervals.

      4c3880bb027f159e801041b1021e88e8 Result

      About a third (107/349, 31%) of patients diagnosed with SCLC from 2010 to 2015 were LS-SCLC, with median age of 67 years. Over the 5-year period, systemic treatments uptake rates and patterns fluctuates. Overall, > 50% received ChemoRT and 65% of the ChemoRT group also received PCI. Curative concurrent RT dose 45 – 55Gy, 25 fractions schedule was more common (55%). Few stage T1a-2a, N0-1 LS-SCLC had surgery (5%). Thirty eight percent of those who received initial curative intent treatments further received some palliative treatments for disease recurrence or progression {8% (2/26) initial Surgery ± Adjuvant & 92% (24/26) ChemoRT}. The median overall survival for the cohort was 24 months (p < 0.001). There were more than 50% survival at 60 months for patients treated with curative 15 fractions concurrent ChemoRT (p < 0.001).

      8eea62084ca7e541d918e823422bd82e Conclusion

      Most patients received ChemoRT while a few had surgery. Concurrent 15 fractions ChemoRT may offer better survival benefits than the 25 fraction schedule. The impact of PCI on LS-SCLC and other survival outcomes will be presented.

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      P1.12-11 - 2010 – 2015 Extensive Stage SCLC Diagnoses in a Canadian Institution: Baseline Characteristics That Impact on the Overall Survival

      16:45 - 18:00  |  Presenting Author(s): Anifat A. Elegbede  |  Author(s): Michelle Dean, Gwyn Bebb

      • Abstract

      Background

      Small cell lung cancer (SCLC) represents only about 13 – 15% of lung cancers but has posed significant challenges due to minimal progress in therapeutics development prior to the recent advent of immunotherapy. Our objective is to establish baseline characteristics and overall survival of Extensive SCLC (ES-SCLC) based on the current conventional therapy for patients diagnosed within a 5 year period at the Tom Baker Cancer Centre, Canada. This information will be crucial in assessing the effectiveness of novel anti-immune checkpoint treatment strategies.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Using the Glans-Look Lung Research (GLR) database, we defined the clinical and demographic features of patients diagnosed with ES-SCLC from 2010 to 2015, determined the rate of systemic treatment uptake, and investigated the impact of prophylactic cranial irradiation and palliative treatments on overall survival. We summarized our findings with descriptive statistics (including Fisher’s Exact test) and Kaplan Meier curves using the SPSS. Statistical significance was set at p value < 0.05 and 95% confidence intervals.

      4c3880bb027f159e801041b1021e88e8 Result

      Among the 2010 to 2015 SCLC diagnoses, 68% (242/349) were ES-SCLC with median age of 68 years. Close to 90% received some form of palliative treatment. Chemotherapy (CT) was a major component of palliative treatments {89% overall, (190/214): 41% CT only, 22% CT & thoracic radiotherapy (RT) and 38% CT & RT-Other sites}. About a third (32%) of patients who received 1st line CT also had a 2nd line (range between 1 – 4 lines). Prophylactic cranial irradiation (PCI) uptake rates were 38% and 11% for CT only and CT & RT respectively. The median overall survival for ES-SCLC within the cohort was 7 months (p < 0.001).

      8eea62084ca7e541d918e823422bd82e Conclusion

      In contrast to advanced stage non-small cell lung cancers, there was high rate of sytemic treatment uptake for ES-SCLC. Overall however, < 20% (41/242) followed through with PCI. Other outcome findings will be presented and discussed.

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      P1.12-12 - A Systematic Review and Meta-Analysis of Early and Late Survival Following Anti-Cancer Therapies for Small Cell Lung Cancer

      16:45 - 18:00  |  Presenting Author(s): Gavin S Jones  |  Author(s): Kelly Elimian, David Raymond Baldwin, Tricia McKeever, Richard Hubbard

      • Abstract

      Background

      Treatments for small cell lung cancer (SCLC) have not changed significantly in contrast to non-small cell where it is more individually tailored. Current guidelines generally have a one size fits all approach to chemotherapy. We conducted the largest systematic review and meta-analysis in SCLC to evaluate early and median survival by different study factors.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We searched EMBASE and MEDLINE for randomized controlled trials and observational cohort studies which reported survival following platinum doublet chemotherapy for SCLC. We calculated overall survival at 30 and 90 days along with the median survival.

      4c3880bb027f159e801041b1021e88e8 Result

      We identified 10,487 titles, 161 were included. Cisplatin + etoposide (n=87 (49.4%)), carboplatin + etoposide (n=36 (20.5%)) and cisplatin + irinotecan (n=23 (13.1%)) were predominantly reported. The commonly reported cause of death within 30 days was neutropaenic sepsis (n=27), disease progression (n=11) and cardiovascular (n=8). Across both stages 30-day survival was 98% (95% CI 98-99%) whilst 90-day was 95% (95% CI 94-96%). Thirty and 90-day survival showed similar patterns to study factors as median survival (summarised in Table 1).

      Limited stage median survival was 18.1 months (95% CI 17.0-19.1). Studies that administered thoracic radiotherapy and PCI had better survival than those that did not. Studies giving carboplatin + etoposide or included poorer PS (0-3) individuals had inferior survival. PCI timing did not show survival differences.

      Extensive stage median survival was 9.6 months (95% CI 8.9-10.3). This was augmented in studies that gave irinotecan + cisplatin and were conducted in Asia. There were no survival differences by cisplatin/carboplatin or median participant age.

      median survival world lung.tif

      8eea62084ca7e541d918e823422bd82e Conclusion

      Neutropenic sepsis accounts for the majority of 30-day deaths and was mostly reported with cisplatin + etoposide. Our findings broadly support guideline recommendations but suggest certain sub-populations e.g. Asian individuals, benefit from targeted treatment with irinotecan + cisplatin. Age should be re-considered as a treatment-deciding factor in extensive stage.

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      P1.12-13 - Impact of Chronic Obstructive Pulmonary Disease on the Survival of Patients with Extensive-Disease Small Cell Lung Cancer

      16:45 - 18:00  |  Presenting Author(s): Eun Joo Kang  |  Author(s): Jung Sun Kim, Suk Young Lee, Ju Won Kim, Yoon Ji Choi

      • Abstract

      Background

      Small cell lung cancer (SCLC) is a highly fatal lung malignancy. Cigarette smoking is an important cause of SCLC, and most patients have heavy smoking history. Also, smoking is an established risk factor of chronic obstructive pulmonary disease (COPD). Therefore, patients who are diagnosed with SCLC have high chance to coincide with COPD. However, the coincidence rate of COPD and SCLC are not known well. Moreover, the impact of COPD on the mortality of patients with SCLC, especially for patients with extensive diesase (ED) is not reported yet. Therefore, we conducted investigation of clinical features and survival differences between patients who were diagnosed with SCLC with COPD or patients without COPD.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We retrospectively reviewed medical records of patients who were diagnosed with SCLC-ED and received treatment between 2002 and 2016 at the Korea University Hospital. Among the 182 patients who were diagnosed with SCLC-ED and received palliative chemotherapy, 125 patients who had pulmonary function test report and previous or current smoking history were included. According to the global initiative for chronic obstructive lung disease (GOLD) classification, COPD was defined as FEV1/FVC <0.70.

      4c3880bb027f159e801041b1021e88e8 Result

      Among 125 patients, COPD was present in 69 (55.2 %) patients. Among the patients with COPD, 48 (69.5%) patients did not know the COPD before the diagnosis of SCLC. Patients in the COPD group were older (mean age ± standard deviation, 68.9 ± 8.2 versus 65.6± 8.4 years; p=0.03). The mean FEV1(L) and predicted percent of FEV1 were 1.7L (67.9%) in COPD group and 2.9L (81.2%) in non-COPD group. Gender, body mass index, amount of smoking, ECOG performance status and neutrophil to lymphocyte ratio were not different between the two groups. Median overall survival of all patients was 8.6 months (95% confidential index [CI], 7.7-9.5). Median overall survival of the first-line chemotherapy between patients with COPD and patients without COPD was not statistically different (p=0.382). Median progression-free survival of the first-line chemotherapy between the two groups also were not different (p=0.372). In the analysis of COPD group, FEV1(L) and predicted percent of FEV1 did not affect survival among the patients with COPD (p=0.289).

      8eea62084ca7e541d918e823422bd82e Conclusion

      In conclusion, the presence of COPD at the diagnosis of SCLC-ED does not affect survival outcome in patients who were treated palliative chemotherapy. Even though the patients have severe obstructive pulmonary disease, active chemotherapy has to be considered with priority for the patients with SCLC-ED.

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      P1.12-14 - Survival of Patients with Small-Cell Lung Cancer Undergoing Surgical Resection

      16:45 - 18:00  |  Presenting Author(s): Shinji Kikuchi  |  Author(s): Junko Okamura, Kentaro Araki, Takahiro Yanagihara, Kojiro Nakaoka, Yusuke Kitazawa, Naohiro Kobayashi, Yukinobu Goto, Yuko Minami, Masataka Onizuka, Hideo Ichimura, Yukio Sato

      • Abstract

      Background

      Small-cell lung cancer (SCLC) prognosis remains poor despite improvements in diagnosis and therapy. Current standard treatment for limited stage SCLC is concurrent chemo-radiotherapy, however recent retrospective studies indicate that surgery is an important treatment modality. We analyzed the overall survival and prognostic predictors of survival in patients who underwent surgical resection.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We reviewed the clinical course of 42 SCLC patients who had undergone complete surgical resection in our hospital between May 1989 and October 2017. Stages were determined or reclassified according to the eighth version of the TNM staging system.

      4c3880bb027f159e801041b1021e88e8 Result

      The mean age at pulmonary surgery was 68.0 years, 37 (88.1%) patients were male, and 2 (4.8%) were never smokers. Preoperative diagnosis of cancer was achieved in 18 (42.9%) patients. The surgical procedures included wedge resection in 6 (14.3%) and lobectomy in 36 (85.7%). There were no perioperative deaths and major postoperative complications. Thirty-two patients (76.2%) received adjuvant chemotherapy and three patients (7.1%) underwent prophylactic cranial irradiation. Pathological stages were 2 cases in IA1, 5 in IA2, 1 in IA3, 6 in IB, 3 in IIA, 8 in IIB, 13 in IIIA, 3 in IIIB, 1 in IVA. The pathology of primary tumor demonstrated 30 (71.4%) pure SCLC and 12 (28.6%) combined SCLC. The overall 5-year survival rate was 57.2% after an average follow-up of 58.7 months. A significantly good survival was observed using univariate analysis in patients with female (p=0.048), preoperative normal serum level of CEA (p=0.013), normal serum level of SCC (p<0.001), pR0 resection (p=0.02), adjuvant chemotherapy (p<0.001), and histological pure SCLC (p=0.002). In preoperative factor, multivariate Cox proportional hazard model analysis revealed that overall survival was shorter in patients with increased SCC levels and cN1or 2.

      8eea62084ca7e541d918e823422bd82e Conclusion

      We conclude that pulmonary resection for early-stage SCLC is a safe and effective treatment strategy, and adjuvant chemotherapy may be useful in patients undergoing surgery in a practical management. Increased SCC levels and cN1 or 2 were identified as prognosis-related criteria for a poor prognosis of resected early SCLC.

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      P1.12-15 - Distinctive Clinical Characteristics of SCLC in Never-Smokers

      16:45 - 18:00  |  Presenting Author(s): Idrees Mian  |  Author(s): Samantha Nichols, Amy Abernethy, Ken Carson, Kathleen Maignon, Aracelis Torres, Jeremy Snider, Garrett M Frampton, Gerald Li, Elad Sharon, Eva Szabo, Anish Thomas

      • Abstract

      Background

      Epidemiologic data suggest that 3% of patients with SCLCs are never-smokers. A large population study is required to describe the characteristics and outcomes of SCLC in never-smokers. Defining SCLC subgroups based on clinical characteristics, specifically smoking status, may lead to treatment advances in this historically recalcitrant cancer.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We performed a multicenter analysis using the Flatiron Health electronic health record-derived database, a nationally representative database comprising patient-level structured and unstructured data curated via technology-enabled abstraction. The cohort consisted of patients with clinician confirmed SCLC diagnosed on or after January 1, 2013. Genomic data from a clinico-genomic database developed by Flatiron and Foundation Medicine was used for a subset of patients that had received next-generation sequencing on the FoundationOne panel. Clinical and genomic characteristics were compared between smokers and never-smokers using descriptive statistics while the presence of other cancers was confirmed via chart review for never-smokers. Association of patient characteristics with overall survival was assessed using a univariate Cox proportional hazards model.

      4c3880bb027f159e801041b1021e88e8 Result

      103 of 4655 (2.2%) SCLC patients were never-smokers. Characteristics of these patients were: female 65%, male 35%; Asian 4.85%, Black 4.85%, White 62.1%; extensive-stage (ES) 68.9%, limited-stage (LS) 20.4%, unknown 10.7%. Compared with smokers (n=4552), never-smokers were more likely to be 80+ years (p=0.040), female (p=0.013), Asian (p<0.001), and present with ES (p=0.038). Based on univariate analyses, poor prognostic factors in never-smokers included sodium < 140 mEql/L (HR=1.95; p=0.028) and ES (HR=2.62; p=0.013). 26 (25%) patients had confirmed history of multiple primary malignancies. Three patients had prior history of organ transplant and two patients had history of pulmonary fibrosis. Survival of never-smokers (8.0 months for ES and 20.6 months for LS) appeared similar to historical data from smokers with SCLC. In the subset of 251 SCLC patients where tumor mutation data was available, never-smokers (n=18, 7.2%) were less likely to have a detectable alteration in TP53 (44.4% vs 95.3%; p<0.001) or RB1 (27.8% vs 76.8%; p<0.001).

      8eea62084ca7e541d918e823422bd82e Conclusion

      The never-smoker subgroup of SCLC patients has important clinical and genomic features that portend diagnostic, prognostic, and therapeutic opportunities. A high-frequency of other malignancies raises concern for neuroendocrine differentiation from other primary tumors. This series represents the largest reported data on SCLC in never-smokers.

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      P1.12-16 - Management of Elderly Small-Cell Lung Cancer Patients in a Romanian Tertiary Care Center

      16:45 - 18:00  |  Presenting Author(s): Lucian Miron  |  Author(s): Teodora Alexa-Stratulat, Bogdan Gafton, Mihai Vasile Marinca, Marius Paduraru, Andrei Luca, Vlad Afrasanie

      • Abstract

      Background

      Small cell lung cancer (SCLC) remains one of the most challenging conditions due to its poor prognosis and lack of effective treatments. Although guidelines recommend aggressive treatment in elderly SCLC patients with good performance status, real-life data indicates that this patient subgroup is still undertreated. The aim of this analysis was to assess survival and management in elderly SCLC patients from North-East Romania.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We performed a retrospective analysis of all elderly patients diagnosed with SCLC and treated in the Regional Institute of Oncology Iasi (a territorial unit responsible for the diagnosis and treatment of cancer patients in Moldova) between 2012 and 2016. For each patient, we collected several types of data regarding patient status, tumor stage and management options that were correlated with overall survival.

      4c3880bb027f159e801041b1021e88e8 Result

      We identified 41 patients diagnosed with SCLC and over 65 years old at the time of diagnosis. Average age was 69.63±3.98, with a median of 69 and a maximum of 78 years. The male to female ratio was 5.83:1, all patients were current or former smokers and performance status was 1 in 76.2% of cases. Most patients (57.1%) were diagnosed in stage IV and received doublet platinum-based systemic treatment in the first line setting. In the subgroup diagnosed with stage III disease, none of the patients received concurrent chemo-radiotherapy and less than half (35.29%) received sequential treatment. Although assessment after first-line treatment was available for less than half of the cases (39.02%), only one patient had progressive disease at that time-point (most were characterized as having a partial response). However, prophylactic cranial irradiation was performed in only 7.31% of cases. Second-line systemic treatment was initiated in 24.39% of cases – the preferred regimen was the CAV protocol followed by oral Topotecan. Overall survival was 11.17 months, with a maximum of 50 months and with statistically significant differences depending on stage and performance status. Age did not influence survival.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Although elderly patients represent an important segment of the individuals affected by SCLC, they are sometimes undertreated and less aggressive management still seems to be the preferred approach despite good performance status and frequent response to first-line therapy. Most likely due to their age or because they delay seeking medical attention, elderly SCLC patients are more often diagnosed in metastatic stages. Our data for Romanian patients is mainly in accordance with available literature, although we found lower overall survival rates.

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      P1.12-17 - Overall Survival and Recurrence After Surgical Resection of Pure and Mixed Large Cell Neuroendocrine Tumors.

      16:45 - 18:00  |  Presenting Author(s): Brooks Udelsman  |  Author(s): Anna F. Farago, Mari Mino-Kenudson, Ashok Muniappan, Douglas Mathisen, Michael Lanuti

      • Abstract

      Background

      Large-cell neuroendocrine carcinoma (LCNC) is an aggressive tumor with poor prognosis and undefined treatment. We performed a retrospective analysis on the outcomes of surgical resection and adjuvant therapy to assess the effectiveness of treatment.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Retrospective review of patients with LCNC who underwent surgical resection at a single-center tertiary care facility from 2002-2017. Survival times were assessed from day of surgery until death. A Kaplan-Meier method for overall survival (OS) and for recurrence was used and compared across prognostic factors using log-rank analysis and a Cox proportional hazard model.

      4c3880bb027f159e801041b1021e88e8 Result

      Sixty-two patients were identified with a median follow up of 3.4 years. Of these, 26 (41.9%) were male and 56 (90.3%) were current or former smokers. The majority of patients underwent a lobectomy/segmentectomy (72.6%), while a smaller percentage (14.5%) underwent wedge resection, and the remainder pneumonectomy or bi-lobectomy (4.8%). Pathologically, 31 (54.4%) were stage I, 20 (35.1%) stage II, and 6 (10.5%) stage III-IV. Additionally, 35 (56.4%) represented pure LCNC while the remaining 27 (43.6%) had a mixed histology. Median OS for resected stage I disease was 11.3 years, decreased to 4.4 years in stage II disease, and was 0.8 years in stage III-IV disease (p = 0.01) (Figure 1). For those that recurred, median time to recurrence was 1.20 years for stage I and 1.15 years for stage II disease. Adjuvant therapy, type of resection, and tumor histology (pure vs. mixed) had no significant impact on OS on unadjusted or adjusted analysis.

      figure1.jpg

      8eea62084ca7e541d918e823422bd82e Conclusion

      LCNC is associated with early recurrence after surgical resection and poor survival for patients with stage III and IV disease. In patients with mixed histology survival and recurrence remain similar to those with pure LCNC tumors.

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      P1.12-18 - Outcome in Small Cell Lung Cancer Patients with Cerebral Recurrence After Prior Prophylactic Cranial Irradiation    

      16:45 - 18:00  |  Presenting Author(s): Lei Zhao  |  Author(s): Jindong Guo, Xuwei Cai, Xiaolong Fu

      • Abstract

      Background

      Prophylactic cranial irradiation (PCI) is a standard therapy for both limited small cell lung cancer (SCLC) and extensive SCLC patients with good responses to first-line treatment. The aim of this study was to examine outcomes in SCLC patients in a single institution who underwent cerebral recurrence after prior PCI.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We retrospectively examined the medical records of 219 consecutive SCLC patients who had initially received PCI(25 Gray in 10 fractions) between June 2007 to June 2017. Data were analyzed with regard to age, sex, smoking status, treatment, disease stage, data of PCI, time to cerebral recurrence, site of cerebral recurrence, re-irradiation after cerebral recurrence and time to death. Survival was estimated by the Kaplan-Meier method. Multivariate analyses were performed by the log-rank and Cox’s proportional hazard model test.

      4c3880bb027f159e801041b1021e88e8 Result

      Of the 219 patients undergoing PCI, 180(82.2%) were LD-SCLC and 39(17.8%) were ED-SCLC. The median age was 59 years and the median follow-up time was 23.7 months. The median overall survival (OS) of all patients from the time of diagnosis was 39.0 months (95%CI, 29.6–48.4), in LD-SCLC it was 47.0 months (95%CI, 35.4–58.6), and in ED-SCLC it was 19.0 months (95%CI, 17.0–21.0). The difference was statistically significant with P=0.000.

      Forty-six patients (21.0%) were diagnosed with cerebral recurrence. 30(65.2%) of these presented with oligometastatic disease and 16(34.8%) had non-oligometastatic disease. Cox multivariate analysis identified disease stage (P=0.043) was the only significantly favorable prognostic factor for cerebral recurrence. The median survival time from PCI was 21.0 months (95%CI, 12.5–29.5), in oligmetastatic disease it was 35.0 months (95%CI, 19.0–51.0), and in non-oligometastatic disease it was 16.0 months (95%CI, 12.1–19.9). The difference was statistically significant with P=0.007. Meanwhile, the median time from PCI to cerebral recurrence was 11.0 months (95%CI, 9.5–12.5), in oligmetastatic disease it was 11.0 months (95%CI, 6.7–15.3), and in non-oligometastatic disease it was 10.0 months (95%CI, 8.4–11.6). There was no statistical significance between the two.

      Among forty-six patients with cerebral recurrence, 34 patients underwent re-irradiation using either Re-WBRT (11patients, 23.9%) or SRS /SRT (23patients, 50.0%), another 12 patients (26.1%) did not accept radiotherapy to brain. The median survival time from cerebral recurrence was 10 months (95%CI, 4.1-16.0) for re-irradiation and 4 months (95%CI, 2.3-5.8) for no radiotherapy group, respectively. The difference was statistically significant with P=0.000.

      8eea62084ca7e541d918e823422bd82e Conclusion

      PCI remains standard therapy for SCLC patients with good responses to first-line treatment. Cerebral recurrence is inevitable, however, cerebral re-irradiation after recurrence is proven to be beneficial for survival.

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      P1.12-19 - Clinico-Pathological Characteristics and Treatment Outcome in Small Cell Lung Cancer: A Single Institutional Experience

      16:45 - 18:00  |  Presenting Author(s): Sandip Ganguly  |  Author(s): Bivas Biswas, Joydeep Ghosh, Raj kumar Shrimali, Saugata Sen, Sumit Mukhopadhyay, Geetashree Mukherjee, Divya Midha, Deepak Dabkara, Archisman Basu, Meheli Chatterjee, Ammara Hassan, Shashanka S Das

      • Abstract

      Background

      Lung cancer is one of the commonest cancer in the world with a high rate of mortality. Small cell lung cancer constitutes around 14% of all lung cancers. Literature on small cell lung cancer is scarce in literature. The aim of the study was to analyze clinical profile of patients with lung cancer and their treatment outcome.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      This is a single institutional data review of patients treated between June 2011 and Dec 2017 with diagnosis of small cell carcinoma of lung. Patients were staged as either localized or extensive disease after appropriate staging work-up. Patients with localized disease were treated with concurrent chemo-radiation with platinum based chemotherapy. Those with extensive disease were treated with platinum based palliative chemotherapy. Clinic-pathological characteristics, treatment details and outcome were recorded in this study. Response assessment was done using RECIST criteria wherever applicable. Patients who received at least 1 cycle of palliative chemotherapy were included for survival analysis.

      4c3880bb027f159e801041b1021e88e8 Result

      Total 128 patients were registered with median age of 62 years (range: 38-86), male:female ratio of 115:13. The ECOG performance status was 0 in 2, 1 in 30 (23%), 2 in 64, (50%) 3 in 29 (22%) and 4 in 3 patients. Ninety-percent (n=112) patients had smoking history and 20% (n=25) patients had symptom of superior vena cava obstruction at baseline. Eleven (9%) patients had localized disease at presentation. Sixteen (12.5%) patients had brain metastasis at presentation. Eighty-two (64%) patients took palliative chemotherapy and eight (10%) of them had localized disease. Chemotherapy regimen was – carboplatin only in 5 (6%), etoposide-carboplatin in 29 (35%) and cisplatin-etoposide in 48 (58%). Patients received median cycle number of 6 (range:1-6). Of the evaluable 58 (71%) patients, initial response was complete response in 2, partial response in 37, stable disease in 15 and progressive disease in 4. Fifteen patients received second-line chemotherapy on progression of disease. After a median follow-up of 6.7months (range: 0.3 - 36.6), median progression-free survival was 8.6 months.. After a median follow up of 12.5 months (range:0.3-36.6), median overall survival was 8.7 months.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Small cell carcinoma in our series had high incidence of advanced stage (91%) and 10% patients were non- smoker. Only 64% patients received palliative chemotherapy and achieved high disease control rate (>90%) in the evaluable patients with median progression-free survival of 8.6 months and median overall survival of 8.7 months.

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      P1.12-20 - Overall Survival with Lurbinectedin Plus Doxorubicin in Relapsed SCLC. Results from an Expansion Cohort of a Phase Ib Trial.

      16:45 - 18:00  |  Presenting Author(s): Martin Forster  |  Author(s): Victor Moreno, Emiliano Calvo, Maria Eugenia Olmedo, Maria Pilar Lopez-Criado, Jose Antonio Lopez-Vilariño, Rafael Nuñez, Carmen Kahatt, Arturo Soto-Matos

      • Abstract

      Background

      Lurbinectedin (PM01183, L) is a new anticancer drug that binds to DNA, inhibits transactivated transcription and modulates tumor microenvironment. Preclinical evidence of synergism was observed for PM01183 in combination with doxorubicin (DOX).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      This multicenter, phase Ib clinical trial found impressive activity in second-line SCLC patients (ORR 67%). An expansion cohort with reduced dose (L 2mg/m2+ DOX 40mg/m2) was implemented to improve safety. SCLC patients <75 years with ECOG PS 0-1 and with no more than one prior chemotherapy line and stable brain metastases were included. DOX was interrupted after 10 cycles continuing with PM01183 alone. Primary G-CSF prophylaxis was not mandatory.

      4c3880bb027f159e801041b1021e88e8 Result

      27 patients treated. Males: 75%; median age: 64 (49-77) years; ECOG PS 0-1: 32%-68%; CNS involvement: 4%; bulky disease (>50 mm): 75%. 88% responded to 1st line (CR in 4%). Median chemotherapy-free interval (CTFI) was 3.5 months (m). 22% refractory (CTFI <30 days) 15% resistant (R) (CTFI 30-90 days) and 63% sensitive (S) (CTFI>90 days). Overall confirmed ORR was 37% (CR in 4%), and 53% (CR in 6%) in S patients. Overall median PFS was 3.4 m (95% CI, 1.5-6.2), being 1.5 m (95%CI, 0.8-3.4) in R pts, and 5.7 m in S patients. Overall survival (OS) data are summarized in the following table.

      OS

      Overall

      Resistant

      Sensitive

      Overall (n=27)

      7.9 m

      (95% CI: 4.9-11.5)

      4.9 m

      (95% CI: 2.3-6.7)

      11.5 m

      (95% CI: 6.0-16.6)

      Excluding CTFI<30days (n= 21)

      10.2 m

      (95% CI: 6.0-12.1)

      6.7 m

      (95% CI: 5.1-8.4)

      11.5 m

      (95% CI: 6.0-16.6)

      Data shown are median and 95% CI.

      Grade 4 neutropenia, anemia or thrombocytopenia appeared in 64%/0%/7% of patients, respectively, and febrile neutropenia (G3/4) occurred in 10%. Non-hematological toxicity was mild and mainly due to fatigue (G3=18%) and nausea (G3=7%).

      8eea62084ca7e541d918e823422bd82e Conclusion

      Lurbinectedin/DOX combination showed remarkable activity as second line in SCLC, especially in sensitive patients (CTFI>90 days). Activity is higher than that reported for CAV or topotecan. OS shows an outstanding improvement in this second-line setting, especially when excluding refractory pts. A phase III clinical trial (ATLANTIS, NCT02566993) is currently ongoing evaluating this combination in relapsed SCLC patients

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      P1.12-21 - Developing a Real-World 3L Comparator to CheckMate 032: Overall Survival (OS) in Patients with Small Cell Lung Cancer (SCLC)

      16:45 - 18:00  |  Presenting Author(s): Lee S Schwartzberg  |  Author(s): Beata Korytowsky, John Penrod, Yong Yuan, Tao Gu, Trong Kim Le, Pranav Samuel Abraham, Giovanni Selvaggi

      • Abstract

      Background

      In the US, no approved standard of care exists for the treatment of relapsed SCLC in 3L setting. This study describes 3L outcomes in US patients with SCLC and creates a matched real-world historical comparator to CheckMate 032, highlighting the relative benefit that nivolumab treatment may offer to patients.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Adult patients receiving 3L therapy for SCLC were selected from the Flatiron Health electronic health record (EHR) database (01Jan2011-30Sep2017). Index date was SCLC diagnosis. A matched cohort was constructed and evaluated based on Inclusion (I)/Exclusion (E) criteria of CheckMate 032. Patients were included if: pretreated with ≥1one platinum-containing regimen; ECOG score of 0 or 1; ≥2 months of continuous medical data. Patients were excluded if: treated with immunotherapy; had brain metastases; autoimmune disease (except type I diabetes); HIV; Hep B/Hep C on/after diagnosis; on immunosuppressive doses of systemic corticosteroids. Kaplan-Meier curves were generated for patients with 3L SCLC from treatment initiation to death. Duration of therapy (DoT) was analyzed as time from start to end of 3L

      4c3880bb027f159e801041b1021e88e8 Result

      2,209 SCLC patients initiated 1L, of which 218(9.8%) received 3L treatment. 92 patients with SCLC matched I/E criteria as in CM 032. Mean age was 64 years; 53% were female; 68% were white; 99% had a history of smoking; and 94% of patients were treated in a community setting. Median follow-up exceeded 15 months. Median and landmark OS (1-year, 18-months, 2-year) and DoT including data for a subset of 3L patients, matched for I/E criteria to CheckMate 032 (n=92), are reported in the table.

      Table: Overall Survival in Third-line SCLC Treatment

      Flatiron Electron Health Record

      CheckMate 032

      All 3L Patients with SCLC

      (N = 218)

      I/E Matched 3L Patients with SCLC

      (N = 92)

      All 3L+ Patients with SCLC

      Median OS (95% CI), months

      3.8 (3.0, 4.2)

      3.8 (2.8, 4.9)

      [Data to be presented at conference]

      1-year OS rate (95% CI), %

      14.1 (9.3, 19.9)

      11.2 (4.9, 20.4)

      18-month OS rate (95% CI), %

      6.7 (3.4, 11.6)

      7.5 (2.5, 15.9)

      2-year OS rate (95% CI), %

      6.0 (2.9, 11.7)

      7.5 (2.5, 15.9)

      Median DoT (SD), months

      2.7 (2.6)

      2.8 (2.2)

      Abbreviations: 3L, third-line; CI, confidence interval; DoT, duration of treatment; Exc, exclusion criteria; Inc, inclusion criteria; OS, overall survival; SCLC, small-cell lung cancer; SD, standard deviation

      8eea62084ca7e541d918e823422bd82e Conclusion

      Poor survival among US patients treated for 3L SCLC emphasizes the need for more effective and tolerable therapies. In CheckMate 032, nivolumab demonstrated considerable activity in heavily pretreated patients when compared to real-world data and may represent a therapeutic option over available treatments.

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    P1.13 - Targeted Therapy (Not CME Accredited Session)

    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Moderators:
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      P1.13-01 - Anti-EGF Antibodies Increase the Effect of ALK and MEK Inhibitors in ALK and KRAS NSCLC and CRC Cell Lines

      16:45 - 18:00  |  Presenting Author(s): Silvia Garcia - Roman  |  Author(s): Jordi Codony-Servat, Miguel-Angel Molina-Vila, Jordi Bertran-Alamillo, Ana Giménez-Capitán, Santiago Viteri, Andrés F. Cardona, Delvys Rodríguez-Abreu, Manuel Cobo Dols, Noemi Reguart, Niki Karachaliou, Erik D'Hondt, Rafael Rosell

      • Abstract

      Background

      Immunization against Epidermal Growth Factor (EGF) has demonstrated efficacy in a phase III trial including unselected NSCLC patients, and we have recently shown that antibodies generated by vaccination (anti-EGF VacAbs) potentiate the effects of TKIs in EGFR-mut cells growing in vitro. In this study, we aimed to determine if anti-EGF VacAbs show antitumor activity in KRAS-mutant (mut) and Anaplastic Lymphoma Kinase (ALK) translocated non-small cell lung cancer (NSCLC) and colorectal cancer (CRC) cells, alone or in combination.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Anti-EGF VacAbs were generated in rabbits. Cell lines were treated with anti-EGF VacAbs alone and in combination with ALK TKIs, trametinib and standard chemotherapeutic agents in ALK translocated (H3122, E13;A20 (v1) and H2228, E6;A20 (v3)) and lung (A549 and H23) and colon (DLD1 and LS174T) KRAS-mut cell lines. Cell viability was analyzed by MTT, changes of total and phosphorylated proteins by Western blot and emergence of resistance by direct microscopic examination in low density cultures.

      4c3880bb027f159e801041b1021e88e8 Result

      Anti-EGF VacAbs suppressed EGF-induced cell proliferation and inhibited EGFR phosphorylation signaling in all cell lines tested. In combination, the anti-EGF VacAbs significantly enhanced the antitumor activity of alectinib and crizotinib in H2228 cells and trametinib in A549, H23 and DLD1 cells. In these cell lines, the antibodies decreased Erk ½ and Akt phosphorylation. Finally, the addition of the anti-EGF VacAbs to the culture medium significantly delayed the emergence of resistant clones to alectinib and crizotinib in H2228 cells. In previous experiments, H2228 cells had shown a stronger dependency on the EGF/EGFR pathway than H3122. Results for the combination with standard chemotherapy in KRAS-mut cell lines will be presented at the meeting.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Anti-EGF VacAbs decreased cell proliferation and inhibited EGFR activation in lung and colon ALK translocated and KRAS-mut cell lines. In addition, they potentiated the effects of trametinib in KRAS-mut cells and TKIs in ALK translocated cells (v3), where they also prevented the emergence of resistance to alectinib and crizotinib. Two clinical trials are currently testing anti-EGF vaccination in advanced NSCLC; the Epical Phase I/II trial, in combination with EGFR TKIs in EGFR-mut patients; and the BV-NSCLC-002 Phase III trial, in combination with chemotherapy in EGFR-wt.

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      P1.13-02 -  eXalt3: Phase 3 Randomized Study Comparing Ensartinib to Crizotinib in Anaplastic Lymphoma Kinase Positive Non-Small Cell Lung Cancer Patients

      16:45 - 18:00  |  Presenting Author(s): Leora Horn  |  Author(s): Yi-Long Wu, Martin Reck, Heather A Wakelee, Chris Liang, Kimberly Harrow, Vance Oertel, Tony S. Mok

      • Abstract

      Background

      Ensartinib (X-396) is a novel, potent ALK small molecule tyrosine kinase inhibitor (TKI). It is well-tolerated and has shown promising activity in NSCLC patients in a phase 1/2 study in patients that were both ALK TKI naïve and patients that received prior crizotinib, as well as those with CNS metastases. The safety profile of ensartinib appears to be different from other ALK TKIs.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      In this global, phase 3, open-label, randomized study, approximately 270 patients with ALK+ NSCLC who have received no prior ALK TKI and up to one prior chemotherapy regimen will be randomized with stratification by prior chemotherapy (0/1), performance status (0-1/2), brain metastases at screening (absence/presence), and geographic region (Asia /other), to receive oral ensartinib (225 mg, once daily) or crizotinib (250mg, twice daily) until disease progression or intolerable toxicity.

      Eligibility also includes patients ≥ 18 years of age, stage IIIB or IV ALK+ NSCLC. Patients are required to have measurable disease per RECIST 1.1, adequate organ function, and an ECOG PS of ≤2. Adequate tumor tissue (archival or fresh biopsy) must be available for central testing. The primary endpoint is progression-free survival assessed by independent radiology review based on RECIST v. 1.1 criteria. Secondary efficacy endpoints include overall survival, response rates (overall and central nervous system [CNS]), PFS by investigator assessment, time to response, duration of response, and time to CNS progression. The study has > 80% power to detect a superior effect of ensartinib over crizotinib in PFS at a 2-sided alpha level of 0.05.

      Phase 3 recruitment began in June, 2016 and currently has 98 active sites in 21 countries. The duration of recruitment will be approximately 28 months. This study is registered with ClinicalTrials.Gov as NCT02767804.

      4c3880bb027f159e801041b1021e88e8 Result

      Section not applicable

      8eea62084ca7e541d918e823422bd82e Conclusion

      Section not applicable

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      P1.13-03 - Ensartinib Treatment Beyond Disease Progression in Stage IV ALK+ Non-Small Cell Lung Cancer

      16:45 - 18:00  |  Presenting Author(s): Leora Horn  |  Author(s): Sandip Patel, Saiama N. Waqar, George R Blumenschein, Kimberly Harrow, Allison Holzhausen, Chris Liang, Gary Dukart, Heather A Wakelee

      • Abstract

      Background

      Anaplastic Lymphoma Kinase (ALK) positive non-small cell lung cancer (NSCLC) patients (pts) benefit from receiving ALK tyrosine kinase inhibitors (TKIs); however, despite initial activity, resistance invariably develops. Disease progression (PD) is sometimes limited to progression which occurs in only one or a few sites and may not occur systemically. Local treatment with radiation while continuing treatment with ensartinib may enable prolonged benefit beyond progression.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Patients who were ALK TKI naïve or had received prior ALK treatment received ensartinib 225mg QD until PD or unacceptable toxicity or investigator discretion. The primary endpoint was safety and tolerability, and the secondary endpoint was pharmacokinetic and preliminary biological activity. Tumor assessment was performed locally every 8 weeks. Post-progression treatment with ensartinib was allowed if the investigator felt the patient was still receiving benefit from ensartinib. Cycles were approximately every 28 days, and radiation therapy after Cycle 1 for isolated CNS metastases was permitted if there was no evidence of progressive disease elsewhere. Post-progression treatment data were captured and analyzed.

      4c3880bb027f159e801041b1021e88e8 Result

      As of the data cut-off (May 01, 2018), 12 pts with progression continued ensartinib treatment post progression (67% with progression only in the CNS, 75% of which had CNS lesions at baseline and 33% with progression only outside the CNS). Of the 12 pts, half of the patients were ALK TKI naïve and half had received at least one prior ALK TKI. Six pts received radiation therapy at the time of initial progression. The initial median Progression Free Survival (PFS) of the 12 pts with post progression treatment was 15.7 months and median secondary PFS (date of initial progression to the date of second progression or end of treatment) was 5.7 months for a combined duration of therapy of 23.8 months. A significantly longer duration of continued therapy was observed in patients who received radiation treatment than those who did not 8.6 mos vs 3.5 mos. The secondary PFS was longer in treatment naïve pts than in pts who received a prior ALK TKI, 7.7 mos vs 5 mos. After the initial progression, excluding lesions treated with radiation therapy, secondary stable disease was observed in 92% of patients. No new or additional safety risk was identified in the pts post progression.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Ensartinib may have clinical benefit in selected patients with NSCLC if continued post-progression. Secondary PFS was longer in patients treated with radiation therapy. Ensartinib was generally well tolerated in these patients treated post progression.

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      P1.13-04 - Integrin β3 Inhibition Enhances the Antitumor Activity of ALK Inhibitor in ALK Rearranged NSCLC

      16:45 - 18:00  |  Presenting Author(s): Mi-Sook Lee  |  Author(s): Ka-Won Noh, Minjung Sung, Yoon-La Choi

      • Abstract

      Background

      Anaplastic lymphoma kinase (ALK)-positive cancers are sensitive to small molecule ALK kinase inhibitors, but most cases experience failure following treatment. Hence, additional drug targets and combination therapeutic treatments are needed. We investigated gene expression that is regulated by the expression of ALK and explored its roles in cancer progression and therapeutic implication.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We screened ALK-rearranged non-small cell lung cancer (NSCLC) cases using immunohistochemistry and fluorescence in situ hybridization, and then conducted multiplex gene expression analysis. We also performed a clinicopathological analysis to validate the findings. Additional cellular experiments, including inhibition and migration assays, and in vivo lung cancer model studies were performed.

      4c3880bb027f159e801041b1021e88e8 Result

      Among patients with ALK-rearranged NSCLC, integrin β3 (ITGB3) was one of the overexpressed genes in comparison with that in ALK-negative NSCLC (P = 0.0003). ALK and integrin β3 expression were positively correlated, and we discovered that high integrin β3 mRNA expression was associated with metastasis and more advanced tumor stages (P <0.005; P < 0.05). Furthermore, we found that inhibition of both ALK and integrin β3 led to increased drug sensitivity in vitro and in vivo (both P < 0.05).

      8eea62084ca7e541d918e823422bd82e Conclusion

      We discovered a positive correlation between ALK and integrin β3 expression levels in ALKrearranged NSCLC. Our findings suggest that high integrin β3 expression in ALK-rearranged NSCLC is associated with tumor progression and a worse prognosis. This demonstrates the prognostic value of integrin β3 and provides a rationale for combination treatment with ALK and integrin β3 inhibitors in patients with ALK-rearranged NSCLC.

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      P1.13-05 - Integrin β3 Inhibition Enhances the Antitumor Activity of Alk Inhibitor in Alkrearranged NSCLC

      16:45 - 18:00  |  Presenting Author(s): Mi-Sook Lee  |  Author(s): Ka-Won Noh, Minjung Sung, Yoon-La Choi

      • Abstract

      Background

      Anaplastic lymphoma kinase (ALK)-positive cancers are sensitive to small molecule ALK kinase inhibitors, but most cases experience failure following treatment. Hence, additional drug targets and combination therapeutic treatments are needed. We investigated gene expression that is regulated by the expression of ALK and explored its roles in cancer progression and therapeutic implication.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We screened ALK-rearranged non-small cell lung cancer (NSCLC) cases using immunohistochemistry and fluorescence in situ hybridization, and then conducted multiplex gene expression analysis. We also performed a clinicopathological analysis to validate the findings. Additional cellular experiments, including inhibition and migration assays, and in vivo lung cancer model studies were performed.

      4c3880bb027f159e801041b1021e88e8 Result

      Among patients with ALK-rearranged NSCLC, integrin β3 (ITGB3) was one of the overexpressed genes in comparison with that in ALK-negative NSCLC (P = 0.0003). ALK and integrin β3 expression were positively correlated, and we discovered that high integrin β3 mRNA expression was associated with metastasis and more advanced tumor stages (P < 0.005; P < 0.05). Furthermore, we found that inhibition of both ALK and integrin β3 led to increased drug sensitivity in vitro and in vivo (both P < 0.05).

      8eea62084ca7e541d918e823422bd82e Conclusion

      We discovered a positive correlation between ALK and integrin β3 expression levels in ALK rearranged NSCLC. Our findings suggest that high integrin β3 expression in ALK-rearranged NSCLC is associated with tumor progression and a worse prognosis. This demonstrates the prognostic value of integrin β3 and provides a rationale for combination treatment with ALK and integrin β3 inhibitors in patients with ALK-rearranged NSCLC.

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      P1.13-06 - First-Line Lorlatinib Versus Crizotinib for Advanced Anaplastic Lymphoma Kinase-Positive (ALK<sup>+</sup>) Non-Small Cell Lung Cancer

      16:45 - 18:00  |  Presenting Author(s): Alice T. Shaw  |  Author(s): Todd M. Bauer, Toshiaki Takahashi, Christina S Baik, Yasushi Goto, Anna Polli, Marina Carpentieri, Jean-François Martini, Ben J Solomon

      • Abstract

      Background

      Lorlatinib and crizotinib are oral tyrosine kinase inhibitors with activity against ALK and ROS1 fusion proteins. Crizotinib is well tolerated and has superior efficacy compared to chemotherapy for treatment of patients with advanced ALK+ non-small-cell lung cancer (NSCLC). However, resistance to crizotinib can develop, and the central nervous system (CNS) is often a site of disease relapse. Second-generation ALK inhibitors, ceritinib and alectinib, have demonstrated activity in crizotinib-naive or resistant treatment settings, and alectinib has been shown to have superior progression-free survival (PFS) compared to crizotinib as first-line therapy. Lorlatinib is a selective, CNS-penetrant ALK inhibitor that has potent activity against ALK and kinase domain resistance mutations, including the difficult-to-treat G1202R mutation.Lorlatinib has shown clinical activity in patients previously treated with crizotinib and other ALK inhibitors, including patients with progressive CNS metastases. This study aims to determine if lorlatinib is superior to crizotinib in prolonging PFS in treatment-naïve patients and to identify candidate biomarkers predictive of clinical efficacy or treatment resistance.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Trial Design

      This global, multicenter, open-label phase 3 study will enroll ~280 treatment-naïve patients. Eligible patients must be aged ≥18 years, have Eastern Cooperative Oncology Group performance status of 0–2 and ≥1 measurable extracranial target lesion not previously treated with radiotherapy. Patients with asymptomatic brain metastases are eligible. Patients will be randomized (1:1) to lorlatinib 100 mg once daily or crizotinib 250 mg twice daily and stratified by presence of brain metastases (yes/no) and ethnicity (Asian/non-Asian). Treatment will continue until disease progression, patient refusal, or unacceptable toxicity. Crossover between treatment arms will not be permitted. The primary endpoint is PFS based on blinded independent central review (BICR) using RECIST v1.1. Secondary endpoints include PFS based on investigator assessment, overall survival, objective response (OR) by BICR and investigator assessment; intracranial (IC) OR (periodic magnetic resonance imaging will be performed for central nervous system evaluation), IC time to progression, duration of response and time to response all by BICR; tumor tissue and peripheral blood circulating free DNA biomarker assessment, adverse events and patient-reported health-related outcomes as assessed by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core-30 EORTC (QLQ-C30) and EORTC Lung Cancer Module (QLQ-LC13), and the 5-level EuroQol 5-dimension questionnaire (EQ-5D-5L). The first patient was screened on April 14, 2017. This study is registered with ClinicalTrials.gov as NCT03052608.

      4c3880bb027f159e801041b1021e88e8 Result

      Section not applicable

      8eea62084ca7e541d918e823422bd82e Conclusion

      Section not applicable

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      P1.13-07 - Epithelial-Mesenchymal Transition Induced the Acquired Resistance to ALK Inhibitor Brigatinib in Lung Cancer Cells Harboring with ALK Fusions

      16:45 - 18:00  |  Presenting Author(s): Keiko Tanimura  |  Author(s): Tadaaki Yamada, Naoko Okura, Junji Uchino, Koichi Takayama

      • Abstract

      Background

      The ALK inhibitors, such as crizotinib and alectinib show a great response to patients with non-small cell lung cancer (NSCLC) harboring ALK fusions. However, the acquired drug resistance is also known as important issues in the treatment with the specific molecular targeted agents, such as EGFR-TKI as well as ALK-TKI. The mechanisms of acquired resistance to ALK-TKI are reported previously, bypass tract signals of EGFR or MET, and Epithelial-mesenchymal transition (EMT). Novel generation ALK inhibitor brigatinib is promising for NSCLC harboring ALK fusions, however, the precise mechanism of the acquired resistance to brigatinib is not fully understood. To elucidate for the novel acquired resistance to brigatinib, we here conducted the cell-based experiments using ALK fusion NSCLC cells.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We established ALK fusion NSCLC cells H3122 (variant 1 E13;A20) and H2228 (variant 3 E6; A20) with the acquired resistance to brigatinib by step-wise methods. ALK inhibitor sensitivity and signal transduction in H3122 and H2228 cells were examined in vitro.

      4c3880bb027f159e801041b1021e88e8 Result

      H3122-brigatinib resistance cell (H3122-BR) and H2228-brigatinib resistance cell (H2228-BR) indicated the cross-resistance to other ALK inhibitors alectinib, crizotinib and lorlatinib. Furthermore, morphological change was observed to spindle shape, and additionally shows decreasing of E-cadherin and increasing of vimentin which are marker of EMT by the western blotting analysis. Moreover, some of these resistant cells cultured with drug-free medium for 4weeks were reversed the sensitivity to ALK-TKIs and cell formation backed to parental cells.

      8eea62084ca7e541d918e823422bd82e Conclusion

      We demonstrated that EMT elicited the acquired resistance to ALK-TKIs under the exposure of brigatinib treatment in ALK fusion NSCLC cells. Further experiments are needed to overcome this drug resistance induced by EMT.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      P1.13-08 - Distribution, Differences in Clinical Characteristics and Resistance Mechanism of ALK Variants in Chinese Lung Cancer Patients.

      16:45 - 18:00  |  Presenting Author(s): Xuefeng Xia  |  Author(s): Jun Zhao, Qin Li, Gen Lin, Xiaorong Dong, Li Liu, Likun Chen, Jianhua Chen, Yong He, Xinghao Ai, Renhua Guo, Wenxian Wang, Chunwei Xu, Rongrong Chen, Yi Xin

      • Abstract

      Background

      ALK rearrangements are established targetable drivers in NSCLC. Recent reports indicate differential progression-free survival to ALK inhibitors according to specific EML4-ALK variant.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      A total of 172 unique Chinese lung cancer patients with tumors harboring ALK rearrangements (ALK+) were enrolled in the study from 2016 to 2018. ALK+ were detected by Ventana, FISH, or next-generation sequencing based ER-Seq method, which enables simultaneously assess single-nucleotide variants, insertions/deletions, rearrangements, and somatic copy-number alterations across at least 59 genes (59-1021). Tissue biopsy was the first choice for NGS mutation profiling, and ctDNA or pleural effusion testing was used as an alternative.

      4c3880bb027f159e801041b1021e88e8 Result

      Of these 172 cases, the median diagnosis age was 50 (range 24-78), 58% were female, 90% was NSCLC. Of the 147 ALK+ cases detected by NGS, we identified 65 (44%) EML4-ALK v1 (E13; A20), 18 (12%) EML4-ALK v2 (E20; A20), 43 (29%) EML4-ALK v3 (E6; A20), 13 (9%) other EML4-ALK, and 8 (5%) non-EML4-ALK rearrangements. 2 new fusion genes were found in non EML4-ALK rearrangements (SRBD1-ALK (EX20; EX20) and CLIP4-ALK (EX9; EX20)), and the CLIP4-ALK patient’s tissue was also ALK positive by Ventana. V1 found a higher proportion of pleural effusion at baseline than non-v1 (12% v.s.5%). Mutation profiling by NGS were performed after disease progression in 55 patients treated with crizotinib. mPFS was 8.1 months, no significant difference existed between v1 and v3 (P=0.69). But the presence of known ALK resistance mechanisms was significantly higher in v3 as compared to non-v3 (67% v.s. 27%, P=0.038).

      8eea62084ca7e541d918e823422bd82e Conclusion

      Next generation sequencing allows for detection of the specific ALK fusion partner and variants, increases the understanding of the biology of ALK+ NSCLC, and may have value to foretell potential mechanisms of resistance.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      P1.13-09 - Efficacy and Tolerance of Osimertinib in Real Word Setting: Results of the French Early Access Program (EXPLORE T790M GFPC Study).

      16:45 - 18:00  |  Presenting Author(s): Jean Bernard Auliac  |  Author(s): Maurice Pérol, David Planchard, Isabelle Monnet, marie Wislez, Helene Doubre, Florian Guisier, eric Pichon, Laurent Greillier, bennedicte Mastroianni, chantal Decroissette, roland Schott, Sylvestre le Moulec, jennifer Arrondeau, Alexis B Cortot, laurence Gerinière, Aldo Renault, catherine Daniel, lionel Falchero, Christos Chouaid

      • Abstract

      Background

      Based on the Phase III AURA3 trial, osimertinib a third-generation EGFR TKI is approved in France in EGFR T790M-positive advanced NSCLC whose disease have progressed on or after first or second generation EGFR TKI.

      Objective: to assess efficacy and tolerance of Osimertinib in real world setting.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Retrospective, multicentric study including T790M-positive advanced NSCLC receiving osimertinib from 07 April 2015 to 27 April 2016 in French early access program. Overall survival (OS) and progression free survival PFS) were analyzed in the whole population, in the subgroup of patients with cerebral metastasis at osimertinib initiation and according to the number of previous treatment lines (1 versus 2 or more).

      4c3880bb027f159e801041b1021e88e8 Result

      The analysis included 205 patients treated in 52 centers; mean age 69.5 ± 11.1 years, female 68.8%, adenocarcinoma 97.5%, EGFR mutations exons 19/21: 66.5%/ 30.5%, never smokers 71.5 %, PS 0-1/2/ 3-4: 54%/18,8%/27.2%, stage IV: 87.4%,presence of cerebral metastasis at osimertinib initiation: 43.7% .

      EGFR T790M mutation diagnosis have been done by liquid biopsy in 34.4 % or on tissue re-biopsy in 65.6%. Patients received a median of 2.8 ± 1.5 lines of treatment before osimertinib initiation. All patients received a first or second generation EGFR TKI before osimertinib. Osimertinib has been used in second line setting in 18% of cases and in third line or more setting in 82%.

      Median PFS was 12.4 (CI 95%: 10.1-15.1) months in the whole population, 9.7 (CI 95%: 7.7-13.5) in patients with cerebral metastasis and 15.8 (CI 95%: 11.9-17) months in patients without cerebral metastasis, (p : 0.2). PFS was not significantly different according to the use of osimertinib as second or third line of treatment: 12.6 (CI 95%: 6.7-17.5) vs 12.4 (CI 95%: 9.7-15.3) months, respectively.

      Median OS since osimertinib initiation was 20.5 (CI 95%: 16.9-24.3) months, 23.06 [18.56;27.83] and 18.00 [12.16;22.21] months in patients without and with cerebral metastasis, respectively. OS was not significantly different according the use of osimertinib as second or third line of treatment: 17.5 (CI 95%: 11.6;27.8) vs 21.7 (CI 95%: 17.3;24.3) months (p=0.4).

      A new biopsy was performed at disease progression on osimertinib in 50 patients: data will be presented.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Efficacy of Osimertinib in real world setting appears similar to that observed in clinical trials in patients with EGFR T790M mutation in ≥2ndline.

      Clinical trial information: Supported by an academic grant from Astra Zeneca

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      P1.13-10 - Aurora Kinase A Drives the Evolution of Resistance to Third Generation EGFR Inhibitors in Lung Cancer

      16:45 - 18:00  |  Presenting Author(s): Sourav Bandyopadhyay  |  Author(s): Khyati Shah, Collin Blakely, Trever G Bivona

      • Abstract

      Background

      Paradigm defining for precision medicine, EGFR inhibitors are a major breakthrough in the treatment of EGFR-mutant non-small cell lung cancer (NSCLC). Although these EGFR-TKI therapies often elicit profound initial therapeutic responses, their effects are transient due to residual disease. This residual disease and subsequent disease progression occurs through tumor evolution and molecular drivers behind the formation, maintenance and evolution of residual disease and acquired resistance have remained elusive. Although in many cases pre-existing clones with bona-fide genetic resistance have been identified, majority of patients have undetectable resistance causing genetic alterations suggesting that non-genetic alterations may drive altered cell state and signaling associated with EGFR inhibitor resistance. Furthermore, in the case of osimertinib now used in first line setting, mechanisms of acquired resistance have been ill defined and no effective second line therapies exist.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Using EGFR mutant lung cancer cells we developed eight distinct in vitro models of acquired resistance to 3rd generation EGFR-TKI inhibitors, osimertinib and rociletinib. We examined the efficacy of drug combinations in vivo using both cell line xenografts and PDX models of EGFR TKI resistance. We measured the level of staining of the candidate biomarker, TPX2, in patients progressing on first and third-generation EGFR TKIs.

      4c3880bb027f159e801041b1021e88e8 Result

      Chemical screens in acquired resistant cell lines revealed that Aurora kinase inhibitors are highly synergistic when combined with third-generation EGFR inhibitors. Resistant cells harbored heightened activation of AURKA caused by upregulation of its co-activator protein TPX2. In in-vitro and in-vivo models of acquired resistance the combination induced potent cell death by reactivating BIM-mediated apoptosis. We found that tumors from the majority of patients progressing on first and third-generation EGFR TKIs harbored high levels of TPX2, indicating that AURKA is likely activated and driving resistance in a significant fraction of EGFR-mutant lung cancers.

      Tracking the kinetics of AURKA activation, we found that AURKA activity is required for the formation and maintenance of residual drug tolerant cells, precursors of acquired resistance. Either single agent EGFR-TKI, the AURKA inhibitor MLN8237 or the combination enhanced the magnitude of response and forestalled the emergence of resistance in vitro as compared to monotherapies. The combination robustly induced tumor regressions in an EGFR L858R PDX tumor model generated from a residual disease surgical specimen.

      8eea62084ca7e541d918e823422bd82e Conclusion

      This synthetic lethal interaction between EGFR TKIs and Aurora kinase inhibitors has important clinical implications for the development of better treatment strategies using EGFR-TKIs and suggest a new paradigm for preventing the emergence of resistance.

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      P1.13-11 - PRO-CTCAE Toxicities in Advanced NSCLC Patients with EGFR Mutations: A Real World Assessment

      16:45 - 18:00  |  Presenting Author(s): Katrina Hueniken  |  Author(s): Manjusha Hurry, Shirley Xue Jiang, Catherine Labbe, M Catherine Brown, Lawson Eng, Hiten Naik, Mindy Liang, Devalben Patel, Penelope Bradbury, Natasha B Leighl, Frances A Shepherd, Wei Xu, Grainne Mary O'Kane, Ryan N. Walton, Geoffrey Liu

      • Abstract

      Background

      The Patient Reported Outcomes of the CTCAE (PRO-CTCAE) tool has not been evaluated in a real-world study of EGFR-mutation positive patients treated with TKIs/chemotherapies. We evaluated its role in capturing clinically-significant toxicities.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      A longitudinal observational study evaluated common EGFR-TKI toxicities using PRO-CTCAE, measured on a five-point scale (1=no symptoms to 5=very severe symptoms) in outpatients with EGFR-mutated (EGFRm) advanced NSCLC.

      4c3880bb027f159e801041b1021e88e8 Result

      Toxicity information was collected for 709 follow-up visits (encounters) from 232 patients. Median age was 64 (range:29-96), 161 (69%) were female and 124 (53%) were Asian. 85 (37%) already had brain metastases at first encounter. 485 encounters were observed from patients stable on treatment, and 187 from patients progressing or with documented progression on their current treatment. 24 patients were treated with osimertinib (97 encounters, 97% in second/subsequent-line), 136 with gefitinib (324 encounters, 95% in first line therapy), 42 were receiving other EGFR-TKIs (118 encounters, 53% in second/subsequent-line), and 29 with chemotherapy (73 encounters, 96% second/subsequent-line). The table below summarizes the treatment-related PRO-CTCAE toxicities self-graded as moderate-to-very-severe by EGFRm patients.

      Proportion of patients reporting highest grade of toxicity as grade 3-5, by PRO-CTCAE

      Gefitinib

      Osimertinib

      Other EGFR TKI

      Chemotherapy

      Diarrhea

      17%

      18%

      24%

      8%

      Constipation

      12%

      4%

      12%

      16%

      Decreased appetite

      10%

      7%

      14%

      26%

      Nausea

      6%

      3%

      4%

      24%

      Vomiting

      1%

      2%

      3%

      16%

      Fatigue

      18%

      12%

      23%

      42%

      Numbness and Tingling

      6%

      7%

      10%

      16%

      Skin Rash

      23%

      12%

      20%

      9%

      Visual Disorders

      (includes dry eye)

      4%

      0%

      3%

      4%

      Total PRO-CTCAE Score, MEDIAN [IQR]

      4 [0,16]

      0 [0,15]

      6 [0,17]

      10 [0,21]

      8eea62084ca7e541d918e823422bd82e Conclusion

      Osimertinib therapy had the most favorable self-reported toxicity profiles of all the therapies in EGFRm patients, followed by gefitinib. Chemotherapy generated the greatest toxicities. The use of PRO-CTCAE was well-accepted by patients in a clinical setting. This confirms trial data supporting favorable toxicities with osimertinib compared to other therapies for EGFRm NSCLC patients.

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      P1.13-12 - EGFR Therapy in ASCL1 Positive Lung Adenocarcinoma

      16:45 - 18:00  |  Presenting Author(s): Farhad Kosari  |  Author(s): Kaustubh Bhinge, Tobias Peikert, Aaron S. Mansfield, MC Aubry, Lin Yang, Prasuna Muppa, Irina V Kovtun, George Vasmatzis, Stephen J Murphy

      • Abstract

      Background

      Greater than 40% of lung adenocarcinomas (LUAD) contain no known driver mutations from point mutation or structural variance analysis. Recently, we discovered that 15-20% of LUAD have abnormally high levels of ASCL1, a key regulator of neuroendocrine differentiation in the lung. ASCL1 in these tumors orchestrates the expression of a network of genes that affect the behavior of tumors and their microenvironments and provide opportunities for treatment that has largely been understudied. The goal of this study was to explore potential therapeutic options in these tumors.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Bioinformatics analyses used public and internally generated expression data from LUAD. In vitro co-immunoprecipitation and cytotoxicity assays were used to determine the interaction between proteins and the sensitivity to EGFR blockers gefitinib and lapatinib. These drugs were also tested in patient derived xenograft (PDX) models from cisplatin resistant brain met LUAD with (A+AD) and without (A-AD) ASCL1 expression.

      4c3880bb027f159e801041b1021e88e8 Result

      Our data demonstrated that ASCL1 acts upstream of RET and promotes chronic over-expression of the oncogene in A+AD. In vitro experiments revealed a strong interactions between wild type EGFR and RET in A+AD which rendered these tumors vulnerable to treatment by EGFR blockers. Furthermore, while EGFR inhibitors blocked tumor growth in the A+AD PDX model, they were completely ineffective in the A-AD PDX model. EGFR therapy also markedly changed key regulators of the tumor microenvironment in favor of anti-tumor immunity. Analysis of TCGA data identified some overlap between A+AD and other LUAD subtypes, such as KRAS or EGFR mutant tumors. Further meta-analysis in a compendium of microarray data in stage-1 LUAD from multiple institutions demonstrated that high expression of wild type RET was significantly associated with a poor overall survival. Furthermore, high expression of EGFR (or its ligand TGFA) and RET imparted an aggressive phenotype in A+AD with overall survival similar to small cell lung cancer. Notably, EGFR, TGFA, and RET did not have any prognostic value in A-AD.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Our data provide strong evidence that patients with A+AD may benefit from a multipronged treatment strategy that include EGFR therapy even in the absence of mutations in EGFR.

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      P1.13-13 - Potent Anti-Tumor Effect of Ganetespib in Acquired EGFR-TKI Resistance NSCLC Cells

      16:45 - 18:00  |  Presenting Author(s): Eisuke Kurihara  |  Author(s): Kazuhiko Shien, Hidejiro Torigoe, Yuta Takahashi, Yusuke Ogoshi, Takahiro Yoshioka, Kei Namba, Hiroki Sato, Hiromasa Yamamoto, Junichi Soh, Shinichi Toyooka

      • Abstract

      Background

      Non-small cell lung cancer (NCSLC) harboring epidermal growth factor receptor (EGFR) mutation shows favorable response to EGFR-tyrosine kinase inhibitors (EGFR-TKIs). However, almost all these patients eventually acquire resistance to EGFR-TKIs, and novel therapeutic strategies to overcome the acquired resistance have been required. The 90-kDa heat shock protein (HSP90) is a chaperon protein expressed at high levels in cancer cells and involved in folding or stabilization of client proteins essential for cancer cell growth and survival. Ganetespib (STA-9090) is one of the second-generation HSP90 inhibitors with potent anti-tumor effect on NSCLC cells. In this study, we evaluated the anti-tumor effect of ganetespib in EGFR-TKI sensitive and acquired resistance NSCLC cell lines.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We treated 4 EGFR-mutant NSCLC cell lines (HCC827, HCC4006, HCC4011 and PC-9), and 5 experimentally established EGFR-TKI (gefitinib) resistance cell lines with ganetespib. The EGFR-TKI resistant mechanism consisted of EGFR T790M second mutation, MET amplification, epithelial-to-mesenchymal transition (EMT) and cancer stem cell-like properties. We determined cell proliferation by MTS assay and calculated the IC50 values. We also performed Western blotting to investigate downstream signaling pathway alterations.

      4c3880bb027f159e801041b1021e88e8 Result

      The IC50 values in parental NSCLC cell lines ranged from 1.3nM to 15nM, and those in acquired EGFR-TKI resistance NSCLC cell lines ranged from 0.87nM to 25nM, which suggests potent anti-tumor effect of ganetespib. In addition, this effect was observed regardless of the resistant mechanisms, including EMT. Ganetespib effectively suppressed the expression of downstream pathway molecules in all examined cell lines including acquired EGFR-TKI resistance NSCLC cell lines. Also, ganetespib effectively induced apoptosis in parental and acquired EGFR-TKI resistance NSCLC cell lines with EGFR T790M mutation or MET amplification.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Ganetespib exhibited potent anti-tumor effect in acquired EGFR-TKI resistance NSCLC cell lines regardless of the resistant mechanisms, suggesting that ganetespib could be a promising therapeutic option in the treatment of NSCLC with acquired EGFR-TKI resistance.

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      P1.13-14 - The Molecular Landscape of Lung Adenocarcinomas with Activating EGFR Gene Mutations Determined by Targeted-Sequencing

      16:45 - 18:00  |  Presenting Author(s): Kamila Wojas-Krawczyk  |  Author(s): Marcin Nicoś, Pawel Krawczyk, Paulina Calka, Marzanna Ciesielka, Katarzyna Reszka, Janusz Milanowski

      • Abstract

      Background

      The analysis of EGFR activating mutations and ALK rearrangement is a routine procedure in qualification of NSCLC patients for molecularly targeted therapy. Targeted sequencing, as a type of NGS, allows more comprehensive analysis of low-frequency variations in suppressors and oncogenes that are commonly mutated in solid tumors. In the following study we analyzed a molecular landscape of NSCLC patients harboring EGFR activating mutations who response for EGFR TKIs.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      The studied group included 19 Caucasian patients (7 male and 12 female, median age 65±12 years, 4 current smokers, 12 non-smokers and 3 former-smokers) with lung adenocarcinoma. 12 (63%) deletions in exon 19, 4 (21%) substitutions Leu858Arg in exon 21, 2 (11%) insertions A763_Y764 in exon 20 and 1 (5%) substitution Thr790Met in exon 20 of EGFR gene were detected using real-time PCR technique. Four non-smoking patients (median age 65±12 years) with lung adenocarcinoma and wild-type (wt) of EGFR gene were a control group. The DNA for the analysis was isolated from FFPE tissue or cellblocks and the mutational landscape was evaluated using Illumina’s TruSight Tumor 26 panel on miSeq platform (Illumina, USA).

      4c3880bb027f159e801041b1021e88e8 Result

      The targeted sequencing confirmed lack of EGFR gene mutations in control group and the presence of EGFR mutations in 84% (16/19) of patients with these mutations confirmed in routine diagnostics - all deletions in exon 19 and substitutions in exon 21 were confirmed. Targeted sequencing did not identify rare mutations in exon 20. NGS compared to real-time PCR technique achieved 86,95% accuracy with 84,21% of sensitivity and 100% of specificity or PPV and NPV values reached 100% and 57,10%, respectively. The targeted sequencing allowed to identify 166 variants in 25 out of 26 genes covered by the analysis. The most frequently mutated suppresors were TP53, MSH6 and APC (38%; 19% and 17% respectively) and oncogenes were MET, PDGFR and EGFR-AS1 (31%, 14% and 13% respectively). The frequency of particular variants was significantly higher in smokers than in non-smokers (p=0,0002; χ²=16,94). U-Man Whitney test showed that the median number of genetic alternations in EGFR mutated group was significantly higher than in wt EGFR group (p=0.0091; median: 17 vs 11 respectively).

      8eea62084ca7e541d918e823422bd82e Conclusion

      The targeted sequencing allowed to detect the most common activating mutations in EGFR gene and numerous variants both in suppressors and oncogenes. NGS showed too low sensitivity for detection of rare EGFR mutations. The molecular landscape was more unpredictable and varied in smokers compare to non-smokers.

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      P1.13-15 - Detection of EGFR Mutations in cfDNA and Development of Resistance

      16:45 - 18:00  |  Presenting Author(s): Grainne Mary O'Kane  |  Author(s): Geoffrey Liu, Tracy Stockley, Muqdas Shabir, Tong Zhang, Lisa Le, Frances A Shepherd, Penelope Bradbury, Natasha B Leighl

      • Abstract

      Background

      Peripheral blood sampling for T790M in patients (pts) failing initial EGFR-TKIs is now standard practice. The value of longitudinal sampling in pts is unknown.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      A study of cell free (cf) DNA analysis in pts with EGFR mutated(m) non-small cell lung cancer (NSCLC) is ongoing at the Princess Margaret Cancer Centre. The ThermoFisher OncomineTM lung assay detecting single nucleotide variants and indels to a limit of 0.05-0.1% variant allele frequency (VAF) was used. Patient clinical details and outcomes were collected prospectively.

      4c3880bb027f159e801041b1021e88e8 Result

      From Oct 2016-Feb 2017, 73 pts with EGFRm NSCLC enrolled and first blood samples were analysed. Most (92%) had mutations in del19 or L858R, including 1 pt with del19/S768I. Uncommon EGFRm were present in 6 (G718X, L861Q, exon20ins). Detectable levels of cfDNA were found in 50 pts (68%). Of 64 pts either starting an EGFR-TKI (n=11,17%), receiving a TKI without progression (PD) (23, 36%) or with PD on a TKI (30, 47%), the presence of the primary EGFRm (n=39, 61%) strongly associated with pre- 1st TKI or PD, p=0.03. Of 53 pts receiving a TKI, the presence of T790M in 31 (58%) associated with PD (p=0.04). Where pts had no radiologic PD evident, the median progression free survival (PFS), taken from blood draw, was 2.1 months (mths) versus 10 mths (HR 2.22, 95% CI: 0.89-5.54 p=0.08) when the primary EGFRm was detected. If T790M was present in cfDNA, the median PFS was 3.0 months versus 9.7 mths, (HR 4.59, 95% CI: 1.43-14.73 p=0.005). In univariable regression analyses the %VAF of the primary EGFRm correlated with PFS (HR 1.15, 95%CI: 1.02-1.29, p=0.02) with a trend in the %VAF of T790M (HR 1.16 95% CI:0.99-1.37, p=0.08). T790M was detected in 3 of 4 pts with T790M -ve tissue, and other co-occurring EGFRm were found in 10 pts including K745R in a pt receiving first-line osimertinib. TP53 (n=10), KRAS (1), PI3KCA(1) and ALK(2)gene mutations were also detected. Interestingly, in 1 pt receiving chemotherapy with T790M+ disease, both the primary EGFRm and T790M were detected in blood at the time of PD.

      8eea62084ca7e541d918e823422bd82e Conclusion

      In addition to the emergence of resistance mutations, the presence of the primary EGFRm in pts receiving EGFR-TKIs may associate with a shorter PFS and therefore may be useful in longitudinal analyses of cfDNA to direct therapy.

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      P1.13-16 - The Diagnostic Accuracy of Circulating Tumor DNA for the Detection of EGFR-T790M Mutation in NSCLC: A Systematic Review and Meta-Analysis

      16:45 - 18:00  |  Presenting Author(s): Francesco Passiglia  |  Author(s): Massimo Di Maio, Sergio Rizzo, Antonio Galvano, Giuseppe Badalamenti, Angela Listì, Nadia Barraco, Lorena Incorvaia, Marta Castiglia, Viviana Bazan, Antonio Russo

      • Abstract

      Background

      This meta-analysis aims at evaluating the diagnostic accuracy of circulating tumor (ct) DNA for the detection of epidermal growth factor receptor (EGFR)-T790M mutation in patients with EGFR-positive advanced non-small cell lung cancer (NSCLC) who progressed to prior EGFR-tyrosine kinase inhibitors (TKIs).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Data from published studies collecting matched blood and tumor tissue samples from patients with EGFR-positive advanced NSCLC who progressed to prior EGFR-TKI were collected by searching in PubMed, Cochrane Library, American Society of Clinical Oncology, European Society of Medical Oncology and World Conference of Lung Cancer meeting proceedings. Studies which evaluated both sensitivity and specificity of plasma-based EGFR-T790M mutation testing by ctDNA analysis were included and pooled sensitivity and specificity with 95% confidence intervals (95% CIs) were calculated.

      4c3880bb027f159e801041b1021e88e8 Result

      A total of twenty-one studies, with 1639 patients, were eligible. The pooled sensitivity of ctDNA analysis was 0.67 (95% CI: 0.64-0.70) and the pooled specificity was 0.80 (95% CI: 0.77-0.83). The positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were 2.67 (95% CI: 1.86-3.82) and 0.46 (95% CI: 0.38-0.54), respectively. The pooled diagnostic odds ratio (DOR) was 7.27 (4.39-12.05) and the AUC of the sROC curve was 0.77. Subgroup analysis by different detection platforms showed that sensitivity, specificity and AUC of ctDNA analysis by real-time (RT)-PCR were: 0.61 (95% CI: 0.57-0.65), 0.82 (95% CI: 0.77-0.87), and 0.70; sensitivity, specificity and AUC of ctDNA analysis by digital (d)PCR were: 0.72 (95% CI: 0.68-0.76), 0.73 (95% CI: 0.67-0.79), and 0.77; sensitivity, specificity and AUC of ctDNA analysis by by next-generation sequencing (NGS) were: 0.87 (95% CI: 0.76-0.95), 0.89 (95% CI: 0.82-0.94), and 0.88, respectively.

      8eea62084ca7e541d918e823422bd82e Conclusion

      The ctDNA analysis represents a promising, non-invasive approach to detect and monitor the T790M mutation status in patients with EGFR-positive advanced NSCLC, with NGS emerging as the most accurate detection platform. Development of standardized methodologies and clinical validation are recommended.

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      P1.13-17 - Multicentre Phase II Trial of First-Line Afatinib in Patients with Suspected/Confirmed EGFR Mutant NSCLC: ctDNA &amp; Long-Term Efficacy

      16:45 - 18:00  |  Presenting Author(s): Adam Januszewski  |  Author(s): Sanjay Popat, Laura Hughes, Mary O’brien, Tanya Ahmad, Conrad Lewanski, Ulrike Dernedde, Petra Jankowska, Clive Mulatero, Riyaz Shah, Jonathan Hicks, Tom Geldart, Mathilda Cominos, Gill Gray, James Spicer, Karen Bell, Simon Roitt, Karen Howarth, Mattia Cinelli, Emma Green, Clive Morris, Yenting Ngai, Allan Hackshaw

      • Abstract

      Background

      Efficacy of afatinib in EGFR mutant patients with comorbidities or those with suspected EGFR mutations unfit for chemotherapy is poorly explored. We evaluated afatinib in this population, with serial plasma ctDNA to investigate the role of molecular EGFR genotyping and monitoring.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Phase-II trial enrolled NSCLC patients with comorbidities precluding chemotherapy, and either (i) EGFR-mutation, PS 0-3, or (ii) suspected EGFR-mutation (tissue unavailable/failed genotyping), never/former-light smoker, adenocarcinoma, and PS 0-2. Afatinib (40mg daily) given until progression/toxicity. Blood samples obtained at baseline and 12-weekly until discontinuation; plasma ctDNA performed using InVisionSeq™ (amplicon-based NGS).

      4c3880bb027f159e801041b1021e88e8 Result

      39 patients recruited (14 UK centres). Median age 72 years; 27 PS 0-1/12 PS 2-3. 21 patients (54%) had known tissue EGFR-mutations. Additional 8 patients with unknown tissue status (8/17;47%), were ctDNA EGFR-mutant, making 74% EGFR-mutant in total (29/39). Combined tissue and ctDNA data identified 21 patients with common mutations (exon 19/L858R), 8 with rare mutations (exon 18/20), and 10 suspected only. Corresponding median PFS of these cohorts were 10.2/3.9/5.3 months, with 6-month PFS of 71/38/50% all exceeding the 30% target; median OS were 24.8/5.7/11.4 months (p<0.001). Therefore, all patient groups benefitted; known EGFR-mutants having best outcomes. In April 2018, 5/39 patients survived >36 months, including 4/39 progression-free (median follow-up 33 months, maximum 55). Patients with ctDNA mutation clearance during afatinib treatment had substantially improved outcomes compared to those without clearance (Figure). 40% (4/10) of mutant cases who discontinued after 3 cycles because of progressive disease developed an exon 20 EGFR-mutation.

      timelyresults2.jpg

      8eea62084ca7e541d918e823422bd82e Conclusion

      Patients unsuitable for chemotherapy with confirmed/suspected EGFR-mutations by tissue or ctDNA benefit from afatinib. Serial ctDNA is a potentially useful stratification and monitoring tool; amplicon-based ctDNA analysis can identify EGFR mutations when tissue is unavailable. Exon 20 mutations were observed at acquired resistance. ctDNA clearance during afatinib treatment is strongly associated with better PFS/OS.

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      P1.13-18 - Exploring the Resistance Mechanism of Osimertinib and Monitoring the Treatment Response Using Plasma ctDNA in Chinese NSCLC Patients

      16:45 - 18:00  |  Presenting Author(s): Yuankai Shi  |  Author(s): Puyuan Xing, Xiaohong Han, Sha Wang, Yutao Liu, Peng Liu, Junling Li, Lianpeng Chang, Yanfang Guan, Zhishang Zhang, Di Wu, Jiarui Yao, Yi Xin

      • Abstract

      Background

      Osimertinib (AZD9291; Tagrisso) is a third generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) known to be effective for patients harboring the EGFR-T790M variant, which is accounts for more than half of the acquired resistance mechanisms to the first generation EGFR-TKIs. However, limited osimertinib resistance-mechanism was reported. Study on potential osimertinib-resistance mechanisms in advanced NSCLC is necessary.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      This study enrolled eight T790M-positive (tissue validated) patients, treated with osimertinib after first generation EGFR-TKI (Erlotinib, Gefitinib, Icotinib) resistance and progressed rapidly. Serial plasma samples were collected until disease progressed. Plasma DNA was extracted and sequenced by target-capture deep sequencing of 1021 previously annotated genes related to solid tumors. Clonal EGFR T790M mutation was defined if mutation was in the cluster with the highest mean variated allele frequency with PyClone, and otherwise subclonal EGFR T790M mutation. Molecular tumor burden index (mTBI) was calculated with the mean variant allele frequency of mutations in trunk clonal population.

      4c3880bb027f159e801041b1021e88e8 Result

      The median progression-free survival (PFS) of these eight rapidly-progressed patients was 3.82 months [95% CI 2.05-5.01] .Targeted capture sequencing of pretreatment ctDNA showed all of the eight patients (100%) were EGFR-positive (Exon19del [n=6] and L858R [n=2]), and seven patients (88%) harbored EGFR T790M mutation, except for the only one patient (P006) who showed an extremely low level of ctDNA. During the Osimertinib treatment, five patients (63%) had osimertinib resistance-related mutations: EGFR C797S (in cis position), G724S, KRAS G12D, PIK3CA E542K, EGFR amplification, and ERBB2 amplification. Among them, two patients had more than one resistance mechanisms: patient P034 had EGFR G724S, KRAS G12D and EGFR amplification, simultaneously; patient P013 had amplification in both EGFR and ERBB2. Other potential resistance mechanisms were identified including EGFR T751I and K754E mutations in P002 and ERBB2 S603 in P013. Notably, the only one patient (P004) who had not been detected to have any known osimertinib resistance mechanism but progressed in 3 months, was demonstrated to harbor a subclonal EGFR T790M mutation by analysis of ctDNA clonal structure. Serial ctDNA monitoring showed mTBI increased when disease progressed in 88% (7/8) patients, except P006, whose mutation were negative at second (stable disease) and third (progressed disease) therapeutic evaluations due to the extremely low level of ctDNA.

      8eea62084ca7e541d918e823422bd82e Conclusion

      This study presented comprehensive the resistance mechanism of osimertinib progressed rapidly in ctDNA including multiple mechanisms co-occurred in same patient. Serial monitoring of plasma ctDNA may be a promising approach to explore resistance mechanism and monitored the treatment response of third generation EGFR-TKI.

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      P1.13-19 - Treatment Cessation for Improved Detection of EGFR-Mutated Circulating Tumor DNA in Advanced Non-Small Cell Lung Cancer (aNSCLC)

      16:45 - 18:00  |  Presenting Author(s): Samer Tabchi  |  Author(s): Stephanie Forte, Raafat Alameddine, Aline Khazzaka, Marie Florescu, Elie Kassouf, Xiaoduan Weng, Mustapha Tehfe, Normand Blais

      • Abstract

      Background

      First/second generation EGFR-tyrosine kinase inhibitors (EGFR-TKI) are eventually met with therapeutic failure in EGFR-mutated (EGFRm) aNSCLC, but post-progression continuation of therapy can delay the need for second line therapy by a median of ~ 3 months. In this context, osimertinib was shown to be effective in T790M mutated EGFR, which occurs in > 50% of cases. T790M detection within circulating tumor DNA (ctDNA) is convenient but has suboptimal sensitivity. The goal of this study is to determine whether temporary cessation of the TKI - beyond initial progression - would allow for increased plasma detection of EGFR mutations.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      EGFRm aNSCLC patients who were still on first/second generation EGFR-TKI beyond initial progression were enrolled. TKI was withheld on day 0. Blood samples were drawn and the NCCN-FACT FLSI-17 questionnaire v2 was administered on days 0 and 6±1. Semi quantitative measurements of EGFR mutations within plasma samples were obtained using the cobas® EGFR Mutation Test v2. Descriptive statistics were reported and paired t-test was used to compare differences in ctDNA yield and quality of life after TKI cessation.

      4c3880bb027f159e801041b1021e88e8 Result

      33 patients were enrolled in 2017. Baseline characteristics and relevant study results are summarized in Table 1. Temporary TKI cessation was safe with no tumor flares reported - questionnaire scores indicate a trend towards improved quality of life one week after TKI cessation. The yield of detection was significantly higher after TKI cessation, but only for the baseline sensitizing mutation.

      Table 1
      Age, Median - years (range) 71(46 - 87)
      Gender, female n (%) 25 (75.8)
      Median time to progression on first/second generation TKI, months (range) 9.76 (0.3 - 46)
      Median time from initial progression to study enrollment, months (range) 1.03 (0.25 - 7.57)
      NCCN-FACT FLSI-17 questionnaire
      - Questionnaire score day 1
      - Questionnaire Score day 6/7

      - 45.81±10.78
      - 48.41±9.91 (p=0.08)
      Baseline EGFR sensitizing mutation
      - Overall detection of ctDNA, n (%)
      - Detection within ctDNA on only one of the two test dates, n (%)

      Semi quantitative index of detected ctDNA
      - Day 1
      - Day 6/7

      - 21 (63.6)
      - 6 (28.5)


      - 5.2±6.2
      - 6.1±6.4 (p=0.04)
      T790M EGFR mutation
      - Overall detection of ctDNA, n (%)
      - Detection within ctDNA on only one of the two test dates, n (%)

      Semi quantitative index of detected ctDNA
      - Day 1
      - Day 6/7

      - 21 (63.6)
      - 6 (28.5)


      - 5.2±6.2
      - 6.1±6.4 (p=0.04)

      8eea62084ca7e541d918e823422bd82e Conclusion

      Our data suggest that TKI cessation can lead to increased shedding of ctDNA in sensitive cells. However, drug withdrawal may not impact the shedding of ctDNA in resistant clones. Irrespective of drug withdrawal, a strategy of repeat testing appears to increase the sensitivity of ctDNA detection and would likely produce more clinically relevant outcomes in comparison with one-time testing.

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      P1.13-20 - MET Protein Expression and Activation During Targeted Therapy in EGFR Mutated Lung Adenocarcinoma

      16:45 - 18:00  |  Presenting Author(s): Silvia Novello  |  Author(s): Riccardo Taulli, Luisella Righi, Fabrizio Tabbò, Federica Massa, Alessandro D'Aveni, Deborah Morena, Marcello Francesco Lingua, Angelica Rigutto, Francesca Napoli, Francesca Picca, Giorgio Vittorio Scagliotti

      • Abstract

      Background

      In EGFR mutated (EGFRm) lung adenocarcinoma (ADC) the tyrosine kinase (TK) receptor MET is involved in acquired resistance to anti-EGFR treatment. We analyzed MET protein expression and activation in EGFRm lung ADC treated with TK inhibitors (TKI).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Patients with advanced EGFRm lung ADC, treated at the Oncology Department - San Luigi Hospital, who underwent tissue biopsy for diagnosis and tissue re-biopsy at disease progression for T790M test (after a negative liquid biopsy) were selected. c-MET (clone SP44) and phosphorylated (p-) MET (Tyr1234/1235, D26) expression was analyzed by immunohistochemistry and evaluated as H-Score (HS).

      4c3880bb027f159e801041b1021e88e8 Result

      Tumor tissues from 18 advanced EGFRm patients (12 female and 6 male; mean age 59 years) were available. On April 2018, 10 patients were alive and 8 were died. 11/18 (61%) cases harbored a T790M point mutation (T790M+) detected at tissue re-biopsy.

      At the baseline tumor tissue, lower c-MET expression levels were found in T790M+ (mean HS value= 135, range 40-250) compared to the T790M negative (T790M-) group (mean HS value= 226, range 100-300) (p=0.02). Furthermore, in T790M+ patients p-MET was expressed in 2/11 cases (18%, HS values=5 and 60) while in the T790M- group p-MET was expressed in 3/7 (43%, HS values=5, 240 and 240) cases (although with no significant p value).

      After first line TKI treatment, in the T790M+ group c-MET expression (mean HS value=140, range 5-300) was augmented in 7 and reduced in 4 cases, while p-MET was positive in 2/11 cases (HS values of 300 and 30). No significant differences in survival were found.

      In the T790M- group the c-MET mean HS value was 152 (range 30-300) and the 4/7 cases with higher c-MET expression levels (HS> 152) had a significant shorter PFS (p=0.02, HR=0.3, median survival: 7.5 vs 24 months). Furthermore, in this group p-MET positivity was maintained in the same 3 cases (with HS values= 240, 180, 10) and the two patients with higher MET activation had short PFS (9 and 6 months) at first line TKI treatment.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Our preliminary analyses suggest that a strong expression of basal c-MET receptor in advanced EGFRm ADC may predict a T790M negative status at disease progression. Furthermore MET higher expression and activation may play a role in acquired resistance to TKI, although a limited number of cases have been analyzed. Thereby, we propose to monitor MET status along treatment and to reconsider MET-directed therapies for a well-selected subset of EGFRm lung ADC patients.

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      P1.13-21 - Clinical Efficacy and Safety of Apatinib Combined with EGFR - TKIs in Advanced Non-Small Cell Lung Cancer with EGFR - TKIs Resistance

      16:45 - 18:00  |  Presenting Author(s): Ruifen Tian  |  Author(s): Xia Song, Yi Guo, Xia Zhang, Wei Guo, Haibo Zhu, Fangfang Shen, Junjun Xu, Xing Zhang

      • Abstract

      Background

      Acquired resistance to EGFR-TKIs frequently occurs in advanced non-small cell lung cancer (NSCLC) patients with sensitizing EGFR mutations. Previous studies have shown that apatinib (a TKI against VEGFR-2) combined with EGFR-TKIs might improve the survival of EGFR-TKIs resistant NSCLC patients. We conducted this trial to investigate the efficacy and safety of apatinib combined with EGFR-TKIs compared with traditional chemotherapy for EGFR-TKIs resistant NSCLC patients.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      This prospective study enrolled advanced NSCLC patients who acquired resistance to the EGFR-TKIs therapy. Patients received apatinib combined with EGFR-TKIs (apatinib in start dose of 250 mg+pior EGFR-TKIs dose) or chemotherapy ( pemetrexed or vinorelbine with platinum). Efficacy was evaluated every 6 weeks based on RECIST 1.1. This study was registered on Chinese Clinical Trail Registry, and the registration number was ChiCTR-OIN-17012051.

      4c3880bb027f159e801041b1021e88e8 Result

      From Mar 2017 to May 2018, 24 patients were enrolled, including 18 patients received apatinib combined with EGFR-TKIs, 6 patients received chemotherapy. In the apatinib group, 83.33%(15/18) patients were available evaluated. The objective response rate was 20% (3/15) and the disease control rate was 100% (15/15). All patients have different degrees of lesion shrinkage. Till May 1, 2018, the median duration of apatinib group treatment was 187 days, and the median PFS has not researched. The most common adverse events in the apatinib group were hypertension, proteinuria, weakness. Five (27.78%) grade 3 hypertension, 3 (16.67%) grade 3 proteinuria and 1 (5.56%) grade 3 diarrhea were observed. Two patients who failed treatment with osimertinib received osimertinib combined with apatinib, got lesions decreased after one cycle. One of the two patients was treated as fifth line treatment. Two patients with brain metastases in the apatinib group got metastases lesions decreased. Two progressive patients got lesions decreased after apatinib dose increasing to 500mg. Of the 7 patients receiving chemotherapy, 6 patients were available evaluated. The objective response rate was 16.67%(1/6) and the disease control rate was 100% (6/6). Major adverse reactions were digestive tract reaction and myelosuppression.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Apatinib combined with EGFR-TKIs may provide a new therapy strategy for NSCLC patients with acquired EGFR-TKIs resistance. Both drugs are oral, which is advantageous in improving the patient's quality of life and the compliance of therapy. Further study with lager samples are needed to validate our findings. Moreover, We will further explore the correlation between genetic mutations, biomarkers and therapeutic efficacy.

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      P1.13-22 - Clinical Features and Outcomes of NSCLC Patients with Uncommon EGFR Mutations Treated with EGFR-TKIs

      16:45 - 18:00  |  Presenting Author(s): Roxana Alina Tudor  |  Author(s): Karen Kopciuk, Michelle Dean, Amanda Jane Williams Gibson, Shannon Mary Otsuka, Gwyn Bebb

      • Abstract

      Background

      Non-small cell lung cancers with common epidermal-growth factor receptor (EGFR) mutations (exon 19 deletion and exon 21-point mutation L858R) are known to greatly benefit from EGFR-tyrosine kinase inhibitors (TKIs). However, much less is known about the treatment responses of EGFR mutations such as L861Q, G719X and double EGFRmut+ carriers. In this study, we report clinicopathological and treatment outcomes of patients harboring such EGFR mutations and treated with EGFR-TKIs.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Between 2009 – 2015, 233 EGFRmut+ NSCLC patients treated at two Alberta-based cancer centres, Tom Baker Cancer Centre (Calgary) and Cross Cancer Institute (Edmonton) were screened retrospectively via the provincial cancer registry and the Glans-Look Lung Cancer Database. Clinicopathological and treatment outcomes were analyzed. Overall survival was assessed using the Kaplan-Meier method and compared using the log-rank test. Outcomes of single versus double EGFRmut+ carrier sub-groups were compared using Fisher’s Exact test.

      4c3880bb027f159e801041b1021e88e8 Result

      42/233 (18%) patients harbored uncommon EGFR mutations: 14/42 (33%) carried single rare EGFRmut+ and 11/42 (26%) carried double EGFRmut+, meanwhile 41% couldn’t be specified. Most frequently detected uncommon single EGFR mutations were G719X (12%) and L861Q (17%). Table 1 summarizes clinical characteristics and TKI efficacy amongst uncommon EGFR mutations. Compared to single EGFR mutants, double EGFR mutation carriers were older (median age 71yrs vs 69 yrs), have a smoking-history (73% vs 50%), experienced longer median OS and PFS (15 and 12 months p < 0.001, vs. 9 and 3 months p = 0.0014 respectively), and were also more likely to continue with a TKI beyond initial-TKI-PD (82% vs 28%).
      table 1_iaslc2018abstract.jpg

      8eea62084ca7e541d918e823422bd82e Conclusion

      Retrospective real-world data illustrating the experience and outcomes of uncommon EGFR mutation carriers was explored in this study. Additionally, our results, although limited by cohort-size, highlights that tumor responses from TKI treatments vary amongst uncommon EGFRmut+ carriers, with most favorable survival responses observed in double EGFR mutants.

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      P1.13-23 - TP53 Mutations as Mechanisms of Primary and Acquired Resistance to Tyrosine Kinase Inhibitors in Patients With EGFR-Mutated NSCLC 

      16:45 - 18:00  |  Presenting Author(s): Paola Ulivi  |  Author(s): Matteo Canale, Vienna Ludovini, Lucio Crinò, Claudio Dazzi, Elisa Chiadini, Laura Capelli, Maximilian Papi, Marita Mariotti, Nicoletta De Luigi, Gabriele Minuti, Daniele Calistri, Sara Baglivo, Rita Chiari, Massimiliano Bonafè, Angelo Delmonte

      • Abstract

      Background

      Around 80% of patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations usually respond to tyrosine kinase inhibitors (TKIs). We previously demonstrated that TP53 mutations are associated with primary resistance to TKIs in patients with EGFR-mutated lung adenocarcinoma (ADC) treated with a first-line TKI. In the present study we investigated whether TP53 mutations are modulated by TKIs, evaluating its status before and after TKI treatment.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Thirty-five patients with EGFR-mutated lung ADC treated with a first-line TKI and who subsequently underwent re-biopsy after disease progression were considered. Tumor tissue was available for evaluation before and after TKI treatment for all patients. EGFR and TP53 mutation analyses were performed by Sanger Sequencing or Next Generation Sequencing methods. The different mutations were evaluated in relation to disease control rate (DCR) [complete response (CR), partial response (PR) or stable disease (SD)] and objective response rate (ORR) (CR, PR).

      4c3880bb027f159e801041b1021e88e8 Result

      Of the 35 patients, 14 (40%) showed a TP53 mutation, 12 in exons 5-8 (5 in exon 5, 2 in exon 6, 2 in exon 7 and 3 in exon 8) and 2 in other exons (1 in exon 2 and 1 in exon 4) of the gene. The group was treated with a first-line TKI and data on response and follow-up were available for 30 patients. Of these, 11 were treated with gefitinib, 11 with erlotinib, 6 with afatinib and 2 with dacomitinib. Overall DCR and ORR were 90% and 77%, respectively. With regard to TP53 mutations, DCR and ORR were 94% and 83%, respectively, in TP53 wt patients, and 83% and 66% in TP53 mutated cases. All 30 patients underwent re-biopsy at progression and 20 (67%) showed T790M mutation in tumor tissue. Of the 10 T790M-negative patients, 5 (50%) had a TP53 mutation which was not present at baseline in 2 cases. Among the patients who were TP53 wild type at baseline, 4 (22%) showed a mutation at disease progression. Data on progression free survival and overall survival are currently being evaluated.

      8eea62084ca7e541d918e823422bd82e Conclusion

      TP53 mutations were associated with a lower response to TKIs in EGFR-mutated patients and may have been acquired during TKI treatment, independently of the T790M mutation.

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      P1.13-24 - EGFR-KDD is Rare and Demonstrates Variable Anti-Tumor Response to Tyrosine Kinase Inhibitors in East Asian NSCLC Population

      16:45 - 18:00  |  Presenting Author(s): Yang W. Shao  |  Author(s): Jinguang Wang, Qiuxiang Ou, Xingyang Xue, Ying Liang, Xue Wu, Xiaonan Wang, Ming You

      • Abstract

      Background

      The kinase domain duplication of epidermal growth factor receptor (EGFR-KDD) has been identified and implicated to be oncogenic in non-small cell lung cancer (NSCLC). However, its frequency and clinical outcomes in lung cancer patients are largely uncertain.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We conducted a multi-center record review of 8064 East Asian NSCLC patients who underwent genetic testing using next-generation sequencing (NGS) targeting the whole exons of EGFR gene as well as introns involved in EGFR-KDD and gene rearrangements. Patients’ demographic and clinical data, including age, gender, histology type, pathological stage, and their responses to tyrosine kinase inhibitor (TKI) treatments were analyzed.

      4c3880bb027f159e801041b1021e88e8 Result

      EGFR-KDD was identified in 11 patients, which is approximately 0.012% of the total NSCLC population reviewed (N=8064), and also consists of 0.05% of all patients with EGFR aberrations (N=2289). Nine patients were identified with the canonical EGFR-KDD form involving the duplication of exon 18 throughout exon 25, while the remaining two cases harbor EGFR exon 14-26 and exon 17-25 duplication, respectively, which have not been previously described. Importantly, all these patients were not identified with any other co-existing known driver mutations, highlighting the potential oncogenic role of this alteration. Three out of five patients with exon 18-25 KDD who received TKI treatments showed partial anti-tumor responses to the therapy, while the other two patients progressed shortly. Our data further indicated that EGFR T790M mutation and EGFR amplification may represent the major resistance mechanisms against targeted therapy in tumors bearing EGFR-KDD.

      8eea62084ca7e541d918e823422bd82e Conclusion

      EGFR-KDD is rare in East Asian NSCLC population with different duplication variants. Tyrosine kinase inhibitors demonstrated variable anti-tumor efficacy in patients harboring EGFR-KDD alteration.

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      P1.13-25 - Efficacy and Safety of Osimertinib in EGFR T790M-Positive Advanced NSCLC Patients with Brain Metastases (APOLLO Study)

      16:45 - 18:00  |  Presenting Author(s): Ligang Xing  |  Author(s): Yueyin Pan, Yuankai Shi, Yongqian Shu, Jifeng Feng, Wei Li, Lejie Cao, Lifeng Wang, Wei Gu, Yong Song, Jinming Yu

      • Abstract

      Background

      Osimertinib has demonstrated promising efficacy in T790M-positive NSCLC patients with central nervous system (CNS) metastases, but there is limited data on Chinese patients. We aim to investigate the efficacy and safety of osimertinib in T790M-positive advanced NSCLC patients with brain metastases and to explore the dynamic genetic changes as well as drug penetration in CNS with paired cerebrospinal fluid (CSF) and plasma samples.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      In this single arm, multi-center, prospective trial (NCT2972333), patients with confirmed EGFR T790M positive by Cobas, advanced NSCLC with brain metastases, who had progressed following first-generation EGFR-TKI treatment, received osimertinib 80 mg qd. The primary endpoint was overall progression free survival (PFSo). Paired CSF-plasma samples were collected at baseline, 6 weeks after treatment and disease progression and analyzed by NGS.

      4c3880bb027f159e801041b1021e88e8 Result

      Thirty-eight eligible patients were enrolled and 12 paired CSF-plasma samples were collected. Baseline characteristics and efficacy results are summarized in Table 1. Median PFSo (60% maturity, 23/38) was 8.4 months (95% CI 5.8-11.0). Adverse events of grade 3 or higher were reported in 39.5% patients. Analyzed in 12 paired samples, the median CSF penetration rate of osimertinib was 31.7% (range 19.8-57.7%), with a median CSF concentration of 10.83nM (range 5.2-30.3nM). T790M mutation was detected in 83% (10/12) of plasma and 17% (2/12) of CSF samples at baseline, with a concordance rate of 8.3% (1/12). Median PFSo was prolonged in patients with EGFR sensitizing mutation clearance at week 6 compared with those with persisting EGFR mutations (not reached vs 2.83 months; HR 0.09, 95% CI 0.02-0.54; p<0.01).

      Table 1. Baseline characteristics and efficacy

      Patients characteristics N=38
      Age, median (range), years 63 (38-74)
      CNS metastases, No (%): brain metastases (BM) / leptomeningeal metastases (LM) / other 35 (92.1%) / 2 (5.3%) / 1 (2.6%)
      Histology, No (%): adenocarcinoma 38 (100%)
      EGFR mutations, No (%):
      T790M with Ex19del / L858R
      22(57.9%) /16 (42.1%)
      Sample type for T790M confirmation No (%): Blood / Tissue 27 (71.1%) / 11 (28.9%)
      Lines of anti-tumor therapy, No (%): 1 / 2 / ≥3 13 (34.2%) / 3 (7.9%) / 22 (57.9%)
      Efficacy Overall Extracranial Intracranial
      Median PFS (months, 95% CI) 8.4 (5.8, 11.0) 10.2 (7.5, 14.0) 10.9 (6.1, NA)
      Objective response rate (ORR) 42.4%(14/33) 39.4%(13/33) 71.9%(23/32)
      Disease control rate (DCR) 90.9%(30/33) 90.9%(30/33) 96.9%(31/32)
      Median Duration of Response (DoR) (months, 95% CI) 8.1 (3.4, NA) 11.1 (5.6, 11.1) 8.3 (5.8, NA)

      8eea62084ca7e541d918e823422bd82e Conclusion

      Osimertinib demonstrated promising efficacy, good blood brain barrier penetration and manageable tolerability in EGFR T790M-positive Chinese advanced NSCLC patients with brain metastases. NGS analysis revealed genetic heterogeneity between plasma and CSF samples and longitudinal genetic analysis may be beneficial to predict the efficacy of osimertinib.

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      P1.13-26 - First-Line Continual EGFR-TKI Plus LAT Demonstrated Survival Benefit in Egfr-Mutant Nsclc Patients with Oligoprogressive Disease

      16:45 - 18:00  |  Presenting Author(s): Qinghua Xu  |  Author(s): Hui Liu, Tao Jiang, Shengxiang Ren, Caicun Zhou

      • Abstract

      Background

      The effect of local ablative therapy (LAT) for oligoprogressive epidermal growth factor receptor (EGFR) mutation non-small cell lung cancer (NSCLC) remains undetermined. This study aimed to investigate the survival benefit of addition of LAT to EGFR-TKIs in EGFR-mutant NSCLC patients with oligoprogression during TKI therapy.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Patients with stage IIIB/IV EGFR mutant NSCLC who had oligoprogressive disease during the first-line EGFR-TKI therapy from March 2011 to February 2016 were identified. The primary research point were progression-free survival1 (PFS1), defined as time of initiation of TKI therapy to Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 defined progress disease (PD) or death and PFS2, defined as time of initiation of TKI therapy to off-TKI PD. The second research piont inclued overal survival (OS) and safety.

      4c3880bb027f159e801041b1021e88e8 Result

      A total of 206 patients were included. The median follow-up time was 42 months (20.0-69.6 months). The median PFS1, median PFS2 and median OS for the related cohort were 10.7 months (95% CI, 10.1-13.3 months), 18.3 months (95% CI, 17.4-19.2 months) and 37.4 months (95% CI, 35.9-38.9 months) respectively. Survival rates of 1 year, 2 years and 3 years were 94.1%, 78.9%, and 54.7%, respectively. Multivariate analysis revealed that female, EGFR exon 19 mutation, one metastatic lesion, partial or complete response to prior EGFR TKIs therapy were the independent prognostic factors. No unexpected toxicities were observed.

      8eea62084ca7e541d918e823422bd82e Conclusion

      The current study suggested that the addition of LAT to EGFR-TKI could provide satisfactory survival benefit for EGFR-mutant NSCLC patients with oligoprogression during first-line EGFR-TKI treatment.

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      P1.13-27 - A Randomized Study of Concurrent vs Sequential Alternating EGFR-TKIs and Chemotherapy for Advanced NSCLC with EGFR Mutations

      16:45 - 18:00  |  Presenting Author(s): He Zhi Yong  |  Author(s): Lin Jing Hui, Li mei Fang, Lin Dong, Xu Ling, Wang Qiang, Xu Hai Peng, Hu hui Hua, Yu zong Yang, Guo ai Ping, Kong wen Cui, Wang Wen Wu, Chen shi Yu, Lai jin Huo, Xie Qiang, Shi Xi, Chen Wu Jin

      • Abstract

      Background

      EGFR-TKIs have been accepted as the standard first-line treatment for EGFR-mutated NSCLC, and EGFR-TKIs in combination with chemotherapy are found to achieve PFS benefits. However, the optimal sequence of EGFR-TKIs and chemotherapy remains controversial until now. This study aimed to compare the efficacy and safety of concurrent versus sequential alternating EGFR-TKIs and chemotherapy for treatment-naive advanced nonsquamous EGFR-mutated NSCLC.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      A multicentre, open-label, parallel, randomized controlled trial was performed. Eligible participants were randomly assigned into Group A (n = 36) and Group B (n = 59). Subjects in Group A were concurrently given EGFR-TKI and platinum-based doublet chemotherapy on day 1, every 3 weeks for 4 to 6 cycles, followed by maintenance therapy with EGFR-TKIs, while patients in Group B received EGFR-TKI alone, and platinum-based doublet chemotherapy was given upon disease progression. Chemotherapy regimens included selected cisplatinum (75 mg/m2) or carboplatin (AUC 5.0) plus pemetrexed (500 mg/m2) or paclitaxel (175 mg/m2) on day 1 of a 21-day cycle. All subjects were administered orally with erlotinib 150 mg QD (n = 40), gefitinib 250 mg QD (n = 30) or icotinib 125 mg TID (n =19), until disease progression or intolerance to adverse events. The primary endpoint was PFS, and the secondary endpoints were OS and safety.

      4c3880bb027f159e801041b1021e88e8 Result

      At a median follow-up of 18 months, 53.4% of patients had progressive disease and 23.2% died. Median PFS was 15.0 months (95% CI, 9.9 to 20.1 months) for the concurrent regimen and 17.5 months (95% CI, 14.4 to 20.5 months) for the sequential alternating regimen (P = 0.614). In addition, administration of EGFR-TKIs alone achieved 12.0 months PFS (95% CI, 9.3 to 14.8 months), which was comparative to the concurrent regimen (P = 0.508). Drug-related grade 3 or 4 adverse events didn’t occur.

      8eea62084ca7e541d918e823422bd82e Conclusion

      This interim analysis demonstrates that concurrent EGFR-TKIs and chemotherapy achieves comparative PFS to sequential alternating EGFR-TKIs and chemotherapy and EGFR-TKIs monotherapy for treatment-naive advanced nonsquamous non-small-cell lung cancer with sensitive EGFR mutations.

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      P1.13-28 - The Functional MDM4 Genetic Polymorphsim as Prognostic Biomarker for Advanced Lung Adenocarcinoma Patients' Survival to EGFR-TKIs Therapy

      16:45 - 18:00  |  Presenting Author(s): Ming Yang  |  Author(s): Nasha Zhang, Huaixin Xing, Jibing Liu

      • Abstract

      Background

      As a mostly used epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), gefitinib significantly prolongs survival of lung adenocarcinoma patients with sensitizing EGFR mutations. However, more than 10% of EGFR mutation-positive patients do not respond and a substantial fraction of responded patients progress after 8-12 months’ treatment. Identification of new biomarkers associated with EGFR-TKIs prognosis would have great clinical potential for individualized treatments. The objective of this study is to investigate associations between the functional MDM4 genetic variant and survival of lung adenocarcinoma patients treated with gefitinib, especially in the patients with active EGFR mutations.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      In this study, a total of 384 patients with stage IIIB or IV lung adenocarcinoma were recruited between January 2009 and June 2013. All patients were treated with gefitinib orally at a daily dose of 250 mg as 1st-line monotherapy. MDM4 rs4245739 A>C genotypes were determined using the MassArray system (Sequenom Inc., San Diego, USA). Dual luciferase reporter gene assays were used to evaluate the function of MDM4 rs4245739 genetic variant in lung adenocarcinoma cell lines A549 and H1299. The differences of patient clinical characteristics and different reporter gene assays were calculated using student's t test or χ2 test. The genotype effects on PFS or OS was estimated using the Kaplan-Meier method and a comparison between survival curves was done with log-rank test. Multivariate Cox regression analysis assessed prognostic factors for PFS or OS. A P value of less than 0.05 was used as the criterion of statistical significance, and all statistical tests were two-sided.

      4c3880bb027f159e801041b1021e88e8 Result

      Among 384 patients, EGFR mutations were positive in 181 patients (47.1%). Median progression-free survival (PFS) and overall survival (OS) for all patients with the rs4245739AC genotype were significantly longer than that of the AA carriers (PFS: 22.9 vs. 10.9 months, P < 0.001; OS: 27.3 vs. 16.5 months, P = 0.003). Notably, in the EGFR mutation-positive subgroup, individuals with MDM4 rs4245739AC genotype showed 14.1 months prolonged PFS (28.8 months vs. 14.7 months; P = 0.022) and 12.2 months prolonged OS (31.4 months vs. 19.2 months; P = 0.047)compared to the AA group. In support of this, reporter gene assays showed that the rs4245739A allele leads to significantly increased MDM4 expression in lung adenocarcinoma cells compared to the C allele (P < 0.05).

      8eea62084ca7e541d918e823422bd82e Conclusion

      MDM4 rs4245739 genotypes may act as prognostic biomarker for patients’ survival to gefitinib therapy and offer help to patient-tailored treatment strategy in lung adenocarcinoma patients with EGFR mutations.

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      P1.13-29 - Overall Response Rate of Nintedanib and Docetaxel in Combination with the Nutraceutical Use of Silibinin in Advanced NSCLC

      16:45 - 18:00  |  Presenting Author(s): Joaquim Bosch Barrera  |  Author(s): José Carlos Ruffinelli, Enric Carcereny, Elia Sais, Sara Verdura, Elisabet Cuyàs, Ramon Palmero, Angel Izquierdo, Teresa Morán, Ernest Nadal, Javier A. Menéndez

      • Abstract

      Background

      The bioactive flavonolignan silibinin, the main component of standardized extracts from the seeds of the milk thistle herb Silybum marianum, has been shown to exhibit significant anticancer activity in preclinical models. Silibinin is a direct inhibitor of pSTAT3, a signal transducer and key transcription factor that is associated with chemoresistance in cancer cells. Our group has shown that oral administration of the silibinin-containing nutraceutical Legasil® could represent the first silibinin formulation with proven clinical benefit as an adjunct cancer treatment in patients with brain metastases. Nintedanib is an orally administered, small-molecule triple angiokinase inhibitor of VEGF1–3, PDGFa and b, and FGFR1–3. The LUME-Lung 1 trial showed that nintedanib significantly extended progression-free survival (PFS) and overall survival (OS) in patients with NSCLC adenocarcinoma when added to docetaxel chemotherapy, with no differences in response rate.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Patients with stage IV NSCLC who failed ≥1 prior treatment were eligible for nintedanib/docetaxel combination. We present retrospective data analysis regarding patients that received nintedanib/docetaxel with or without combination with up to 5 capsules (630 mg)/day of Legasil®.

      4c3880bb027f159e801041b1021e88e8 Result

      Fifty-nine patients were enrolled in the study: median age, 60y (range: 43–79); male, 46 (78%). All the cases had adenocarcinoma histology. All patients had received first line therapy and 13 (22%) patients had >2 prior lines of treatment. A higher overall response rate (ORR) was observed in the group receiving Legasil® supplementation: ORR 55.5% versus 22%, p=0.02. No statistically significant differences in the median PFS were observed in the two arms: 2.34 months (95% confidence interval [CI] 1.83–2.91) for nintedanib/docetaxel combination (n=41) versus 4.99 (95%CI 0.94–9.05) for nintedanib, docetaxel and Legasil® triple combination (n=18) (p=0.241) at the data cut-off of January 2018. In the control group (n=41), ORR was greater in patients with known KRAS (n=8) or EGFR (n=3) mutations: 45% versus 13%, p=0.028.

      8eea62084ca7e541d918e823422bd82e Conclusion

      The inhibition of pSTAT3 with silibinin may increase tumor responses to nintedanib/docetaxel combination. In addition, patients with known KRAS or EGFR mutations may show higher tumor responses to nintedanib/docetaxel combination.

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      P1.13-30 - Neutrophil-to-Lymphocyte Ratio as a Prognostic Factor and its Relationship to NSCLC Patient Outcomes in the REVEL Trial

      16:45 - 18:00  |  Presenting Author(s): Aafia Chaudhry  |  Author(s): Edward B Garon, Anne S. Tsao, Martin Reck, Benjamin P Levy, Carla Visseren-Grul, Huzhang Mao, Andreas Sashegyi

      • Abstract

      Background

      Neutrophil-to-lymphocyte ratio (NLR) reflects underlying levels of systemic inflammation and has prognostic importance in solid tumors. Higher baseline NLR is an independent negative prognostic factor in advanced non–small cell lung cancer (NSCLC) and may indicate more aggressive disease. An exploratory analysis from REVEL demonstrated benefits of ramucirumab(RAM)/docetaxel(DOC) in NSCLC patients with rapidly progressing and refractory disease. We investigated the relationship between pretreatment NLR, prognosis and response to RAM/DOC.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Pretreatment NLR was analyzed by dividing absolute neutrophil count by absolute lymphocyte count from peripheral blood. Multiple NLR cutoffs ≥4 were evaluated for prognostic significance by analyzing overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Kaplan-Meier analysis and Cox proportional hazards regression model were used for analyzing OS and PFS, and Cochran-Mantel-Haenszel test for ORR.

      4c3880bb027f159e801041b1021e88e8 Result

      Pretreatment NLR was determined for 1224 REVEL patients (n=611 RAM/DOC, n=613 placebo [PBO]/DOC), among whom 51%, 40%, and 32% had NLR ≥4, 5, and 6, respectively. Baseline characteristics were balanced between arms in NLR subgroups and the REVEL intent-to-treat (ITT) population. Patients with higher NLR values had worse OS, PFS, and ORR compared to the ITT population. For all NLR cutoff values, OS, PFS and ORR were improved in patients treated with RAM/DOC compared to patients receiving PBO/DOC (Table). Efficacy and safety outcomes across high NLR subgroups were consistent with those in the ITT population.

      table 1.jpg

      8eea62084ca7e541d918e823422bd82e Conclusion

      In this exploratory analysis of REVEL, higher pretreatment NLR was an independent prognostic factor indicating poorer survival outcomes. Treatment benefit with RAM/DOC was preserved in patients with elevated NLR and was consistent with REVEL ITT results. NLR is an inexpensive and reproducible blood test and may provide a simple way to identify patients with more aggressive disease who can benefit from treatment with RAM/DOC in second-line NSCLC.

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      P1.13-31 - Safety and Tumour Hypoxia Modifying Effect of Buparlisib with Radiotherapy in NSCLC: A Phase I Dose Escalation Study 

      16:45 - 18:00  |  Presenting Author(s): Michael Skwarski  |  Author(s): Daniel R McGowan, Kevin M Bradley, John D Fenwick, Fergus V Gleeson, Amanda Horne, Timothy Maughan, W Gillies McKenna, Seid Mohammed, Ruth J Muschel, Stasya M Ng, Niki Panakis, Victoria Y Strauss, Robert Stuart, Katherine A Vallis, Ruth E Macpherson, Geoffrey S Higgins

      • Abstract

      Background

      The Ras/PI3K/Akt pathway plays an important role in determining intrinsic and extrinsic tumour radiosensitivity. Buparlisib (BKM120) is a highly specific pan class-1 PI3K inhibitor. Pre-clinically, this class of agents radiosensitises tumours by direct effects on intrinsic radiosensitivity and by reducing tumour hypoxia. We therefore assessed the safety and determined the maximum tolerated dose (MTD) of buparlisib in combination with radiotherapy in patients with NSCLC and investigated its effect on tumour hypoxia.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      BKM120 was a single centre, open-label, dose-escalation and dose-expansion phase 1 trial. Patients with advanced stage NSCLC received 2 weeks of oral buparlisib. Palliative thoracic radiotherapy (20Gy in 5 fractions) was delivered during the second week of treatment. 18F-fluoromisonidazole (FMISO) PET scans were used to assess tumour hypoxic volume (HV) before and after 1 week of buparlisib treatment. HV was defined as the volume with a tumour-to-blood F-MISO uptake ratio ≥ 1.4.

      4c3880bb027f159e801041b1021e88e8 Result

      From June 2013 to August 2017, 21 patients were recruited. 11 patients were registered to the dose escalation phase with 9 evaluable for MTD analysis: 3 in Cohort 1 (50mg OD), 3 in Cohort 2 (80mg OD) and 3 in Cohort 3 (100mg OD). No DLT was reported therefore 100mg OD was declared the MTD and 10 patients received this dose in the expansion phase. Of all patients who received buparlisib (n=21), 1 SAE (Grade 3 hypoalbuminaemia) was possibly related to buparlisib (5%). The most common buparlisib-related AEs were fatigue (8.3%) and nausea (3.3%). 93.9% of all AEs with any relation to buparlisib were ≤ Grade 2. There was no reported radiotherapy associated toxicity. 15 patients were evaluable for tumour hypoxia imaging analysis. Median change in HV in Cohort 1 (n=3), Cohort 2 (n=3) and Cohort 3 combined with the expansion cohort (n=9) was 7%, -18% and -20%, respectively.

      8eea62084ca7e541d918e823422bd82e Conclusion

      This is the first clinical trial of a specific PI3K inhibitor with concurrent radiotherapy in NSCLC. This combination was found to be safe and well-tolerated. This study provides clinical evidence that PI3K inhibition rapidly reduces tumour hypoxia and therefore warrants further trials combining this class of agents with radiotherapy.

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      P1.13-32 - Comparison Between Immune-Mediated Pneumonitis and Pneumonia in Patients Treated with PD-1/PD-L1 Therapy

      16:45 - 18:00  |  Presenting Author(s): Mi Young Kim  |  Author(s): Cherry Kim, Yeon Joo Kim, Chang-Min Choi, Jin-Hwan Kim

      • Abstract

      Background

      Immune-mediated pneumonitis (IMP) is an uncommon but potentially fatal toxicity of anti–programmed death-1 (PD-1)/programmed death ligand 1 (PD-L1) therapy for non-small cell lung cancer. The purpose of study was to compare clinical and radiographic findings between IMP and pneumonia by pathogen.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      From 2014 to 2017, a total of 154 patients who received anti–PD-1/PD-L1 therapy were identified. Among these, IRP developed in 9 (5.8%) and pneumonia in 30 (19.5%), which were confirmed through multidisciplinary approach. CT findings (reticulation, consolidation, ground glass opacity [GGO], interlobular septal thickening, micro- [<10mm] and macro-nodules [≥10mm], bronchial wall thickening, bronchiectasis, pleural effusion, and lesion distribution/bilaterality) and clinical features (symptom, smoking history, cancer staging, laboratory findings, underlying disease, prior radiotherapy history) were compared between IRP and pneumonia. Grade and outcome of IRP were also investigated.

      4c3880bb027f159e801041b1021e88e8 Result

      In chest CT, diffuse reticulation (44.4% vs.0%, P=0.02), patchy/diffuse GGO (100% vs. 50%, P=0.01), and interlobular septal thickening (66.7% vs. 10%, P=0.002) were significantly more frequent in IRP than in pneumonia, whereas macronodule (0 vs. 36.7%, P=0.033) was significantly more common in pneumonia than IRP. IRP significantly showed peripheral location (77.8% vs. 16.7%, P=0.001) and bilateral distribution (44.4% vs. 3.3%, P=0.007). However, there were no significant differences in clinical findings between IRP and pneumonia. Among the IRP patients, 66.7% (6 of 9) of cases were grade 3, and 66.7% improved with drug holding/steroid therapy. The median onset duration of IRP from the first prescription was 126 days (range, 40-669), the median time for improvement was 43 days (range, 21-45), and the median time to death due to IRP was 18 days (range, 11-55).

      8eea62084ca7e541d918e823422bd82e Conclusion

      Several CT findings including diffuse reticulation, patchy/diffuse GGO, and interlobular septal thickening with bilateral and peripheral distribution were more frequent in IRP than pneumonia by pathogen. Clinical findings were overlapped.

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      P1.13-33 - Ex Vivo 2*2*2 Tumor Tissue Explant Culture for Precision Medicine in Immunotherapy and TKI progressors in Lung Cancer

      16:45 - 18:00  |  Presenting Author(s): Nir Peled  |  Author(s): Susmita Ghosh, Moshe Elkabets, Kiran Kundu, Laila Roisman, Dina Levitas, Angel Porgador

      • Abstract

      Background

      Lung cancer is one of the leading causes of cancer mortality worldwide. Despite of remarkable progress made in the lung cancer therapy, an unmet need is there in tailoring the appropriate patient specific therapy due to a variety of treatment options. Our aim was to develop a high-throughput drug screening method of tumor ex-vivo analysis (TEVA) which can predict patient-specific drug response and thus can be used for personalized cancer treatment.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Freshly operated tumor tissue samples from non small cell lung carcinoma (NSCLC) patients were received from Soroka Medical Center, Israel and implanted in NSG mice to form PDXs. We developed a method that enabled us to cut the PDXs into 2*2*2mm tissue explants and then treated with clinically relevant drugs (Genomics/proteomics suggested) in 48 well plates for 24 hours. TMA blocks were prepared and IHC was performed. Parameters, such as Ki67, TUNEL and respective signalling molecules (pMAPK, pPRAS40) were chosen to predict the drug response ex vivo and a score was given to each drug based upon those parameters.

      4c3880bb027f159e801041b1021e88e8 Result

      8 NSCLC patients have been enrolled so far. Implantation rate was 75%. 15 drugs combinations have been developed to test the most common conditions, i.e. progression on EGFR TKIs, progression on immunotherapy and progression on chemotherapy. Preliminary results indicate a potential role for MET blockade in immune-resistant as well as in EGFR progressors. We also observed that the TEVA score correlated with the genomics/proteomics based drug results.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Overall, this low cost, fast, relatively simple and efficient method can bypass the necessity of drug validation in mice and can be used for multiple drug screening to select a precise patient specific drug. The method is feasible and expose ways to overcome acquired resistant to novel drugs.

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      P1.13-34 - Changes in Radiomic Features Between Baseline and Two Weeks Post-Nivolumab Treatment Are Predictive of Pathologic Complete Response

      16:45 - 18:00  |  Presenting Author(s): Kaustav Bera  |  Author(s): Mohammadhahi Khorrami, Prateek Prasanna, German Corredor-Prada, Vamsidhar Velcheti, Anant Madabhushi

      • Abstract

      Background

      Programmed cell death immune checkpoint inhibitors have been approved by the FDA to treat stage III unresectable NSCLC or Stage IV metastatic lung adenocarcinoma. However, the response rate to such therapy is limited to 19%. Currently, there are no clinical biomarkers to identify patients who are likely to derive benefit from Nivolumab. Our aim was to explore whether changes in intratumoral and peritumoral radiomic texture features between baseline and 2-week post-treatment CT scans could predict immunotherapy response.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Surgical biopsy specimens (pre-treatment) and CT scans from 73 NSCLC patients with pre- and 2-week post-Nivolumab treatment were acquired. Patients with an objective response (complete/partial) per RECIST after two cycles of Nivolumab were defined as “responders” and patients with progressive disease were defined as “non-responders”. 454 intra-tumoral texture, 24 shape features and 7426 features from annular rings (15 annular rings each, 2mm each) outside the expert-annotated nodules were extracted from the baseline and post-treatment scans. Besides, 76 features quantifying compactness of tumor infiltrating lymphocytes (TILs) were extracted from the surgical specimens. A linear discriminant analysis(LDA) classifier was trained using the most predictive features identified on the discovery set(n=29) and validated on the test set(n=44). To investigate the radio-pathomic associations, a pair­wise Spearman correlation was performed between each radiomic and TIL feature.

      4c3880bb027f159e801041b1021e88e8 Result

      A combination of 6 intra-tumoral, 3 peri-tumoral and 1 shape delta radiomic feature yielded an AUC of 0.93 ± 0.085 within the discovery set and a corresponding AUC = 0.91 within the validation set. Lymphocyte density was found to be negatively(r=-0.5) correlated with a peritumoral Gabor feature from the first annular ring.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Change in texture features extracted from baseline and post-Nivolumab treated CT scans were predictive of pathological response. Association of these texture features with TIL compactness may provide a deeper understanding of immune response and corresponding imaging phenotypes.

      untitled.png

      6f8b794f3246b0c1e1780bb4d4d5dc53

      • Abstract

      Background

      Oxygen deprivation (hypoxia) is associated with worse non-small cell lung cancer (NSCLC) outcomes and predicts poor response to NSCLC treatments, including radiotherapy. There is an unmet need to develop non-invasive hypoxia biomarkers. We report the first preclinical and clinical evidence that oxygen-enhanced MRI (OE-MRI) can map and quantify therapy-induced change in NSCLC hypoxia.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      In the preclinical study, radiation-induced changes in OE-MRI were first examined in a Calu-6 xenograft model of NSCLC. Tumours received a single 10Gy fraction of radiotherapy (n=9), chemoradiotherapy (5 x 2Gy fractions plus cisplatin; n=6) or control (n=9). Mice were imaged longitudinally using a multi-parametric MRI protocol (diffusion-weighted imaging (DWI), OE and dynamic contrast-enhanced (DCE)-MRI) at days 0, 3, 6 and 10 in all groups and then at day 13 (control), day 18 and 25 (radiotherapy) and day 18 (chemoradiotherapy). Pathology was obtained at cull in imaged mice and in a separate Calu6 cohort treated with a single 10Gy radiotherapy fraction (n=6) or control (n=9) at day 10. In the clinical study, twenty three stage I-IV NSCLC patients underwent an identical multi-parametric MRI for protocol development (n=6), twice prior to radiotherapy (n=10) and after 14±4 radiotherapy fractions (n=12). In all tumours we quantified the validated MRI hypoxia biomarker perfused oxygen-refractory (Oxy-R), which identifies absence of OE-MRI signal change in perfused tumour.

      4c3880bb027f159e801041b1021e88e8 Result

      By day 10, perfused Oxy-R (hypoxic) volume decreased relative to control in xenografts treated with either radiotherapy (p=0.029) or fractionated chemoradiotherapy (p=0.047). Hypoxia modification persisted in chemoradiotherapy treated tumors to day 16 and in radiotherapy treated tumors to day 22 (both p<0.001). Pimonidazole immunohistochemistry at day 10 showed lower hypoxic fraction in tumors treated with radiotherapy (p=0.026), relative to time matched controls. In addition, imaged xenografts also showed lower hypoxic fractions in radiotherapy (p=0.042) and chemoradiotherapy (p=0.041) treated tumors, relative to size matched control at cull. In the clinical study, OE-MRI was safe, feasible and well-tolerated. Perfused Oxy-R (hypoxic) volume demonstrated excellent repeatability with interclass correlation coefficient of 0.961 (95% CI 0.858-0.990). Visual inspection revealed that MRI hypoxia maps were spatially repeatable across a range of tumour and hypoxic volumes. In the absence of volumetric tumour change, perfused Oxy-R (hypoxic) volume decreased at mid-treatment (3.23 cm3 (95% CI 0-9.41 cm3)), compared to baseline (4.16 cm3 (95% CI 0-10.6 cm3)); p=0.0150.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Our findings support using OE-MRI to detect and monitor hypoxia in clinical trials of hypoxia-modifying therapies or radiotherapy dose painting studies in patients with NSCLC.

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      P1.13-36 - Randomized Phase 2 Trial of Seribantumab in Combination with Erlotinib in Patients with EGFR Wild-Type Non-Small Cell Lung Cancer

      16:45 - 18:00  |  Presenting Author(s): Lecia Sequist  |  Author(s): Jhanelle Elaine Gray, Wael A Harb, Robert C. Doebele, Manuel R; Modiano, David Michael Jackman, Maria Quintos Baggstrom, Akin Atmaca, Enriqueta Felip, Mariano Provencio, Manuel Cobo Dols, Bambang Adiwijaya, Geoffrey Kuesters, Walid Kamoun, Karen Andreas, J Marc Pipas, Sergio Santillana, Byoung Chul Cho, Keunchil Park, Frances A Shepherd

      • Abstract

      Background

      Seribantumab (MM-121) is a fully human IgG2 monoclonal antibody that binds to human epidermal growth factor receptor 3 (HER3/ErbB3), to block heregulin (HRG/NRG)-mediated ErbB3 signaling and induce receptor downregulation. This open-label, randomized Phase 1/2 study evaluated safety and efficacy of seribantumab in combination with erlotinib in advanced NSCLC. Here, we report the activity of seribantumab in combination with erlotinib, versus erlotinib alone, in patients with EGFR wild-type tumors and describe the potential predictive power of HRG.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Patients with EGFR wild-type NSCLC were assigned randomly to receive seribantumab plus erlotinib or erlotinib alone. Patients underwent pre-treatment core needle biopsy, and archived tumor samples were collected to support pre-specified biomarker analyses.

      4c3880bb027f159e801041b1021e88e8 Result

      One hundred twenty-nine patients received seribantumab/erlotinib (n=85) or erlotinib alone (n=44). Median estimated PFS in the unselected ITT population was 8.1 and 7.7 weeks in the experimental and control arm, respectively (HR=0.822; 95% CI, 0.37 to 1.828; P=0.63). In patients whose tumors had detectable HRG mRNA expression, treatment benefit was observed in the seribantumab/erlotinib combination (HR=0.35; 95% CI, 0.16 to 0.76; P=0.008). In contrast, in patients whose tumors were HRG negative, the HR was 2.15 (95% CI, 0.97 to 4.76; P = 0.059).

      8eea62084ca7e541d918e823422bd82e Conclusion

      The addition of seribantumab to erlotinib did not result in improved PFS in unselected patients. However, pre-defined retrospective exploratory analyses suggest that detectable HRG mRNA levels identified patients who might benefit from seribantumab. An ongoing clinical trial is validating this finding in patients with advanced NSCLC and high HRG mRNA expression (NCT02387216).

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      P1.13-37 - Clinical Evaluation of Plasma-Based (cfDNA) Genomic Profiling in Over 1,000 Patients with Advanced Non-Small Cell Lung Cancer

      16:45 - 18:00  |  Presenting Author(s): Hai T Tran  |  Author(s): Vincent K Lam, Mayra E Vasquez, Lingzhi Hong, Rivka Colen, Nabil A Elshafeey, Islam Safwat Ali Hassan, Eric A Prado, Vassiliki A Papadimitrakopoulou, George R Blumenschein, Brett W. Carter, George R. Simon, Lauren Byers, Mehmet Altan, Yasir Y Elamin, Richard B Lanman, Victoria M. Raymond, Anne S. Tsao, Don Lynn Gibbons, Frank Fossella, Jianjun Zhang, John V Heymach

      • Abstract

      Background

      Tumor genomic information from a simple blood collection revealing actionable mutation can improve clinical outcome without the need for an invasive tissue biopsy. We report on the clinical utility of a cell-free DNA (cfDNA) next generation sequencing (NGS) blood test in our patients with non-small cell lung cancers (NSCLC) and the outcome of treatments with targeted therapies based on the reported mutations.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      From May 2015 to February 2017, 1078 blood samples from 1011 consecutive patients with a diagnosis of NSCLC were collected and analyzed using next-generation sequencing of cfDNA with a panel of up to 70 cancer-related genes at a CLIA-certified lab (Guardant360, Guardant Health, Redwood City, CA) with reported sensitivity of 0.02% mutant allele fraction with high specificity (> 99.9999%) (CCR 2018 (17):3831). Patients in this retrospective study received targeted therapy as indicated by cfDNA molecular profiling. Tumor response was evaluated by RECIST V1.1 and standard clinical evaluation.

      4c3880bb027f159e801041b1021e88e8 Result

      From 1011 patients, 1078 cfDNA tests sent (additional follow-up tests: 1 in 64 patients and 2 in 3 patients). In 223/1011 (22%) patients had cfDNA report with at least 1 targetable mutations; with 48/223 (22%) patients meeting criteria for this retrospective review. Study population were 31 female:17 male, median age of 63 years (ranged:31-94). The rationale for the blood test included: insufficient tissue or not available (32%), addition to tissue molecular analysis (17%), alternative to tissue biopsy(10%), on-going treatment evaluation/resistance (41%). Mutations included:EGFR T790M (15), EGFR exon 19del (12), EGFR L858R (9), EGFR exon 20 insertion (4), EGFR others (1), ALK gene fusions (5) and MET exon 14 skipping (2). The median line of therapy was 2(ranged:1-7) with 28 patients receiving TKI as 1st line of therapy based on cfDNA mutations. With targeted treatments based on ctDNA results, the responses (RECIST V1.1) were: CR(3), PR(26), SD(14) and PD(4); median PFS was 8.5 months (ranged:1-26mos) for the overall population with 4 patients still receiving targeted therapy. Median PFS was 9.5 months (ranged:1-20 months) for those receiving TKI as 1st line.

      8eea62084ca7e541d918e823422bd82e Conclusion

      This is the largest analysis of response rates with cfDNA directed therapy in advanced NSCLC and demonstrates positive clinical outcomes in patients treated with targeted therapy based on plasma identified biomarkers.

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      P1.13-38 - Inter-Organ Heterogeneity on Mechanisms of Targeted Drug Resistance -Central Nervous System (CNS) vs Extra CNS-

      16:45 - 18:00  |  Presenting Author(s): Seiji Yano

      • Abstract

      Background

      Molecular-targeted drugs are generally effective against tumors containing driver oncogenes, such as EGFR, ALK, and NTRK1. However, patients harboring these oncogenes frequently experience a progression of central nervous system (CNS) metastasis, such as brain metastasis and leptomeningeal carcinomatosis (LMC), during treatment. While secondary mutations including EGFR-T790M, ALK-L1196M, and NTRK1-G595R, are known to induce highly resistance to corresponding targeted drugs, involvement of these highly resistance mutations in CNS metastasis resistance is largely unknown.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We developed various in vivo imaging models for brain metastasis and LMC with human cancer cell lines, including the EGFR-exon 19 deletion-positive PC-9 lung adenocarcinoma cells, the EML4-ALK-positive A925L lung adenocarcinoma cells, and TPM3-NTRK1-positive KM12SM colon cancer cells. Using these CNS metastasis models, we examined the inter-organ heterogeneity on mechanisms of resistance to targeted drugs.

      4c3880bb027f159e801041b1021e88e8 Result

      While PC-9 cells inoculated in subcutaneous space acquired EGFR tyrosine kinase inhibitor (EGFR-TKI) resistance by EGFR-T790M mutation, they inoculated in leptomeningeal space became resistance by MET copy number gain. Unlike EGFR-T790M mutation, MET copy number gain could cause intermediate resistance to EGFR-TKI in vitro. Similarly, A925L cells inoculated in leptomeningeal space acquired ALK-TKI resistance by EGFR ligand overexpression. Moreover, KM12SM cells inoculated in the brain acquired entrectinib resistance by NTRK1-G667C mutation. Since both EGFR ligand overexpression and NTRK1-G667C mutation caused intermediate resistance to targeted drugs in vitro, mechanisms which cause intermediate resistance may be sufficient to develop resistant tumors in CNS presumably due to limited drug distribution to CNS.

      8eea62084ca7e541d918e823422bd82e Conclusion

      These observations indicate inter-organ heterogeneity on mechanisms of targeted drug resistance. Therefore, careful diagnosis of resistance mechanism in CNS metastasis may be necessary when treat the patients who develop CNS metastasis with targeted drug resistance.

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      P1.13-39 - Epidermal Growth Factor Receptor Mutation Among Non-Small Cell Lung Cancer Patients in Trinidad and Tobago: Frequency and Trends

      16:45 - 18:00  |  Presenting Author(s): Aaron Haralsingh  |  Author(s): Mark West

      • Abstract

      Background

      Almost 70% of non-small cell lung cancer (NSCLC) patients present with unresectable disease and may benefit from chemotherapy or biologic therapy. Mutation testing now plays a vital role in their diagnostic work-up to determine which patients are more likely to receive benefit from biologic therapies. The rate of epidermal growth factor receptor (EGFR) mutations varies significantly across geographic regions and ethnicities, ranging from 13% to 64% in some areas. Several subgroups such as females, East Asians, never-smokers and those with adenocarcinoma histology have the highest reported rates of EGFR mutations. Regionally, the French West Indies reports an EGFR mutation rate of 36%. The frequency of the EGFR mutation among NSCLC patients in Trinidad and Tobago has not been previously reported in the literature.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      An observational, retrospective study was done using data obtained from the Lung Malignancy Unit (LMU) based at the Eric Williams Medical Sciences Complex (EWMSC). The EWMSC is the sole referral centre in Trinidad and Tobago for lung cancer and the LMU is responsible for co-ordinating clinical and educational services regarding lung cancer nationwide.The study population was limited to primary NSCLC patients presenting to the EWMSC from January 2014 to June 2017 whose biopsy samples were sent for EGFR testing and received either a positive or negative result. Patients’ clinical data was entered onto a spreadsheet and analysed using Microsoft Excel.

      4c3880bb027f159e801041b1021e88e8 Result

      The data for 94 patients with NSCLC were analysed. 68 of these patients were male, while 58 admitted to a history of smoking. EGFR mutations were present in 39.4% of this study population. Females demonstrated a significantly higher EGFR mutation rate than males (73.1% vs 26.5%, p < 0.0001). Smoking status was found to be significantly associated with differences in EGFR mutation status (p < 0.01). The mean age of presentation was similar despite of EGFR mutation status. Although a larger number of EGFR positive patients compared to EGFR negative patients had adenocarcinoma histology (97.3% vs. 89.5%), this was not found to be statistically significant (p = 0.29).

      8eea62084ca7e541d918e823422bd82e Conclusion

      The frequency of EGFR mutations in this study population (39.4%) was higher than most regions of the world but similar to that reported in the French Antilles. Sex and smoking status were significantly associated with differences in EGFR mutation status.

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      P1.13-40 - Rapid, Robust and Durable Responses to Larotrectinib in Patients with TRK Fusion Non-Small Cell Lung Cancer

      16:45 - 18:00  |  Presenting Author(s): Anna F. Farago  |  Author(s): Shivaani Kummar, Shannon Ibabekci, Stefani Corsi-Travali, Scott Cruickshank, Michael C. Cox, Nora C. Ku, Alexander Drilon

      • Abstract

      Background
      Neurotrophic tyrosine receptor kinase (NTRK) gene fusions are oncogenic independent of tumor lineage and are widely distributed across cancers. NTRK gene fusions were first reported in lung cancer in 2013 (Vaishnavi et al Nat Med 2013). Larotrectinib is a potent and highly selective oral tropomyosin receptor kinase (TRK) inhibitor in clinical development. Initial data of treatment of 55 patients with TRK fusion cancer resulted in an investigator-assessed objective response rate of 80%, and 71% of patients still in response at one year (Drilon et al., NEJM 2018). We report here on the safety and efficacy of larotrectinib in 4 patients with NSCLC from the 55 patient dataset.
      a9ded1e5ce5d75814730bb4caaf49419 Method
      Patients with previously treated lung adenocarcinoma were treated under clinical trial and enrolled based on a molecular report of NTRK gene fusion from a CLIA-certified lab. Larotrectinib was administered at 100 mg BID until disease progression or lack of clinical benefit. Tumors were assessed by investigators every 8 weeks using RECIST v1.1 criteria.
      4c3880bb027f159e801041b1021e88e8 Result

      As of July 17, 2017, four patients with adenocarcinoma of the lung who had progressed after 1 or more lines of platinum-based chemotherapy for advanced disease were enrolled. Three patients harbored an NTRK1 fusion and one an NTRK3 fusion. Three of 4 patients had a partial response or complete response confirmed on a subsequent scan. One patient with a possible brain metastasis demonstrated regression of mass on MRI. Responses were rapid and robust, with a time to response ranging between 49 and 56 days. At the time of analysis, 3 patients continued to have an ongoing response ranging between 5.7 and 12 months. The other patient had stable disease and progressed outside of the CNS after 300 days of treatment and continued on larotrectinib for clinical benefit. Larotrectinib was well tolerated, with 3 of 4 patients having grade 1 events only.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Larotrectinib treatment resulted in rapid and durable responses and had a well tolerated adverse event profile with no CNS progressive events in patients with previously treated lung cancer harboring NTRK gene fusions. These results strongly support the inclusion of NTRK gene fusions as part of routine testing for patients with lung cancer.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      P1.13-41 - In Vitro Evaluation for Optimal MET-TKI Selection in Lung Cancers with MET Mutations Including Exon 14 Skipping

      16:45 - 18:00  |  Presenting Author(s): Toshio Fujino  |  Author(s): Kenichi Suda, Yoshihisa Kobayashi, Masaya Nishino, Takamasa Koga, Shuta Ohara, Masato Chiba, Masaki Shimoji, Toshiki Takemoto, Tetsuya Mitsudomi

      • Abstract

      Background

      MET exon 14 skipping mutation present in 3-5% of adenocarcinoma of the lung is an emerging driver gene alteration. Clinical responses of these tumors to MET-TKI have been reported. However, response rates are not very satisfactory compared with EGFR/ALK/ROS1 TKI. Therefore, it is necessary to create in vitro model system to understand sensitivity/resistance mechanism for various types of MET-TKI, to establish optimal treatment strategy.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We introduced MET exon 14 skipping mutation as well as Y1003F, D1010Y which had been also reported to be present in lung cancer, to mouse pro-B cell line, Ba/F3. Since Ba/F3 requires interleukin 3 (IL-3) for its growth, IL-3 independent growth of Ba/F3 indicates that transduced mutation is oncogenic. The growth inhibitory assays were then performed using 9 MET-TKIs that include all classes of MET-TKIs ; Type Ia (crizotinib), Type Ib (capmatinib, tepotinib, savolitinib and AMG337) , Type II (cabozantinib, merestinib and glesatinib) and Type III (tivantinib).

      4c3880bb027f159e801041b1021e88e8 Result

      Ba/F3 transfected with wild-type MET did not grow in the absence of IL-3, while all transfected with any of three mutated MET did so. In general, all type Ia/b / type II inhibitors were active for any of 3 MET mutations. Interestingly MET point mutations (Y1003F/D1010Y) were more sensitive to type Ib inhibitors except AMG337 than type II, while exon 14 skipping was likely to be more sensitive to type II inhibitors than type Ib compared with point mutations. IC50 / Cmax of cabozontinib was least for exon 14 skipping while that of capmatinib was least for Y1003F and D1010Y, suggesting most promising activity of these drugs (Table).

      table.png

      8eea62084ca7e541d918e823422bd82e Conclusion

      We found that the MET exon 14 skipping, Y1003F, and D1010Y mutations were all oncogenic in Ba/F3 system. Several type I/II inhibitors especially cabozantinib and capmatinib are expected to be active for treating lung cancer patients with MET mutations.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      P1.13-42 - Activity of Novel HER2 Inhibitor, Poziotinib, for HER2 Exon 20 Mutations in Lung Cancer and Mechanism of Acquired Resistance

      16:45 - 18:00  |  Presenting Author(s): Takamasa Koga  |  Author(s): Yoshihisa Kobayashi, Kenji Tomizawa, Yuichi Sesumi, Toshio Fujino, Masaya Nishino, Shuta Ohara, Masato Chiba, Masaki Shimoji, Kenichi Suda, Toshiki Takemoto, Tetsuya Mitsudomi

      • Abstract

      Background

      Oncogenic HER2 mutations are present in 2-4% of adenocarcinoma of the lung. However, clinical trials of HER2 inhibitors such as afatinib or neratinib has been unsatisfactory. Recently, a novel HER2 inhibitor, poziotinib has been developed and clinical trial results are being expected. Here, we evaluated poziotinib in comparison with pre-existing TKIs using Ba/F3 system. We also derived resistant clones against poziotinib and investigated their resistant mechanism.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We introduced three common HER2 mutations into Ba/F3 cells (i.e. G776delinsVC (VC), A775_G776insYVMA (YVMA) and P780_Y781insGSP (GSP)) which account for 13, 72, 9% of HER2 mutations in human lung cancer, respectively. We defined sensitivity index (SI) as an IC90divided by trough concentration of a given drug at the recommended dose for humans in the literature, as a surrogate for drug activity in humans. Poziotinib activity was compared with 8 TKIs (afatinib, osimertinib, erlotinib, neratinib, lapatinib, dacomitinib, irbinitinib, and AZ5104). In addition, we created resistant clones by exposing poziotinib in the presence of N-ethyl-N-nitrosourea (ENU) and HER2 secondary mutations were searched.

      4c3880bb027f159e801041b1021e88e8 Result

      All drugs but lapatinib showed the highest activity against VC (Table). In contrast, YVMA was most resistant in all but neratinib and poziotinib. For most common YVMA, poziotinib was the only drug that had SI of less than 10 (Table). Furthermore, poziotinib was most potent for VC and GSP except dacomitinib for GSP (Table). We established 19 poziotinib-resistant clones, all of which harbored C805S secondary mutation of the HER2 gene homologous to C797S of the EGFR gene.

      Ctrough [nM] YVMA VC GSP
      Afatinib 69 28 5.4 12
      Dacomitinib 166 20 4.4 6.6
      Erlotinib 2969 337 22 98
      Osimertinib 400 40 4.5 30
      Neratinib 100 11 11 28
      Lapatinib 516 133 117 91
      Poziotinib 20 6.0 2.7 10
      Irbinitinib 520 34 33 16
      AZ5104 50 60 8.0 48

      8eea62084ca7e541d918e823422bd82e Conclusion

      Poziotinib showed the most potent activity against HER2 exon 20 mutations. We also found that secondary C805S HER2 mutation was the common mechanism of acquired resistance, which most likely inhibit covalent binding of poziotinib with HER2.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      P1.13-43 - Molecular and Imaging Predictors of Response to Ado-Trastuzumab Emtansine in Patients with HER2 Mutant Lung Cancers: An Exploratory Phase 2 Trial

      16:45 - 18:00  |  Presenting Author(s): Bob T. Li  |  Author(s): Michael Offin, Todd Hembrough, Fabiola Cecchi, Ronglai Shen, Zachary T. Olah, Elizabeth Panora, Mackenzie Myers, Edyta B. Brzostowski, Darren Buonocore, Michelle S Ginsberg, Charles M. Rudin, Mark G Kris, Gregory Weitsman, Paul R. Barber, Tony Ng, Gary A. Ulaner, Maria E Arcila, Maurizio Scaltriti

      • Abstract

      Background

      Ado-trastuzumab emtansine is a HER2 targeted antibody drug conjugate (ADC) that has demonstrated clinical activity in patients with HER2 mutant lung cancers, independent of HER2 protein expression. We hypothesize that the degree of HER2 homo- and/or heterodimerization may lead to preferential trastuzumab binding and internalization, and may serve as a predictor of response to HER2 ADC.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Patients with metastatic HER2 mutant lung cancers were enrolled in a phase 2 trial of ado-trastuzumab emtansine, treated at 3.6mg/kg IV every 3 weeks. The primary endpoint was overall response rate (ORR) using RECIST v1.1. An expansion cohort included patients assessed using PERCIST, with pre-treatment 89Zr-trastuzumab PET/CT as correlative HER2-targeted imaging. HER2 mutation was identified by next generation sequencing (NGS), and tumors with adequate tissue were subsequently tested by fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), quantitative protein mass spectrometry, as well as quantitative HER2-HER3 heterodimerization by fluorescence lifetime imaging microscopy - Förster resonance energy transfer (FLIM-FRET).

      4c3880bb027f159e801041b1021e88e8 Result

      A total of 35 patients with HER2 mutant lung cancers were treated across 2 cohorts. ORR was 44% (8/18, 95% CI 22-69%) for RECIST cohort, and 46% (6/13, 95% CI 19-75%) for PERCIST cohort with 4 patients awaiting response assessment. Responders were seen across mutation subtypes (A775_G776insYVMA, G776delinsVC, V659E, S310F, L755P). Concurrent HER2 amplification was observed in 6 of 35 (17%) patients by either NGS or FISH. IHC ranged from 0 to 3+ and did not predict response. HER2 protein expression was low or absent in 15/18 cases tested by mass spectrometry. HER3 overexpression was seen in 7/18 cases tested and among them 5/6 evaluable patients had a partial response. FLIM-FRET efficiency was tested positive for HER2-HER3 heterodimer, which has been shown to be affected by the symmetrical heterodimer interface mutations (Claus et al, 2018), in 3 patients thus far and 1 of them had a partial response. Pre-treatment 89Zr-trastuzumab PET/CT showed increased uptake in 3/8 patients tested to date, and all 3 patients subsequently had partial metabolic response.

      8eea62084ca7e541d918e823422bd82e Conclusion

      This study confirmed the efficacy of ado-trastuzumab emtansine in patients with HER2 mutant lung cancers. HER2-containing dimers as indicated by HER3 overexpression or FLIM-FRET efficiency, and HER2-targeted imaging with 89Zr-trastuzumab PET/CT, may predict response to HER2 ADCs.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      P1.13-44 - Safety, PK, and Preliminary Antitumor Activity of the Oral EGFR/HER2 Exon 20 Inhibitor TAK-788 in NSCLC

      16:45 - 18:00  |  Presenting Author(s): Joel W. Neal  |  Author(s): Robert C. Doebele, Gregory J Riely, Alexander Spira, Leora Horn, Zofia Piotrowska, Daniel B Costa, Steven Zhang, Dean Bottino, Jian Zhu, David Kerstein, Shuanglian Li, Pasi A Jänne

      • Abstract

      Background

      TAK-788 (AP32788) is an investigational tyrosine kinase inhibitor (TKI) with potent, selective preclinical activity against activating EGFR and HER2 mutations, including exon 20 insertions. We report early results of a phase 1/2 first-in-human, open-label, multicenter study of TAK-788 (NCT02716116).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Patients with advanced non-small cell lung cancer (NSCLC) refractory to standard therapy received daily oral doses (5–120 mg) of TAK-788 in the ongoing dose-escalation phase (3+3 design). Preliminary antitumor activity (by RECIST v1.1), safety, and PK are reported for patients who received ≥1 dose.

      4c3880bb027f159e801041b1021e88e8 Result

      As of 8-Sep-2017, 34 patients (median age, 60 y; female, 65%; ≥2 prior anticancer therapies, 88%; Table) were treated with TAK-788; 10 remain on treatment at data cutoff. AUC0‑24,ss increased in a dose-proportional manner over the dose range evaluated; the effective t1/2 was ~16 (range 6–28) h. The most common treatment-emergent AEs (TEAEs; ≥20%) were diarrhea (47%), nausea (26%), and fatigue (21%). Grade ≥3 TEAEs in ≥2 patients (excluding disease progression) were dyspnea (n=3, 9%) and anemia, asthenia, dehydration, lung infection, pleural effusion, pneumonia, and pneumonitis (n=2 each, 6%). Two DLTs, both pneumonitis, were reported (80 mg, grade 3; 120 mg, grade 5). Of 14 evaluable patients, 3 had PR (80 mg, n=2, both confirmed; 120 mg, single PR awaiting confirmation), 6 had SD (40 mg, n=3; 80 mg, n=2; 120 mg, n=1), and 5 had PD as best response (40 mg, n=3; 80 mg, n=1; 120 mg, n=1). All patients with PR had EGFR exon 20 insertions.

      8eea62084ca7e541d918e823422bd82e Conclusion

      TAK-788 exhibits antitumor activity in patients with EGFR exon 20 insertions with an AE profile consistent with other EGFR TKIs. Phase 2 will begin after determination of the RP2D, with 4 molecularly defined cohorts in NSCLC. Updated data will be presented, including the recommended phase 2 dose (RP2D).

      Baseline Characteristics

      5 mg

      (n=4)

      10 mg

      (n=5)

      20 mg

      (n=5)

      40 mg

      (n=6)

      80 mg

      (n=7)

      120 mg

      (n=7)

      Total

      (n=34)

      Mutation type,a %

      Common EGFR mutations (exon 19 deletion / L8585R) 25 20 0 0 0 0 6
      EGFR-T790M+ 0 0 0 0 14 0 3
      EGFR exon 20 insertion 50 40 60 83 71 57 62
      HER2 0 20 40 17 14 29 21
      a One patient (20 mg) had both EGFR and HER2 mutations; 1 patient (80 mg) had EGFR exon 20 insertion + T790M.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      P1.13-45 - Coexistence of Activating BRAF and KRAS Mutations in Lung Cancer Patients

      16:45 - 18:00  |  Presenting Author(s): yingyi Wang

      • Abstract

      Background

      Activating mutations in both KRAS and BRAF gene can stimulate mitogen-activated protein kinase (MAPK) signaling. So BRAF and KRAS mutations are generally mutually exclusive from each other, acting as an alternative oncogenic driver in NSCLC. There was occasionally case reports of coexistence of BRAF and KRAS mutations in colorectal cancer, lung squamous cell carcinoma. However, to our knowledge, there was no systemic studies in this area

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We retrospectively analyzed mutation profiling of 2000 consecutive lung cancer samples in our institute. Mutation profiles were analyzed using hybridization capture based next-generation sequencing (NGS), which enables the simultaneous detection of single-nucleotide variants, insertions/deletions, rearrangements, and copy-number alterations of at least 59 genes (range 59 – 1021 genes).

      4c3880bb027f159e801041b1021e88e8 Result

      Sixty-three patients with activating BRAF mutation was analyzed in the study, including 48 lung adenocarcinoma, 3 squamous cell lung cancer, 1 lung adenosquamous cell carcinoma, 1 lung large cell carcinoma and 10 lung cancer patients with unspecified pathology. The most common BRAF mutation, BRAF V600E, was identified in 33 patients. BRAF Non-V600E mutation was identified in 30 patients, including G469A/V/R (7), D594G/N (6), K601E/N (6), G464V (3), G466A/V (3), G596R (2), K483E (1), N486_P490del (1) and N581S (1) mutations. Among the 63 patients, 8 (12.7%) had coexistence of activating KRAS mutation. Concurrence of activating KRAS mutation (G12A/D/S, G13D) was identified in 3 of the 30 patients with BRAF V600E mutations, with 2 of the 3 patients had previous EGFR-TKI treatment. The patient with KRAS G12S, G13D, and BRAF V600E mutation but without EGFR sensitive mutation had poor response to chemotherapy. On the contrary, activating KRAS mutation (G12D/V, G13D, A146V) was identified in 5 of the 33 patients with BRAF non-V600E mutation, with only one patient had EGFR-TKI sensitive mutation and previous EGFR-TKI treatment.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Coexistence of activating KRAS mutation is not uncommon in NSCLC patients with BRAF mutations, especially in patients with non-V600E mutations. Therefore, therapeutic choice for patients with BRAF non-V600E mutation need comprehensive consideration of companion mutations. Moreover, previous EGFR-TKI may increase the incidence of concurrence of generally mutually exclusive mutations.

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    P1.14 - Thymoma/Other Thoracic Malignancies (Not CME Accredited Session)

    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Moderators:
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      P1.14-01 - Current Practices in the Management of Malignant Pericardial Effusions: A Survey Amongst Members of the European Society of Thoracic Surgeons.

      16:45 - 18:00  |  Presenting Author(s): Edward J Caruana  |  Author(s): Luca Bertolaccini, Piergiorgio Solli, Marco Scarci

      • Abstract

      Background

      Malignant pericardial effusion (MPE) is a rare presentation, is associated with a high morbidity and mortality, and may be challenging to manage.

      We sought to determine the current practice in the management of MPE among members of the European Society of Thoracic Surgeons (ESTS).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      A cross-sectional survey examining the case volume, initial workup, urgent and non-urgent management of MPE was developed by the authors, following a review of the literature. The survey was circulated to ESTS membership in an internet-based survey format, between February and April 2016.

      4c3880bb027f159e801041b1021e88e8 Result

      136 consultant thoracic surgical colleagues responded; representing 43 countries across 5 continents, and with an average (mean±SD) of 14±9 years’ independent practice. Annual volume of MPE referral was 9±12 cases (median, range = 5, 0 to 80).

      Echocardiography (88%), computed tomography (85%) and pericardial fluid cytology (54%) are the preferred initial investigations.

      In clinically stable patients, pericardiocentesis is the preferred (60%) intervention in first-presentations; with 80% of patients with recurrent effusions being offered pleuro-pericardial fenestration (66% thoracoscopically, 14% thoracotomy). 43 to 50% of respondents would use an intrapericardial sclerosant as part of their management of recurrent MPEs, depending on primary pathology.

      The preferred approach options in patients with cardiac tamponade are ultrasound-guided pericardiocentesis (56%), subxiphoid pericardiotomy (26%) and landmark pericardiocentesis (11%).

      Only 24% of respondents felt that their practice was informed by published clinical guidelines, with 53% expressing a need for updating of current guidance.

      8eea62084ca7e541d918e823422bd82e Conclusion

      There is much variation, and reported uncertainty, in the management of MPEs in clinical practice. There is, additionally, lack of engagement with currently-available clinical guidance.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      P1.14-02 - Predicting Stent Failure in Malignant Esophageal Obstruction

      16:45 - 18:00  |  Presenting Author(s): Tommi Kalle Markus Järvinen  |  Author(s): Ilkka Ilonen, Jari Räsänen

      • Abstract

      Background

      Esophageal malignant obstruction is commonly caused by esophageal cancer and seldom caused by malignant disease not originating from the esophagus. Malnutrition and feedin intolerance are commonly present. Palliation is commonly achieved with insertion of an esophageal stent, which has been deemed safe and effective in previous trials. Our objective was to assess the factors predicting the failure of stent treatment in malignant obstruction of the esophagus.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      This was a retrospective cohort study with primary end point of stent failure. Stent failure is defined here as any major complication caused by the stent (perforation, fistula, etc.), migration of the stent the stomach or any need for non-planned urgent removal of the stent. Patient demographic details, stent insertion details (indication, date, location, size, type of stent), complications related to stent-insertion, operations associated with stent insertion, and possible time of death were collected.

      4c3880bb027f159e801041b1021e88e8 Result

      Between March 2005 and December 2013 there were 410 esophageal stents placed for treatment of malignant obstruction. The most common pathology was esophageal cancer (N = 333, 81.2%), lung cancer was the cause in 44 (10.7%) and mesothelioma and breast cancer were found were both found in 5 patients (1.2%), the remaining 23 patients had cancers of various histologies. Median OS was 149 days from stent insertion (IQR: 63-297 days). Stent failure rate in the first 6 months was 27.3% (N = 112) with median time to failure being 46 days (IQR: 9-105). Cox multivariate regression analysis was done by backwards elimination method with a p-value limit of 0.2, the results are shown in Table 1.

      Table 1 Multivariate Cox regression analysis of factors affecting stent failure
      HR 95% CI p
      Age 0.96 0.97-1.00 0.112
      Proximal stent location* 1.68 1.15-2.44 0.00714
      *Top edge under 25 cm from incisors

      8eea62084ca7e541d918e823422bd82e Conclusion

      In the setting of malignant obstruction of the esophagus, stent failure rate is related to the location of the inserted stent. More proximal stents have a higher rate of failure in multivariate analysis (HR =1.68, p = 0.00714).

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      P1.14-03 - Phase II Trial of Amrubicin and Cisplatin Chemotherapy for Invasive Thymoma: WJOG5509L

      16:45 - 18:00  |  Presenting Author(s): Keita Kudo  |  Author(s): Makoto Nishio, Yoshimasa Shikraisi, Akira Ono, Isamu Okamoto, Yasuo Iwamoto, Yuusuke Ookuma, Katsuhiro Okuda, Kohei Akiyoshi, Kazumi Nishino, Shigeki Mituoka, Koichi Azuma, Kiyonobu Ueno, Toyohisa Iriki, Kenji Sugio, Yasutaka Chiba, Yuichi Ishikawa, Kazuhiko Nakagawa, Nobuyuki Yamamoto

      • Abstract

      Background

      Background: Platinum and anthracycline combination chemotherapy has been considered as the standard treatment for invasive thymoma for a long time. The clinical activity of amrubicin (AMR)—an anthracycline agent—has been previously reported in the treatment of small cell lung cancer (SCLC). The aim of this study was to evaluate the efficacy and safety of the combination of AMR and cisplatin (CDDP) in patients with advanced or recurrent invasive thymoma.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Methods: Patients were eligible for inclusion in the study if they met the following criteria: were chemo-naive; not amenable to curative surgery or radiotherapy; and presented with histologically confirmed invasive thymoma in each site. The patients received AMR (35 mg/m2, on days 1–3) and CDDP (60 mg/m2, on day 1) every 3 weeks, for up to 4 cycles. The primary endpoint was the objective response rate (ORR) assessed by an independent review, and the secondary endpoints were overall survival (OS) and toxicity profile of the patients. Based on the SWOG 2-stage design, the planned sample size of 40 patients was determined to reject the ORR of 60% under the expectation of 80% with a power of 0.85 and a type I error of 0.05. This trial is registered with the UMIN Clinical Trials Registry, number UMIN000003933.

      4c3880bb027f159e801041b1021e88e8 Result

      Results: From August 2010 to November 2014, a total of 26 patients were enrolled at 14 institutions in Japan. During the planned interim analysis in April 2014, the ORR of the 20 patients who had been enrolled so far, was assessed via independent review and found to be 55.6% (11/20), resulting in the early termination of this study because of its futility. In the final assessment, the ORR was 54.2% (95% confidence interval, 32.8–74.4) and the disease control rate was 95.8%. The OS did not reach the median value. The major grade 3 or 4 toxicities noted were neutropenia (96.2%), anemia (26.9%), anorexia (11.5%) and febrile neutropenia (26.9%), albeit these were transient and manageable. There was one treatment-related death.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Conclusions: The combination of AMR with CDDP had minimal activity on invasive thymoma. Thus, we do not recommend further study of this regimen.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      P1.14-04 - Stereotactic Body Radiation Therapy for Pleural Recurrences of Thymoma

      16:45 - 18:00  |  Presenting Author(s): Cecile Le Pechoux  |  Author(s): Fabiano Emmanuelle, Angela Botticella, Gustin Pierre

      • Abstract

      Background

      Pleural recurrences are not uncommon as a result of thymoma evolution; yet there is no therapeutic standard for their treatment. The purpose of this study was to evaluate the efficacy and tolerability of stereotactic body radiation therapy (SBRT) for the treatment of pleural metastasis.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      A single institution retrospective study of the patients treated with SBRT using Novalis and VMAT, with doses of 30Gy in 5 fractions or 40Gy in 10 fractions. Treatment responses were evaluated using TDM and/or TEP TDM

      4c3880bb027f159e801041b1021e88e8 Result

      In the period 2014-2017, 10 patients (6 women, 4 men) with a median age of 51 and a total of 21 pleural recurrences were treated with SBRT. Initial Masaoka-Koga stages were: 1 I, 3 IIb, 3 III, 2 IVa and 1 unknown. Nine of them had previously been treated for other pleural recurrences (7 had surgery, 2 conformational RT and 3 chemotherapy).

      All patients were treated for one to three recurrence locations, either successively or at the same time. At the time of last follow-up, only one patient had died following the metastatic evolution of their thymoma.

      With a median follow-up for the lesions of 20 months, local control was very good, since all lesions were reduced to a smaller, non-progressive mass or in complete metabolic response.

      No patient developed Grade 3 or higher acute or late toxicity.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Treatment of pleural recurrences of thymoma using SBRT with moderate doses allowed for good local control without increased toxicity, constituting a good alternative to surgery. This treatment could furthermore delay the use of chemotherapy.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      P1.14-05 - The Association of Pulmonary Function with Survival After Treatment in Patients with Esophageal Cancer

      16:45 - 18:00  |  Presenting Author(s): Hsien-Chi John Liao  |  Author(s): Pei-Wen Yang, Jang-Ming Lee

      • Abstract

      Background

      Previously studies have found that inadequate pulmonary function of the patients with esophageal cancer can associate with higher risk of postoperative pulmonary complications which can lead to a higher risk of mortality in the perioperative period or long term follow-up. In this study, we investigate the prognostic effect of pulmonary function for the patients of esophageal cancer after treatment.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      From 2004~2016, 732 esophageal cancer patients underwent surgical treatment were enrolled. They received pulmonary function before treatment, and 542 (74.04%) underwent pre-operative concurrent chemoradiotherapy (CCRT) before surgery. Patients were divided into three groups by pulmonary function level (FEV<80%, inadequate pulmonary function; 80% < FEV1 < 100%, adequate pulmonary function; FEV1 > 100%, well pulmonary function). We use multivariate analysis including all of the possible factors to evaluate overall survival and progression-free survival after surgery.

      4c3880bb027f159e801041b1021e88e8 Result

      As the result, we found that cancer staging, neo-adjuvant CCRT, operation method and pre-operative FEV1 were found statistically significant for survival after treatment. As compared to patients with FEV1 less than 80% of prediction, patients with EFV1 more than 80% had an around thirty percent of decreasing mortality rate after surgery (p = 0.034). The cox-regression with survival analysis also revealed that patients with better lung function, had significantly better progression-free survival (P<0.05, respectively) than those with poor lung function. Besides, the grouping by CCRT-pCR (pathologic complete response) also had similar results. It maybe due to pulmonary function is a important immunological factor in those esophageal cancer patients.

      fig_1.jpg

      8eea62084ca7e541d918e823422bd82e Conclusion

      Although the patient selection, surgical technique, and other postoperative management have been markedly improved in recent years, the morbidity rate after esophagectomy for esophageal cancer remains high. Recent studies lead us pay attention to the perioperative and postoperative care, but they may ignored the pulmonary function disturbance is one of the major contributing factor for long-term and progression-free survival.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      P1.14-06 - Treatment Outcomes of Patients with Thymic Carcinoma: A Monocentric Experience of Sequential Regimens Modality

      16:45 - 18:00  |  Presenting Author(s): Margaret Ottaviano  |  Author(s): Mario Giuliano, Pasqualina Perrone, Marianna Tortora, Margherita Muratore, Sabino De Placido, Giovannella Palmieri

      • Abstract

      Background

      Thymic carcinoma (TC) compared with thymoma has a lower incidence rate and is more likely to be diagnosed in advanced-stage disease, with a worst prognosis. Platinum combination regimen is widely recognized as the best treatment in the first line setting, followed by other systemic therapies, such as cytotoxic drugs and target agents, with the aim of achieving control disease and prolonging survival. Since there is limited information about the optimal treatment modality in TC, this study aims to identify the most promising therapeutic sequence in terms of efficacy and toxicity profile.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We conducted a monocentric retrospective analysis of patients (pts) with un-resectable-metastatic TC, referred to our Rare Tumors Reference Center over a 15-year period. All pts with confirmed histological diagnosis, treated with at least three lines of therapy were included in the analysis. For each identified sequence treatment, progression free survival (PFS) and overall survival (OS), according to RECIST 1.1 and toxicity profile according to CTCAE v 4.0, were determined.

      4c3880bb027f159e801041b1021e88e8 Result

      Among 52 patients with advanced TC, 17 of them (32.6%) treated with at least three lines of chemotherapies and target agents (imatinib, sunitinib, everolimus) were included in the study. Three main therapeutic sequences were identified: 1) platinum-based therapy - platinum-based therapy – target agent (7 pts); 2) platinum-based therapy – capecitabine and gemcitabine combination-therapy – target agent (5 pts); 3) platinum- based therapy – target agent – no platinum-based chemo (5 pts). The median OS from the start of first-line chemotherapy was 67 months with no significant difference among sequences, with an OS respectively of 83, 67 and 106 months (p< 0.99). Also for PFS, with a median value of 33 months, there was registered no significant difference, with respectively 33, 38 and 32 months (p< 0.99). A different toxicity profile was instead revealed, with no adverse events more than grade 2 for the second and third sequence, and, conversely, toxicity of grade 3 registered in more than 50% of the pts in first sequence. Asthenia, emesis and pancytopenia which required hospitalization in 3 pts, were the most frequent.

      8eea62084ca7e541d918e823422bd82e Conclusion

      To our knowledge, this is the first data analysis of sequential regimens modality in patients with advanced TC. Since the efficacy of each treatment sequence did not vary significantly, we suggest to administer the therapy sequence with the better toxicity profile. Moreover, considering the median survival outcome reached, we support the need to refer these patients to reference center with high expertise.

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      P1.14-07 - Intraoperative Detection of Circulating Tumor Cells in Pulmonary Venous Blood During Metastasectomy for Colorectal Lung Metastases

      16:45 - 18:00  |  Presenting Author(s): Severin Schmid  |  Author(s): Uyen-Thao Le, Bernward Passlick, Jussuf Thomas Kaifi

      • Abstract

      Background

      Circulating tumor cells (CTC) have been studied extensively in various tumor types and are a well-established prognosticator in colorectal cancer (CRC). This is the first study to isolate CTC directly from the tumor outflow in secondary lung tumors.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      From 24 patients with CRC who underwent pulmonary metastasectomy in curative intent blood was drawn intraoperatively from the pulmonary vein (tumor outflow). In 22 samples CTC-enumeration was performed using CellSieve™-microfilters and immunohistochemical- and Giemsa-staining. Additionally 10 blood samples were analyzed using the CellSearch®-System.

      4c3880bb027f159e801041b1021e88e8 Result

      We could isolate more CTC in pulmonary venous blood (total 41, range 0-15) than in samples taken from the periphery at the same time (total 6, range 0-5, p=0.09). Tumor positive lymph nodes correlated with presence of CTC in pulmonary venous blood as in all cases CTC were present (p=0.006).

      8eea62084ca7e541d918e823422bd82e Conclusion

      Our findings suggest a tumor cell release from pulmonary metastases in CRC and a correlation of CTC isolated from the tumor outflow with established negative prognostic markers in metastasized CRC. The presented data warrant further investigations regarding the significance of local tumor compartments when analyzing circulating markers and the possibility of tumor cell shedding from secondary lung tumors.

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      P1.14-08 - The Usefulness of the Hemiclamshell Thoracotomy in Thoracic Surgery

      16:45 - 18:00  |  Presenting Author(s): Masanori Tsuchida  |  Author(s): Terumoto Koike, Seijiro Sato, Akihiko Kitahara, Tetsuya Goto, Akihiro Nakamura, Yuki Shimizu, Masaya Nakamura

      • Abstract

      Background

      The antero-lateral approach provides good exposure of the cervicothoracic region and enables removal of lesions that develop in this complex anatomic area.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We retrospectively evaluated the indications and outcomes of the hemiclamshell approach in patients undergoing tumor resection in thoracic surgery. Eleven lung cancer patients and one non seminomotous germ cell tumor of the mediastinum who underwent tumor resection via hemiclamshell approach in our department, between 2007 and 2018 were studied retrospectively, analyzing the indications, morbidity and outcome.

      4c3880bb027f159e801041b1021e88e8 Result

      The indications were apical tumors with vascular invasion in four, giant mass (10, 17, 21cm in tumor diameter) with superior or inferior vena cava invasion in three, aortic arch invasion in one, sternal invasion in one, mediastinal lymph node metastasis in the left upper lung cancer in one, and pulmonary artery aneurysm after left upper lobectomy in one. In eleven lung cancer patients, combined resection of the neighboring organ was performed in nine organs among eight patients: subclavian artery in two, carotid artery in one, aorta in one, superior vena cava in one, chest wall in two, phrenic nerve in one, and pericardium in one. One-month mortality was 0%. Operative morbidity was observed in four patients (33%): two patients suffered from deep wound infection, one from a chylothorax, and one from pleural effusion. R0 resection was achieved in eleven patients.

      8eea62084ca7e541d918e823422bd82e Conclusion

      The hemiclamshell approach was associated with relative high morbidity rate but no mortality. Hemiclamshell is suitable for tumours of the cervicothoracic junction with vascular invasion and giant tumors, providing good access for control of the large vessels including pulmonary artery and vein.

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      P1.14-09 - Outcome After Lung Resection for Primary Lung Carcinomas/Metastasis in Patients with Performed Total Laryngectomy for Laryngeal Carcinoma

      16:45 - 18:00  |  Presenting Author(s): Huseyin Melek  |  Author(s): Gamze Çetinkaya, Necati Çıtak, Berker Özkan, Fahmin Amirov, Fatma Nur Kaya, Zerrin Sungur, Yunus Aksoy, Ahmet Sami Bayram, Alper Toker, Adnan Sayar, Cengiz Gebitekin

      • Abstract

      Background

      Total laryngectomy remains the treatment of choice for recurrent / persistent laryngeal carcinoma after radiotherapy or chemoradiotherapy. These patients with laryngeal carcinoma are at risk for developing both pulmonary metastasis and second primary lung cancer. Because of the persistent tracheostomy, postoperative management after lung resection is usually a difficult process. Ineffective evaluation of preoperative pulmonary functions, failure of single lung ventilation due to short trachea, inadequate respiratory physiotherapy are frequently encountered problems. The purpose of this study is to evaluate the outcomes of lung resection in patients with persistent tracheostomy due to laryngeal carcinoma.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Between Jan 2006- Jan 2016, the data of 9247 patients who underwent lung resection at three different centers were retrospectively examined. The study group consisted of 68 patients (62 male, mean age 59.49 ± 11.4 (31-82)) who had persistent tracheostomy due to laryngeal carcinoma. Patient preoperative evaluation parameters, operation techniques, postoperative complications and survival were analyzed.

      4c3880bb027f159e801041b1021e88e8 Result

      The mean time between the two operations was 55.68 ± 64.8 (3-312) months. Pulmonary tumors were located in the upper lobe in 53 patients (77.9%), in the lower lobe in 11 patients (16.1%), in the middle lobe in 2 patients (3%) and bilaterally in 2 patients (3%). Lung resection was performed with thoracotomy in 53 patients (78%) and videothoracoscopy in 15 patients (22%). Extent of lung resection was sublobar resection in 28 patients (41.2%), lobectomy in 37 patients (54.4%) and pneumonectomy in 3 patients (4.4%). Histopathological examination revealed squamous cell carcinoma in 53 (78%) patients and other non-small cell lung carcinomas in 15 (22%) patients. Postoperative complications were present in 24 patients (35.3%). The most common complications observed were prolonged air leak in 7 patients (10,3%), space in 6 patients (8.8%) and pneumonia in 5 patients (7.3%). Mortality was seen due to respiratory insufficiency in 2 (2.9%) patients who underwent right lower bilobectomy and right pneumonectomy. The 5-year survival rate after lung resection was 31.6% and the median follow-up time was 32 months ± 8.45.

      8eea62084ca7e541d918e823422bd82e Conclusion

      This study shows that the presence of a tracheostomy should not be considered a risk factor for pulmonary resection if there is close cooperation between pulmonary medicine, anesthesia and thoracic surgery clinics. In these patients, besides other lung resections, videothoracoscopic lung resections can be performed safely and good oncologic results can be obtained.

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      P1.14-10 - Surgical Treatment of a Rare Case of Clear Cell Carcinomatous Transformation of a Diaphragmatic Endometriosis Focus

      16:45 - 18:00  |  Presenting Author(s): Angela De Palma  |  Author(s): Mariagrazia Lorusso, Rosatea Quercia, Ondina Pizzuto, Giuseppe Garofalo, Angela Fiorella, Elena Maiolino, Giulia Nex, Marcella Schiavone, Giulia De Iaco, Gabriella Serio

      • Abstract

      Background

      Thoracic endometriosis is an ectopic, unusual localization of endometrial tissue in endothoracic organs. The development of thoracic endometriosis can be determined by the embolization of endometriotic foci to the lung by lymphatic, hematic or trans-diaphragmatic way. We report a rare case of carcinomatous transformation of a diaphragmatic endometriosis focus, successfully treated with surgery.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      A 46-year old woman, with a history of previous operation for bilateral endometriotic pelvic cyst, presented to our institution with dyspnoea and massive right pleural effusion, which was treated with chest drainage. After drainage, chest and abdomen computerized tomography (CT) and magnetic resonance imaging (MRI) showed a large (7 x 6 cm), roundish, inhomogeneous, capsulated mass of the right hemidiaphragm, causing compression of the adjacent lung and liver. Fiberbronchoscopy showed an extrinsic compression of subsegmental bronchi of the basal pyramid of the right lung. After cardio-respiratory function evaluation, the patient underwent videothoracoscopic pleural biopsies with frozen section negative for malignancy, therefore we converted in antero-lateral thoracotomy and a radical surgical resection of the diaphragmatic mass, en-bloc with the adherent and apparently infiltrated lung and hepatic parenchyma, was performed.

      4c3880bb027f159e801041b1021e88e8 Result

      Postoperative course was uneventful. Histopathology revealed a clear cell carcinoma deriving from a malignant transformation of an ectopic diaphragmatic endometriosis focus; Ki67 was > 50%; PI3KCA and BRAF genes were not mutated. Total body 18F-fluorodeoxyglucose positron emission tomography (FDG-PET)/CT showed bilateral increased ovarian uptake, thus the patient underwent radical abdominal hysterectomy, with diagnosis of endometriosis, and subsequent adjuvant chemotherapy for the diaphragmatic clear cell carcinoma. Total body CT scan at 7 months from surgery shows neither local recurrence, nor distant metastases.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Thoracic endometriosis requires a multidiciplinary approach and management. In our experience, surgery represented the treatment of choice, in order to ensure oncological radicality, in a young patient with a rare condition of carcinomatous transformation of a diaphragmatic endometriosis focus, which should be considered among the possible evolutions of endometriosis. To the best of our knowledge, this is the first reported case of radical surgical treatment of a clear cell carcinomatous transformation of a diaphragmatic endometriosis focus.

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      P1.14-11 - The Expression Pattern of Programmed Death-Ligand 1 According to the Pathological Type of Malignant Thymic Epithelial Tumors

      16:45 - 18:00  |  Presenting Author(s): Shunta Ishihara  |  Author(s): Satoru Okada, Hiroshi Ogi, Yoshinori Kodama, Kyoko Itoh, Alexander Marx, Masayoshi Inoue

      • Abstract

      Background

      Malignant thymic epithelial tumors (TETs) have pathological types ranging from low-grade to high-grade malignancy, while the pattern of PD-L1 expression remains unclear. We investigated PD-L1 expression in TETs and verified the pattern of expression associated with the pathological type.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We examined 66 malignant TETs. Immunohistochemical evaluation of PD-L1 expression was performed using anti-PD-L1 antibody (SP263). We calculated the tumor cell positive rate (Total Proportion Score: TPS) of PD-L1 expression. The discrimination of the tumor region was confirmed by immunostaining with anti-pan-cytokeratin antibody (AE1AE3). PD-L1 expression was examined for each type of histological classification of TETs. We classified a High TPS group (H group) and Low TPS group (L group) using a TPS cut-off value of 25% and examined the correlation with clinical background and prognosis. We classified Type B2, B3, and thymic carcinomas into a high-malignancy group. PD-L1 expression was also digitally analyzed based on Whole Slides Imagings (WSI) for objective analysis as Digital TPS.

      4c3880bb027f159e801041b1021e88e8 Result

      We identified WHO histological types (Type A/AB/B1/B2/B3/metaplastic tumor/thymic carcinomas = 8/19/5/15/6/2/11). In Type A, PD-L1 expression was low in most cases and the median of TPS was 22%. In Type AB, Type A and B regions showed low and high TPS, respectively, and the median was 23%. In Type B1, TPS was low in most cases and the median was 26%. In Type B2, TPS was higher than that in Type B1, and the median was 69%. In Type B3, TPS was high (>50%) in all cases and the median was 86%. The PD-L1 expression of thymic carcinomas ranged from low to high and the median was 28%. Metaplastic tumors showed scanty PD-L1 expression. The High PD-L1 group showed more advanced disease stages according to the Masaoka stage and TMN classification, and the TPS of Type B2 and B3 was significantly higher than that of Type A, AB and B1. The disease-free survival rate was significantly lower in the H group than that in the L group. When we examined the prognosis in high-malignancy group, there were no significant differences in the disease-freel and overall survival rates by TPS. Based on measurements using WSI, Digital TPS correlated with visual TPS (correlation coefficient=0.85,pvalue<0.001).

      8eea62084ca7e541d918e823422bd82e Conclusion

      TETs had the characteristic features of the PD-L1 expression according to histological types. Type B2 and B3 thymomas was higher PD-L1 expression than the other types of TETs.

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      P1.14-12 - GTF2I Mutation in Thymomas: Indian and German Study

      16:45 - 18:00  |  Presenting Author(s): Deepali Jain  |  Author(s): Prerna Guleria, Rajinder Parshad, Alexander Marx

      • Abstract

      Background

      Point mutation (L404H) of GTF2I gene on chromosome 7 has been identified in thymic epithelial tumors; most predominantly in A and AB histotypes and associated with good prognosis. The objective of this retrospective analysis was to assess the frequency of GTF2I mutation in Indian and German thymomas and correlate with WHO histotypes.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      A cohort of Indian and German thymomas of different histotypes was retrieved from the archives. Clinicopathological details were obtained from case files. Hematoxylin-eosin stained slides were reviewed and histopathological subtypes along with Masaoka-Koga staging were determined. The available blocks were selected for DNA extraction. Tumors rich in cancer cells (>50%) were evaluated for GTF2I mutation using Sanger sequencing. Primer for Exon 15 of GTF2I gene was designed using NCBI and Primer 3 (v.0.4.0) software. Results were compiled and analysed.

      4c3880bb027f159e801041b1021e88e8 Result

      A total of 126 resection specimens were retrieved comprising 23 (18.2%) Type A, 30 (23.8%) Type AB 16 atypical A/AB (12.6%) and 30 (23.8%) Type B thymomas. Remaining 27 cases belonged to 18 thymic carcinomas, 2 sclerosing mediastinitis, 2 metaplastic thymomas, 1 thymolipoma, and 4 non-thymomatous lesions.

      Out of a total of 69 A/AB thymomas, 53 (76.8%) were positive including 88% (22/25) Indian and 65.9 % (29/44) German cases. 26% (18/69) A/AB were negative. All Indian B histotypes (n=9) were negative, whereas 4 German B thymomas (4/21; 19%) were positive for GTF2I mutation. No mutations were found in non-thymomatous pathologies.

      Among 34 Indian cases, there was equal gender distribution, median age was 48 years and 31 were in lower stage groups (Stage I and II). Clinical details and follow up available in 17 of 34 cases had a median follow up of 14 months and revealed presence of myasthenia gravis in 76.5% cases. Recurrence seen in 3 cases revealed high risk morphology (2 Type B histotypes and 1 atypical A) and one death of Type A was due to myasthenic crisis.

      8eea62084ca7e541d918e823422bd82e Conclusion

      The similarity of Indian and German (and previously published American) cohorts of A/B and type B thymomas in term of GTF2I mutation frequencies suggests a thymus-specific microenvironmental mutagenic mechanism and argues against a relevant impact of environmental or ethnic (germ line) factors. The unusually high prevalence of Myasthenia gravis among the Indian thymomas warrants further analysis to exclude referral bias.

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      P1.14-13 - PD-L1 Immuno-Expression Assay in Thymomas: A Study from India

      16:45 - 18:00  |  Presenting Author(s): Deepali Jain  |  Author(s): Prerna Guleria, Nuzhat Husain, Saumya Shukla, Sunil Kumar, Rajinder Parshad

      • Abstract

      Background

      Programmed death ligand 1 (PD-L1), an immune check point inhibitor, is known to be expressed in several malignancies and is being considered as a prognostic factor and a potential immunotherapeutic target. Recent development of anti-PD-1/L1 antibodies has demonstrated anticancer activity of these agents in various neoplasms. The aim of this study was to characterize PD-L1 expression in thymomas and to determine whether PD-L1 represents a therapeutic target in unresectable thymomas. A correlation with clinicopathological features and previously published studies in the literature was established.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Tissue microarrays were prepared from selected blocks of thymomas and immunohistochemistry (IHC) using SP263 clone of PD-L1 was performed. Cases were considered as PD-L1 positive or negative based on percentage of stained thymic epithelial cells; if these were <25 or >25 percent. Results were compared clinically and with previously published studies using Google and Pubmed search engines.

      4c3880bb027f159e801041b1021e88e8 Result

      Of 84 cases of thymoma, 69 (82.1%) revealed PD-L1 positivity in more than 25% cells. 94.23% of type B thymoma subtypes (B1/B2/B3) were PD-L1 positive (P<.001). There was no correlation of PD-L1 with age, gender, myasthenia gravis, the tumor size or stage of disease. So far, 9 studies of PD-L1 expression in thymic epithelial tumors are available in the literature; most of which showed PD-L1 expression in higher stage and B histotype however percentage positivity varied from 53.7% to over 90%.

      8eea62084ca7e541d918e823422bd82e Conclusion

      PD-L1 expression is frequent in type B (B1/B2/B3) thymomas. It can be easily evaluated by IHC even on small biopsies in unresectable cases. PD-L1 immunoassay will serve as a potential indicator for benefit from anti-PD-L1 antibody immunotherapy in thymomas thereby enabling improved clinical evaluation as well as prognostic stratification of patients.

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      P1.14-14 - Histotyping of Indian Thymomas: A Comprehensive Clinicopathologic Study

      16:45 - 18:00  |  Presenting Author(s): Deepali Jain  |  Author(s): Prerna Guleria, Rajinder Parshad, Prabhat Malik, Sunil Kumar

      • Abstract

      Background

      Thymomas are rare, but most common anterior mediastinal lesions. The WHO 2015 classification has defined criteria of classifying these into various subtypes. The histomorphologic spectrum of thymic epithelial tumors (TET) in Indian population has not been explored. We aimed to study the histomorphology of TETs in the Indian patients with clinico-pathological correlation.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      It was a retrospective, tertiary referral centre, study. All cases of morphologically confirmed, surgically resected specimens and small biopsies diagnosed as TETs since 2009 were included. Clinical details and histology slides were reviewed using the Modified Masaoka-Koga staging system and WHO 2015 classification. Clinico-pathological correlation and survival analysis was done. Comparative review from other published Indian studies was performed.

      4c3880bb027f159e801041b1021e88e8 Result

      We identified 219 cases of TETs (138 resections and 81 biopsies). Most common histo-morphologic type was B2 and most frequent stage was I. Clinically, higher stage tumors were found mostly in men (P=.008) and these were type B thymomas (P=.01). Association of myasthenia gravis was prevalent in women (P=.02) and in lower stages (P=.04). Survival analysis revealed significant association between recurrence and tumor stage. Although thymic carcinoma was diagnosed on biopsy, no resectable case was identified.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Literature lacks detailed histotyping of TETs from India. Indian thymomas are most commonly stage I tumors of B2 and AB histotypes. Resected thymic carcinomas are conspicuously absent in Indian cohort. We hope that broadening the spectrum of recognized pathologic manifestations of Indian thymomas will help global database for future studies.

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      P1.14-15 - Prevalence of Mediastinal Tumors Using Low-Dose Spiral Computed Tomography in Healthy Population

      16:45 - 18:00  |  Presenting Author(s): Ikuma Kasuga  |  Author(s): Hiromi Maezawa, Sanae Gamo, Yoshimi Yokoe, Yuri Yanagihara, Hatsune Yoshino, Yuri Sato, Eriko Imazeki, Yumiko Sakano, Daisuke Takahashi, Masaru Sato, Kazuyo Wakabayashi, Osamu Otsubo

      • Abstract

      Background

      Background: Compared with lung tumors, mediastinal tumors occur less frequently, but the precise incidence of mediastinal tumors in healthy populations is still unknown. Chest radiographic screening is a commonly used conventional method for the detection of thoracic tumors. However, early phase detection of mediastinal tumors is difficult due to the location of these tumors. Using low-dose spiral computed tomography (LDCT), this study aimed to investigate the precise incidence of mediastinal tumors, including that of small early phase masses that cannot be detected by radiography.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Methods: Among people who underwent medical check-ups consecutively for 8 years (from April 2010 to March 2018) at our institution, those who also underwent LDCT were enrolled in this study. In total, this study included 3,414 individuals. The presence of mediastinal tumor in these individuals was investigated.

      4c3880bb027f159e801041b1021e88e8 Result

      Results: Thirty-two cases of mediastinal tumor (0.9%) were detected using LDCT, of which 20, 5, 4, and 3 were anterior, superior, middle, and posterior mediastinum tumors, respectively; this was a higher prevalence than that reported in our country (0.1%-0.8%). Of the 32 cases, 17 were further examined, and finally, in some of these cases, the tumors were successfully surgically resected. The remaining 15 cases were followed-up periodically owing to the presence of small benign nodular lesions. Among the 32 cases, tumors of only 3 cases were detected using chest radiography.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Conclusion: The prevalence of mediastinal tumor is higher than that previously reported in our country. Compared with chest radiography, LDCT contributes to the early phase detection of mediastinal tumors.

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      P1.14-16 - DNA Methylation of GNG4、GHSR、HOXD9 and SALL3 Genes Predict Malignant Behavior of Thymic Epithelial Tumors

      16:45 - 18:00  |  Presenting Author(s): Reina Kishibuchi  |  Author(s): Kazuya Kondo, Shiho Soejima, Mitsuhiro Tsuboi, Koichiro Kajiura, Yukikiyo Kawakami, Naoya Kawakita, Toru Sawada, Hiroaki Toba, Mitsuteru Yoshida, Hiromitsu Takizawa, Akira Tangoku

      • Abstract

      Background

      Our previous studies showed that DNA methylation of cancer-related genes-DAP-K, p-16, MGMT, HPP1 genes in thymic carcinoma (TC) was higher than that in thymoma (Lung Cancer 64:155-, 2009, 83:279-, 2013). Genome-wide screening for aberrantly methylated CpG islands was performed in 7 TC samples and 8 type-B3 thymoma samples using HumanMethylation 450 K BeadChip (Illumina, Santa Clara, CA, USA) analysis. We identified 22 genes as commonly hypermethylated in TC comparing with B3 thymoma. We picked up 4 cancer-related genes; GNG4, GHSR, HOXD9 and SALL3 from those genes as the most significant hypermethylated gene.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      In total, 47 thymic tumour samples (thymoma; 31, carcinoma; 16) and 18 paired normal tissues were obtained from patients with histologically proven thymic epithelial tumor (TET), who underwent surgery at the Tokushima University Hospital (Tokushima, Japan) between 1990 and 2016. The methylation status of TET samples was validated by pyrosequencing.

      4c3880bb027f159e801041b1021e88e8 Result

      DNA methylation of GNG4 gene in TC was significantly higher than that in thymoma (34.6% versus 8.9%). In other 4 genes, DNA methylation in TC was significantly higher than that in thymoma (GHSR; 59.3% vs 34.2%, HOXD9; 37.3% vs 12.3%, SALL3; 33.5% vs 7.2%). In GHSR and HOXD9 genes, DNA methylation in thymoma was significantly higher than that in normal thymus. And in GNG4 and SALL3, DNA methylation in thymoma was similar to that in normal thymus.

      8eea62084ca7e541d918e823422bd82e Conclusion

      DNA methylation of several cancer-related genes in TC was significantly higher than that in thymoma or normal thymus. Epigenetic alteration may be related to progression or malignancy in TET.

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      P1.14-17 - Identification of Molecular Subtypes of Thymic Epithelial Tumors and Novel Treatments Using a Computational Biological Model

      16:45 - 18:00  |  Presenting Author(s): Sukhmani Kaur Padda  |  Author(s): Yesim Gokmen-Polar, Sunil S Badve, Sumath M Vasista, Kabya Basu, Ansu Kumar, Shireen Vali, Taher Abbasi, Heather A Wakelee

      • Abstract

      Background

      The histologic classification of thymic epithelial tumors (TETs) is based on the description of both epithelial cell morphology and relative abundance of lymphocytes. Here, we used a computational biological model (CBM) approach on The Cancer Genome Atlas (TCGA) dataset to identify molecular subtypes of TETs and associated predicted therapeutic options.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Whole exome sequencing and gene expression data from the TCGA TET dataset (n = 102) along with the IUTAB-1 cell line was input into CBM software (Cellworks Group, San Jose, CA) to build an unsupervised classification model beyond molecular subtypes previously reported (Loehrer PJ ASCO 2017). The CBM generated a disease specific protein network map using PubMed and other online resources. Using computer simulation, disease biomarkers unique to each tumor were identified within the protein network maps. Among the tumors simulated, 6 molecular clusters were identified (TH1-TH6). The CBM digital drug library was tested against these molecular subtypes and the cell growth score (i.e. cell proliferation, viability, and apoptosis) was analyzed.

      4c3880bb027f159e801041b1021e88e8 Result

      The CBM identified 6 molecular subtypes among 102 TET patients. Among subtypes with a GTF2I mutation, TH1, TH4, and TH6 also had chromosomal aberrations in chromosome 22 and 9. Deletion of chromosome 22 was present in TH1, deletion of chromosome 9 in TH4 and TH6, and also amplification of chromosome 22q in TH4. Among GTF2I wild type subtypes, chromosome 22q deletion and complex cytogenetics were present in TH2, trisomy of chromosome 1 in TH3, and HRAS mutations and chromosome 2 amplification in TH5. The IUTAB-1 cell line had a GTF2I mutation and mapped to the TH4 molecular subtype. The CBM predictions of sensitivity of TH4 subtype to Nelfinavir (AKT inhibitor) and Panobinostat (histone deacetylase inhibitor) along with resistance to Everolimus (MTOR inhibitor) were validated in vitro. There were two molecular subtypes for which Everolimus was predicted to be sensitive, TH1 and TH6.

      8eea62084ca7e541d918e823422bd82e Conclusion

      We present an updated classification of TETs based on a CBM approach and associated potential novel therapeutic options that could be further validated in clinical trials.

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      P1.14-18 - The Promising Role of Sunitinib Rechallenge in Heavily Pre-Treated Thymic Carcinoma: A Case Report

      16:45 - 18:00  |  Presenting Author(s): Giovannella Palmieri  |  Author(s): Margaret Ottaviano, Marianna Tortora, Pasqualina Perrone, Carmen Giusy Rea, Sabino De Placido, Mario Giuliano

      • Abstract

      Background

      The clinical management of thymic carcinomas (TC), remains very challenging, however thanks to the optimization of therapeutic strategy, the 50% of patients is still alive at 5 years. The promising role of sunitinib, a multi tyrosine kinase inhibitor (TKI), has been recently confirmed in several prospective trials, but no data about the rechallenge modality administration are already available. In the case here reported, we illustrate an impressive response disease in a very heavily pre-treated TC after sunitinib rechallenge.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      In August 2013, a 45-year-old caucasian male was referred to our Institution, for a diagnosis of un-resectable/metastatic TC. A systemic therapy strategy was planned.

      4c3880bb027f159e801041b1021e88e8 Result

      Anthracycline-platinum-based chemotherapy was delivered as first, for total 6 cycles, obtained a partial response (PR) with more than 60% of disease reduction (DR). After a brief drug holiday, because of lung progression, the patient underwent capecitabine-gemcitabine combination-chemotherapy. In August 2014, he progressed after 6 cycles and was candidate to start sunitinib at standard dose of 50 mg daily/4 weeks on/2weeks off, in off-label modality. A dose reduction at 50 mg/daily/1 week on/1 week off was made due to persistent diarrhea G2, thrombocytopenia G2 and asthenia G3. Surprisingly, with no more toxicities, he achieved an important partial response with more than 70% of DR, maintained for total 26 months. Unfortunately, a new lung disease progression was registered and oral etoposide at dosage of 50 mg/die 3 weeks on/1 week off was started, without any results. Considering the great response obtained in the first line chemotherapy and envisioning the opportunity to revert target therapy resistance, as already demonstrated for other solid malignancies, 3 cycles of carboplatinum-paclitaxel were delivered, obtained stable disease. Analysis with NGS and microsatellities instability, were performed, with no results useful for the therapeutic decision process. In October 2017, because of the brilliant response achieved with sunitinib and considering the free interval of 12 months, a sunitinib rechallenge was established at 50 mg/daily 1 week on/1 week off. An impressive disease reduction, which is still ongoing, was revealed, no side effects were reported.

      8eea62084ca7e541d918e823422bd82e Conclusion

      This reported experience, shows sunitinib rechallenge effectiveness for prolonged control disease in thymic carcinoma, despite the number of previous treatments administered before the first and the second drug delivery. A personalized dose reduction can be used for treating heavily pre-treated thymic malignancies to better manage the toxicity profile. Rechallenge with TKI in previous responder patient, should be included routinely in the strategy for the treatment of refractory disease.

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      P1.14-19 - Hemagglutinating Virus of Japan Envelope (HVJ-E: Inactivated Viral Nanoparticles) Against Chemotherapy-Resistant Pleural Mesothelioma

      16:45 - 18:00  |  Presenting Author(s): Kazuma Sakura  |  Author(s): Chunman Lee, Yasufumi Kaneda, Takashi Nakano, Shinji Atagi, Yoshihisa Kadota, Kozo Kuribayashi, Muneyoshi Kuroyama, Takashi Kijima, Atsushi Kumanogoh, Meinoshin Okumura

      • Abstract

      Background

      Hemagglutinating virus of Japan envelope (HVJ-E) derived from inactivated replication-defective Sendai virus possess the various antitumor activities. HVJ-E enhances multiple antitumor immunities such as activation of dendritic cells, induction of natural killer cells and CTL, and suppression of regulatory T cells, and it induces direct tumor-killing by the induction of cell death through the RIG-I/MAVS pathway by direct administration into the tumor.

      We performed the phase I dose escalation safety/tolerability and preliminary efficacy study of intra-tumoral and subcutaneous administration of HVJ-E in patients suffering from chemotherapy-resistant malignant pleural mesothelioma.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We performed the dose upward titration clinical study for checking the safety, drug tolerance, and preliminary efficacy of the intra-tumoral and subsequent subcutaneous administration of HVJ-E. We administrated HVJ-E to the patients 4 times per 2 weeks (the first was intra-tumoral, and residual 3 times were subcutaneous injection), and then washed out the drug from the body for 2 weeks. This cycle was repeated 2 times. We observed the patients for 8 weeks, and evaluated them by CTCAE, modified RECIST, and PERCIST.

      4c3880bb027f159e801041b1021e88e8 Result

      Three patients were enrolled as a low-dose group, and three patients were enrolled as a high-dose group. There was no discontinuation of the administration due to the severe adverse events.

      Results;

      The mean disease duration from confirmed diagnosis to this trial was 2.27 years (0.6-4.5 years). We defined the primary endpoint as an assessment of dose limiting toxicity related with HVJ-E. Neither serious adverse events (SAE) nor DLT were observed during the observation period. The following symptoms were observed. Fever (83.3%), and the local symptoms at injection site, for example, rubor, swelling, or induration (100%) were observed, but the local relapse of mesothelioma at the injection site was not observed. It was confirmed that the intra-tumoral and subcutaneous administration of HVJ-E was safe for chemotherapy-resistant pleural mesothelioma patients, because these AEs were transient and slight.

      The efficacy as a secondary endpoint was evaluated with modified RECIST, and PERCIST. DCR of low dose level cohort was 0% (0/3), because of PD, meanwhile, high dose level cohort indicated 100% (3/3). Consequently, the DCR of all cases who had treated with HVJ-E was 50% (3/6) by mRECIST, meanwhile, the DCR evaluated by PERCIST was 100%.

      8eea62084ca7e541d918e823422bd82e Conclusion

      It was suggested that HVJ-E was useful for disease control of advanced pleural mesothelioma patients without severe adverse events. Now we do the next step trial for malignant pleural mesothelioma and melanoma with high dose of HVJ-E.

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      P1.14-20 - The Expression of DNA Methylation of GAD1 Gene is an Indicator of Malignant Behavior in Thymic Epithelial Tumor.

      16:45 - 18:00  |  Presenting Author(s): Kazuya Kondo  |  Author(s): Shiho Soejima, Nuliamina Wusiman, Reina Kishibuchi, Mitsuhiro Tsuboi, Koichiro Kajiura, Yukikiyo Kawakami, Naoya Kawakita, Toru Sawada, Hiroaki Toba, Mitsuteru Yoshida, Hiromitsu Takizawa, Akira Tangoku

      • Abstract

      Background

      Genome-wide screening for aberrantly methylated CpG islands was performed in 7 thymic carcinoma (TC) samples and 8 type-B3 thymoma samples using HumanMethylation450 K BeadChip (Illumina, Santa Clara, CA, USA) analysis. We identified 22 genes as commonly hypermethylated in TC comparing with B3 thymoma. GAD1(glutamic acid decarboxylase 1)was one of the most significant hypermethylated genes in TC. GAD1 is the enzyme that synthesizes GABA. Recent some reports showed that it is significantly increased in neoplastic tissues. However, the mechanism underlying this increase remains elusive. In this study, we examine mRNA and protein expressions and DNA methylation of GAD1 in thymic epithelial tumors (TETs).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      In total, 49 thymic tumour samples (A; 5, AB; 2, B1; 4, B2; 11, B3; 9, carcinoma; 18) and 20 paired normal tissues were obtained from patients with histologically proven TET, who underwent surgery at the Tokushima University Hospital (Tokushima, Japan) between 1990 and 2016. The methylation status of thymic epithelial tumor samples was validated by pyrosequencing in a larger cohort. The expression status was analysed by quantitative polymerase chain reaction (PCR) and immunohistochemistry (IHC).

      4c3880bb027f159e801041b1021e88e8 Result

      The previous study (Oncogene 2015, 1–14) showed that the key locus responsible for GAD1 reactivation was mapped to a DNA methylation-sensitive CTCF-binding site (CTCF-BS3) within the third intron of GAD1. We targeted this region for pyrosequencing. Pyrosequencing confirmed that DNA methylation of GAD1 gene of TC was significantly higher than that of thymoma (36.5% versus 7.3%, p<0.001), and that DNA methylation of GAD1 gene of thymoma was similar to that of normal thymus (7.3% vs 8.6%). Quantitative PCR and IHC staining revealed that GAD1 mRNA and protein expression levels of TC were higher than those of thymoma (RT-PCR; 8.84 vs 0.72). There were not differences of DNA methylation and expression of GAD1 among subtype of thymoma according to WHO histologic classification. There was a tendency of hypermethylated GAD1 gene in Stage IV comparing with other Stage (Masaoka’s clinical staging).

      8eea62084ca7e541d918e823422bd82e Conclusion

      TC frequently had DNA methylation of CTCF-binding site 3 in GAD1 gene, and high levels of mRNA and protein of GAD1. GAD1 may represent an epigenetic therapeutic target in TC.

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      P1.14-21 - Circulating Biomarkers in Thymic Epithelial Tumors

      16:45 - 18:00  |  Presenting Author(s): Clemens Aigner  |  Author(s): Daniel Valdivia, Danjouma Cheufou, Benjamin Fels, Stephan Puhlvers, Gerhard Weinreich, Dirk Theegarten, Till Plönes, Khaled Mardanzai, Mohamed Zaatar, Balazs Hegedus, Georgios Stamatis

      • Abstract

      Background

      Thymic epithelial tumors are the most common mediastinal tumors. Surgery is the mainstay of treatment and complete resection provides the best survival rate. Nevertheless, advanced tumors may require multimodal therapy and additional prognostic factors beyond tumor stage and histological classification might help to risk-stratify patients and personalize the treatment course.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Between 1999 and 2017 202 patients with thymic epithelial tumors were operated in our center. The preoperative C-reactive protein (CRP) and lactate dehydrogenase (LDH) levels as well as clinical follow-up were retrospectively collected and the association of circulating biomarkers with clinicopathological parameters and their impact on overall survival was analyzed.

      4c3880bb027f159e801041b1021e88e8 Result

      115 male and 87 female patients were included in the study with 59.5 (±13.1) years mean age at the time of operation. 30 patients (including 12 male patients) suffered from myasthenia gravis. Thymic carcinoma was associated with high CRP (> 1mg/dl) when compared to thymoma cases (34% vs 12%, p=0.001). While LDH levels did not show such association, there was a strong tendency for increased mean LDH levels in Masaoka 4 patients (252.5±18.9 vs 220.5±6.1, p=0.063). Overall survival was analyzed in the thymic carcinoma subcohort. 90% of the patients were treated in a multimodal approach and received chemo- and/or radiotherapy in adjuvant or neoadjuvant setting. Median overall survival was 11.3 years. The Masaoka stage (1-3 versus 4) was a significant prognostic factor (HR 0.23, 95%CI 0.07 to 0.77, p=0.017). Elevated CRP (> 1mg/dl) did not show prognostic power for overall survival (HR 0.82, 95%CI 0.77 to 1.33, p=0.76). In contrast increased preoperative LDH level (>200 U/L) resulted in poorer outcome (HR 0.32, 95%CI 0.09 to 1.13, p=0.076).

      8eea62084ca7e541d918e823422bd82e Conclusion

      Circulating biomarkers show association with advanced disease stage in thymic epithelial tumors. Importantly, preoperative LDH levels carry prognostic information in thymic carcinoma and could be used to risk stratify surgically treated patients in multimodal treatment settings.

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      P1.14-22 - The Prognostic Role of the Suppressor of Cytokine Signaling-5 (SOCS5) in Esophageal Squamous Cell Carcinoma

      16:45 - 18:00  |  Presenting Author(s): Pei-Wen Yang  |  Author(s): Ya-Han Chang, Jang-Ming Lee

      • Abstract

      Background

      Expression of cytokines and growth factors have been shown to be highly correlated with the prognosis in esophageal squamous cell carcinoma (ESCC), a dead disease with poor prognosis. The suppressor of cytokine signaling (SOCS) family of proteins are key factors in the feedback system that regulates the expression of cytokines and growth factors in cells. Yet the role of the SOCS family of proteins in ESCC is hardly known.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We analyzed the prognostic effects of 16 single nucleotide polymorphisms (SNPs) within the SOCS family of genes in 632 ESCC patients using MassARRAY system. The underlying mechanisms of SOCS SNPs effect on prognosis was analyzed using luciferase assay. The possible functions of SOCS5 in ESCC cells were analyzed by transiently over-expression.

      4c3880bb027f159e801041b1021e88e8 Result

      We repeatedly observed that the 3 SNPs in SOCS5, SOCS5:rs3814039, SOCS5:rs3738890, and SOCS5: rs3768720, were significantly correlated with both overall (OS) and progression-free survival (PFS) of ESCC patients (rs3814039, p=0.032 for OS and p=0.009 for PFS; rs3738890, p=0.016 for OS, and p=0.008 for PFS; rs3768720, p=0.005 for OS and p=0.002 for PFS). SOCS5: rs3768720 was also significantly associated with distant metastasis (Ptrend=0.028). The luciferase assay revealed that SOCS5:rs3814039 and SOCS5: rs3738890 might influence the prognosis by regulating SOCS5 expression. Functional analysis demonstrated SOCS5 was able to regulate epidermal growth factor receptor (EGFR) expression and migration activity of ESCC cells.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Our study demonstrates the roles of SOCS5 in ESCC prognosis. The genetic polymorphisms of SOCS5 could serve as a novel therapeutic biomarker for improving the prognosis of ESCC.


      migration assay.jpg

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      P1.14-23 - Thymoma: An Epidemiological and Clinico-Pathological Profile in Nepalese Population.

      16:45 - 18:00  |  Presenting Author(s): Sandhya Chapagain Acharya  |  Author(s): Rashmey Pun

      • Abstract

      Background

      Thymomas and thymic carcinomas are most common tumor of anterior mediastinum representing 0.5 % to 1.5% of all the malignancies. Surgery is the main stay of treatment with adjuvant radiation recommended for the invasive thymomas. It accounts for 0.1% of all the malignancies as per National Cancer Registry Nepal. Because of the rarity of the tumor we aim to review the profile of patient with thymic tumor in our patient population.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      All the patient with diagnosis of thymoma attending the Department of Clinical oncology, National Academy of Medical Sciences (NAMS), Bir Hospital, Nepal during 2009 -2015 was evaluated. We reviewed the record of all registered, histologically diagnosed thymoma and thymic carcinomas and are presented in this study.

      4c3880bb027f159e801041b1021e88e8 Result

      Total of 51 record with thymoma and thymic carcinomas were reviewed out of which 71% (36) patient were male. The mean age was 46.99 years with youngest being 18 years and the eldest 70 years of age. Most common presenting symptom was shortness of breath (37%), followed by cough (23%0, generalized weakness (14%), dysphagia (14%) and drooping of eyelid (12%). About 29.41% of patient was diagnosed with myasthenia gravis. 14% of patients were diagnosed on stage II, 57% on stage III and 29% with stage IV (modified Masaoka clinical stage). WHO pathological stage B 39%(20) [(B1-12%(6), B2-18%(9), B3-10%(5)] was most common, with A 24%(12), AB 20%(10), and C 18%(9). 11% of patient underwent upfront surgery. Neoadjuvant therapy was offered for 63%(32) with 68.75%(22) resectability rate. 27% were eligible only for palliative treatment. About 95% patient received chemotherapy and 90.19% patient received radiation therapy either curative or palliative. 62.74% received curative radiation. 62.74% (32) patients are still on regular follow up with no signs of relapse.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Multimodality therapy remains the main stay of treatment for thymomas rendering the disease curative. Significant number of patient received neoadjuvant chemotherapy therapy followed by surgery and adjuvant radiation therapy. WHO Type B seems to be more frequent type. Thymoma is quite often associated with myasthenia gravis without adverse effect on prognosis. However, in view of limited study due to rarity of the disease various aspects yet to be explored.

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      P1.14-24 - External Radiotherapy Concurrent with Cisplatin Plus 5- Flurouracil in Locally Advanced Carcinoma of Esophagus

      16:45 - 18:00  |  Presenting Author(s): Rashmey Pun  |  Author(s): Sandhya Chapagain Acharya

      • Abstract

      Background

      Esophageal cancer is the eighth most common cancer in the world with the high rates of local recurrence and metastasis. As per the data of National Cancer Registry Nepal it ranks among the top ten cancers with 2.6% prevalence. Definitive concurrent chemo radiotherapy (CCRT) is the standard for the non surgery patients, and the use of Cisplatin with 5-Flurouracil is the common chemotherapy regimen.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      A prospective and comparative study was undertaken from 2014-2015 to evaluate the effect of CCRT in patients with locally advanced carcinoma of esophagus in our patient population.The eligibilty criteria included locally advanced, ECOG score of <2. Patients received chemo radiotherapy (50Gy / 25fractions) and Cisplatin 75mg/m2 on Day 1 and 5-Flurouracil 1000mg/m2 on Day 1- Day 4 every 4 weeks apart on weeks 1 and 5. Radiation only group received 64 Gy/33 fractions.

      4c3880bb027f159e801041b1021e88e8 Result

      40 patients were enrolled in the study. Among these patients 65.0% were male and the disease was prevalent at 55-64 years age group. 72.5% of the patients were smokers, 55.0% were alcohol consumers and 20.0% were Tobacco chewers. The most common site of the primary tumor was the mid thoracic region of the esophgus consisting of 62.5%. The combined modality of treatment was toxic but managable with supportive care. Thre were 4 drop outs, 1 from CCRT group and 3 from Radiation (RT) alone group due to the progression of the disease. 65.0% attained partial response and 25.0% achieved complete response in the CCRT group which was in favor of CCRT in comarison to the RTalone group.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Concurrent chemoradiotherapy yields high locoregional control, in comparison to radiotherapy alone in patients with locally advanced esophgeal carcinoma. Definitive chemoradiotherapy has shown promising results and appears to be superior to RT alone as the sole modality of treatment. Cisplatin and 5-Flurouracil concurrently with radiation therapy is economical alternative with tolerable toxicity profile in resource constraint settings like ours.

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      P1.14-25 - Pulmonary Metastasis from Oral Cancer – Who Survive Without Recurrence After Pulmonary Metasectomy?

      16:45 - 18:00  |  Presenting Author(s): Chihiro Takasaki  |  Author(s): Masashi Kobayashi, Hironori Ishibashi, Kenichi Okubo

      • Abstract

      Background

      Oral cancer often performs local recurrence or a neck lymph node metastasis, so pulmonary metastasis from oral cancer is very rare and there have been few reports.. The aim of this study was to evaluate the efficacy of surgical resection of oral cancer pulmonary metastases.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Between April 2006 and December 2017, 14 patients with oral cancer pulmonary metastases underwent thoracic operations. We considered their clinicopathological features and prognosis.

      4c3880bb027f159e801041b1021e88e8 Result

      There were ten men and four women with median age of 66.5 years (range, 27-76). All tumors were squamous cell carcinoma. Primary sites were tongue (seven patients), gum (three patients), and the mouth bottom (two patients). Five patients had partial resection and nine patients underwent lobectomy or larger operation. Eight of the nine patients who had lobectomy also had systematic lymph node dissection. Overall survival rate after metastasectomy was 46.9% at five years. Overall survival rate at five years by lobectomy with systematic lymph node dissection tended to have a better prognosis than by partial resection or lobectomy without lymph node dissection(p=0.08). Among the patients who had systematic lymph node dissection, lymph node metastasis were found in five patients. However, three of the five got long-term survival (more than two years) in spite of the metastasis.

      8eea62084ca7e541d918e823422bd82e Conclusion

      For patients with oral cancer pulmonary metastasis, surgical resection especially lobectomy with lymph node desection is recommended.

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      P1.14-26 - Long Term Outcome and Clinicopathological Features of Thymic Carcinoma - A Retrospective Study of 25 Cases at a Single Institution

      16:45 - 18:00  |  Presenting Author(s): Hiroto Tanaka  |  Author(s): Kaoru Kaseda, Kyohei Masai, Takashi Ohtsuka, Yuichiro Hayashi, Tomoyuki Hishida, Hisao Asamura

      • Abstract

      Background

      Thymic carcinoma is a rare and invasive mediastinal tumor and the optimal treatment is not well defined currently. According to the Clinical report from Japanese Association for Research on the Thymus in 2015, surgical resection is the mainstream of treatment, and the 5-year overall survival was 61%. The patient with complete resection with a 5-year survival of 89%, 68%, 60% for stages I, II & III and IV, respectively. In order to clarify the long-term outcome and prognostic indicators in our facilities, we reviewed our institutional experience with cases of surgical resection for thymic carcinoma.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      A single-institution retrospective study of patients operated for thymic carcinoma. Between 1998 and 2017, 25 patients with thymic carcinoma underwent surgical resection, and their clinical and pathological data were retrospectively reviewed. Overall survival (OS) rates were compared using a log- rank test and Survival curves were plotted using the Kaplan–Meier method.

      4c3880bb027f159e801041b1021e88e8 Result

      Twenty-five patients underwent surgery for thymic carcinoma. The IASLC/ITMIG thymic epithelial tumors Stage according to the 8thedition of the TNM classification was I in 9 patients, II in 6, III in 5, IV in 5. A complete resection was achieved in ten patients (40%) that were no recurrence and death in the follow-up period. There was no fetal complication and no postoperative mortality. Adjuvant radiotherapy and/or chemotherapy was offered to 22 patients. The median follow-up period was 37 months. The 5-year overall survival rate for all the patients were 78.2%. Patients who underwent an incomplete resection had a significantly worse survival as compared to those with complete resection in univariate analyses (p < 0.01).

      8eea62084ca7e541d918e823422bd82e Conclusion

      Our result indicated that complete resection could impact the overall survival of patients with thymic carcinoma after surgical resection.

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      P1.14-27 - Differentiation Between Each Thymic Epithelial Tumor According to WHO Classification Scheme by Using MDCT Findings

      16:45 - 18:00  |  Presenting Author(s): Yutthaphan Wannasopha  |  Author(s): Siriphat Olankitcharoen, Sarawut Kongkarnka, Apichat Tantraworasin, Juntima Euathrongchit

      • Abstract

      Background

      Thymic epithelial tumors are the uncommon mediastinal tumors but are the most common primary tumors of the anterior mediastinum. Computed tomography (CT) is the imaging modality of choice for assessment in patients suspected thymic epithelial tumor. The objectives of this study were to assess the CT features of various types of thymic epithelial tumors on the basis of the 2004 WHO classification and to identify the specific CT findings for differentiation between each thymic epithelial tumor.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      A retrospective study reviewed CT findings of 35 patients with thymic epithelial tumors, who underwent surgical resection from January 2010 to April 2017 and had available pre-operative chest CT study. The tumors were reclassified into six types of thymic epithelial tumors (A, AB, B1, B2, B3 and thymic carcinoma) on the basis of the 2004 WHO classification system. The CT findings including the size (longest diameter), margin, shape, presence of focal area of low attenuation of necrosis or cystic change, mediastinal fat invasion, great vessels invasion, degree and pattern of tumor enhancement, presence of tumor calcification and presence of mediastinal lymphadenopathy (short axis diameter more than 10 mm), the presences of pleural effusion, pleural mass, pulmonary nodule, pericardial effusion and extrathoracic metastasis were evaluated.

      4c3880bb027f159e801041b1021e88e8 Result

      Our study consisted of 20 (57.14%) men and 15 (42.86%) women, age 15-78 years (mean 51.25 years). Pathological proven into 30 thymomas (85.71%) and 5 cases (14.29%) of thymic carcinomas. The 30 thymomas were classified according to WHO classification; type A in 5 (14.29%), type AB in 4 (11.43%), type B1 in 5 (14.29%), type B2 in 9 (25.71%), and type B3 in 7 (20%) patients. The tumor sizes of type A, AB, B1, B2 & B3 thymomas and thymic carcinoma were 6.2±1.97, 8.1±2.17, 4.9±2.47, 6.8±3.04, 4.7±1.87, and 9.6±2.78 cm, respectively. No definite CT manifestation that distinguishes between each different WHO pathological type of thymoma with statistical significance. The tumor dimension > 8 cm, irregular margin, mediastinal fat invasion, great vessel invasion, lymphadenopathy, pericardial effusion and extrathoracic metastasis could differentiate between thymoma and thymic carcinoma (P-value <0.05). Great vessel invasion and extrathoracic metastasis had high sensitivity (80%), specificity (100%), PPV (100%) and NPV (96.77%) for diagnosis thymic carcinoma.

      8eea62084ca7e541d918e823422bd82e Conclusion

      No definite CT manifestation that distinguishes between each different WHO pathological types of thymomas. Tumor size more than 8 cm, irregular margin, presence of mediastinal fat invasion, great vessel invasion, mediastinal lymphadenopathy or extrathoracic metastasis favors the diagnosis of thymic carcinoma.

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      P1.14-28 - Frequent Genetic Alterations and Their Clinical Significance in Patients with Thymic Epithelial Tumors

      16:45 - 18:00  |  Presenting Author(s): Song Xu  |  Author(s): Hongyi Zhang, Xiongfei Li, Renwang Liu, Tao Shi, Jun Chen

      • Abstract

      Background

      Thymic epithelial tumors (TETs) are relatively rare neoplasms originating from the epithelial cells of the thymus. Due to the variety of different histology and low incidence, the current knowledge about the genetic alterations and prognostic factors of these tumors is still limited.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Twenty-four specimens from Chinese patients with resected TETs were collected and sequenced by next-generation technology with 56 cancer-related hotspot genes. The somatic mutation data of TETs was also retrieved from TCGA database (The Cancer Genome Atlas) (n=123). Overall survival was evaluated using Kaplan-Meier methods and compared with log-rank tests.

      4c3880bb027f159e801041b1021e88e8 Result

      We analyzed 12 thymoma (type A, n =3; type AB, n=2; type B1/B2, n = 4; type B3, n = 3) and 12 thymic carcinoma in this study. At least one gene mutation was detected in 15 cases out of total 24 tumors. Half of thymoma and seventy-five percent of thymic carcinoma exhibited genetic alterations, respectively. Twenty-seven gene mutations were detected in total 24 tumors. The most frequent gene mutation of thymoma is BRCA1(25.0%, 3/12), while TP53 mutation is the most commen in thmic carcinoma (25.0%, 3/12). CDKN2A mutaion was exclusively observed in thymic carcinoma (16.7%, 2/12). Our and TCGA cohorts both demonstrated that TETs who presented TP53 mutation had a worse disease free survival and overall survival.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Comprehensive genomic analysis suggests that the molecular phenotype of thymoma and thymic carcinoma has a distinct difference. TP53 and CDKN2A mutations might play an essential role in the pathogenesis in thymic carcinoma. Lastly, TP53 is the potential biomarker of poor prognosis in TETs.

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      P1.14-29 - Surgical Treatment for Metastatic Lung Tumors from Various Sarcomas

      16:45 - 18:00  |  Presenting Author(s): Hiromasa Yamamoto  |  Author(s): Kei Namba, Katsuhito Takahashi, Junichi Soh, Kazuhiko Shien, Takeshi Kurosaki, Shinji Ohtani, Mikio Okazaki, Seiichiro Sugimoto, Masaomi Yamane, Takahiro Oto, Shinichi Toyooka

      • Abstract

      Background

      Sarcomas are known to be one of the aggressive malignant tumors. They often develop multiple pulmonary metastasis, and thus systemic therapy is a treatment of choice for metastatic lung tumors. However, effective chemotherapeutic treatments have not yet been established. Surgical resection for metastatic lung tumors is a therapeutic option to control the disease, although it is not a curative therapy.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Between January 2006 and April 2018, 396 pulmonary resections were performed for 219 sarcoma patients with metastatic lung tumors in Okayama University Hospital. Among them, 129 sarcoma patients who underwent pulmonary metastasectomy between January 2006 and December 2014 were retrospectively reviewed. In total, 229 pulmonary resections were performed. We analyzed the following factors: age, sex, site of primary lesion, histology, operative procedures, size of the largest lesions resected, maximum number of the resected tumors, postoperative complications, and survival rate.

      4c3880bb027f159e801041b1021e88e8 Result

      In total, 939 metastatic nodules were resected. Average number of tumors per intervention was 4.1 (range 1-19). These sarcoma patients consisted of 31 males and 98 females, and their average age was 53.6 years (range 14-80 years). Leiomyosarcoma was the most common histological subtype (n = 72, 55.8%) and uterus was the most common location of the primary disease (n = 55, 42.6%). Operative procedures were composed of 173 partial resections, 31 segmentectomies with or without partial resections, 24 lobectomies with or without partial resections, and 1 basal segmental auto-transplantation after pneumonectomy. The postoperative complications were limited, showing that pulmonary metastasectomies for sarcomas are acceptable. Overall 3-year survival after the first pulmonary metastasectomy was 49.5%, and multivariate analysis revealed that the survival was significantly better for the group with disease-free interval of more than 2 years or the size of the largest resected lesion less than 30 mm.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Surgical resections for metastatic lung tumors from various sarcomas were performed without major complications, indicating the acceptable feasibility. If disease-free interval is more than 2 years and the size of the largest resected lesion is less than 30 mm, patients may maximally benefit from surgical resection.

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      P1.14-30 - Prognostic Factors for Sarcoma Patients with Lung Metastasis Who Underwent Extended Pulmonary Resection

      16:45 - 18:00  |  Presenting Author(s): Haruchika Yamamoto  |  Author(s): Kei Namba, Hiromasa Yamamoto, Junichi Soh, Kazuhiko Shien, Takeshi Kurosaki, Shinji Ohtani, Mikio Okazaki, Seiichiro Sugimoto, Masaomi Yamane, Takahiro Oto, Shinichi Toyooka

      • Abstract

      Background

      Since the effects of chemotherapy and molecular targeting agents for sarcoma with lung metastasis are limited, pulmonary metastasectomy can become one of the treatment options for the control of disease. Partial resection is the first choice of surgical procedure for lung metastasis to preserve pulmonary function. As for the tumors which occur at hilum or are too large for partial resection, the extended resection such as segmentectomy or lobectomy is occasionally required while the clinical impact of these procedures is unknown. In this study, we examined preoperative prognostic factors of sarcoma patients who underwent segmentectomy or lobectomy for lung metastasis.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      During January 2006 to December 2014, a total of 129 patients underwent pulmonary resection for lung metastasis of sarcoma at Okayama University Hospital. Among them, 40 patients (31%) underwent segmentectomy or lobectomy. The 3-year survival rate was evaluated by univariate (KaplanMeier method) and multivariate (Cox proportional hazard model) analyses with log-rank test.

      4c3880bb027f159e801041b1021e88e8 Result

      Among 40 patients, the median age was 55 years old (range, 17 to 76). Thirty-five patients (88%) were female. Thirty patients (75%) harbored two or more distant metastatic lesions at initial diagnosis and 21 patients (52.5%) suffered from bilateral lung metastasis at the first lung metastasectomy. Median maximum diameter of the maximum lung tumor and median number of the lung metastasis was 30 mm (range, 8 to 110) and 3 (range, 1 to 19), respectively. Eight patients (20%) had two years or more disease-free interval at the first lung resection. The 3-year survival rate was 36.8% in the entire cohort. The univariate analyses revealed that the 3-year survival rate was significantly better in the patients with smaller size of lung metastasis (50.5% in the tumors with maximum diameter ≤ 30mm vs 20.7% in those > 30mm, P < 0.01), unilateral lung metastasis (45.6% vs 29.5% for bilateral, P < 0.05), and the absence of metastatic lesion at initial diagnosis (50.9% vs 28.1% for the presence, P < 0.05). Smaller numbers of lung metastasis and longer disease-free interval showed favorable prognosis with marginal significance (P < 0.1). The multivariate analysis with the above five factors revealed that unilateral lung metastasis at the first pulmonary metasetasectomy was an independent favorable prognostic factor (HR 2.41, 95%CI 1.09 to 5.32, P < 0.05).

      8eea62084ca7e541d918e823422bd82e Conclusion

      Extended pulmonary resection such as segmentectomy or lobectomy may be considered for the patients with sarcoma lung metastasis especially when the tumors are unilateral.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P1.15 - Treatment in the Real World - Support, Survivorship, Systems Research (Not CME Accredited Session)

    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Moderators:
    • +
      • Abstract

      Background

      The combination of RT and programmed death 1 (PD-1) inhibitors seems augment antitumor immune responses. The aim of this study was to assess the outcome of patients (pts) with NSCLC previously undergone to RT before receiving nivolumab, a PD-1 inhibitor

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We conducted an observational, retrospective analysis of 95 consecutive pts with advanced NSCLC who received any RT within 10 months prior nivolumab, as clinically indicated, at seven Italian institutions. Tumor response to treatment was defined according to RECIST criteria version 1.1. Median overall survival (OS) and the 95% confidence interval (CI) were estimated with the Kaplan -Meier method.

      4c3880bb027f159e801041b1021e88e8 Result

      95 pts (median age 66 years [range 41-82]; male:63.2%) with advanced NSCLC (adenocarcinoma [adc]:66.3%; squamous cells [sqc]:33.7%) were treated with nivolumab after RT. Median OS was 11.9 months (mo) [95% CI, 6.6-17.2 (adc: 13.0 mo [95% CI,6.7-19.3], sqc 10.5 mo [95%CI,3.9-17.1]). Median progression free survival (PFS) was 6.3mo [95% CI,4.6-8.0] (adc: 6.4 mo[ 95% CI,4.5-8.3]; sqc: 3.7 mo [95% CI,0.0-8.3]). A better performance status (PS) according to ECOG scale was associated with an improved OS (PS 0[38 pts]: 17.9 mo [95% CI,12.3-23.5; p<0.0001]; PS1[50pts]: 6.9 mo [95%CI,3.2-10.6]; PS2[7pts]: 4.4 mo [95% CI,3.9-4.9]). Median OS in 70 pts who received ≤ 1 previous systemic therapy was 13.0 mo [95% CI, 10.4-15.6] and in 25 pts who received ≥2 prior lines was 7.4 mo [95% CI, 1.8-12.9]. Median OS in 69 pts (72.6%) receiving extracranical RT was 12.0 mo [95%CI,6.6-17.4] and in 26 (27.4%) pts with cranial RT was 11.7 mo [95%CI,NE]; p=0.31. Median OS was shorter in 36 pts receiving bone-RT [7.3 mo; 95% CI, (0-15.3)] when compared with 59 pts receiving extra-bone RT [14.4 mo; 95% CI, (10.3-18.5); p=0.007]. Median OS in 68 pts aged < 70 years was 11.9 mo [95% CI,6.5-17.3] and in 27 elderly (≥ 70 years) was 12.0 mo [95% CI, 3.8-20.1]. 1 (1.0%) complete response, 25(26.3%) partial response, 28(29.5%) stable disease and 41 (43.2%) progressive disease have been observed.

      8eea62084ca7e541d918e823422bd82e Conclusion

      This study shows that combining irradiation with nivolumab for the treatment of advanced NSCLC leads to improve OS and promote tumor control both locally and distantly.This potentially synergistic effect was comparable among pts regardless previous lines of therapy, histology, type of RT and age.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      P1.15-02 - Migration Differences in Small Cell vs Non-Small Cell Lung Cancer

      16:45 - 18:00  |  Presenting Author(s): Shruti Bhandari  |  Author(s): Danh C Pham, Christina Pinkston, Malgorzata Oechsli, Goetz H Kloecker

      • Abstract

      Background

      Every year there is a population diagnosed with lung cancer (LC) that does not receive initial treatment upon diagnosis and then “migrates” to other hospital systems before ultimately getting treatment. We aimed to compare migration rates between non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) and potential factors associated with migration.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      As part of the Kentucky Lung Cancer Education Awareness Detection Survival (LEADS) Collaborative, 29 of 32 Kentucky hospital registries contacted provided LC data of 7660 patients from 2012-2014. Data collected included age at diagnosis, stage, overall survival (OS), sex, race, insurance and treatment history. Treatment included any combination of surgery, radiation, or chemotherapy. Hospital records were matched to Kentucky Cancer Registry records to determine the number of hospitals visited for treatment. Patient treatment and migration patterns were analyzed with a logistic regression model along with additional post-hoc analysis. Difference in rates was calculated by chi-square test.

      4c3880bb027f159e801041b1021e88e8 Result

      Among the 7660 LC patients, 81% were NSCLC and 19% were SCLC. Most patients were treated at their initial hospital - NSCLC (73%) and SCLC (82%) (p value<0.01). However, among the untreated patients, 616 (36%) of NSCLC patients migrated to a different hospital compared to only 23 (8%) of SCLC patients (p value<0.01). Migration of NSCLC patients to another hospital was associated with Stage I-III disease, younger age (66.4 vs 72.2 years), with initial hospitals missing treatment modalities and patients having private insurance. In NSCLC, compared to patients treated initially, patients treated after migration lived longer (591 vs 505 days) and particularly had longer survival with stage III (563 vs 495 days) and IV disease (379 vs 300 days). Too few patients with SCLC migrate to assess association with OS and other patient characteristics.

      8eea62084ca7e541d918e823422bd82e Conclusion

      There is a significant difference in rates of initial treatment between NSCLC and SCLC that could be due to perceived urgency to treat SCLC. This analysis shows highly significant 4-fold increase in migration rate of NSCLC as compared to SCLC. This could be explained by newer and better treatment options available at referral centers for NSCLC and a lack of these options for SCLC. Increasing research and new innovations in NSCLC will likely drive more patients to migrate in future.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      P1.15-03 - Clinical Characteristics of Long-Term Survivors With Nivolumab in Pretreated Advanced NSCLC<br /> from Real-World Data (RWD)

      16:45 - 18:00  |  Presenting Author(s): Antonio Calles  |  Author(s): Miguel Garcia, Miriam Lobo, Rosa Álvarez Álvarez

      • Abstract

      Background

      We have previously analyzed real-world data (RWD) from patients with metastatic NSCLC that progressed to chemotherapy and were subsequently treated with immune-checkpoint inhibitors (ICI). This included patients with performance status of 2, brain metastases, concomitant use of steroids, unknown PD-L1 status, systemic antibiotics during the previous month, and without restriction in the number of previous lines received. Now, with a longer follow-up, we aimed to analyze the baseline clinical characteristics in long-term survivor patients.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We performed a retrospective study of previously treated advanced NSCLC patients that received nivolumab at 3 mg/kg every 2 weeks outside clinical trials from our institution in Madrid (Spain) between January 2015 and April 2018. We used RWD to analyze the clinical characteristics of patients who were alive 2 years after the start of ICI.

      4c3880bb027f159e801041b1021e88e8 Result

      A total of 38 pts fulfilled inclusion criteria. 7 pts (18%) where alive 2 years after the first dose of nivolumab. Median age at diagnosis was 63 years (53-72 years). 6 pts (86%) had history of tobacco smoking, and 6 pts (86%) had non-squamous histology. 3 pt had ECOG 0 (43%), 3 pts had ECOG 1 (43%) and one pt had ECOG 2 (14%). Median number of previous lines was 3; 3 pts received nivolumab in second line, 3 pts in fourth line and one pt in fifth line. All pts were diagnosed with primary advanced disease. 2 of the pts (29%) had brain metastases and 1 pt (14 %) had ≥ 4 metastatic locations. 2 pts had use antibiotics in the month before and 1 pt used steroids. Best response to nivolumab per RECIST 1.1 criteria included 3 partial responses (43%), and 2 each (29%) had stable and progressive disease. Only 2 pts had no evidence of disease progression during > 2 years at last follow-up when the database was lock (April 2018). Five pts discontinued treatment due to disease progression.

      After progression, 1 pt continued treatment with nivolumab, 1 pt started osimertinib (EGFR mutant previously treated with TKI and chemotherapy, and confirmed T790M+), and 3 pts started chemotherapy followed by retreatment with ICI. No patients discontinued due to adverse events.

      8eea62084ca7e541d918e823422bd82e Conclusion

      In our RWD experience, nivolumab resulted in a 2-years survival rate of 18% in previously treated advanced NSCLC patients. Clinical characteristics from real world patients do not predict for long term benefit of nivolumab. Immunological biomarkers are necessary to better select pts who will derive long-term benefit from immunotherapy.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      P1.15-04 - Practice Patterns Regarding Multidisciplinary Cancer Management for NSCLC and implemetantion: Results of National Survey in México

      16:45 - 18:00  |  Presenting Author(s): Saul Campos-Gomez  |  Author(s): Karen A Campos-Gomez, Omar Macedo-Pérez, Juan J Valdéz Andrade, Oscar Arrieta

      • Abstract

      Background

      To manage patients with advanced lung cancer in the most effective way, experts from different disciplines need to be engaged. This has resulted in introduction of the multidisciplinary team (MDT) approach. Because of these advantages, current clinical guidelines recommend discussing the diagnostic and therapeutic plan with an MDT for localized or locally advanced Non-Small Cell Lung Cancer (NSCLC). However, studies suggest despite the advantages of multidisciplinary care, the proportion of new lung cancer diagnoses that are formally discussed in Lung Cancer MDM are disappointing low, in the order of 28–29%. An Australian survey suggests that only one third of hospitals have a multidisciplinary team.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      However, it is unclear how specialists view current evidence about multidisciplinary team (MDT) approach and how they would incorporate into practice. We sought to understand specialist opinions about evidence regarding treatment of NSCLC and how this translates into clinical practice implementation.This study was conducted to explore specialist opinions about multidisciplinary team approach of NSCLC, how this translates into practice and the implementation in Mexico.

      4c3880bb027f159e801041b1021e88e8 Result

      We collected a total of 60 completed responses (50%), 77% were medical oncologist, 7% surgical oncologist and 17% radiation oncologists. Of these 34% mainly worked in private and 66% in public healthcare Systems. Seventy two percent of all physicians were < 40 years, 25% between 40 and 50 years of age and 22% were 50 years of age or older. Young doctors (up to 5 years of service) accounted for 45 %, with a median length of practice of 12 years. More than two-thirds of physicians were male. Approximately 58% of respondents stated that exist a MDTs for NSLC in their institutions. The Core members of the multidisciplinary cancer team usually include an oncologist (medical, surgical, radiation), pathologist and radiologist in the 65% of the teams. Approximately 55% of respondents stated that MDTs met regularly. Forty two of survey responders do not have a MDT but can discusses new cases directly with surgical oncologist o radiologist.

      8eea62084ca7e541d918e823422bd82e Conclusion

      While multidisciplinary care has emerged as the standard of care for lung cancer management. The challenge for the future is how to more fully integrate multidisciplinary care into the management of all patients with lung cancer in México.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      P1.15-05 - The Frequency and Spectrum of EGFR Exon 20 Insertions in NSCLC: A Global Literature Review

      16:45 - 18:00  |  Presenting Author(s): Victoria Crossland  |  Author(s): Shuanglian Li, Aaron Galaznik

      • Abstract

      Background

      There are limited epidemiological data on non-small cell lung cancer (NSCLC) patients with non-classical (uncommon) epidermal growth factor receptor (EGFR) mutations. In light of ongoing development of TAK-788, we describe the global frequency and spectrum of EGFR exon 20 insertions in NSCLC based on a comprehensive literature review as well as highlight possible regional variations.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      A literature search was conducted to identify publications reporting the frequency of EGFR exon 20 insertions in unselected NSCLC patients. PubMed and ASCO, ESMO, and IASLC meeting abstracts were searched up to April 2018 using the following keywords: non-small cell lung cancer, epidermal growth factor receptor, exon 20, insertions and uncommon mutations. Only publications in English were included. The pooled frequency of EGFR exon 20 insertions for each country were determined, and insertion variants (where available) were described at the global level.

      4c3880bb027f159e801041b1021e88e8 Result

      A total of 26 studies from 25 countries were included, reporting on 569 patients with EGFR exon 20 insertions among 41,321 NSCLC patients. The highest mutation frequency was seen in China (2.9%) and the lowest in Indonesia (0.1%). When pooled by country, exon 20 insertions were found in 0.1−2.1% of all NSCLC.

      frequency of egfr exon 20 insertions in patients with nsclc.jpg

      Over 50 insertion variants were reported, covering amino acids 761−774. The most commonly detected mutations included D770_N771insSVD, V769_D770InsASV, H773_V774InsH, H773_V774insNPH, and A763_Y763insFQEA.

      8eea62084ca7e541d918e823422bd82e Conclusion

      The frequency of EGFR exon 20 insertions was 0.1−2.1% of NSCLC patients, with a high variability in both length and position of insertions within exon 20. Currently, available data are sparse and come primarily from studies based on single-center experiences, with data gaps across several large geographic regions and populations. Results also indicate a need to further explore underlying geographic variations in epidemiology. Larger, multi-center global studies will further help to refine the frequency of exon 20 insertions and other uncommon mutations in NSCLC.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      P1.15-06 - Integrative Quality Improvement for Management of Lung Cancer in Uganda

      16:45 - 18:00  |  Presenting Author(s): Semujju David

      • Abstract

      Background

      Uganda is currently engaged in quality improvement initiatives for cancer patients. One of them is the creation of an integrative quality system, consisting of guideline development, quality indicators definition and feedback to hospitals. This approach has already been successfully implemented for five types of cancers: rectum (in collaboration with development partners), breast, testis, oesophagus and stomach. Building on previous experience, the study presents the development of a set of quality indicators (QIs) for the management of lung cancer.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We followed the standardized MOH methodology to identify, select, test and measure the indicators. Because patients may be in contact with different hospitals (for instance, be diagnosed in one hospital but receive treatment – surgery or radiotherapy – in another), we developed a specific algorithm to attribute each patient to the centre where he/she was diagnosed or received treatment (surgical centre or centre of radiotherapy). The method to test the feasibility of identifying comorbidities of patients based on their pharmaceutical billing data during the year before the cancer diagnosis is also described.

      4c3880bb027f159e801041b1021e88e8 Result

      The results of this project made clear that we need more complete and accurate reporting of data to allow more precise and correct evaluation of the quality of care for lung cancer patients in Uganda. Quick and fluent data collection would make it possible to provide comprehensive feedback to care providers on a regular and timely basis. To make this happen, investments in data registration and analysis will be necessary.

      8eea62084ca7e541d918e823422bd82e Conclusion

      When benchmarking results between hospitals, cautious interpretation is warranted. The use of funnel plots avoids spurious ranking of hospitals and outlier dots can reliably designate either good or bad performers. Statistical modeling can often only partially account for differences in case-mix and other biases. Judging quality of care delivered by a hospital is further hindered by the often small number of patients treated per hospital. Hence, from a sheer statistical point of view, small volumes of activity make it impossible to offer an acceptable level of assurance about the quality delivered to the patient.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      P1.15-07 - Geriatric Oncology - Lung Cancer in Elderly Patients and Palliative Treatment: Prospective Analysis of A. C. Camargo Cancer Center

      16:45 - 18:00  |  Presenting Author(s): Mauro DS Donadio  |  Author(s): Audrey CF de Oliveira, Luciana M Leite, Malu VR Barbosa, Tiago C Felismino, Marcelo P Corassa, Vladmir CC de Lima, Victor HF de Jesus, Aldo LA Dettino

      • Abstract

      Background

      Special attention is required by elderly population, due to chemotherapy (ch) risks and comorbidities, which may limit the capacity to deliver optimal cancer care. We aimed to describe the clinical features and survival outcomes of elderly patients (pts) with lung adenocarcinoma (ADC) treated with non-curative intent at A. C. Camargo Cancer Center.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We evaluated all pts aged 70+ with lung ADC treated with ch or target therapy in 1st or 2nd-line from 2007 to 2015 who underwent a comprehensive geriatric assessment (CGA), in a convenient prospective series. We used summary statistics to describe the population. Overall survival (OS) was calculated according to Kaplan-Meier method, from CGA date to last follow-up or death. We performed univariate and multivariate analysis in order to look for potential prognostic factors for OS.

      4c3880bb027f159e801041b1021e88e8 Result

      CGA was done in 55 pts aged ≥70y with lung ADC. The median age was 76y and 22% had ECOG ≥ 2. Half of pts were male. 51% had polypharmacy (≥5 drugs). Pts were functionally classified according to activities of daily living (ADL): 76% as Katz A and 50% as Lawton ≤27. 68.5% were at risk for malnutrition or malnourished. The median age-adjusted Charlson Comorbidity score was 10 – remembering that 4+ is considered clinically significant. 61% had ≥2 comorbidities and 26 pts had at least 2 metastatic sites. CNS was affected in 7.5% of the cases and liver in 9.2%. 79.6% of the pts underwent ch and the others received target therapy. After follow-up of 29m, median OS was 17.1 months (13.5-27.8m). In univariate analysis, significantly worse survival outcomes were observed for pts with ECOG 2-4 (HR 10.6; p < 0.001), increasing number of sites of metastases (HR 2.2; p = 0.04) and hepatic metastasis (HR 6.03; p < 0.001). In the multivariate analysis, male gender, ECOG 2-4 and liver metastasis were associated with higher risk of death.

      8eea62084ca7e541d918e823422bd82e Conclusion

      ADL, an important part of CGA, showed little prognostic value in our small population. Pts with ECOG 2-4 or hepatic metastasis were those that presented the highest risk of death. CGA is a good tool to help in stratifying risk of elderly cancer pts and is mandatory in cost-benefit analysis to identify the best treatment to each individual patient.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      P1.15-08 - Implementation and Feasibility of the Assessment of EGFR Mutation in NSCLC Using Liquid Biopsy at an Argentinean University Hospital

      16:45 - 18:00  |  Presenting Author(s): Carolina Gabay  |  Author(s): Nazareth Rusjan, Krasnapolski Martin, Mara Bonet, Erica Rojas Bilbao, Monica Castro

      • Abstract

      Background

      Molecular characterization of lung cancer is standard of care. Almost 85% of NSCLC patients have advanced disease at diagnosis, being a challenge get enough tissue for diagnosis. That´ s why using less invasive methods as liquid biopsy by determining cftDNA (circulating free tumor DNA) represents a promising tool. The detection of EGFR mutations in plasma by Therascreen (EGFR RGQ Mutation Kit) showed a sensitivity and specificity of 65.4% and 100 % respectively. It is also useful to detect TKI´s resistance previous to clinical progression. The advantages of using PCR, even there are more sensitive methods available, are its simplicity and cost.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We will prospectively recruit EGFR mutation-positive (n=40) NSCLC patients. Plasma samples are collected: baseline, after three months of treatment, every six months and at the time of progression. We report our first interim analysis. We evaluate the concordance of EGFRm in tissue and plasma with the implementation of the Therascreen test (Qiagen). We test other available plasma EGFRm detection kit (EGFR Plasma Mutation Analysis Kit, Entrogen) (n=10)

      4c3880bb027f159e801041b1021e88e8 Result

      Since February 2017, plasma EGFRm status could be determined in 17 out of 22 NSCLC patients with EGFRm in tissue. L858R was present in 9 (53%), del19 in 7 (42%), del19+T790M in 1 (5%). Baseline plasma analyzed with Therascreen and Entrogen kits showed similar sensitivity of 61.1% and 66% respectively. Only 1/11 pt had discordance between both kits (Therascreen negative , entrogen DEL19+T790M ).

      In 17 analyzed ptes, median age was 59 (51-76) years. Most of the population were women (88%), were never smokers (58%), had stage IV disease (58%). Frequent site of metastasis was bone (n=7). With a median follow up of 18 months (12-23), 7/15 (56%) patients who experienced clinical progression were detected also in plasma. Two patients presented T790M in plasma without evidence of disease progression until last follow-up (July 2018). We also observed two patients with mutations detected out of range to be considered as positive which became positive for these mutations during the follow up.

      8eea62084ca7e541d918e823422bd82e Conclusion

      This is the first work showing a cohort of EGFRm patients prospectively analyzed by successive liquid biopsies in a public institution in Argentina. We could successfully obtain cftDNA and analyze it by two commercial kits. The sensitivity of both kits was comparable to previous reports. The study is ongoing and more samples will be analized to shed light about the plasma dynamics of EGFRm related to clinical behavior.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      P1.15-09 - Trends in Lung Cancer Survival in Lithuania

      16:45 - 18:00  |  Presenting Author(s): Vaida Gedvilaite  |  Author(s): Edvardas Danila, Saulius Cicenas, Giedre Smailyte

      • Abstract

      Background

      Lung cancer is the most common cancer-related death worldwide. The prognosis of lung cancer is unfavourable and improvements in survival in recent decades have been minimal. The aim of this study is to describe the most recent survival rates by sex, age group, extent of disease and histology of lung cancer in Lithuania.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      The study is based on the Lithuanian Cancer Registry database covering a population of around 3 million residents according to 2011 census. The analysis included patients with primary invasive lung cancer diagnosed in 1998-2012 who were at least 15 years old at the time of diagnosis. Patients were followed-up with respect to vital status until December 31, 2012. Cases notified by the death certificate only were excluded. Five-year relative survival estimates were calculated using period analysis. Relative survival was calculated as the ratio of the observed survival of cancer patients and the expected survival of the underlying general population. The latter was calculated according to the Ederer II method using national life tables for Lithuanian population stratified by age, gender and calendar year.

      4c3880bb027f159e801041b1021e88e8 Result

      In our study the overall 5-year relative survival was low, but increased slightly from 6,4% in 2003-2008 to 7.9 % 2009-2012. Positive changes in survival were evident in both sexes, in almost all age groups and for all histological groups and disease stages. Adenocarcinoma relative survival increased from 6.7% in 2003-2008 to 12.8% in 2009-2012 and squamous cell carcinoma increased from 7.4% in 2003-2008 to 11.1% in 2009-2012. Patients with small cell carcinoma had the worst survival (2.9% in 2003-2008 and 3.6% in 2009-2012). Only less than 10% of lung cancer cases were diagnosed localised and proportion of those tumours decreased slightly (from 8.5% to 7.6%). In 2009-2012 relative survival of localised stage lung cancer was 43 %, locally advanced – 19,9%, regional disease - 6% and metastatic disease – 0.7%.The highest number of lung cancer was diagnosed with distant metastases and proportion of metastatic tumours increased from 35.1% to 37.8%. 5-year relative survival was higher in women (9.4 % in 2003-2008 and 12.6 % in 2009-2012) than in men (5.8 % in 2003-2008 and 7% in 2009-2012).

      8eea62084ca7e541d918e823422bd82e Conclusion

      Despite low overall survival, there were positive changes in survival in both sexes, in almost all age groups and for all histological groups and disease stages. The high proportion of metastatic disease at the time of diagnosis was the main factor that influenced low survival rates.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      P1.15-10 - Comparison of Selected Colombian National Administrative Cancer Registry (NACR) Data in Lung Cancer with the U.S.

      16:45 - 18:00  |  Presenting Author(s): Robert Hsu  |  Author(s): Lizbeth Acuna Merchan, Gilberto de Lima Lopes

      • Abstract

      Background

      Lung cancer (LC) is the seventh leading cause of cancer in Colombia and the leading cause of cancer mortality in the United States. In Colombia, previous estimates of lung cancer have been limited to city specific cancer registry (Cali Cancer Registry) and broad estimates from GLOBOCAN. The Colombian Health Ministry in 2015 created the National Administrative Cancer Registry (NACR) to obtain national cancer data. We investigated selected 2016 NACR data and compared it to data from the U.S. to gauge for areas of improvement in lung cancer delivery.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We obtained NACR data compiled from the Colombian Department of Health Ministry regarding lung cancer from 2015-2016. We compared this to U.S. data consisting of Surveillance, Epidemiology, and End Results (SEER) and National Cancer Database (NCDB) data from 2003-2015.

      4c3880bb027f159e801041b1021e88e8 Result

      NACR data in 2016 shows incidence of 1.7 cases per 100,000 and mortality of 2.5 cases per 100,000. SEER data from 2015 shows incidence of 47.2 cases per 100,000 and mortality of 40.6 cases per 100,000. NACR data shows average age of 66 (IQR = 65.7-66) while NCDB data shows median age to be in the age 60-69 category. NACR data in 2016 shows that 14.02% of 849 diagnosed LC patients received surgery compared to 24.83% of 168,093 diagnosed non-small cell lung cancer and small cell lung cancer patients in 2015 from the NCDB. NACR data demonstrates that of those receiving chemotherapy with documented regimens (n=275), 52% received carboplatin, 28.3% received pemetrexed, 27.6% received cisplatin, 25.4% received paclitaxel, 10.9% received bevacizumab, and 5.1% received erlotinib. In comparison, SEER data from 2000-2011 show metastatic NSCLC patients receiving antineoplastic agents (n = 2022) with increasing use of pemetrexed (39.2%), erlotinib (20.3%), and bevacizumab (18.9%) and declining use of paclitaxel (38.7%), gemcitabine (17.0%), and vinorelbine (5.7%). NACR data shows median wait time from diagnosis to first treatment of 31 days (IQR=14-62, n=346) compared to NCDB data showing median wait time of 35 days from diagnosis to first treatment.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Data shows significantly higher incidence and mortality in the U.S.; this is multifactorial due to screening and data reporting. Comparison shows higher rates of surgery and use of biologics in the U.S. There were similar wait times from diagnosis to first treatment and age of LC patients. Limitations include limited reporting on chemotherapy, radiation, and staging. Future improvements from a Colombian standpoint will include outcomes data collection, increased screening, resources for surgery, and updated access to antineoplastic agents.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      P1.15-11 - Lung Cancer as One of Multiple Cancers: A Population-Based Study in Estonia 1995-2015

      16:45 - 18:00  |  Presenting Author(s): Jana Jaal  |  Author(s): Marju Kase, Katrin Sak, Marika Saar, Markus Vardja, Margit Mägi

      • Abstract

      Background

      Due to recent developments in cancer prevention, early diagnosis and treatment, more cancers are detected at earlier stages and more patients are cured. As a result, the burden of second and further primary malignancies in a growing and ageing population has remarkably increased over the last decades. Lung cancer is one of the most frequent but most deadly types of cancer. Whether this type of malignancy has a considerable role among multiple cancers is not known. Therefore, the aim of the present study was to assess lung cancer cases as one of the multiple cancers in Estonia.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We used the data from the Estonian Cancer Registry (ECR), a population-based registry with nationwide coverage (total 1.3 million inhabitants). The ECR provided data on all lung cancer cases and associated multiple cancer cases diagnosed in Estonia 1995‒2015.

      4c3880bb027f159e801041b1021e88e8 Result

      During the time period of 20 years, 146541 cancer cases (ICD-10 C00-C97 and in situ cancers D00-D09) were recorded. Lung cancer cases (n=16350) comprised 11% of all malignancies. Out of all diagnosed lung cancer cases, 10% of patients had multiple cancers (n=1619). Lung cancer as first multiple cancer was diagnosed in 398 patients (25%; 338 men, 60 women; median age 67 years, range 31-87 years). Lung cancer as second cancer was diagnosed in 1130 patients (70%; 851 men, 279 women; median age 67 years, range 32-91 years). Ninety one patients had lung cancer as their third cancer (5%; 67 men, 24 women; median age 66 years, range 32-79 years). None of the patients had lung cancer as fourth or further multiple cancers. Next to lung cancer, patients had mostly melanoma and other malignant tumors of skin (18%), malignant neoplasms of digestive organs (18%), male genital organs (18%) and urinary tract (13%) as well as respiratory tract cancers including new lung primaries (10%). Other types of cancers represented 23% of malignancies. After first diagnosis of lung cancer, second tumor was diagnosed approximately 5 months (median) later. As second multiple cancer, lung cancer was diagnosed 7 years (median) after the first cancer diagnosis. Lung cancer as third cancer developed approximately 2 years (median) after the second diagnosis of malignant tumor.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Multiple cancers are common among lung cancer patients in Estonia. Particular attention is needed, when patient with lung cancer develops skin changes, gastrointestinal and genitourinary symptoms or presents with newly developed respiratory tract complaints.

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      P1.15-12 - Real World Applications of Next-Generation Sequencing of Non-Small Cell Lung Cancer in the Veteran Population

      16:45 - 18:00  |  Presenting Author(s): Jeremy Kratz  |  Author(s): Gil Harmon, David Kosoff, Doug Wubben, Ryan Laughlin, Anne Traynor, Dustin Deming, Mark Burkard, Ticiana A. Leal

      • Abstract

      Background

      Population studies to date have demonstrated decreased rates of driver mutations in non-small cell lung cancer (NSCLC) for veterans with prior tobacco use who receive care at Department of Veterans Affairs (VA) facilities. Causes of this reduced rate have not been identified, but may result in underutilization of broadly based genetic tumor profiling. The VA recently expanded next-generation sequencing (NGS) to include both tissue and liquid biopsies for comprehensive genetic profiling for patients (pts) with advanced malignancy. Herein, we describe clinical utility of NGS from our retrospective cohort of a rural-based NSCLC veteran population.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We performed a retrospective cohort analysis of 79 veterans with metastatic NSCLC from 07/2015-04/2018. A trainee-initiated quality improvement initiative in 07/2017 disseminated education at the VA facility about the role of NGS testing for non-squamous NSCLC, with support from the University of Wisconsin Precision Medicine and Molecular Tumor Board. Baseline demographics, time to tissue biopsy, and genetic tumor profiling were analyzed; clinical outcome data were collected including overall survivial and progression-free survival.

      4c3880bb027f159e801041b1021e88e8 Result

      As expected, the cohort was predominantly male (91.1%), with tobacco use (median 45 pk-yrs, 95% >5 pk-yrs) and median age 69 yrs. For molecular profiling, 52% had sufficient tissue at metastatic diagnosis, 20% underwent repeat biopsy within 30 days, 17% underwent biopsy after 30 days, and 11% presented with comorbidity resulting in empiric or palliative management. After implementation of the quality improvement project, the frequency of genetic profiling increased compared to pre-expanded NGS availability in the following targets: EGFR (59% v. 90%), ALK (65% v. 90%), ROS1 (35% v. 90%), and BRAF (8% v. 60%). Actionable targets were identified in EGFR 15.4% (5/39 pts), ALK (1/41), ROS1 (1/24), and BRAF (1/11); additional mutations in NTRK1, NTRK3, ERBB2, and FGFR1 were detected.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Our preliminary results demonstrate that the availability and use of NGS was associated with increased rates of comprehensive genetic profiling in a largely rural veteran population. Ongoing work will expand this retrospective cohort to more thoroughly characterize barriers to diagnosis and target-specific frequency over historical advances in precision oncology. We will review how these genetic profiles may offer both prognostic and predictive value by reporting clinical outcomes between targeted therapy and early applications of immunotherapy within the veteran population.

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      P1.15-13 - Wait Times for Diagnosis and Treatment of Lung Cancer Across the Province of Quebec, Canada

      16:45 - 18:00  |  Presenting Author(s): Catherine Labbe  |  Author(s): Simon Martel, Brigitte Fournier, Carole Saint-Pierre

      • Abstract

      Background

      Multiple clinical practice guidelines recommend rapid evaluation of patients with suspected lung cancer. Diagnostic pathways and wait times vary considerably from one centre to another.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We retrospectively reviewed medical records of all patients (n=1217) across the province of Quebec who had a biopsy-proven diagnosis of lung cancer between February 1st and April 30th, 2017. Median wait times for diagnosis and treatment were calculated.

      4c3880bb027f159e801041b1021e88e8 Result

      Patient characteristics are shown in Table 1. Median wait times for investigation and treatment are shown in Table 2. There were variations between centres and regions.

      Characteristic

      No (%)

      Age, years, mean (range)

      68.5 (20-94)

      Male sex

      585 (48)

      Smoking status

      Former or current smoker

      Never smoker

      Unknown

      1120 (92)

      60 (5)

      37 (3)

      ECOG performance status

      0

      1

      ≥2

      Missing

      416 (34)

      358 (30)

      393 (32)

      50 (4)

      Histology

      Adenocarcinoma

      631 (52)

      Squamous cell carcinoma

      284 (23)

      NSCLC NOS

      70 (6)

      SCLC

      178 (15)

      Other

      54 (4)

      TNM stage

      I

      213 (18)

      II

      114 (9)

      III

      227 (19)

      IV

      475 (39)

      Limited SCLC

      40 (3)

      Extensive SCLC

      138 (11)

      Missing

      10 (1)

      Known positive EGFR mutation status (n=395 tested)

      Known positive ALK translocation status (n=387 tested)

      PD-L1 TPS (n=386 tested)

      <1%

      1-49%

      ≥50%

      Number of investigations per patient, median (IQR)

      28 (7)

      6 (2)

      85 (22)

      151 (39)

      150 (39)

      7 (6, 8)

      Tumor board review

      194 (16)

      Final diagnostic procedure

      Flexible bronchoscopy

      338 (28)

      EBUS/EUS

      223 (18)

      Transthoracic needle biopsy

      301 (25)

      Thoracoscopy

      139 (11)

      Biopsy of metastatic site

      145 (12)

      Sputum cytology

      1 (0)

      Thoracentesis

      61 (5)

      Mediastinoscopy

      Missing

      2 (0)

      7 (1)

      ECOG = Eastern Cooperative Oncology Group; NSCLC = non-small cell lung cancer; NOS = not otherwise specified; SCLC = small cell lung cancer; EGFR = epidermal growth factor receptor; ALK = anaplastic lymphoma kinase; TPS = tumor proportion score; IQR = interquartile range; EBUS = endobronchial ultrasonography; EUS = endoscopic ultrasonography.

      Table 2 – Median wait times for investigation and treatment

      Investigation or treatment interval

      Pts (n)

      Median wait, days (IQR)

      Referral to first appointment with specialist

      972

      2 (0, 7)

      First appointment to diagnosis

      1152

      18 (8, 43)

      Diagnosis to first treatment

      930

      22 (5, 42)

      Referral to first treatment

      737

      58 (28, 89)

      Abnormal imaging to first treatment

      902

      72 (39, 111)

      Surgery

      268

      109 (80, 142)

      Radiation

      362

      59 (28, 98)

      Systemic therapy

      330

      62 (35, 92)

      8eea62084ca7e541d918e823422bd82e Conclusion

      To our knowledge, this is the largest multicentre review of wait times for diagnosis and treatment of lung cancer with detailed characteristics of patients. Data will be completed and updated prior to the meeting, to try to identify specific factors associated with longer wait times.

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      P1.15-14 - Pneumonia in Patients with Lung Cancer of South Korea: A Nationwide Population Based Study

      16:45 - 18:00  |  Presenting Author(s): Hyun Woo Lee  |  Author(s): Joonho Jung, Jaesung Heo

      • Abstract

      Background

      We analyzed the prevalence of pneumonia in lung cancer survivors using claims data from the Health Insurance Review and Assessment Service (HIRA) in South Korea.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We defined pneumonia among a nationwide cohort of 173,390 patients who were diagnosed with lung cancer and underwent surgery from January 1, 2010 to December 31, 2014, based on HIRA claim data. Descriptive statistics were calculated to estimate the frequency of pneumonia using diagnostic code and utilization pattern at medical institutions.

      4c3880bb027f159e801041b1021e88e8 Result

      Thirty two thousand five hundred lung cancer survivors (19.8%) were diagnosed with pneumonia. The overall frequency of influenza increased from February (n=8089) and peaked in May (n=9,654). Over 59.06% (57,979) of claims for pneumonia treatment were in the clinic, whereas general hospitals accounted for 40.94% (40,184). Among 101,351 claims, admission rate increased as patients get older and the average length of hospitalization was 4.8 days. Elderly breast cancer survivors over 70 years old had the longest length of hospitalization at 6.2 days.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Lung cancer survivors are more susceptible to pneumonia than non-cancer survivors. It is important not only to raise the vaccination rate among young cancer survivors, but also to quickly identify symptoms and begin treatment for pneumonia in elderly cancer survivors.

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      P1.15-15 - Real-World Experience with Afatinib after Failure of First-Generation Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor

      16:45 - 18:00  |  Presenting Author(s): Chong-Kin Liam  |  Author(s): Gwo-Fuang Ho, Chee-Shee Chai, Adlinda Bt Alip, Yong-Kek Pang

      • Abstract

      Background

      Afatinib, a second-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) is the recommended first-line treatment for patients with advanced non-small cell lung cancer harbouring sensitizing EGFR mutations. The role of afatinib after failure of first-generation EGFR-TKIs is controversial.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      A retrospective observational study of patients with EGFR mutant advanced NSCLC receiving second-line afatinib after failure of first-generation EGFR-TKI in University Malaya Medical Center from 1st December 2014 to 30th April 2018.

      4c3880bb027f159e801041b1021e88e8 Result

      The demographic and clinical characteristics of 27 patients treated with afatinib after failure of first-generation EGFR-TKI are shown in Table 1. Twenty-three patients received gefitinib and 4 patients received erlotinib as first-line treatment. The mPFS with first-line treatment was 11.9 months. Fifteen patients had progression of disease (PD) following second-line afatinib with mPFS of 4.2 months and median time-to-treatment failure of 5.7 months. The mPFS2 conferred by first-line first-generation EGFR-TKI and second-line afatinib was 18.4 months. The overall response rate to second-line afatinib was 18.5% (5/27) while the disease control rate as 70.3% (19/27).

      Two patients who had PD on first-generation EGFR-TKI due to T790M mutation received second-line afatinib while waiting for compassionate access to osimertinib. Nine of the 15 patients (69.2%) with PD on afatinib underwent investigations for resistance mechanisms. Three patients had T790M mutation, one of whom had concomitant small cell lung cancer transformation. c-MET amplification was detected in another 3 patients. One patient each had EML4-ALK rearrangement and epithelial mesenchymal transition.

      table 1.jpg

      8eea62084ca7e541d918e823422bd82e Conclusion

      Afatinib conferred a modest mPFS benefit after failure of first-generation EGFR-TKI. The mPFS of sequential treatment with first-generation EGFR-TKI followed by afatinib seems longer than the mPFS of first-line afatinib in phase 3 randomised controlled trials. Apart from T790M mutation, the resistance mechanisms to second-line afatinib in our patients are more heterogenous.

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      P1.15-16 - ALKConnect: An Anaplastic Lymphoma Kinase Positive (ALK+) Non-Small Cell Lung Cancer (NSCLC) Patient Insights Network

      16:45 - 18:00  |  Presenting Author(s): Huamao M Lin  |  Author(s): Xiaoyun Pan, Hui Huang, Gabriella Salvatore, Scott Clarke, Howard West

      • Abstract

      Background

      ALK+ NSCLC is a subset of NSCLC present in ~3-5% of NSCLC patients. Little is known about ALK+ NSCLC patients’ unique journeys, their perspectives on the burden of disease, and their ‘real-world’ treatment experiences. Online patient networks provide opportunities to gain valuable insights into outcomes meaningful to patients, directly from patients. The objective of this study is to develop an ALK+ NSCLC patient network to facilitate patient interaction and to conduct patient-centered research including understanding unmet needs, patient preferences, health-related quality of life (HRQoL), and product differentiation.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      The ALKConnect Patient Insights Network (www.alkconnect.com) will be a patient-focused registry that directly collects information from patients living with ALK+ NSCLC. Patients meeting study criteria will be enrolled in the online survey over a 2-year period. Inclusion criteria are US, adult, English-speaking patients with ALK+ NSCLC providing written, informed consent, internet access, and willing to answer regular e-surveys. Retrospective and cross-sectional ‘real-world’ data that will be collected include demographics, clinical characteristics including ALK+ NSCLC disease history and status, comorbidities, past and present treatment experiences and outcomes, quality of life, patient preferences, healthcare resource use, and work productivity. Supplementary data may be collected through uploading of electronic medical records.

      4c3880bb027f159e801041b1021e88e8 Result

      The ALKConnect Patient Insights Network will systematically characterize the natural history of ALK+ NSCLC and its treatment and the overall impact on patients. The data collected will be reported descriptively for the population overall and by subgroups of interest (e.g., age, sex) where sample sizes permit. The associations between treatment history/disease status and patient-reported outcomes including symptom severity, HRQoL (e.g., responses to the MD Anderson Symptom Inventory lung cancer module [MDASI-LC]), healthcare resource use, and work productivity will be analyzed. Longitudinal trends will be evaluated to enable a better understanding of the impact of ALK+ NSCLC over time. All de-identified information gathered from ALKConnect will be shared with the ALK+ NSCLC community, including patients, caregivers, healthcare professionals, advocacy organizations, and fellow researchers.

      8eea62084ca7e541d918e823422bd82e Conclusion

      We present ALKConnect, an online ALK+ NSCLC patient insights network directly from patients. ALKConnect will provide patients with ALK+ NSCLC opportunities to share their treatment experiences, disease burden, HRQoL, and preferences. Through dissemination to scientific and medical communities, researchers will gain first-hand insights into ALK+ NSCLC patients’ experiences of care, and into opportunities for addressing patients’ unmet needs.

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      P1.15-17 - Risk Factors of Local Recurrence in EGFR-Mutant Stage III-pN2 Adenocarcinoma After Complete Resection: A Multi-Center Real-World Cohort Study

      16:45 - 18:00  |  Presenting Author(s): Hui Liu  |  Author(s): Qi-Wen Li, Bo Qiu, Wenhua Liang, Jun-Ye Wang, Wan-Ming Hu, Shuang-Bing Xu, Steven H Lin, José Luis López, Nai-Bin Chen, Tian Zhang, Minzhang Guo, Yi Zhao, Song-Ran Liu, Qianwen Liu, Jin-Yu Guo, Ling-Zhi Cai, Si-Yu Wang, Xin Wang, Lan-Jun Zhang, Tie-Hua Rong, Zhen-Tao Yu, Jing-Ping Yun, Gang Wu, Li Zhang, Vincent (Wentao) Fang, Hao Long, Qing-Song Pang

      • Abstract

      Background

      Postoperative radiotherapy (PORT) of complete resected stage IIIA non-small cell lung cancer with N2 nodal involvement remained contentious. Our previous study suggested low locoregional recurrences in epidermal growth factor receptor (EGFR) mutant patients. We sought to launch a multi-center large cohort study to evaluate the risk factors of locoregional recurrence in R0 resected EGFR mutant III-pN2 patients without PORT, producing evidence for the design of adjuvant regimens.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Three-hundred and fifty-nine consecutive patients with complete resected, pathological approved stage III-pN2 lung adenocarcinoma with sensitive EGFR mutation (exon 19 or exon 21) have been investigated. Patients were excluded if they received induction therapy (7.5%) or PORT (9.6%). Three hundred cases have been analyzed. Clinicopathologic characteristics, pretreatment work-ups, EGFR mutant status and patterns of failure were documented. Patients were sub-staged by the International Association for the Study of Lung Cancer (IASLC)/ the Union for International Cancer Control (UICC) 7th classification on N2 disease. Risk factors of locoregional recurrence-free survival (LRFS) were evaluated by univariate and multivariate analyses.

      4c3880bb027f159e801041b1021e88e8 Result

      According to IASLC/UICC 7th classification, there were 198 (66.0%) patients with unforeseen N2 (N2a), 36 (12.0%) with minimal/single station N2 (N2b), 41 (13.7%) with selectively centrally located N2 (N2c) and 25 (8.3%) with bulky and/or multilevel N2 (N2d). After surgery, 70 (23.3%) patients were treated with adjuvant tyrosine-kinase inhibitors (TKIs), while other 230 (76.7%) were free from adjuvant TKIs. With median follow-up of 28.5 (range:6-133) months, the 2-year LRFS, distant metastasis-free survival (DMFS), disease-free survival (DFS) and overall survival (OS) were 88.3%, 65.3%, 57.7% and 89.7%. Ultimately, 15.7% (47/300) patients developed locoregional recurrences. Distant metastasis was the predominant failure pattern. Multivariate analysis indicated that N2d disease (HR: 2.65, p=0.030) and extranodal extension (HR: 3.48, p<0.001) were risk factors of LRFS.

      8eea62084ca7e541d918e823422bd82e Conclusion

      R0 resected stage III-pN2 NSCLC patients with sensitive EGFR mutation (exon 19 or exon 21) tended to present limited N2 disease and low locoregional recurrences. Patients without bulky N2, multilevel N2, and extranodal extension might be refrained from PORT. Further studies evaluating the optimal radiotherapy approach for completely resected N2-positive NSCLC are required for validation.

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      P1.15-18 - The Impact of Patient Age on Clinical Outcomes in NSCLC: A National Study

      16:45 - 18:00  |  Presenting Author(s): Yanyan Lou  |  Author(s): Rami Manochakian, Jordan Cochuyt, David Hodge, Sikander Ailawadhi

      • Abstract

      Background

      Treatment of NSCLC is rapidly advancing. Clinical outcomes and treatment modalities for patients in each age group remain unknown. This study investigates the treatment modalities in each age group and the impact of patients’ age on survival.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      The National Cancer Database with NSCLC between 2004-2014 was used. Overall survival (OS) and treatments were analyzed by age groups, accounting for multivariates.

      4c3880bb027f159e801041b1021e88e8 Result

      A total of 2,327,158 NSCLC patients were included. Median OS is 114.6, 76.7, 52.6 and 33 months for stage I lung cancer patients at age <60, 60-69, 70-79 and ≥ 80 respectively (p<0.0001). Median OS is 7, 5.9, 4.6 and 3.3 months for stage IV patients at age <60, 60-69, 70-79 and ≥ 80 respectively (p<0.0001). The impact of age on survival is cross all stages. Younger patients are associated with larger tumor size and higher percentage of stage V at time of diagnosis. Patients with age ≥ 80 are associated with high income, high education and pacific region. Despite comparable comorbidity, patients with age ≥ 80 are treated differently and received much less aggressive therapy at each stage (p<0.0001).

      8eea62084ca7e541d918e823422bd82e Conclusion

      The overall survival of NSCLC is significantly impacted by patient’s age. Under-treatment in elderly patients might contribute to poor survival.

      figure 1.jpg

      final tabel 1.jpg

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      P1.15-19 - Treatment of Choice for First-Line Therapy of EGFR-Mutated Stage IIIB Lung Adenocarcinoma Based on the Real World Data

      16:45 - 18:00  |  Presenting Author(s): Shun Lu  |  Author(s): Xiangyun Ye, Ding Ding, Ziming Li, Xiaomin Niu, Gu Linping

      • Abstract

      Background

      There is a lack of consensus on the choice of first-line therapy for stage IIIB EGFR-mutated lung adenocarcinoma.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      A prospectively maintained database at the Shanghai Chest Hospital was used to identify patients who received therapy for stage IIIB EGFR-mutated lung adenocarcinoma between 2015 and 2017. Clinicopathological data were extracted from the database and analyzed. Patients were stratified into four groups based on the therapy they received; chemotherapy alone, chemoradiation (concurrent or sequential), first-generation EGFR-TKI, or surgical resection with or without chemoradiation. Log-rank test and Kaplan-Meier method were used to determine significant differences in the progression free survival (PFS) between treatment groups

      4c3880bb027f159e801041b1021e88e8 Result

      Of the 114956 patients treated at the institution during the study period 85 (0.07%) were eligible for the study. 12 patients (14.1%) received chemotherapy, while 19 (22.4%), 30 (35.3%) and 24 (28.2%) received chemoradiation, EGFR-TKI and surgery respectively. The common mutations included Del19 (N=35, 41.18%), L858R (N=42, 49.41%), G719X (N=4, 4.71%) and S768I (N=2, 2.35%).

      The median PFS was shorter in patients who only received chemotherapy (8.5 months) as compared to those managed with chemoradiation (14.6 months), EGFR-TKI (16.2 months) or resection (18.6 months) (p=0.04,figure 1b). No statistically significant difference was observed in PFS between EGFR-TKI and chemoradiation (p=0.86), or EGFT-TKI and resection (p=0.90). A subgroup analysis of patients with N3 disease resulted in similar findings (figure1c).

      20180504143009.jpg

      8eea62084ca7e541d918e823422bd82e Conclusion

      In conclusion, when used as a first-line therapy chemoradiation, EGFR-TKI and resection with or without chemoradiation can achieve similar PFS, which is superior to that of patients receiving chemotherapy alone. Further studies are required to elucidate the efficacy of EGFR-TKI as a first-line or as maintenance therapy for these patients.

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      P1.15-20 - Diagnosis and Treatment Delay Among Patients with Lung Cancer in Mexican Population

      16:45 - 18:00  |  Presenting Author(s): Omar Macedo-Pérez  |  Author(s): Fernando Talavera-Caro, Iván Lyra-González, Katya Campos-Peralta, Nora Sobrevilla-Moreno, Miguel Angel Alvarez-Avitia, Edgardo Jiménez-Fuentes

      • Abstract

      Background

      In Mexico, lung cancer is the seventh in incidence and first in mortality. Diagnosis in advanced stages accounts >70% of cases. We analyze factors associated with a late diagnosis and delay in the beginning of treatment.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Observational, cross-sectional study carried-out from August to October 2017 in the National Cancer Institute of Mexico (INCan). An interview was conducted to identify: 1) onset of symptoms, 2) time elapsed to seek medical attention, 3) number of doctors visited, 4) diagnosis established prior to cancer diagnosis pulmonary, 5) time elapsed from diagnosis of cancer until admission to INCan and 6) Time elapsed from diagnosis to start treatment.

      4c3880bb027f159e801041b1021e88e8 Result

      414 patients included and main characteristics are included in the next table

      Mean age 64 years (±12.98)
      Genre 58% females
      Histology

      Adenocarcinoma - 74.6%

      Epidermoid - 9.7%

      Other – 15.7%
      Clinical Stage

      I - 5.5%

      II - 3.7%

      III - 16.2%

      IV - 74.6%
      Physicians/Clinical Assessments Before Diagnosis

      1 physician – 25%

      2 physicians – 22.9%

      ≥3 physicians – 33.1%
      Risk factor

      Smoker – 44.7%

      Wood smoke – 32%

      Asbestos – 6%

      Passive smoker – 6%

      Median time from beginning of symptoms to start of oncologic treatment are shown in the next image

      image1.2.tif

      8eea62084ca7e541d918e823422bd82e Conclusion

      In Mexico, lung cancer is diagnosed in advanced stages due to a lack of clinical suspicion in primary care physicians. Delay from initial medical assessment to specialized center referral is considered an opportunity window. Identification of these factors will lead to establishment of public health policies that ensures improvement of diagnostic approach and the timely reference and initiation of treatment in specialized centers to improve the prognosis.

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      P1.15-21 - Creating an Optimal Care Coordination Model to Improve Multidisciplinary Care for Lung Cancer Patients on Medicaid

      16:45 - 18:00  |  Presenting Author(s): Amanda Kramar  |  Author(s): Amy M Marbaugh, Thomas Asfeldt, Randall A Oyer, Christopher S Lathan, Matthew P Smeltzer, Vikki G Nolan, Meredith A Ray, Nicholas R. Faris, Mary Catherine Nalan, Walter I Stevens, Lorna Lucas, Raymond U. Osarogiagbon

      • Abstract

      Background

      The Association of Community Cancer Centers (ACCC) created an Optimal Care Coordination Model (OCCM), which provides a comprehensive self-assessment tool designed to orient cancer programs to achieving patient-centered, multidisciplinary care. The OCCM is designed to help cancer programs, regardless of resources, location, or population, improve care for lung cancer patients, especially those on Medicaid.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Using findings from an environmental scan (April 2016) and visits to 5 US cancer programs to explore current care models (July-October 2016), a Technical Expert Panel developed the OCCM, which has 13 defined Assessment Areas and utilizes an evaluation matrix (Table 1).

      To validate the OCCM, a competitive application process among ACCC’s membership used a comprehensive institutional quantitative and qualitative questionnaire. Applicants completed a self-assessment using the OCCM and then developed quality improvement projects designed to move their OCCM-scored care delivery performance from baseline to a higher level over a 12-month implementation period. Seven US community cancer centers were selected as Testing Sites. Quantifiable outcome measures were identified for each site, standardized across sites, and collected by a centralized data coordinating center.

      Table 1

      OCCM Assessment Areas

      1. Patient Access to Care

      8. Survivorship Care

      2. Prospective Multidisciplinary Case Planning

      9. Supportive Care

      3. Financial, Transportation, and Housing

      10. Tobacco Cessation

      4. Management of Comorbid Conditions

      11. Clinical Trials

      5. Care Coordination

      12. Physician Engagement

      6. Treatment Team Integration

      13. Quality Measurement and Improvement

      7. Electronic Health Records and Patient Access to Information

      Level 1:

      Optimal care coordination for lung cancer care has a low priority as evidenced by fragmented care.

      Level 2:

      Early progress in coordinating care is underway.

      Level 3:

      Reflects average or typical care coordination.

      Level 4:

      Exceeds the average and reflects a cancer program’s ongoing commitment to the pursuit of optimal care coordination.

      Level 5:

      Defined by optimal care coordination with a patient-centered focus. Depending on the assessment area, achieving Level 5 performance will require significant time, effort, and resources.

      Patient Focus:

      Optimal care coordination must be patient-centered, which requires understanding of what is important to patients and their caregivers, including their knowledge, goals, needs, desires, social connections, and resources for care. This requires the cancer program to educate and engage patients and caregivers to facilitate shared decision-making and patients’ participation in their care.

      Quality Measures and Metrics:

      Each assessment area requires at least one measurable parameter. Optimal care coordination requires analysis and development of an action plan for continuous improvement. These parameters should include both evidence-based and institution-specific benchmarks that address patient outcomes, patient experience, and cost effectiveness. These measures and metrics should be continuously measured and fed back to key institutional stakeholders for ongoing quality improvement.

      4c3880bb027f159e801041b1021e88e8 Result

      Table 2 shows Assessment Areas being validated and patient demographics.

      Table 2

      Site 1

      Site 2

      Site 3

      Site 4

      Site 5

      Site 6

      Site 7

      TOTAL

      Project # 1 Selected Assessment Area(s)

      #2

      #7

      #10

      #2

      #1

      #5 & #9

      #1

      Project # 2 Selected Assessment Area

      #8

      #11

      n/a

      #10

      n/a

      n/a

      #2

      8 of 13 Assessment Areas being validated

      N=50

      N=29

      N=77

      N=53

      N=76

      N=101

      N=35

      N=421

      Age

      Median

      (IQR)

      70

      (57-76)

      74

      (63-76)

      71

      (57-76)

      65

      (60-71)

      68

      (61-75)

      61

      (55-65)

      66

      (60-73)

      68

      (61-74)

      n (%)

      n (%)

      n (%)

      n (%)

      n (%)

      n (%)

      n (%)

      n (%)

      Sex

      Male

      29 (58)

      14 (48)

      40 (52)

      27 (51)

      49 (64)

      48 (48)

      18 (51)

      225 (53)

      Female

      21 (42)

      15 (52)

      37 (48)

      26 (49)

      27 (36)

      52 (51)

      17 (49)

      195 (46)

      Race

      Caucasian

      46 (92)

      23 (79)

      76 (99)

      51 (96)

      73 (96)

      47 (47)

      27 (77)

      343 (81)

      African American

      4 (8)

      1 (3)

      2 (4)

      5 (5)

      6 (17)

      18 (4)

      Asian

      4 (14)

      8 (8)

      12 (3)

      Other/

      Unknown

      1(1)

      1 (1)

      8(8)

      2 (6)

      12 (3)

      Not reported

      1 (3)

      2 (3)

      29 (29)

      32 (8)

      Insurance

      Commercial

      7 (14)

      7 (24)

      13 (17)

      8 (15)

      29 (38)

      8 (8)

      9 (26)

      81 (19)

      Medicare

      38 (76)

      20 (69)

      55 (71)

      37 (70)

      40 (53)

      28 (28)

      21 (60)

      239 (57)

      Medicaid

      4 (8)

      2 (7)

      6 (8)

      8 (15)

      6 (8)

      63 (62)

      4 (11)

      93 (22)

      None/Self-Pay

      2 (3)

      1 (1)

      3 (1)

      Smoking Status

      Active Smoker

      14 (28)

      10 (34)

      27 (35)

      17 (32)

      38 (50)

      34 (34)

      11 (31)

      151 (36)

      Former Smoker

      20 (40)

      15 (52)

      44 (57)

      34 (64)

      28 (37)

      51 (50)

      23 (66)

      215 (51)

      Never Smoker

      7 (14)

      3 (10)

      2 (3)

      2 (4)

      7 (9)

      9 (9)

      30 (7)

      Not reported

      2 (3)

      1 (1)

      3 (1)

      Stage at Diagnosis

      Stage 0

      2 (3)

      2 (<1)

      Stage I

      9 (18)

      4 (14)

      21 (27)

      1 (2)

      9 (12)

      9 (9)

      2 (6)

      55 (13)

      Stage II

      1 (2)

      2 (7)

      10 (13)

      5 (9)

      3 (4)

      7 (7)

      28 (7)

      Stage III

      6 (12)

      5 (17)

      11 (14)

      3 (6)

      4 (5)

      13 (13)

      2 (6)

      44 (10)

      Stage IV

      6 (12)

      3 (10)

      8 (10)

      14 (26)

      13 (17)

      18 (18)

      4 (11)

      66 (16)

      Not reported/ Missing

      28 (56)

      15 (52)

      25 (32)

      30 (57)

      47 (62)

      54 (53)

      27 (77)

      226 (54)

      *Percentages may not add to 100 due to missing data

      8eea62084ca7e541d918e823422bd82e Conclusion

      Project implementation and patient accrual are ongoing at all Testing Sites through September 2018.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      P1.15-22 - Patterns of Palliative and Psychosocial Care in Stage IV Non-Small Cell Lung Cancer (NSCLC) Patients

      16:45 - 18:00  |  Presenting Author(s): Tahir Mehmood

      • Abstract

      Background

      The primary goals of management of stage IV NSCLC patients are palliation of symptoms and maintenance of quality of life. Patients need adequate access to specialist palliative care (PC) and psychosocial care (PSC) in order to achieve these goals. The aims of this study were to evaluate referrals to PC and PSC services with Stage IV NSCLC and identify factors associated with utilization of these services.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Research findings of >150 published, peer-reviewed research articles including quantitative and qualitative studies of stage IV NSCLC patients and their families, were summarized around the realities of living with disease. 13 surveys of ~8,000 stage IV NSCLC patients were examined for common concerns. Modified Poisson regression was used to analyze significant factors associated with referrals to PC and PSC. Cox regression was used for multivariate survival analysis.

      4c3880bb027f159e801041b1021e88e8 Result

      A total of 923 patients were identified. The median age was 69 years, 63% were male. Active treatment was received by 65% of patients with 34% receiving chemotherapy and 65% receiving radiotherapy. Eighty-three percent of patients were referred to PC, with 67% occurring within 8 weeks of diagnosis. Eighty-two percent of patients were referred to PSC, with referrals to social workers being most frequent (76%) followed by specialist nursing (26%) and psychology/psychiatry (16%). On multivariate analysis, radiotherapy treatment, M1b disease and residential location were associated with PC referrals, and radiotherapy treatment, PC referral and residential location were associated with PSC referrals. Age, language spoken, country of birth, socioeconomic status, year of diagnosis and multidisciplinary team discussion were not significant factors in referral to either service. The median overall survival was 4.3 months and one year survival was 19%. On multivariate analysis, factors associated with improved survival were active treatment, chemotherapy and multidisciplinary team discussion.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Rates of referral to PC and PSC services were high in this cohort suggesting good access to care. Greater referrals were particularly associated with patients undergoing radiotherapy. There were no sociodemographic barriers to referral. Some geographic differences were noted in referrals to both services. Further investigation into referral gaps will guide service delivery to improve quality of life and care for future patients.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      P1.15-23 - Factors Affecting Treatment in Non-Small Cell Lung Cancer Patients

      16:45 - 18:00  |  Presenting Author(s): Phuong T Ngo  |  Author(s): Christina Pinkston, Danh C Pham, Goetz H Kloecker

      • Abstract

      Background

      Lung cancer continues to be the leading cause of cancer deaths with Kentucky having the highest incidence of lung cancer. Despite advances in treatment and subsequent survival improvements, a significant number of non-small cell lung cancer (NSCLC) patients remain untreated. Factors such as age, stage at diagnosis and insurance status appear to play an important role in this disparity.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      In the Kentucky LEADS Collaborative, 27 of 31 (81%) Kentucky hospital registries provided all NSCLC data from 2012-2015. Variables collected included hospital accreditation by the Commission on Cancer (CoC), patient age at diagnosis, stage, race, number of comorbidities, insurance status, and overall survival (OS). Treatment included combinations of surgery, radiation, chemotherapy or immunotherapy. Hospital records were matched to the Kentucky Cancer (KCR) records and analyzed with a logistic regression model along with additional post-hoc analysis.

      4c3880bb027f159e801041b1021e88e8 Result

      Of the 13,975 patients diagnosed with NSCLC, 10,367 (74.2%) were treated leaving 3,608 (25.8%) untreated. Overall survival reported as person-days was significantly longer for the treated versus untreated patients (593 days vs 161 days). Neither race nor gender showed statistical significance while age at the time of diagnosis was significant with the untreated patients being diagnosed at a mean age of 72 and the treated patients at a mean age of 66 (p=<0.001). The mean average of comorbidities reported was 4.1 for treated patients and 4.4 for untreated patients though the specific comorbidities were not discernable. Treatment versus lack of treatment was also significantly associated with stage at the time of diagnosis with 87.9% vs 12.1% for stage I, 88.2% vs 11.8% for stage II, 73.9% vs 26.1% for stage III, and 64.2% vs 35.8% in stage IV; untreated patients tended to present at a later stage than those who received treatment with OR 2.91 (95% CI 2.57-3.28) for stage III and OR 4.28 (95% CI 4.29-5.41) for stage IV. Lastly, insurance proved to be an important factor with untreated patients more likely to have Medicaid, Medicare or be uninsured.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Treatment for lung cancer is correlated with improved outcomes and yet a large number of patients are still untreated. We aimed to assess these barriers to treatment and found untreated patients were more likely to be older, diagnosed at a later stage, and not have private insurance. While therapies are constantly changing and improving, it is important to factor in the many barriers that still exist in preventing patients from being treated.

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      P1.15-24 - Small Cell Lung Cancer: Clinical Characteristics and Survival of a Spanish Cohort of 221 Patients

      16:45 - 18:00  |  Presenting Author(s): Virginia Calvo  |  Author(s): Beatriz Núñez, Raquel Gómez, Juan Cristobal Sánchez, Blanca De La Puente, Cristina Alfaro, Laura Núñez, Mariola Blanco, Isabel Curto, Maria Soriano, Miriam Méndez, Ana María Morito, Fabio Franco, Mariano Provencio

      • Abstract

      Background

      Lung cancer is the leading cause of death from cancer, of which 15% corresponds with small cell lung cancer (SCLC) subtype, directly related with tobacco. SCLC is the most aggressive subtype with an elevated percentage of metastatic patients at diagnosis and a poor prognosis.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      A cohort of 221 patients diagnosed of SCLC were retrospectively analyzed in our center between 2008-2016.

      Patient data was analyzed for baseline demographics and stage at diagnosis.

      Progression free survival (PFS) and overall survival (OS) analysis were made comparing SCLC stage at diagnosis.

      4c3880bb027f159e801041b1021e88e8 Result

      The median age at diagnosis was 64 years and 74% were male, of whom 33% were older than 70 years. Only 0.5 % were never smokers and 16% had history of other malignancies, mostly related with tobacco. At diagnosis, 67% were metastatic and 88% symptomatic.

      Complete baseline characteristics shown at Table 1.

      PFS was 13.5 versus 6.83 months in located versus metastatic disease (p = 0.000) and median OS was 21.2 versus 8.5 months comparing located and metastatic stage (p = 0.000).

      Kaplan-Meier curves shown at Image 1.

      Table 1. Complete baseline characteristics.
      BASELINE CHARACTERISTICS ALL PATIENTS (n=221)
      SEX 164 (74%) male; 57 (26%) female
      AGE AT DIAGNOSIS 64 years (IQR 58-71); 65 years (IQR 59-73) male; 61 years (IQR 55-68) female.
      PATIENTS OLDER THAN 70 YEARS 72 (33%); 60 males and 12 females
      SMOKING HABIT

      Smoker --> 137 (61.9%)

      Former smoker --> (> 365 days without smoking) à 81 (36.65%)

      Never smoker --> 1 (0.45%)

      Unknown --> 2 (0.9%)
      SMOKING PACK YEAR 58 pack/year; 60 pack/year male and 50 pack/year female

      AGE AT THE BEGINNING OF TOBACCO HABIT

      16 years
      STAGE

      Stage I --> 10 (5%)

      Stage II --> 8 (4%)

      Stage III --> 53 (24%)

      Stage IV --> 150 (67%)

      ECOG

      0-1--> 191 (86.4%)

      2--> 23 (10.4%)

      3--> 7 (3.2%)

      CARDIOPULMONARY DISEASE

      COPD 23%

      HBP 47%

      DM 25%

      DL 43%

      Cardiopathy 19%
      HISTORY OF OTHER MALIGNANCIES 16%, most frequent: bladder cancer 7 (20.6%); head and neck cancer 6 (17.7%); lung cancer 4 (11.8%)
      FAMILIAR HISTORY OF LUNG CANCER 39%
      SYMPTOMS AT DIAGNOSIS Cough 42%; weight loss 30%; pain 28%; dyspnoea 27%; asthenia 21%
      TREATMENT

      8.2% palliative treatment

      91.8% active treatment (98.8% standard treatment with platinum-based chemotherapy and 1.2% clinical trial)
      PROGRESSION FREE SURVIVAL

      13.5 (IQR 7.4-40.8) months in located and 6.8 (IQR 4.8-10.2) in metastatic disease compared with (p = 0.000)

      OVERALL SURVIVAL

      21.2 (IQR 10.8-39.6) months in located and 8.5 (IQR 3.9-15.5) in metastatic disease with (p = 0.000)

      12 AND 24-MONTHS OVERALL SURVIVAL

      Located: 73% and 42% respectively

      Metastatic: 33% and 15% respectively

      overall survival.png

      8eea62084ca7e541d918e823422bd82e Conclusion

      SCLC is mostly diagnosed at metastatic stage, but even in located disease prognosis is poor, so investigation is needed to improve PFS and OS.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      P1.15-25 - Has Lung Cancer Radiotherapy Utilisation Changed over Time in New South Wales, Australia?

      16:45 - 18:00  |  Presenting Author(s): Shalini K Vinod  |  Author(s): Andrew Oar, Gabriel Gabriel, Jesmin Shafiq, Michael Barton, Geoff Delaney

      • Abstract

      Background

      Evidence based indications suggest that 73% of all Australian lung cancer patients would benefit from radiotherapy at diagnosis. In 2001-2002, the radiotherapy utilisation (RTU) rate in NSW for lung cancer was 39%. Since then a number of new radiation oncology centres have opened and the number of linear accelerators increasing from 29 to 46. There has also been an increase in the number of lung cancer multidisciplinary teams. We aimed to evaluate whether there had been any change in RTU for lung cancer in NSW from 2001-2002 to 2009-2011.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      All patients diagnosed with lung cancer in NSW between 1/1/2009 and 31/12/2011 were identified from the NSW Central Cancer Registry (NSWCCR). Data linkage with the Admitted Patients Data Collection, Retrospective Radiotherapy Data and Clinical Cancer Registry was performed to ascertain radiotherapy treatment within 1 year of diagnosis. Patients with non-lung cancer pathologies and those who lived closer to interstate radiotherapy centres were excluded. Patients with a clinical diagnosis of lung cancer (no pathological confirmation (NPC)) were included.

      4c3880bb027f159e801041b1021e88e8 Result

      A total of 10,712 patients were identified through NSWCCR of which 947 patients were excluded leaving 9,765 patients for analysis. The median age was 71 years and 60% were males. Histopathology was NSCLC, SCLC and NPC in 76%, 12% and 13% respectively. Stage was I&II in 12%, III in 12%, IV in 28% and unknown in 47%. The overall RTU for lung cancer was 40%. RTU was 43% for NSCLC, 56% for SCLC and 8% for NPC. RTU by stage compared to previous figures is shown in Table 1.

      Table-1 Radiotherapy utilisation rate by stage of lung cancer, NSW 2001-2002 and 2009-2011

      Histology

      Stage

      RTU N (%) (2001-2002)

      RTU (%) (2009-2011)

      NSCLC

      I

      76(26)

      201(27)

      II

      35(39)

      164(41)

      III

      170(55)

      753(72)

      IV

      258(49)

      1,497(66)

      Unknown

      17(22)

      544(18)

      Total

      556(43)

      3,159(43)

      SCLC

      I-III

      39(47)

      157(80)

      IV

      61(32)

      280(61)

      Unknown

      1(17)

      202(41)

      Total

      101(36)

      639(56)

      NPC

      I

      12(22)

      12(43)

      II

      4(33)

      3(50)

      III

      11(35)

      17(71)

      IV

      20(27)

      37(60)

      Unknown

      5(8)

      25(2)

      Total

      52(23)

      94(8)

      OVERALL

      Total

      709(39)

      3,892(40)

      8eea62084ca7e541d918e823422bd82e Conclusion

      Increased RTU was seen in some groups of patients including Stage III-IV NSCLC, Stage I-IV SCLC and Stage I-IV NPC. Despite an increase in resources, overall RTU for lung cancer has remained unchanged over the last decade.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      P1.15-26 - A Review of Colombian National Administrative Cancer Registry (NACR) Data to Evaluate Healthcare Delivery and Biologics Use

      16:45 - 18:00  |  Presenting Author(s): Brian Anthony Pico  |  Author(s): Robert Hsu, Jaime Gonzalez Diaz, Lizbeth Acuna Merchan, Gilberto de Lima Lopes

      • Abstract

      Background

      The Office of High Cost of the Colombian Health Ministry created the National Administrative Cancer Registry (NACR) data first in 2015 to provide comprehensive cancer data to improve cancer outcomes while serving as a model for other resource-limited countries. Despite new targeted therapies throughout the world, the benefits of these therapies have not reciprocated in lower resource settings, notably in Latin America. The purpose of this study is to investigate aspects of the NACR data that underscore some of the health care limitations of lung cancer treatment in Colombia.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We obtained National Administrative Cancer Registry (NACR) data from the High-Cost Diseases Office (Cuenta de Alto Costo [CAC]) collected in 2015 and released in 2016. All cancer cases diagnosed in the country are reported by payers and providers otherwise there are no payments for services rendered, assuring that the registry is representative. We use descriptive statistics for presentation of data and comparisons.

      4c3880bb027f159e801041b1021e88e8 Result

      A total of 3,082 patients were analyzed of which 2,043 (66.29%) had contributive insurance, 820 (26.60%) had subsidized insurance, and 98 (3.18%) had special or exempt insurance. Four patients (0.12%) had no insurance. Of newly diagnosed patients, the median number of days from suspicion to diagnosis was 27 days (IQR = 12-45 days, n = 491) with the predominant range of patients with contributive insurance being 30-59 days, and for subsidized insurance being 15-29 days. The median number of days from diagnosis to first treatment was 31 days (IQR=14-62, n=346) with the predominant range for patients with both contributive and subsidized insurance being 30-59 days. There was a greater percentage of Stage IV cancers in patients with subsidized (34%) than contributive (23%) insurance. Of those receiving chemotherapy (n=275), 52% received carboplatin, 28.3% received pemetrexed, 27.6% received cisplatin, 25.4% received paclitaxel, 10.9% received bevacizumab, and 5.1% received erlotinib; no patients received nivolumab or pembrolizumab.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Based on findings from NACR, the wait time from suspicion to treatment took nearly two months underscoring the need for better streamline of lung cancer care. Also, data shows a low percentage of use of newer therapies, including EGFR-targeted agents despite a high prevalence of mutations, which are present in around a quarter of patients in Colombia (Raez, 2017). Colombia can strongly benefit from increased access to molecular testing and biologics given the future direction of lung cancer therapy.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      P1.15-27 - Patient Characteristics, Treatment Patterns and Survival for Unresectable Stage III NSCLC in Ontario, Canada.

      16:45 - 18:00  |  Presenting Author(s): Soo Jin Seung  |  Author(s): Manjusha Hurry, Ryan N. Walton, William Kenneth Evans

      • Abstract

      Background

      In anticipation of new treatment strategies for unresectable stage III NSCLC, we undertook a retrospective study to determine how these patients have been managed in Ontario, Canada and their survival by treatment approach.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Individuals diagnosed with stage III NSCLC between April 1, 2010 and March 31, 2015 were identified in the Ontario Cancer Registry (OCR). Patients with stage III disease were considered to be unresectable if no surgery was undertaken within 3 months of diagnosis. Initial treatments included: radiation (classified as curative or palliative based on treatment intent, body region, dose/fraction, number of fractions); chemotherapy categorized as single or doublet IV chemotherapy, single chemo+RT, doublet chemo+RT, oral targeted therapy. Concurrent chemo+RT (cCRT) was defined as an overlap between chemotherapy and RT, while sequential chemo+RT (sCRT) had no overlap and a 30-day window between treatments. Survival was calculated from date of diagnosis to death.

      4c3880bb027f159e801041b1021e88e8 Result

      24,729 individuals were diagnosed with NSCLC in Ontario during the study period; 5,243 (21.2%) were stage III and 4,542 (18.4%) were stage III unresectable. Mean age of the unresectable group was 69.7±10.3 years; 54.2% were male. 64.2% of patients were treated within 3 months of diagnosis. The frequency of treatment approach was: cCRT (21.6%), palliative RT (21.3%), curative RT (20.2%), no treatment (19.6%), chemotherapy (11.6%), sCRT (4.9%) and targeted therapy (0.7%). Median survival (IQR) was 2.9 yrs (1.7-4.8) for targeted therapy, 2.0 yrs (1.0-5.5) for cCRT, 1.4 yrs (0.7-3.4) for curative RT, 1.4 yrs (0.7-3.1) for chemotherapy, 1.2 yr (0.6-2.9) for sCRT, 0.6 yrs (0.3-1.2) for palliative RT and 0.5 yrs (0.2-1.2) for no treatment (Figure 1).

      Figure 1. Kaplan-Meier survival curves for stage III unresectable lung cancer patients based on treatment type.

      stage iii survival curve.jpg

      8eea62084ca7e541d918e823422bd82e Conclusion

      Although cCRT is generally considered standard of care for stage III unresectable NSCLC, patients in Ontario receive various treatment approaches. Survival outcomes vary widely.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      P1.15-28 - Real World Treatment Patterns and Survival of Stage IV Non-Small Cell Lung Cancer (NSCLC) in Ontario, Canada.

      16:45 - 18:00  |  Presenting Author(s): Soo Jin Seung  |  Author(s): Manjusha Hurry, Ryan N. Walton, William Kenneth Evans

      • Abstract

      Background

      The majority of NSCLC patients are diagnosed with stage IV disease. With the development of targeted therapies for advanced NSCLC, it has become important to understand which patients are being treated with systemic therapies and to what benefit.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We conducted a longitudinal, population-level study to determine the treatment patterns and survival in patients with stage IV NSCLC in Ontario, Canada between April 1, 2010 and March 31, 2015 from the Ontario Cancer Registry (OCR). Individuals were further identified as having non-squamous disease, and those who received an EGFR-TKI (afatinib, erlotinib, gefitinib) were assumed to be EGFR mutation-positive (EGFR+). Survival was calculated from date of diagnosis to death.

      4c3880bb027f159e801041b1021e88e8 Result

      24,729 individuals were diagnosed with NSCLC. Approximately half (12,159; 49.2%) had stage IV disease, including 10,103 with non-squamous disease, of whom 508 were categorized as EGFR+. The mean age for the stage IV non-squamous and EGFR+ cohorts were 68.7±11.0 years and 69.1±10.4 years, respectively; 49.3% and 60.8% were female, respectively. The most frequent treatments for stage IV non-squamous patients were palliative radiotherapy (RT) (46.7%) and systemic therapy (14.9%). Patients received no treatment in 26.7% of cases. 75.6% of the EGFR+ cohort received gefitinib, with the majority receiving no subsequent treatment (44.6%). Of EGFR+ patients receiving a second-line treatment, 20.1% received palliative RT and 18.7% received chemotherapy. Mean and median survival times (IQR) for the stage IV non-squamous patients were 0.9±0.0 years and 0.4 (0.2-1.0) years, respectively. Substantial variation in survival was noted by treatment (Figure 1). Mean and median survival times (IQR) for the EGFR+ cohort were 1.9±0.1 years and 1.5 (0.9-3.0) years, respectively.

      Figure 1. Kaplan-Meier survival curves for stage IV non-squamous NSCLC patients based on treatment

      stage iv survival curve.jpg

      8eea62084ca7e541d918e823422bd82e Conclusion

      Relatively few patients with stage IV non-squamous NSCLC receive any systemic therapy. Survival is generally very poor, but best in the subgroup of EGFR+ patients.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      P1.15-29 - Impact of Radiation Therapy Quality Assurance on Progression-Free and Overall Survival in Randomized Trials of Lung Cancer

      16:45 - 18:00  |  Presenting Author(s): Yu Yang Soon  |  Author(s): Aidan Tan, Ivy Ng, Teng Hwee Tan, Jeremy Chee Seong Tey

      • Abstract

      Background

      To evaluate if the estimates of treatment effect differ between randomized trials (RCTs) that reported radiation therapy quality assurance (RTQA) and RCTs, which did not report RTQA, for treatment of lung cancer (LC) [C1] using curative intent thoracic radiation therapy (TRT).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We searched MEDLINE for eligible meta-analyses (MAs) of RCTs of LC. For each trial in the selected MAs, we reviewed if RTQA was performed and extracted the hazard ratios (HR) with 95% confidence interval (CI) for progression-free (PFS) and overall survival (OS). We quantify the differences in the estimated intervention effect on PFS and OS by a ratio of HRs (rHRs): the HR for trials that performed RTQA to that of trials that did not perform or report RTQA. An rHR more than 1 would indicate a larger HR for trials that performed RTQA compared to trials that did not perform or report. We estimated a combined rHR across MAs using a random effects MA model. We performed a meta-regression analysis to adjust for potential confounders including cancer type, comparisons type, sample size and single-vs-multi center trial .

      4c3880bb027f159e801041b1021e88e8 Result

      We included six MAs that comprised of six comparisons and 50 RCTs (22 reported RTQA; 28 did not). Trials that performed RTQA showed similar intervention effect on PFS (rHR 0.96, 95% CI 0.82 to 1.12, P value (P) = 0.57, I squared (I2) = 0%) and OS (rHR 1.00, 95% CI 0.88 to 1.15, P = 0.94, I2 = 0%) compared to trials that did not perform or report RTQA, with low heterogeneity across individual MAs. There was no significant change in the summary rHRs after adjusting for potential confounders.

      8eea62084ca7e541d918e823422bd82e Conclusion

      The conduct of RTQA did not modify the estimates of intervention effects on progression-free and overall survival in randomized trials of lung cancer treated with curative intent thoracic radiation therapy.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      P1.15-30 - Survival of Patients with Advanced NSCLC Treated with First-Generation EGFR-TKIs at a Cancer Hospital in Thailand, 2011-2016

      16:45 - 18:00  |  Presenting Author(s): Sitthi Sukauichai  |  Author(s): Chokaew Tovanabutra, Sirentra Wanlikitkul, Kittisak Chomprasert

      • Abstract

      Background

      This study was to find the survival in advanced NSCLC patients treated with an EGFR-TKI in a real-life practice.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      The researcher conducted this retrospective study by review medical records in stage IIIB-IV NSCLC patients treated with first-generation EGFR-TKIs at Chonburi Cancer Hospital from January, 2011 to December, 2016 and follow up until December, 2017.

      4c3880bb027f159e801041b1021e88e8 Result

      This study enrolled 50 patients with median follow up time 16.78 months. The median age of patients was 58.5. There were female (46%), non-smoking (62%) and adenocarcinoma (90%). The patients received an EGFR-TKI by purchase by themselves (52%), reimbursement system (32%) and compassionate use (14%), additionally Eastern Cooperative Oncologic Group (ECOG) performance statuses were 0-1 (54%), 2-4 (28%) and non-available (NA) (18%).Treatment responses stratified by line of therapy and EGFR status were shown (table)

      EGFR-TKIs

      treatment

      EGFR

      mutation status

      Response to

      an EGFR-TKI

      Total

      (N)

      PR SD PD NA

      First-line (1L)+ maintenace (MN)

      (n=16+2)

      Sensitive 3 1 0 0 4
      Wild-type 0 2 0 0 2
      Unknown 4 4 2 2 12

      Second-line (2L)

      (n=18)

      Sensitive 1 3 0 0 4
      Wild-type 0 0 1 1 2
      Unknown 5 2 4 1 12

      Third-ine or more (>/=3L)

      (n=14)

      Sensitive 2 1 0 0 3
      Wild-type 0 0 1 1 2
      Unknown 1 1 5 2 9
      Total (N) 16 14 13 7 50

      The overall survivals (OS) of the patient receiving an EGFR-TKI as 1L or MN (n=18), 2L (n=18) and >/=3L (n=14) were 15.86 (95%CI, 10.26-21.46), 10.87 (95%CI, 0.00-28.29) and 20.23 (95%CI, 6.26-34.21) months (p=0.392), respectively. Regarding EGFR status, the OS of patients with EGFR sensitive mutation (n=11), wild-type (n=6) and unknown (n=33) were 30.75 (95% CI, 13.76-47.74), 7.91 (95% CI, 0.00-20.45) and 13.99 (95%CI, 9.17-18.82) months (p=0.086), respectively.

      Multivariate analysis indicated that age >/=70 years old (p=0.047) ,current or former smoking (p=0.012), ECOG performance status 2-4 or NA (p<0.001), received EGFR-TKIs by payment (p=0.033) or compassionate use (p<0.001) were the unfavorable prognostic factors for the OS.

      8eea62084ca7e541d918e823422bd82e Conclusion

      The OS of the patients harboring EGFR sensitive mutation at our hospital was comparable to those of other pivotal studies. Clearly, patients harboring EGFR wild-type had the OS much shorter than those of the sensitive mutation group. In real practice at that time, two-third of patients still have not been proved their EGFR statuses before starting an EGFR-TKI and often received it as second-line or more.

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      P1.15-31 - Survival and Patterns of Care Comparing Black and White Patients With All Stages of NSCLC: An NCDB Analysis

      16:45 - 18:00  |  Presenting Author(s): Melissa Ana Liriano Vyfhuis  |  Author(s): Søren M. Bentzen, Surbhi Grover, Charles B. Simone, Pranshu Mohindra

      • Abstract

      Background

      Race and other socioeconomic factors continue to influence survival in patients with non-small cell lung cancer (NSCLC). Recent population-based studies have paradoxically shown a survival advantage in the black population compared to white patients with stage III NSCLC. To further investigate this, we analyzed stage-wise overall survival (OS) and patterns of care in black patients as compared to white patients with NSCLC using the National Cancer Database (NCDB).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      All black and white patients within the NCDB with biopsy-proven, stages I-IV NSCLC from 2004-2013 were analyzed. Associations between demographics was assessed using c2-tests. Guideline concordant care (GCC) and non-guideline concordant care (NGCC) were defined for each stage as per NCCN guidelines. OS between the races were analyzed using the log-rank test and the multivariable Cox proportional hazards regression.

      4c3880bb027f159e801041b1021e88e8 Result

      When compared to white patients, black patients were younger at presentation (</=60years: 36.2% vs. 22.5%, p<0.001), had a lower household income (<$30,000: 37.9% vs. 11.5%, p<0.001), twice as likely to not have insurance (6.4% vs. 2.9%, p<0.001) and were diagnosed with more advanced disease (stage I: 18% vs. 24.9%, stage II: 6.1% vs. 6.9%, stage III: 25.9% vs. 23.7%, stage IV: 50% vs. 44.5%, p<0.001).

      White patients were more likely to undergo GCC in stages I-III when compared to black patients (stage I: 77% vs. 69.6%; stage II: 68.5% vs. 65.3%; stage III: 52.8% vs. 51.9%) but had a very similar incidence of GCC in stage IV (stage IV: 66.7% vs. 67.3%, p<0.001).

      Black race was associated with a 17%, 5%, and 3% increase risk of NGCC in stage I (OR: 0.835, 95% CI: 0.817-0.852, p<0.001), stage II (OR: 0.947, 95% CI: 0.916-0.978, p=0.001) and stage III (OR: 0.970, 95% CI: 0.954-0.985, p<0.001) disease, respectively, when compared to white patients in multivariate analysis (MVA). While in stage IV, being black predicted for a 4% greater receipt of appropriate treatment (OR: 1.041, 95% CI: 1.028-1.054, p<0.001).

      In the Cox MVA, race was not linked to OS in stage I or II disease, but being black predicted for a 3% lower risk of death in stage III and IV (stage III: HR: 0.973, 95% CI: 0.965-0.982, p<0.001; stage IV: HR: 0.967, 95% CI: 0.961-0.973, p<0.001).

      8eea62084ca7e541d918e823422bd82e Conclusion

      Black patients with NSCLC had similar or slightly improved OS when compared to white patients after accounting for socioeconomic demographics, staging and patterns of care. To explain this contradictory finding, further research should investigate biological differences between the two races.

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      P1.15-32 - Real World EGFR Mutation Profile from 1699 Non-Small Cell Lung Cancer Patients in Eastern China

      16:45 - 18:00  |  Presenting Author(s): Wei Wang  |  Author(s): Minhua Ye, Xiaomai Wu, Dongqing Lv, Feng-Ming Spring Kong, Haihua Yang

      • Abstract

      Background

      The EGFR mutation frequency and mutation types had significant geographic differences. The purpose of this study was to evaluate prevalence, clinical characteristic in eastern China which has not been reported.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      From March 2016 to March 2018 who were newly diagnosed or postoperative recurrence NSCLC received EGFR mutation detect were included analysis. Commercially available ARMS-PCR kits were used to detect EGFR mutations.

      4c3880bb027f159e801041b1021e88e8 Result

      A total of 1699 consecutive NSCLC patients included in our study. The median age was 64 years (range 23-91), with 892 (52.5%) were male and 807 (47.5%) male. There were 852 (50.2%) with EGFR mutations out of 1699 patients in the total population. EGFR mutations were more frequent in female (64.9%) patients than in males (36.8%). Considering the frequency of mutations according to histology, adenocarcinomas (835/1495, 55.9% ) show mutations more often than squamous carcinoma (4/142, 2.82%), other NSCLC histology (13/62, 21.0%). The rate of EGFR mutation in total was lower in biopsy specimen (246/613, 40.1%) than in surgical specimen (557/993, 56.1%) or cytology specimen(49/93, 52.69%). A total of 755 (88.6%) harboring a common EGFR mutation were identified: among the 755, the most EGFR mutation type was the point mutation L858R at 21 exon (49.5%), followed by exon 19 deletion (39.1%). Ninety-seven (11.48%) patients harboring uncommon EGFR mutation, the exon 20 INS (34.0%) was the most frequently observed mutation among the uncommon EGFR mutations. The detailed EGFR mutation type were show in table1.

      Table1. The detailed EGFR mutation type

      Mutation type

      Case number

      Percentage of all cases

      Percentage of uncommon mutation

      common mutation

      L858R

      422

      49.53%

      19-del

      333

      39.08%

      uncommon mutation

      20-Ins

      33

      3.87%

      34.0%

      L858R/T790M

      18

      2.11%

      18.6%

      G719X

      14

      1.64%

      14.4%

      L861Q

      11

      1.29%

      11.3%

      G719X/S768I

      5

      0.59%

      5.2%

      L858R+S768I

      5

      0.59%

      5.2%

      S768I

      4

      0.47%

      4.1%

      19-del/T790M

      3

      0.35%

      3.1%

      G719C

      1

      0.12%

      1.0%

      L858R/19-del

      1

      0.12%

      1.0%

      L858R/20-Ins

      1

      0.12%

      1.0%

      T790M

      1

      0.12%

      1.0%

      EGFR: Epidermal growth factor receptor.

      8eea62084ca7e541d918e823422bd82e Conclusion

      In our eastern China cohort, the most common EGFR mutation was L858R, differing from previous reported data in Asian population describing 19 deletion was the most common EGFR mutation. The frequency of EGFR mutations in biopsy specimen population was lower than both in surgical specimen and cytology specimen.

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      P1.15-33 - Real-World Data on Prognostic Factors for Overall Survival in NSCLC Patients Treated with Bevacizumab Combination Therapy

      16:45 - 18:00  |  Presenting Author(s): Shang-Gin Wu  |  Author(s): Wei-Yu Liao, Chao-Chi Ho, Jin-Yuan Shih, Chong-Jen Yu

      • Abstract

      Background

      Bevacizumab is used as combination with chemotherapy as 1st-line treatment for non-squamous cell carcinoma. In order to understand the influence of bevacizumab on different combination medication response, this study aimed to identify independent prognostic factors for overall survival (OS) of NSCLC patients receiving bevacizumab treatment in real-world practice.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We performed retrospective collected non-squamous cell carcinoma patients undergoing bevacizumab treatment and analyzed their response and overall survival to bevacizumab. Demographic data, TTF-1 stain status, EGFR mutation status, and survival data were collected. Survival data analysis were plotted by the Kaplan–Meier method and compared by the log-rank test.

      4c3880bb027f159e801041b1021e88e8 Result

      From November 2009 to October 2015, 114 non-squamous cell carcinoma patients treated with bevacizumab were enrolled for analysis. The median overall survival was 21.9 months. There were 11 patients who received continuous bevacizumab beyond disease progress of 1st-line treatment and in all treatment courses. They had longer overall survival than those (N = 103) who did not received bevacizumab in all treatment courses (p = 0.003). The patients harboring positive TTF-1 tumor also had a longer overall survival than those harboring negative TTF-1 tumors (p = 0.025). Multivariate analysis revealed that patients harboring tumor with positive staining of TTF-1 (p < 0.001) and those received bevacizfig-2(20180226).jpgumab in all treatment course (p = 0.013) had a longer median OS.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Non-squamous cell carcinoma patients receiving bevacizumab beyond 1st-line treatment failure, as all treatment course, had a longer median OS than those received bevacizumab in partial course.

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      P1.15-34 - Treatment Patterns and Outcomes of Stage III Non-Small Cell Lung Cancer (NSCLC): Real World Evidence of How our Patients Fare

      16:45 - 18:00  |  Presenting Author(s): Dimas Yusuf  |  Author(s): Ryan N. Walton, Manjusha Hurry, Winson Y Cheung

      • Abstract

      Background

      Most patients withstage III non-small cell lung cancer (NSCLC) develop metastases and succumb to their cancer. New treatment strategies, including concurrent chemo–RT (cCRT) followed by adjuvant immunotherapy, are improving outcomes, but need to be contextualized with real world data. In this study, we described population-based treatment patterns and outcomes for stage III NSCLC in a large Canadian province.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Through the provincial cancer registry, patients diagnosed with stage III NSCLC from April 1st 2010 to March 31st 2015 were identified. Using electronic medical records and administrative claims, stage III patients were merged with treatment and survival information. Patient characteristics, treatment patterns, and outcomes were analyzed.

      4c3880bb027f159e801041b1021e88e8 Result

      6,438 patients were diagnosed with NSCLC, including 1,151 (17.9%) with stage III disease. Median age at diagnosis was 70 years (22–94); 50.2% were male. The majority were stage IIIA (61.2%); the remainder was stage IIIB (36.4%) or unspecified (2.4%). Most patients received palliative RT (32.8%), supportive care until progression (24.8%), or palliative chemotherapy (14.8%) as initial treatments. Relatively few underwent cCRT (11.7%) or trimodality therapy (1.7%). Resection was performed on 14.8% of patients. Within the resected cohort, the majority (47.6%) did not receive further perioperative treatment, while others had surgery as part of trimodality (11.2%) or alongside perioperative chemotherapy (37.1%). Overall, the median OS (mOS) was 13.3 months (0–NR). Initial treatment strategy predicted outcomes (p< 0.05). Patients who underwent cCRT had mOS of 23.8 months (1.1–not reached [NR]). mOS for patients who initially received palliative chemotherapy or RT was 11.1 months (0.3–NR), and 6.2 (0–NR) with supportive care (Figure 1).

      Figure 1: Kaplan–Meier curves for stage III NSCLC stratified by treatment class

      wclc stage iii abstract figure 1.png

      8eea62084ca7e541d918e823422bd82e Conclusion

      Treatment rates for cCRT and trimodality therapy in our cohort appear lower than expected despite evidence supporting the benefits of these strategies. Use of other treatment options was associated with poorer outcomes.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      P1.15-35 - Real World Outcome of Different Administrations Endostar Combined With Chemotherapy in Driver Gene Mutation Negative Advanced NSCLC

      16:45 - 18:00  |  Presenting Author(s): Yongchang Zhang  |  Author(s): Zhongtai Wang, Chunhua Zhou, Nong Yang

      • Abstract

      Background

      To compare the efficacy and safety of different administration endostar combined with platinum-based chemotherapy with first-line treatment of driver gene mutation negative advanced NSCLC patients, and provides real-world evidence for optimum administration of endostar.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      From April 2014 to April 2017, 88 driver gene mutation negative patients who received platinum-based chemotherapy alone or combined with endostar were retrospectively enrolled in this project. All the patients were divided to three groups, including platinum-based chemotherapy alone (arm A), combined with 14 days endostar (7.5 mg/m2, d1-14, q21d, arm B) and 7 days endostar (15 mg/m2, d1-7, q21d, arm C). The primary endpoint was median overall survival (OS). The secondary endpoints were median progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). The efficacy and safety was evaluated every 2 cycles.

      4c3880bb027f159e801041b1021e88e8 Result

      Of all the 88 enrolled patients, the median OS was 20 months in endostar groups (arm B and arm C) and 10 months in chemotherapy alone group (arm A, P<0.001). The median PFS was months and 4.5 months respectively (P=0.073). The median OS was 22 months (arm B) and 14 months (arm C, P = 0.01). The median PFS was 6 months in arm B, 6.5 months in arm C, and 4.5 months in arm A. The ORR were 44.4%, 22.2% and 20.6% for arm B (P=0.046), arm C (P=0.877) and arm A respectively. The DCR were 88.9%, 77.8% and 64.7% for arm B (P=0.046), arm C (P=0.266) and arm A respectively. There is no meaningful difference in OS between arm B and arm C (P=0.111), as well as ORR (P=0.074) and DCR (P=0.234), but a meaningful difference in PFS (P=0.044). The incidence of adverse event in the three groups was 22.2%, 3.7%, and 11.6%, respectively. There was no new occurring intolerant adverse event.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Endostar plus platinum-based doublet chemotherapy can significantly improve short-term and long-term outcomes in driver gene mutation negative advanced NSCLC. The administration of 14 days endostar compared to 7 days has no significant improvement in efficacy, but results in a higher incidence of adverse events.

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      P1.15-36 - A Better Real World Practice for Pemetrexed in First-Line Treatment of Advanced Mon-Squamous Non-Small Cell Lung Cancer

      16:45 - 18:00  |  Presenting Author(s): Yongchang Zhang  |  Author(s): binjie Yan, Haiyan Yang, Nong Yang

      • Abstract

      Background

      To investigate the real world practice of first-line pemetrexed combined with different drugs in patients with advanced Non-squamous non-small cell lung cancer.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      A total number of 164 patients from February 2012 to August 2017 in Hunan Cancer Hospital in the combination of pemetrexed with cisplatin were enrolled in this study. All the patients were divided into 5 groups: PC-P (pemetrexed combined with platinum for 4 cycles and pemetrexed maintenance, arm A), PCA-PA (Pemetrexed plus platinum and bevacizumab 4cycles, pemetrexed combined with bevacizumab maintenance, arm B), PC (pemetrexed combined with platinum chemotherapy 4 cycles, arm C), PCA (pemetrexed with platinum chemotherapy, plus bevacizumab 4 cycles without maintenance, arm D), PC-EGFR TKI (pemetrexed plus platinum chemotherapy 4 cycles, and then EGFR TKI as maintenance treatment, arm E). Efficacy and safety of pemetrexed was performed in each group comparing with each major clinical data.

      4c3880bb027f159e801041b1021e88e8 Result

      According to retrospective study , the median PFS for arm A, B, C, D and E were 13 months, 12 months, 5 months, 5 months, 15.8 months respectively; the median OS was 27 month, 21 months, 15 months, 11 months and 31 months respectively. Arm A and Arm C, Arm B and Arm D achieved statistically different on PFS (p<0.05). And Arm A and Arm C, Arm B and Arm D also achieved statistical differences between OS (p<0.05). In the multivariate regression analysis of all patients, we found that the ECOG PS score may be an independent prognostic factor for death from lung cancer patients. Among all the patients, 35 (21.4%) patients presented with non-hematologic serious adverse event (grade 3 and 4). There was no new occurring intolerant adverse event comparing with other clinical trials.

      8eea62084ca7e541d918e823422bd82e Conclusion

      In this real world study, pemetrexed proved to be high efficacy and well tolerant in advanced NSCLC. The efficiency of maintenance pemetrexed treatment group achieved significantly better outcome than the non-maintenance treatment group. In addition, ECOG PS score may be an independent prognostic factor for the death of patients in lung cancer. There was no new occurring intolerant adverse event comparing with previous clinical trials, the main adverse events in this study were also focused on non-hematologic toxicity. This is consistent with clinical trials.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      P1.15-36a - Assessment of Depression Among Advanced Stage Lung Cancer Patients in Developing Country

      16:45 - 18:00  |  Presenting Author(s): Guru Sharan Sah  |  Author(s): Ashok Sapkota, Jay Ram Adhikari, Jayananda Prasad Singh, Nirdesh Pokhrel

      • Abstract

      Background

      Lung cancer is most common cancer and leading cause of death in developing country. Among lung cancer patients, depression is common and has been associated with increased morbidity and mortality.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      The study was conducted in 79 patients diagnosed with advanced stage lung cancer attending medical oncology department of B. P. Koirala Memorial Cancer Hospital, Nepal. A set of questionnaire was used to interview and collect the data. Beck’s Depression Inventory (BDI-II) and its Nepali translated transcript was used to assess the depressive symptoms of patient. Based on score, depression was classified as Minimal depression, Mild Depression, Moderate Depression and Severe Depression. Verbal consent was taken before each interview to address the rights of the patient.

      4c3880bb027f159e801041b1021e88e8 Result

      This study revealed lung cancer was predominant in male patients (55.7%). Patients age ranged from 42 years to 81 years with mean age 65.59 years. Among all the patients evaluated only 45/79 (57%) patients were aware of their disease status. 34 patients were unknown about their diagnosis. All the patients evaluated were found to be depressed in several degrees. 11/79 (13.9 %) of the patients had minimal, 27/70 (34.2%) had mild, 12/79(32.30%) had moderate and 29/79 (36.7%) had severe forms of depression. Depression was common in both sexes. Interestingly most of patients who were explained about their disease status had moderate to severe depression but those patients who were unknown about their disease status tend to have minimal to mild depression (table 1). The association between awareness of disease status and severity of depression were statistically significant.
      img_6194.jpg

      8eea62084ca7e541d918e823422bd82e Conclusion

      The study reveals that there is high prevalence of depression among lung cancer patients in developing country. Thus all lung cancer patients need screening and appropriate management for depression also.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P1.16 - Treatment of Early Stage/Localized Disease (Not CME Accredited Session)

    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Moderators:
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      P1.16-01 - Prognostic Variables Associated with Improved Outcomes in Stage III NSCLC Patients Treated with Consolidation Pembrolizumab

      16:45 - 18:00  |  Presenting Author(s): Bilal Anouti  |  Author(s): Sandra Althouse, Greg Durm, Tim Breen, Nasser Hanna

      • Abstract

      Background

      HCRN LUN 14-179 is a phase II trial of consolidation pembrolizumab following concurrent chemoradiation for the treatment of patients with stage III NSCLC. Time to metastatic disease, PFS, and OS appear superior to historical controls of chemoradiation alone. Unfortunately, not all patients benefit from consolidation immunotherapy. We performed a univariate analysis evaluating variables associated with PFS, metastatic disease, and OS.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We conducted a retrospective analysis from patients enrolled on HCRN LUN14-179. Data collected included age, sex, stage, smoking status, PD-L1 status, >G2 vs <G1 adverse event, <G2 vs. >G3 pneumonitis, duration of pembrolizumab (<4 vs. >4 cycles), chemotherapy regimen, PS 0 vs 1, time to start pembrolizumab (<6 vs. >6 weeks from radiation), V20 (<20% vs. >20%), and total radiation dose. Univariate Cox regression was performed to determine the variables associated with 3 endpoints: time to metastatic disease/death; progression free survival; and overall survival.

      4c3880bb027f159e801041b1021e88e8 Result

      From April 2015 to December 2016, 93 patients were enrolled and 92 were included in the efficacy analysis (1 patient was ineligible). For time to metastatic disease or death, improved outcomes may be associated (p<0.1) with stage IIIA, non-squamous cell, >4 cycles of pembrolizumab, and V20< 20%. For PFS, improved outcomes (p<0.1) may be seen for females, stage IIIA, non-squamous histology, PD-L1 [-] tumors, >4 cycles of pembrolizumab, and V20< 20%. For OS, improved outcomes (p<0.1) may be seen for non-squamous histology, PD-L1 [-], >4 cycles of pembrolizumab, V20< 20%, and <G2 pneumonitis.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Non-squamous NSCLC, PD-L1 [-] tumors, and V20 <20% may be associated with prolonged time to metastatic disease or death, PFS, and OS for patients with stage III NSCLC treated with chemoradiation followed by pembrolizumab.

      Variable

      Alive without metastatic disease

      Alive without progression

      Alive

      IIIA (n=55)

      IIIB (n=37)

      69% p=0.12

      51%

      56% p=0.21

      41%

      69% p=0.13

      59%

      Non-SCCA (n=51)

      SCCA (n=41)

      69% p=0.11

      54%

      55% p=0.21

      44%

      75% p=0.16

      61%

      PD-L1 [-] (n=11)

      PD-L1 [+] (n=42)

      82% p=0.13

      57%

      64% p=0.19

      40%

      91% p=0.07

      62%

      > 4 pembro (n=77)

      < 4 pembro (n=15)

      67% p=0.01

      33%

      55% p=0.04

      27%

      75% p=0.001

      33%

      V20 < 20% (n=19)

      V20> 20% (n=59)

      79% p=0.07

      54%

      63% p=0.08

      39%

      79% p=0.15

      61%

      G < 2 pneumonitis (n=87)

      G > 3 pneumonitis (n=5)

      63% p=0.28

      40%

      51% p=0.61

      40%

      70% p=0.16

      40%

      Female (n=33)

      Male (n=59)

      67% p=0.37

      59%

      67% p=0.11

      59%

      73% p=0.51

      66%

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      P1.16-02 -  Support and Information Needs for Patients with NSCLC Receiving Concurrent Chemo-Radiotherapy: Findings from the INSIGHT Study.

      16:45 - 18:00  |  Presenting Author(s): Jackie Fenemore  |  Author(s): Grant Punnett, Janelle Yorke, Fiona Blackhall, Delyth McEntee, Marie Eaton, Hilary Neal

      • Abstract

      Background

      The curative intent pathway for patients with non-small cell lung cancer (NSCLC) is complex and burdensome. Concurrent chemotherapy and radiotherapy (chemo-radiotherapy) is used as first line treatment for inoperable stage 3 cancer,and requires the patient to attend multiple investigational procedures, separate appointments for chemotherapy and radiotherapy, intensive monitoring during treatment and multiple follow-up visits post treatment for up to 5 years to monitor late-toxicities and disease recurrence.The aims of this study are to identify the information needs of patients and their carers at key points along the treatment pathway and the preferred methods for information provision. A grant was awarded by the NLCFN to fund this patient experience, qualatative research study.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Semi-structured interviews were conducted with 15 patients, and their carer dyads where appropriate, recruited from a cancer centre in Manchester, U.K.

      4c3880bb027f159e801041b1021e88e8 Result

      Data collection is now complete with 15 patients recruited, of whom 6 were interviewed with a carer dyad. Thematic analysis is on-going and has been employed inductively to identify some of the emerging themes and key issues from the data collected. These include; preferred means of receiving information and level of information given, burden of treatment and earlier access to supportive care, information about life after treatment and the after effects of treatment, and preferred methods to access appropriate support.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Further research is needed into the on-going needs of this patient cohort and data collection so far highlights areas for consideration when providing information to this patient cohort.

      Emerging themes highlight that a specific booklet on concurrent chemo/radiotherapy would be preferred, covering all aspects of treatment, including a personalised treatment plan to include, where relevant mask wearing, the impact of side effects of treatment and how assess support. Early indications are that patients prefer a combination of verbal, written and visual information giving.

      Collaboration work to link these patients on the concurrent treatment pathway in with early supportive care is optimal.Implementation of this service as part of the Concurrent treatment pathway will commence as a pilot study in July 2018, to assess the impact of earlier intervention to manage disease burden and treatment side effects, with an aim to reduce hospital admissions.

      The evidence suggests further work is needed to improve information giving and support to these patients both pre and post treatment. Additional advice is required to support proactive management, to enhance recovery, whilst addressing the fear and anxiety patients and carers experience due to uncertain outcomes.

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      P1.16-03 - Prognostic Significance of PD-L1 in Stage II/III Non-Small Cell Lung Cancer

      16:45 - 18:00  |  Presenting Author(s): Mustafa Karaca  |  Author(s): Deniz Tural, Ahmet Özet

      • Abstract

      Background

      Prognostic significance of PD-1/PD-L1 axis expression in non-small cell lung cancer (NSCLC) remains uncertain despite being a predictive biomarker for novel immunotherapeutics. In this study, we have investigated PD-1/PD-L1 expression and its effect on disease prognosis and overall survival in stage II-III NSCLC patients.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Clinic and pathologic features of stage II and stage III NSCLC patients were retrospectively analyzed from patients’ records in this study. PD-1 and PD-L1 immunohistochemistry staining were carried out to archived tumor specimens of the eligible patients. Percentages of PD-1 positive lymphocytes, PD-L1 positive tumor cells and PD-L1 positive tumor infiltrating immune cells were evaluated and considered as positive if ≥1% of the cells displayed staining.

      4c3880bb027f159e801041b1021e88e8 Result

      Sixty-six male (89,2%) and 8 female (10,8%) of total 74 patients were eligible for the study. Thirty-three (44,6%) patients were diagnosed as stage II disease while 41 patients (55,6%) were diagnosed as stage III. PD-1 expression, PD-L1 expression in tumor cells and PD-L1 expression in tumor infiltrating immune cells were positive in 83,8% (n = 62), 45,9% (n = 34), 67,6% (n = 50) of total 74 patients, respectively.Three-year overall survival (OS) rate was calculated as 57,7%. Univariate analyses did not reveal any significant difference in 3-years OS between those with PD-1 and PD-L1 expression in tumor infiltrating immune cells and those without expression. (p = 0,413 and p = 0,099; respectively) However, 3-years OS was more favorable in those with PD-L1 expression in tumor cells than in those without PD-L1 expression (76,6% vs %41%, p = 0.031). In multivariate analyses, a positive trend was revealed in 3-years OS between those with PD-L1 expression in tumor cells and those without expression. (HR: 0,405; 95% CI: 0,153, 1,074; p = 0,069)

      8eea62084ca7e541d918e823422bd82e Conclusion

      Conclusions: In this study, better prognosis was obtained with positivity of PD-L1 in tumor cells. Therefore, it should be taking into consideration while designing adjuvant immunotherapy trials which are generally formed with stage I-III NSCLC patients, that expression of PD-1/PD-L1 pathway may have a positive prognostic effect.

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      P1.16-04 - Outcomes of Patients < 70 or ≥70 Years of Age in PACIFIC

      16:45 - 18:00  |  Presenting Author(s): Mark A Socinski  |  Author(s): Mustafa Özgüroğlu, Augusto Villegas, Davey Daniel, David Vicente, Shuji Murakami, Rina Hui, Jhanelle Elaine Gray, Keunchil Park, Mark David Vincent, Francesco Perrone, Lynne Poole, Catherine Wadsworth, Phillip A. Dennis, Scott J Antonia

      • Abstract

      Background

      In the Phase 3 PACIFIC study of durvalumab versus placebo in patients with stage III, unresectable NSCLC without progression after concurrent chemoradiotherapy (cCRT), the co-primary endpoint PFS was significantly longer with durvalumab (stratified HR 0.52, 95% CI, 0.42–0.65; P<0.0001). In a prespecified analysis, PFS benefit with durvalumab was observed regardless of a 65-year age cutoff. However, median age at NSCLC diagnosis is 70 (CA Cancer J Clin, 2014). We therefore performed subgroup analyses to explore outcomes using a 70-year age cutoff.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      PACIFIC (NCT02125461) was a Phase 3, randomized, double-blind, all-comers study of patients with WHO PS 0/1 who did not progress following ≥2 cycles of platinum-based cCRT. Patients were stratified by age, sex, and smoking history and randomized (2:1) 1–42 days after cCRT to receive durvalumab 10 mg/kg IV Q2W or placebo up to 12 months. Co-primary endpoints were PFS (BICR, RECIST v1.1) and OS (not available). Secondary endpoints included ORR, time to death/distant metastasis (TTDM), and safety. Between-treatment endpoint comparisons were performed for patients <70 and ≥70 years.

      4c3880bb027f159e801041b1021e88e8 Result

      As of Feb 13, 2017, 713 patients were randomized; 78% and 22% were <70 and ≥70 years, respectively. Baseline patient and tumor characteristics were generally well balanced across subgroups. However, patients ≥70 were more likely to be male, have PS 1, and, within the placebo arm, to be Asian. Older patients more commonly received carboplatin-based CT than younger patients. Durvalumab demonstrated PFS benefit compared with placebo, regardless if patients were <70 years (median 16.9 vs 5.6 months, HR=0.53, 95% CI: 0.42–0.67) or ≥70 years (median 12.3 vs 6.1 months, HR=0.62, 95% CI: 0.41–0.95). Durvalumab improved TTDM (<70 years: HR=0.53, 95% CI: 0.39–0.71; ≥70 years: HR=0.66, 95% CI: 0.39–1.13) and ORR (<70 years: 27.6% vs 15.4%; ≥70 years: 31.9% vs 17.6%) regardless of age. Younger patients on durvalumab received treatment longer (median total duration 45.5 vs 36.0 weeks). Regardless of treatment, older patients discontinued more due to AEs (durvalumab: 22.0% vs 13.7%; placebo: 16.1% vs 7.8%) and had more grade 5 AEs (durvalumab: 10.9% vs 2.7%; placebo: 9.1% vs. 4.5%). Among patients receiving durvalumab, older patients experienced more all-cause SAEs (42.6% vs 24.9%) and grade 3/4 AEs (41.6% vs 29.4%) but fewer AESIs (56.4% vs 67.9%) than younger patients.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Patients achieved clinical benefit with durvalumab regardless of age. Increased AEs/SAEs observed in older patients across treatments may reflect age/cCRT related morbidity.

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      P1.16-05 - Effect of Induction Chemotherapy in the PACIFIC Study

      16:45 - 18:00  |  Presenting Author(s): David R. Spigel  |  Author(s): Johan F. Vansteenkiste, Martin Reck, Heather A Wakelee, Mustafa Özgüroğlu, Davey Daniel, Augusto Villegas, David Vicente, Rina Hui, Shuji Murakami, Luis Paz-Ares, Lynne Poole, Catherine Wadsworth, Phillip A. Dennis, Scott J Antonia

      • Abstract

      Background

      The Phase 3 PACIFIC study of patients with stage III, unresectable NSCLC without progression after concurrent chemoradiotherapy (cCRT) demonstrated significantly longer PFS with durvalumab versus placebo (stratified HR 0.52; 95% CI 0.42–0.65; P<0.0001). Overall, 26% and 29% in the durvalumab and placebo groups, respectively, received induction chemotherapy (ICT) before cCRT. Here, we report exploratory analyses of baseline characteristics, disposition, and outcomes from this study based on the presence or absence of prior ICT.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      PACIFIC (NCT02125461) was a Phase 3, randomized, double-blind study of patients with WHO PS 0/1 and any tumor PD-L1 status without progression after ≥2 cycles of platinum-based cCRT. Patients were stratified by age, sex and smoking history and randomized (2:1) to durvalumab 10 mg/kg IV Q2W or placebo up to 12 months. Co-primary endpoints were PFS (blinded independent central review, RECIST v1.1) and overall survival (not available). We investigated associations between the presence/absence of ICT and disposition, baseline characteristics, and efficacy and safety endpoints.

      4c3880bb027f159e801041b1021e88e8 Result

      As of February 13, 2017, 713 patients were randomized; 27% had prior ICT. Baseline characteristics were similar between treatment arms; however, patients with ICT were generally younger, less frequently Asian, had lower incidence of squamous histology, and more often had stage IIIB disease. There were no differences between groups in terms of prior RT dose. PFS benefit with durvalumab was demonstrated irrespective of ICT use (ICT: HR=0.61, 95% CI, 0.41–0.88; no ICT: HR=0.54, 95% CI, 0.42–0.69). Similarly, ORR with durvalumab was numerically higher than with placebo irrespective of ICT use (ICT: 16.1% vs 13.1%; no ICT: 32.9% vs 17.1%). ICT did not affect treatment duration for durvalumab or placebo. Between-treatment safety differences were minimal across subgroups; however, patients with ICT experienced fewer SAEs, treatment-related SAEs and pneumonitis/radiation pneumonitis regardless of treatment arm.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Durvalumab demonstrated clinical benefit irrespective of ICT. The safety profile of durvalumab was consistent in patients with or without ICT. A lower rate of toxicity was observed in patients with ICT regardless of treatment arm.

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      P1.16-06 - Expanded Efficacy and Safety Analysis of PACIFIC Based on a PD-L1 Cutpoint of 25%

      16:45 - 18:00  |  Presenting Author(s): Alexander Spira  |  Author(s): David Planchard, Byoung Chul Cho, Mustafa Özgüroğlu, Davey Daniel, Augusto Villegas, David Vicente, Rina Hui, Shuji Murakami, Luis Paz-Ares, Anne-Marie Boothman, Lynne Poole, Catherine Wadsworth, Phillip A. Dennis, Scott J Antonia

      • Abstract

      Background

      In the Phase 3 PACIFIC study of patients with stage III, unresectable NSCLC without progression after concurrent chemoradiotherapy (cCRT), PFS was significantly longer with durvalumab versus placebo (stratified HR 0.52; 95% CI 0.42–0.65; P<0.0001). We report exploratory analyses of PACIFIC outcomes by PD-L1 expression assessed in tumor samples collected prior to cCRT.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      PACIFIC (NCT02125461) was a Phase 3, randomized, double-blind study of patients with WHO PS 0/1 without progression after ≥2 cycles of platinum-based cCRT. Eligibility was irrespective of PD-L1 expression; archived samples were optional for testing (VENTANA PD-L1 [SP263] assay). No samples were obtained after cCRT, prior to infusion with durvalumab or placebo. Patients were randomized (2:1) to durvalumab 10 mg/kg IV Q2W or placebo up to 12 months, stratified by age, sex and smoking history. Co-primary endpoints were PFS (blinded independent central review, RECIST v1.1) and OS (not available). Secondary endpoints included ORR and safety. We investigated associations between subgroups of patients with PD-L1 expression on tumor cells (TC) of <25% or ≥25% and efficacy.

      4c3880bb027f159e801041b1021e88e8 Result

      As of February 13, 2017, 713 patients were randomized; 451 (63.3%) had known PD-L1 status (TC<25%, 64.7%; TC≥25%, 35.3%; Table). Baseline characteristics and prior therapy (including best response to prior therapy) were generally well balanced between arms across both PD-L1 subgroups. PFS benefit with durvalumab was demonstrated irrespective of PD-L1 status (HR 0.59; 95% CI, 0.43–0.82 for TC<25% and HR 0.41; 95% CI, 0.26–0.65 for TC≥25%) (Table). ORR was greater with durvalumab compared to placebo regardless of PD-L1 status (Table). The overall safety profile of durvalumab in each PD-L1 subgroup was consistent with the ITT population treated with durvalumab.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Durvalumab demonstrated clinical benefit and had a well-tolerated, manageable safety profile irrespective of PD-L1 status obtained from archival tumor samples prior to cCRT.

      PD-L1 TC<25%

      PD-L1 TC≥25%

      Durvalumab (n=187)

      Placebo
      (n=105)

      Durvalumab (n=115)

      Placebo
      (n=44)

      Completed 12 months treatment, n (%)

      74 (39.6)

      35 (33.3)

      55 (47.8)

      13 (29.5)

      PFS*

      Median (95% CI), months

      16.9 (11.0–NR)

      6.9 (5.0–11.0)

      17.8 (11.1–NR)

      3.7 (2.0–13.2)

      HR (95% CI)

      0.59 (0.43–0.82)

      0.41 (0.26–0.65)

      ORR

      n=170

      n=96

      n=108

      n=40

      n (%)

      [95% CI]

      50 (29.4)

      [22.7–36.9]

      19 (19.8)

      [12.36–29.17]

      31 (28.7)

      [20.4–38.2]

      6 (15.0)

      [5.71–29.84]

      *In the overall ITT population, median PFS was 16.8 months (95% CI, 13.0–18.1) with durvalumab (n=476) vs. 5.6 months (95% CI, 4.6–7.8) with placebo (n=237), with an HR of 0.52 (95% CI, 0.42–0.65; P<0.001) (stratified log-rank); PD-L1 assessment was not required in the study; in PD-L1 unknown patients, median PFS was 14.0 months (95% CI, 9.2–NR) with durvalumab (n=174) vs. 6.4 months (95% CI, 3.8–9.0) with placebo (n=88), with an HR of 0.59 (95% CI, 0.42–0.83) (unstratified Cox proportional hazards model); ORR for n evaluable patients included unconfirmed responses. ITT, intention-to-treat; NR, not reached; ORR, objective response rate; PFS, progression-free survival.

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      P1.16-07 - Cost-Effectiveness of Pembrolizumab as 1st Line Treatment for Metastatic NSCLC Patients with High PD-L1 Expression in Singapore

      16:45 - 18:00  |  Presenting Author(s): Wan Ling Tan  |  Author(s): Min Huang, Sheenu Chandwani, Tun-Ying Hsu, Seng Chuen Tan, Daniel S.W. Tan

      • Abstract

      Background

      Pembrolizumab, an immune checkpoint inhibitor, has been approved as monotherapy for 1st line treatment of metastatic NSCLC with PD-L1 tumor proportion score (TPS) ≥50% based on the pivotal Keynote (KN)-024 study. This study aims to evaluate the cost-effectiveness of pembrolizumab compared with standard-of-care (SoC) platinum-based chemotherapy in patients with TPS≥50% from a societal perspective in Singapore based on results from KN024.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      A known partitioned-survival model was adapted to estimate progression-free survival, overall survival, costs of treatments, adverse events and disease management, and health utilities over a time horizon of 20 years. The maximum treatment duration of 2 years was applied for pembrolizumab. Clinical and resource utilization inputs were based on data from KN024 study and input from local oncologists. Unit costs captured both patients’ payments and government subsidies. Utility scores in different health states were based on EQ-5D data from KN024 with weighting indices suggested by a local quality-of-life study. An annual discount rate of 3% was applied and a series of sensitivity and scenario analyses were conducted to address uncertainty.

      4c3880bb027f159e801041b1021e88e8 Result

      For 1st line treatment for NSCLC patients with TPS≥50%, pembrolizumab monotherapy is estimated to result in 0.91 quality-adjusted-life-years (QALY) gained. The projected incremental cost for pembrolizumab is S$141,979 compared to SoC, leading to an incremental cost-effectiveness ratio (ICER) of S$155,630 per QALY gained. A similar ICER of S$156,862 is observed in a scenario analysis whereby all patients are tested for PD-L1 and those with high PD-L1 expression are treated with pembrolizumab. With a Pembrolizumab Patient Access Program (PAP), the ICER is estimated to be S$95,279 per QALY. In another scenario analysis where government subsidies and claim limits of Medishield / Medisave are considered, the estimated ICER is S$46,308 per QALY from the Ministry of Health (MOH) perspective.

      8eea62084ca7e541d918e823422bd82e Conclusion

      For NSCLC patients with TPS≥50%, the ICER in the base-case for pembrolizumab as 1st-line treatment is $155,630 – which is between 2-3x gross domestic product (GDP) per capita of Singapore (S$73,167) in 2016, whereas the estimated ICER with Pembrolizumab PAP is 1-2x GDP per capita. Depending on threshold boundaries adopted, 1st line pembrolizumab for patients with similar profile (TPS ≥50%) as those in KN024, would be a cost-effective treatment compared to SoC in Singapore.

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      P1.16-08 - Weekly Nab-Paclitaxel Plus Carboplatin as Neoadjuvant Therapy for IIIA-N2 Lung Squamous Cell Carcinoma: A Prospective Phase II Study

      16:45 - 18:00  |  Presenting Author(s): Changli Wang  |  Author(s): Yu Zhang, Jian Quan Zhu, Dongsheng Yue, Xiaoliang Zhao, qiang Zhang, Hui Chen

      • Abstract

      Background

      To evaluate the safety and antitumor activity of weekly nab-paclitaxel combined with carboplatin in patients with advanced stage IIIA-N2 NSCLC patients with squamous histology

      a9ded1e5ce5d75814730bb4caaf49419 Method

      From April 2015 to August 2017, 36 treatment-naive, pathologically diagnosed IIIA-N2 lung squamous cell carcinoma patients were enrolled and given two cycles of weekly nab-paclitaxel (100mg/m2, day1,8,15 of a 21-day cycle) plus Carboplatin (AUC = 5 at day 1, q3w) as neoadjuvant therapy. Then resectability was assessed and surgery was performed for resectable lesions. Post-operative adjuvant chemotherapy regimens is the combination of Nab-paclitaxel (100mg/m2, qw x 6) and carboplatin (AUC 5, Q3W x 2) for patients with PD, adjuvant chemotherapy regimen will be changed. The primary objective is the safety and efficacy, and the secondary objectives are quality of life and the role of prognostic biomarker SPARC.

      4c3880bb027f159e801041b1021e88e8 Result

      Of 36 patients, 3 stopped treatment due to patient decision. 33 were finally evaluated and 1 is still on treatment. Significant tumor volume shrinkage was seen in some patients after the neoadjuvant therapy. 66.7% patients achieved partial response (PR), 21.2% patients achieved stable disease (SD). Disease control (PR +SD) rate was 87.9%. Finally, 23 patients underwent surgical resection, the respectability rate was 69.7%. 12.1% occurred disease progress and failed to achieve resection, including 3 with local progress and 1 with pulmonary metastatic nodule; Among 22 PR pts, 4 failed to achieve resection, in which 1 was due to heart function, the other 3 due to personal unwillingness. 2 of 7 with stable disease failed to achieve resection; the pathological improvement in T stage and N stage before and after treatment was 81.8% (18/22) and 50% (11/22) respectively. The major adverse event was neutropenia (grade I and II) and no serious AE was found.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Nab-paclitaxel in combination with Carboplatin showed promising ORR rate and resection rate in of IIIA-N2 lung squamous cell carcinoma. The regimen could be a new chemo option as the neoadjuvant treatment. PFS and OS data will be reported after follow up completing.

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      P1.16-09 - Surgical Result of Pathologic Stage III a Non Small Cell Lung Cancer: Have We Improved?

      16:45 - 18:00  |  Presenting Author(s): Ching-Yang Wu

      • Abstract

      Background

      Non small cell lung cancer was the leading cause of cancer death worldwide. five-year survival of pathologic stage IIIa still remain poor and the management remain controversial. Many new medicines and surgical techniques were utilized as treatment for pathologic stage IIIIa patient. The aim of study was tried to analyzed the survival impact of these treatment modalities and the stage migration effect during new TNM staging classification system.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      From Jan 2005 to Jun 2014, there were 166 pathologic stage IIIa patients were enrolled into study. All patients were follow up till 2016/7. Patients were divided into two groups since year 2010 because of difference of surgical technique switch. Medical records were reviewed retrospectively and survival status were analyzed.

      4c3880bb027f159e801041b1021e88e8 Result

      From January 2005 to May 2014, 166 patients who had received tumor resection and were confirmed as pathologic stage IIIa by 7th AJCC stage classification system were included for further analysis. The 5-year disease free and overall survival rates were 24.9% and 38.2%, respectively. Patients who received neoadjuvant therapy showed inferior disease free survival compared with those without neoadjuvant therapy. ( p< 0.0001). Patients who presented as adenocarcinoma and received tumor resection showed better overall survival than non-adenocarcinoma patients. (p=0.0011) Because the operation method was shifted to video-assisted thoracoscopic surgery in the year 2010, we analyzed survival status separately before and after 2010. In addition, we found that patients who received tumor resection and were conformed as pathologic stage IIIa adenocarcinoma has had better overall survival than other subgroups. (p =0.0005) 28 patients who were identified stage migration had worse disease-free and overall survival.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Disease free survival of pathologic stage IIIa patients remain unchanged but overall survival had much improvement. Patients who presented with adenocarcinoma who received tumor resection during 2010 to 2014 has better survival. This may be related to medical improvement but further investigation was warranted. Stage migration and worse disease and overall survival for those presented as 3b in new stage classification were identified. Different treatment strategy was needed for these patients who were identified stage migration.

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      P1.16-10 - Marginal Features Analyses of Lung Adenocarcinoma for Survival Prediction

      16:45 - 18:00  |  Presenting Author(s): Geewon Lee  |  Author(s): Ho Yun Lee, Hyunjin Park

      • Abstract

      Background

      Tumor microenvironment is a complex mixture of assorted cells and extra-cellular components which make up an amazingly dynamic area that includes signaling interactions between cancer cells and their surrounding tissue. Tumor microenvironment makes up the peripheral portion of the tumor and major changes in this area has been reported to be associated with a poor prognosis. However, very few studies have investigated the tumor marginal features quantitatively extracted from CT images using a radiomics approach. We aimed to clarify the relationship between tumor marginal features and the micropapillary pattern and correlated with survival.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We enrolled 334 patients who underwent complete resection for lung adenocarcinoma. Quantitative histologic subtyping was performed for the whole tumor. Using a radiomics approach, quantitative CT analysis was performed and 82 marginal features were extracted. Clinical variables and marginal features were correlated with survival. Using selected clinical variables and marginal features a prognostic model was calculated with subsequent internal and external validation.

      4c3880bb027f159e801041b1021e88e8 Result

      Among various subtypes, solid predominant adenocarcinomas had the lowest proportion (6.9%) of combined micropapillary pattern. At univariate analysis, patient age, tumor size, and multiple marginal features (convexity, surface area, compactness, maximum 3D diameter, sphericity, surface-to-volume ratio, mean pixel value, median pixel value, entropy, uniformity, skewness, kurtosis, roundness factor, solidity, and lacunarity)were predictive of survival. At multivariate cox proportional analysis, convexity (P=0.017), kurtosis (P<0.001), and patient age (P=0.006) were identified as being predictive of survival. Ten-fold cross-validation tests demonstrated that our prediction model significantly classified patients according to survival (P<0.001). Although lower than internal validation, the prediction model also worked at external validation.figure.jpg

      8eea62084ca7e541d918e823422bd82e Conclusion

      Marginal radiomics features of convexity and kurtosis reflect the tumor microenvironment and were predictive of patient survival in lung adenocarcinomas.

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      P1.16-11 - Monitoring of Early Stage Lung Cancer Using Liquid Biopsies.

      16:45 - 18:00  |  Presenting Author(s): Alexander Dobrovic

      • Abstract

      Background

      This study aims to validate the use of chromosome rearrangements as tumour-specific biomarkers for the detection of circulating tumour DNA (ctDNA) to enable monitoring of cancer using digital PCR.We consider that rearrangements are the best source of robust disease markers that can be used for every lung cancer patient without a clear truncal mutation. The current high cost of the whole genome sequencing required for identification of chromosome rearrangements is offset by the low cost, high sensitivity and specificity of the subsequent assays.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Methods for ctDNA detection using chromosome rearrangements that leverage advances in next generation sequencing (NGS), bioinformatics and droplet digital PCR (ddPCR) have now been developed by our laboratory.

      4c3880bb027f159e801041b1021e88e8 Result

      We are using whole genome sequencing and bioinformatic analysis of lung tumour samples. The genomic sequence was aligned to the human reference genome (hg19). Rearrangements were identified using the GRIDSS algoriths. Large numebers of potential genomic rearrangements ithat could be used as a biomarker to detect ctDNA were identified in each tumour. These were used to design primers which were used to monitor the success of surgical resection and to detect early relapse.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Patients with early-stage primary tumours are the group in which appropriately timed therapeutic intervention is most likely to make a clinical difference. Our study assesses ctDNA in a large cohort of lung cancer patients with early-stage primary tumours that are being treated with the primary aim of cure. In addtion, whole genome sequencing also identifies genomic information such as rare functional rearrangements and mutational burden which can also be used in patient management.

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      P1.16-12 - Identification of a Biomarker Panel in Resected NSCLC That Predicts Patient Outcomes and Benefit from Adjuvant Chemotherapy

      16:45 - 18:00  |  Presenting Author(s): Stacy Grieve  |  Author(s): Matthew Finniss, Ayush Ray, Jonathan Moore, Alli Muragesan, Jane Agar, Cenk Acar, Tony Reiman

      • Abstract

      Background

      Adjuvant chemotherapy for resected NSCLC improves overall survival by approximately 10%. Physicians need tools to predict which patients are most likely to benefit from chemotherapy, sparing those unlikely to benefit. A 15-gene expression profile (GEP) published by Zhu et al is both prognostic and predictive of benefit from adjuvant chemotherapy. The aim of this study is to translate this GEP into a readily applicable immunohistochemistry (IHC) panel.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We constructed NSCLC tissue microarrays at the Saint John Regional Hospital and semiquantitatively assessed the IHC expression and prognostic significance of proteins encoded by 7 of the genes in the Zhu panel for which commercial antibodies were available.

      4c3880bb027f159e801041b1021e88e8 Result

      In 62 patients with resected stage II-III NSCLC, the prognostic significance of IHC assays for four proteins were concordant with the Zhu GEP results. Low FOSL2 (OS, HR = 2.6; p = 0.0231; PFS, HR = 3.3; p = 0.0052), and low ATP1B1 (PFS, HR = 2.0; p = 0.0338) were adverse prognostic factors. High STMN2 and low TRIM14 expression trended towards worse OS and PFS. Multivariate analysis verified the prognostic impact of the four assays. These markers could also be integrated as a panel with retained prognostic value (OS, HR=2.1, p=0.03).

      8eea62084ca7e541d918e823422bd82e Conclusion

      An IHC panel with results concordant to the Zhu GEP is prognostic. Ongoing studies will examine the prognostic and predictive impact of this IHC panel in larger, independent datasets. If the panel turns out to be robust and predictive, it will have potential clinical application as a tool to select patients for adjuvant chemotherapy.

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      P1.16-13 - Photo Dynamic Therapy (PDT) in Our Hospital

      16:45 - 18:00  |  Presenting Author(s): Fumihiko Hoshi  |  Author(s): Akira Sakurada, Masafumi Noda, Tetsu Sado, Yasushi Matsuda, Hisashi Oishi, Shunsuke Eba, Yoshinori Okada

      • Abstract

      Background

      Lung cancer is the leading cause of cancer death worldwide. A large part of lung cancer is diagnosed at an advanced stage, but the number of lung cancer diagnosed at an early stage are increasing due to improved diagnostic imaging techniques. In Japan, sputum cytology for mass screening provides chances to detect very early stage centrally located lung cancer which is good adaptation of PDT.

      Although PDT is less invasive therapy which enable us to treat the patients with poor pulmonary function or poor performance status. It is important to clarify the therapeutic outcome and the morbidity after PDT such as airway narrowing, pneumonia, and sunlight hypersensitivity.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We analyzed 14 patients who received PDT in Tohoku University Hospital between January 2010 and April 2017 retrospectively and evaluated the therapeutic outcome of PDT.

      4c3880bb027f159e801041b1021e88e8 Result

      14 cases were all male and the average age was 71. Nine cases were detected in cancer screening examinations and other 5 cases were detected accidentally while observing other diseases. Lung cancer existed in trachea 1, in segmental bronchi 4, in sub segmental bronchi 7, and more peripheral lesion 2. All 14 cases were pathologically squamous cell carcinoma. In 2 cases, we performed PDT twice. In 3 cases, we performed surgical resection after PDT. Within follow-up period after PDT, 5 cases developed metachronous lung cancer and were treated with surgical resection or radiation therapy. After these therapies 11 cases alive without recurrence, 1 case alive with recurrence, 1 case died from original disease, and 1 case died from other disease. Only one case suffered airway narrowing after PDT, but other 13 cases had no morbidity.

      8eea62084ca7e541d918e823422bd82e Conclusion

      We concluded PDT is a good treatment in early stage centrally located lung cancer with good outcomes and little morbidity rates.

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      P1.16-14 - Impact of Smoking on Treatment Outcome in Early Squamous Cell Lung Cancer (T1N0)

      16:45 - 18:00  |  Presenting Author(s): Junghee Lee  |  Author(s): Tae Ho Kim, Byung Jo Park, Jong Ho Cho, Hong Kwan Kim, Yong Soo Choi, Jae Ill Zo, Young Mog Shim, Jhingook Kim

      • Abstract

      Background

      Smoking is the major risk factor for squamous cell lung cancer. However, squamous cell lung cancer in never-smoker is known to have poor survival outcomes. We compared clinicopathologic features and outcomes between smokers and never-smokers in resected early squamous cell lung cancer (T1N0).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      An institutional database was reviewed retrospectively between 1994 and 2016 (N = 445). Eligible patients included completely resected squamous cell lung cancer, less than 3 cm in tumor size, and without N1 or N2 involvements. Patients were stratified by gender and smoking status.

      4c3880bb027f159e801041b1021e88e8 Result

      423 (95%) smokers and 20 (5%) never-smokers were identified. The median age of never-smokers was 66 years (range, 39 - 83), and 11 of these patients were female (55%). The median age of smokers was 66 (range, 42 - 84), and most of them were male (97.9%). The T stage were distributed equally in both groups. In smokers, 84 (19.9%) patients experienced recurrence whereas only 1 patient (5%) of never-smokers occurred distant metastasis (p < 0.001). Distant metastasis was most frequent recurrence pattern in smokers (n= 40), but locoregional recurrence also a fairly frequent pattern (n = 30). The 5-year overall survival rates and recurrence free survival rates were 70.9% and 61.5% in smokers and were 64.1% and 64.1% in never-smokers respectively (p = 0.65, and 0.34, respectively).

      8eea62084ca7e541d918e823422bd82e Conclusion

      There was no significant differences in clinicopathologic features and outcomes between smokers and never-smokers in early squamous cell lung cancer.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      P1.16-15 - Evaluation of Emphysema Severity by 3D-CT for Predicting Postoperative Respiratory Complications and Prognosis of Lung Cancer

      16:45 - 18:00  |  Presenting Author(s): Yojiro Makino  |  Author(s): Yoshihisa Shimada, Sachio Maehara, Junichi Maeda, Masatoshi Kakihana, Naohiro Kajiwara, Tatsuo Ohira, Norihiko Ikeda

      • Abstract

      Background

      Emphysema is one of the main causes of respiratory complications and perioperative mortality and morbidity in lung cancer patients. We have used 3D-CT for depicting emphysematous areas as low attenuation areas (LAAs) and visual scores based on Goddard classification (Goddard score: GS). This study aimed to investigate the effectiveness of the 3D-CT function analysis of emphysema severity and its association with respiratory complications and prognostic outcomes.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      The study included 504 patients who underwent preoperative 3D-CT for surgical simulation followed by resection for lung cancer from October 2010 to March 2015. GS and LAA% (LAA / total lung volume) were measured using 3D-CT data. We studied the relationship between the development of postoperative respiratory complications/ overall survival (OS) and independent variables including age, sex, forced expiratory volume in 1 second as percent forced vital capacity (FEV1%), histology, smoking status, surgical procedure, GS, and LAA%.

      4c3880bb027f159e801041b1021e88e8 Result

      Postoperative respiratory complications were observed in 69 patients (13.6%). These included prolonged air leakage > 7 days (n = 22), pneumonia (n = 13), bronchial fistula (n = 4), atelectasis (n = 5), pulmonary fibrosis (n = 3), empyema (n = 5), recurrent nerve paralysis (n = 2), chylothorax (n = 5), pleural effusion (n = 3) and other respiratory-related adverse events (n = 7). The ROC curves for respiratory complications determined using the GS and LAA% dichotomized at each cut-off level (1 and 0.7%, respectively) showed that the events were observed in 32% of the patients with GS ≥ 1 and in 25% of the patients with LAA% ≥ 0.7. On multivariate analyses, the GS or LAA% was significantly correlated with postoperative respiratory complications (p < 0.001 and p = 0.016, respectively). Univariate and multivariate analysis using the Cox regression model for prognosis also showed GS was significantly associated with unfavorable OS among 362 patients with pathological Stage I NSCLC patients (p = 0.039). Five-year OS rates in these patients with or without emphysema were 84.0% and 94.1%, respectively (p < 0.001).

      8eea62084ca7e541d918e823422bd82e Conclusion

      Preoperative measurement of GS and LAA% using 3D-CT in patients with lung cancer, particularly with the coexistence of emphysema, was beneficial for predicting postoperative respiratory complications and prognosis in lung cancer patients.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      P1.16-16 - Automatic Intratumor Segmentation in CT of NSCLC: An Alternative to PET Metabolic Subregions

      16:45 - 18:00  |  Presenting Author(s): Qintao Qiu  |  Author(s): Jinghao Duan, Xue Sha, Guanzhong Gong, Yong Yin

      • Abstract

      Background

      PET images provide heterogeneous metabolic information in precision radiation treatment planning and the radiation dose given to high metabolic volumes should be escalated. However, PET scanning will increase the radiation dose received by patients. The aim of this study was to evaluated the feasibility of automatic intratumor segmentation in CT of NSCLC patients based on level-set evolution and cell automaton algorithm and assess the consistency with PET metabolic subregions.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      The PET and plan-CT imaging data set of 17 patients who have diagnosed with NSCLC were randomly collected. First, the gross tumor volume (GTV) was defined using a threshold of 40% SUVmax on PET. Then, rigid registration was used to align PET images to plan-CT images and the GTV was mapped to the CT image subsequently. The subregions which describe heterogeneity of voxel gray-level intensities were then automatic segmented using an algorithm combined level-set evolution and cell automaton in GTVCT. Meanwhile, the three metabolic subregions in GTVPET were delineated using threshold interval a) 40%-60% SUVmax, b) 60%-80% SUVmax, and c) 80%-100% SUVmax. To evaluate the consistency with PET metabolic subregions, we calculated the spatial overlap by Dice’s similarity coefficient (DSC).

      4c3880bb027f159e801041b1021e88e8 Result

      wclc-figure-jpg.jpg

      In total, 21 GTV pairs acquired from CT and PET data set were used to evaluate the feasibility of method proposed in this study. The GTVCT was automatically divided into three heterogenous subregions based on its difference on grays-level intensities and regional connectivity of voxel and 63 subregions were acquired. The average DSC value calculated from subregion in CT and PET is 0.725 with interval (0.321,0.905).

      8eea62084ca7e541d918e823422bd82e Conclusion

      Our study revealed that there is a significant correlation between PET metabolic information and CT gray-level intensity. The automatic segmentation of subregion in CT images may can serve as an alternative to the metabolic region delineated in PET.

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      P1.16-17 - The Role of Quantitative Metabolic Metrics on FDG-PET/CT in Predicting Pathological Invasive Factors in cN0 Lung Adenocarcinoma

      16:45 - 18:00  |  Presenting Author(s): Takehiko Tanaka  |  Author(s): Yoshihisa Shimada, Yojiro Makino, Junichi Maeda, Masaru Hagiwara, Tetsuya Okano, Masatoshi Kakihana, Naohiro Kajiwara, Tatsuo Ohira, Jun Matsubayashi, Norihiko Ikeda

      • Abstract

      Background

      Growing evidence suggests that FDG-PET/CT has greatly contributed the preoperative investigation of early-stage lung cancer. The maximum standardized uptake values (SUVmax) of the primary lesion is widely reported to be associated with prognosis in NSCLC while other metabolic metrics, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) have been explored as a measure of metabolic tumor burden in recent years. The purpose of this study is to investigate the role of quantitative metabolic metrics in predicting the incidence of pathological invasive factors including microscopic vascular invasion, pleural invasion, and lymph node metastasis in cN0 lung adenocarcinoma.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We examined 265 patients with clinical stage 0-II(cN0) adenocarcinoma. Pre-operative PET/CT and subsequent complete resection was performed for all the patients during the period from August 2012 to July 2017. The maximum tumor and solid-part diameter on HRCT and the three metabolic metrics on PET/CT measured by the SYNAPSE VINCENT (Fujifilm Medical, Tokyo, Japan) as the volume viewer softwarewere observed. In the current study, MTV was defined as the total tumor volume with an SUV > 2.5 while TLG was calculated as meanSUV x MTV. We assessed the relationship between these parameters and the incidence of pathological invasive factors.

      4c3880bb027f159e801041b1021e88e8 Result

      Among 265 patients, 18 (7%) patients were clinically staged as 0, 205 (77%) as IA, 32 (12%) as IB, and 10 (4%) as II, respectively. Pathological vascular invasion, pleural invasion, and lymph node metastasis were found in 100 (38%), 53 (20%), and 45 (17%) patients, respectively. SUVmax, MTV, and TLG were dichotomized at cut-off level by the receiver operating characteristic (ROC) curves for pathological invasive factors (SUVmax of 4.4, MTV of 0.75mm3, and TLG of 2.6, respectively). ROC curve yielded area under the curve values of 0.812, 0.915, and 0.882 for SUVmax, MTV, and TLG, respectively. Univariate analysis showed that SUVmax (Hazard Ratio (HR), 27.185; p<0.001), MTV (HR, 24.580; p<0.001), TLG (HR, 24.580; p<0.001), maximum tumor size (HR, 2.495; p<0.001), solid-tumor size (HR, 7.830; p<0.001), c-stage (HR, 14.418; p<0.001), and sex (HR, 1.882; p=0.013) were significantly associated with the incidence of pathological invasive factors. Multivariate analysis showed that SUVmax was the independent predictor (HR, 7.006; p=0.001). The frequency of pathological invasive factors of patients with SUVmax > 4.4, MTV > 0.75mm3, and TLG > 2.6 were 82%, 84%, and 84%, respectively.

      8eea62084ca7e541d918e823422bd82e Conclusion

      In cN0 early-stage lung adenocarcinoma, the measurement of SUVmax, MTV, and TLG on FDG-PET/CT was beneficial for the prediction of pathological invasive factors.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      P1.16-18 - Role of ERCC1/2 Single Nucleotide Polymorphism (SNP) on Treatment Response in Patients with Lung Cancer Undergoing Radiation Therapy

      16:45 - 18:00  |  Presenting Author(s): Yaping Xu  |  Author(s): Yaoyao Zhu, Chenxue Jiang, Yun Chen, Qinghua Xu, Jianguo Feng, JianYue Jin

      • Abstract

      Background

      Radiation therapy plays an important role in the treatment of lung cancer. The protein excision-repair cross-comlementation 1 (ERCC1) and protein excision-repair cross-comlementation 2 (ERCC2) are the key enzymes in NER pathway. Studies showed that ERCC1/2 were associated with susceptibility and efficacy of chemotherapy in lung cancer, but the association between ERCC1/2 SNPs and radiotherapy were seldom reported.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Eighty-seven peripheral blood samples were collected from patients with NSCLC before they received radiotherapy in our department from November 2014 to October 2017. The peripheral blood leukocyte DNA was isolated and SNP genotypes were detected by competitive allele-specific PCR. Seven SNPs in ERCC1/2 were analyzed. Data was collected both before and after radiotherapy from blood serum. Elisa was used to detect ERCC1 expression. The association between the changes of expression of ERCC1 during radiotherapy and efficacy, risk of RILI and SNPs in ERCC1 was analyzed.

      4c3880bb027f159e801041b1021e88e8 Result

      ERCC1 re3212961 minor allele A was associated with a better response to radiotherapy in NSCLC patients. Survival analyses showed that G/G genotype had favorable OS than A/A genotype (P=0.012). Cox regression analysis indicated that ERCC1 rs11615 G/G genotype was associated with decreased risk of death. Subgroup analyses indicated that patients with G/G genotype who received high BED radiotherapy had better OS (median not reached vs. 21.5 months, 95%CI:15.3-27.7,P=0.011) and PFS (median not reached vs. 19.9 months, 95%CI:8.6-31.2,P<0.001) than low BED subgroup. There was no significant association between ERCC1/2 SNPs and RILI. The ERCC1 expression in serum was significantly increased after radiotherapy. However, the changes of ERCC1 expression showed no association with efficacy of radiotherapy, risk of RILI or SNPs of ERCC1/2.

      8eea62084ca7e541d918e823422bd82e Conclusion

      ERCC1 rs3212961 was related with short-term curative efficacy. ERCC1 rs11615 was an independent prognostic factor in NSCLC, which could serve as biomarker, because G/G genotype had favorable OS and PFS, and was associated with decreased risk of death. There was no significant correlation between ERCC1/2 SNPs and RILI. The changes of ERCC1 expression after radiotherapy showed no association with efficacy of radiotherapy, risk of RILI or SNPs of ERCC1/2.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      P1.16-19 - Neither Maximum Tumor Size nor Solid Component Size Was the Best Prognosticator for Subsolid Nodule

      16:45 - 18:00  |  Presenting Author(s): Erjia Zhu  |  Author(s): Chang Chen

      • Abstract

      Background

      Solid component size is used to define the T stage of subsolid nodule in the eighth edition TNM stage classification. Our study aimed to explore whether solid component size was the best parameter for T staging.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We retrospectively reviewed the clinical data of 431 cTis-T3N0M0 subsolid nodule from Shanghai Pulmonary Hospital. Maximum tumor size, solid component size and tumor size in mediastinal window were carefully recorded. Prognostic ability of different turmor size was compared by time-dependent receiver operating curve.

      4c3880bb027f159e801041b1021e88e8 Result

      Survival revealed maximum tumor size, solid component size and tumor size in mediastinal window were statistical significant predictors. However, solid component size performed the worst of them, relatively.wclc 3.tiffwclc 2.jpg

      8eea62084ca7e541d918e823422bd82e Conclusion

      Tumor size remains a common used parameter for nodule evaluation. Solid component size maybe not the best parameter for T staging.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      P1.16-20 - A Systematic Review and Meta-Analysis of Stereotactic Body Radiation Therapy Versus Surgery for Patients with Non-Small Cell Lung Cancer

      16:45 - 18:00  |  Presenting Author(s): Christopher Cao  |  Author(s): Andreas Rimner, James Huang, David R. Jones

      • Abstract

      Background

      Stereotactic body radiation therapy (SBRT) is the preferred treatment modality for patients with inoperable early-stage NSCLC. However, comparative outcomes of SBRT versus surgery for high-risk patients remain controversial. The primary aim of the present meta-analysis was to assess the overall survival of SBRT versus surgery in matched and unmatched patient cohorts. Secondary endpoints included cancer-specific survival, disease-free survival, disease recurrence, and perioperative outcomes.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      A systematic review was performed through online databases using predefined criteria. The most updated studies were selected for meta-analysis according to unmatched and matched patient cohorts.

      4c3880bb027f159e801041b1021e88e8 Result

      Thirty-two studies were identified in the systematic review. Surgery was associated with superior overall survival in both unmatched (OR 2.49, 95% CI 2.10–2.94, p<0.00001) and matched (OR 1.71, 95% CI 1.52–1.93, p<0.00001) cohorts. Cancer-specific survival, disease-free survival, and freedom from locoregional recurrence were found to be superior after surgery compared to SBRT, in both unmatched and matched cohorts. However, SBRT was associated with fewer perioperative mortalities.

      figure 1.png

      pic final.png

      8eea62084ca7e541d918e823422bd82e Conclusion

      Current evidence suggests that surgery is superior to SBRT in mid- and long-term clinical outcomes. However, improved outcomes after surgery may at least be in part due to an imbalance of baseline characteristics. Mortality outcomes for SBRT were also more favorable in the perioperative period.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      P1.16-21 - Phase I / II Study of Carboplatin, Nab-Paclitaxel, and Concurrent Radiotherapy for Patients with Locally Advanced NSCLC

      16:45 - 18:00  |  Presenting Author(s): Yuko Kawano  |  Author(s): Tomonari Sasaki, Hiroyuki Yamaguchi, Katsuya Hirano, Makoto Nishio, Miyako Satouchi, Shinobu Hosokawa, Ryotaro Morinaga, Kazutoshi Komiya, Kouji Inoue, Yuka Fujita, Ryo Toyozawa, Tomoki Kimura, Kosuke Takahashi, Kazuo Nishikawa, Junji Kishimoto, Yoichi Nakanishi, Isamu Okamoto

      • Abstract

      Background

      We performed an open-label, multicenter phase I/II study (UMIN ID 000012719) to prospectively evaluate the efficacy and safety of the combination of nab-paclitaxel plus carboplatin (nab-P/C) with concurrent thoracic radiotherapy in unresectable stage III non-small cell lung cancer.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      In the phase I study (standard 3+3 design), escalating doses of weekly nab-paclitaxel were given along with weekly carboplatin area under the plasma concentration time curve (AUC) 2 and concurrent radiotherapy 60 Gy in 30 fractions, followed by 2 cycles of nab-paclitaxel (100 mg/m2 on Days 1, 8 and 15) plus carboplatin (AUC 6 on Day 1). In the phase II study, nab-P/C at recommend dose (RD) was administered.

      4c3880bb027f159e801041b1021e88e8 Result

      In the Phase I study, 11 patients were enrolled with 9 evaluable for dose limiting toxicity (DLT). At level 1 (nab-paclitaxel 40mg/m2), none of 3 patients experienced DLT. At level 2 (nab-paclitaxel 50mg/ m2), 1 of 6 patients experienced DLT: grade 3 leukopenia requiring a second consecutive skip in the administration of weekly nab-P/C. Level 2 was defined as the RD. A total of 56 patients including 6 patients who received at dose of RD, were evaluable for the efficacy and safety. Of the 56 patients for safety analysis, common toxicities in the concurrent phase included grade 3/4 leukopenia (60.7 %), neutropenia (26.8 %), anemia (7.1 %), anorexia (7.1 %), esophagitis (5.4 %) and febrile neutropenia (1.8 %). In one patient, grade 3 pneumonitis was observed. There were no treatment-related deaths. The objective response rate was 76.8 % (95% confidence interval (CI), 64.2 to 85.9 %). The median progression-free survival was 11.8 months (60% CI, 10.6 to 16.2 months, 95% CI, 8.2 to 20.8 months), and the median overall survival was not reached.

      8eea62084ca7e541d918e823422bd82e Conclusion

      This is the first study to demonstrate encouraging feasibility and activity for concurrent chemoradiation with nab-paclitaxel 50 mg/m2 and CBDCA AUC 2 in patients with locally advanced NSCLC.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      P1.16-22 - Meta-Analysis of Stereotactic Ablative Radiotherapy Versus Surgery for Early Stage Lung Cancer.

      16:45 - 18:00  |  Presenting Author(s): Janusz Kowalewski  |  Author(s): Maciej Dancewicz, Mariusz Kowalewski

      • Abstract

      Background

      The standard of care for operable, stage I, non-small-cell lung cancer (NSCLC) is lobectomy with mediastinal lymph node dissection or sampling. Stereotactic ablative radiotherapy (SABR) for inoperable stage I NSCLC has shown promising results, but two independent, randomised, phase 3 randomized controlled trials (RCTs) included few patients and closed early due to slow accrual. We aimed to assess overall survival with SABR versus surgery by pooling data from RCTs and adjusted observational studies.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We performed a systematic review and meta-anaysis according to PRISMA (Preferred Items Reporting for Systematic Reviews and Meta Analyses) guidelines. The search process covered a period untill 28th of February 2018. Search terms were: SABR, stereotactic body radiation therapy, radiotherapy, lung-, pulmonary- cancer. Studies comparing SABR vs surgery for NSCLC were ellegible if reported adjusted survival data. Approaches including propensity scoring, inverse probability weighting and multivariate regressions were only considered. Survival was calculated by pooling available Hazard Ratios (HRs) in random-effects model. Studies were then stratified based on their design (RCT[s] vs Adjusted nRCT[s]). HRs were digitized from the available Kaplan-Meier curves.

      4c3880bb027f159e801041b1021e88e8 Result

      12031.jpgNineteen studies were retrieved that enrolled 23,534 patients. Among them two RCTs (N=58 pts). In overall analysis SABR was associated with significantly worsened survival as compared to surgery group: HR (95%CIs): 1.64 (1.38-1.94); p<0.001; when analyzed separately, adjusted nRCT[s] favored surgery: HR for comparison SABR vs surgery: 1.66 (1.40-1.97); p<0.001; among RCTs only, SABR was associated with a statistical trend for improved survival: HR (95%CIs): 0.14 (0.02-1.17); p=0.07. There were significant statistical differences between RCTs and adjusted nRCTs Pinteraction=0.02.

      8eea62084ca7e541d918e823422bd82e Conclusion

      SABR could be an option for treating early stage NSCLC but there was significant discrepancy between RCTs and non-RCTs regarding survival after SABR as compared to surgery; more adequately powered randomized studies are needed before conclusions on efficacy of SABR can be drawn.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      P1.16-23 - Long-Term Survival Analysis of Surgery in Potential Stereotactic Ablative Radiotherapy Candidates of Non-Small Cell Lung Cancer

      16:45 - 18:00  |  Presenting Author(s): Shaolei Li  |  Author(s): Shanyuan Zhang, Yuanyuan Ma, Yue Yang

      • Abstract

      Background

      The aims of this study were to evaluate the long-term survival outcomes and strengthen the primacy of surgery in potential stereotactic body radiotherapy candidates.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      A total of 541 patients with clinical stage I peripheral non-small cell lung cancer from January 2005 to December 2014 were enrolled in the current study. All patients who were potential stereotactic ablative radiotherapy candidates underwent lobectomy and systematic lymph node dissection including level 13 and 14 without preoperative therapy. According to the recommendation of the 8th edition of TNM stage, combined with our own experience, we divided the N stage into N1a (only level 13-14 positive), N1b (level 10-12 positive), N2a1 (skip single N2), N2a2 (single N2 with N1) and N2b (multiple N2). Survival curves were estimated by the Kaplan–Meier method.

      4c3880bb027f159e801041b1021e88e8 Result

      Among all patients, 25.0% had occult lymph node involvement, 12.8% were N1 and 12.2% were N2. Among 32 T1a patients only 1 case (3.0%) patients had N1a positive without other N positive. In 104 cases of T1b, the positive rates of N1a, N1b, N2a1, N2a2 and N2b were 0.8%, 5.9%, 0.8%, 2.5% and 1.7%, respectively. Among the 86 patients with T1c, the positive rate of each station was 5.4%, 11.5%, 3.8%, 8.5%, and 4.6%, respectively. Of the 184 patients with T2a, N1 accounted for 14.6% , and N2 accounted for 11.5%. The 3-year, 5-year and 10-year disease free survival (DFS) of all 541 clinical stage I patients were 82.8%, 74.0%, 64.7%, and the overall survival (OS) were 91.3%, 85.4% and 77.0% respectively. The 3-year, 5-year and 10-year DFS of postoperatively pathological stage I patients were 90.0%, 81.0%, 72.5%, and the OS were 94.4%, 91.1% and 85.0%, respectively.

      T /N category

      N0

      N1a

      N1b

      N2a1

      N2a2

      N2b

      1a

      32(97.0%)

      1(3.0%)

      0

      0

      0

      0

      1b

      104(88.1%)

      1(0.8%)

      7(5.9%)

      1(0.8%)

      3(2.5%)

      2(1.7%)

      1c

      86(66.2%)

      7(5.4%)

      15(11.5%)

      5(3.8%)

      11(8.5%)

      6(4.6%)

      2a

      184(70.8%)

      13(5.0%)

      25(9.6%)

      8(3.1%)

      12(4.6%)

      18(6.9%)

      8eea62084ca7e541d918e823422bd82e Conclusion

      In view of the high rate of lymph node metastasis in clinical stage I lung cancer, surgical resection is still the preferred treatment.

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      P1.16-24 - Impact of Tumor Location &amp; Dosimetric Predictors for Chest Wall Toxicity in Single Fraction SBRT for Stage I Non-Small Cell Lung Cancer

      16:45 - 18:00  |  Presenting Author(s): Gregory M.M. Videtic  |  Author(s): Bindu Manyam, Kyle Verdecchia, Chandana A. Reddy, Neil M Woody, Tingliang Zhuang, Kevin L Stephans, Aditya Juloori

      • Abstract

      Background

      Single fraction stereotactic body radiation therapy (SF-SBRT) is an acceptable regimen for treatment of peripheral Stage I Non-Small Cell Lung Cancer (NSCLC). Rates of chest wall toxicity (CWT) are not stratified by distance of tumor to chest wall (CW) and dosimetric parameters are not well defined. We sought to determine the relationship of tumor location and dosimetric parameters with CWT in SF-SBRT.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      An IRB-approved prospective SBRT registry of 1,462 patients (pts) was used to identify pts treated with 30 Gy or 34 Gy in one fraction. Tumors were ≤ 5 cm, node-negative, and ≥ 2 cm from the proximal tracheo-bronchial tree. The CW was retrospectively contoured (3 cm soft-tissue structure). Gross tumor volume was measured as abutting, ≤ 1 cm, 1-2 cm or > 2 cm from the CW. CWT was graded according to CTCAE 3.0 criteria. Rates of CWT were compared using unpaired t-test. Logistic regression analysis was used to identify tumor and dosimetric parameters associated with CWT.

      4c3880bb027f159e801041b1021e88e8 Result

      This study included 146 lesions treated with SF-SBRT. Median follow-up was 23.8 months. There were 80 pts (55%) treated with 30 Gy and 66 pts (45%) treated with 34 Gy. The rate of CWT was 30.6% for lesions abutting CW, 8.2% for ≤ 1 cm from CW, 3.8% for 1-2 cm from CW, and 5.7% for > 2 cm from CW. Grade ≥ 3 CWT was modest (1.4%). Tumor abutment (OR 6.5; p=0.0005), BMI (OR 1.1; p= 0.02), rib D1cc (OR 1.01 per Gy; p= 0.03), CW D1cc (OR= 1.08 per Gy; p=0.03), and CW D5cc (OR 1.10 per Gy; p= 0.01) were significant predictors for CWT on univariate analysis. Tumor abutment was the only significant predictor for CWT (OR 7.5; p= 0.007) on multivariate analysis. CWT occurred in only 1 out of 40 pts with CW D5cc < 18 Gy, while our model suggested a 15% risk of CWT with D5cc of 27.2 Gy to CW.

      8eea62084ca7e541d918e823422bd82e Conclusion

      The rate of CWT is significantly associated with distance from the CW. When considering lesions adjacent to the CW, the rate of CWT in this series (30.6%) does not appear to exceed rates in the published fractionated SBRT literature (20-33%). Location adjacent to CW should not be a contraindication to SF-SBRT. CW D1cc and D5cc may be used as predictors of CWT rates. As most CWT is low-grade and self-limited, these dosimetric parameters should be utilized as a guideline, rather than an absolute constraint.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      P1.16-25 - A Propensity Score Model for Appropriate Treatment Selection (Sublobar Resection vs. SBRT) In Patients With cStage I NSCLC

      16:45 - 18:00  |  Presenting Author(s): Yukinori Matsuo  |  Author(s): Toyofumi Fengshi Chen-Yoshikawa, Masatsugu Hamaji, Takamasa Mitsuyoshi, Takashi Shintani, Yusuke Iizuka, Makoto Sonobe, Hiroshi Date, Takashi Mizowaki

      • Abstract

      Background

      Stereotactic body radiotherapy (SBRT) and sublobar resection (SLR) are current treatment options for patients with cStage I non-small-cell lung cancer (NSCLC) who are operable, but at high risk for lobectomy. However, optimal selection of the two treatments remains controversial. Purposes of this study are to identify pre-treatment factors affecting treatment decision and to evaluate their impact on outcomes.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We retrospectively reviewed patients who underwent SBRT or SLR for cStage I NSCLC because of medical comorbidity between 2003 and 2009. Patients who were with performance status of 2 or worse, those who had no data on pre-treatment pulmonary function test, or those who had no histological confirmation of NSCLC were excluded. A propensity score (PS) model of treatment decision (0 toward SBRT, and 1 toward SLR) was generated using stepwise logistic regression incorporating pre-treatment factors.

      4c3880bb027f159e801041b1021e88e8 Result

      Ninety-two and 65 patients who underwent SBRT and SLR, respectively, were enrolled into this analysis. Median potential follow-up period was 8.6 years. The following factors remained in the PS model after stepwise selection: age, sex, Charlson comorbidity index (CCI), body mass index (BMI), forced expiratory volume in 1 second (FEV1) and tumor diameter. Old age, male, CCI of 1 or more, underweight BMI and large tumor had coefficients toward SBRT (Table).

      In a cohort with PS of 0.5 or more, overall survival was significantly better in SLR patients than in SBRT patients (79.5% and 47.5% at 5 years, respectively; P = 0.004). In a cohort with PS<0.5, whereas, overall survival was similar between SLR and SBRT (43.3% and 39.7% at 5 years, respectively; P = 0.805).

      Coefficients for propensity score
      Factors Coefficients
      (Intercept) (3.95)
      Age per 10y -0.53
      Sex female 0 (ref)
      male -0.62
      CCI 0 0 (ref)
      1 -0.41
      >=2 -0.97
      BMI underweight -0.98
      normal 0 (ref)
      overweight 0.44
      FEV1 per 1L 0.84
      Tumor diameter per 1cm -0.34

      8eea62084ca7e541d918e823422bd82e Conclusion

      The PS model would help appropriate treatment selection for high-risk operable patients. Although patients with PS of 0.5 or more benefit from SLR, SBRT provides comparable outcomes for patients with PS<0.5.

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      P1.16-26 - Safety of SABR (Stereotactic Ablative Body Radiotherapy) for Central Non-Small Cell Lung Cancers (cNSCLC) with 50 Gray in 5 Fractions (50Gy/5f)

      16:45 - 18:00  |  Presenting Author(s): Robert Rulach  |  Author(s): Jonathan Hicks, Graeme Lumsden, Stephen McKay, Vivienne Maclaren, Jennifer Macphee, Karen Moore, Margaret Omand, Michael Sproule, Suzanne Currie, Andrew Aitken, Richard Ferguson, Peter Houston, Ronan Valentine, Stephen James Harrow

      • Abstract

      Background

      SABR using 60Gy/3f (or equivalent) caused high toxicity when used for cNSCLC. To determine a safe SABR dose for cNSCLC, the phase I/II RTOG 0813 trial used 50Gy/5f as a baseline. From 2013, 50Gy/5f was adopted for inoperable early-stage cNSCLC at the West of Scotland Cancer Centre, a tertiary-level oncology unit. We report our prospectively collected toxicity and efficacy data.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Patients with cNSCLC were identified from the radiotherapy database. cNSCLC was defined as lung cancers within 2cm of the proximal bronchial tree, or the planning target volume (PTV) abutting the mediastinal pleura/pericardium. Patient and treatment characteristics were obtained from electronic medical records. All patients received 50Gy/5f on alternate days with a volumetric arc therapy plan using TrueBeam linear accelerators. Toxicity was assessed in a centralised follow-up clinic 2 weeks, 6 weeks, 3 months, 6 months, 1 and 2 years after treatment using Common Toxicity Criteria Adverse Events version 3. Patients had a CT scan at 3 months post-treatment. Subsequent CT scans were at the discretion of the treating clinician.

      4c3880bb027f159e801041b1021e88e8 Result

      50 patients (31 females, 19 males, median age 75.1 years old) were identified with T1-2N0M0 cNSCLC. 84% were medically unfit for surgery. 40% had biopsy-proven NSCLC. All patients completed treatment on schedule. Two patients died within 90 days of treatment, one from a chest infection, the other cause of death was unknown. Table 1 describes the early and late toxicity. Over a median follow-up of 24 months, there were 20 deaths, 8 unrelated to cancer, and 12 due to cancer recurrence. The median progression free survival and overall survival are 26.0 months (95% confidence interval: 16.4, 35.6 months) and 28.6 months (95% confidence interval: 21.3, 35.8 months) respectively.

      world lung abstract table 1.jpg

      8eea62084ca7e541d918e823422bd82e Conclusion

      This study has demonstrated that 50Gy/5f is a safe dose and fractionation for early-stage inoperable cNSCLC, with outcomes comparable to other series.

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      P1.16-27 - Using Rates of Clinical Brachial Plexopathy after Lung SBRT to Better Characterize the Tolerance of the Brachial Plexus

      16:45 - 18:00  |  Presenting Author(s): Kyle Verdecchia  |  Author(s): Bindu Manyam, Chandana A. Reddy, Kevin Rogacki, Tingliang Zhuang, Gregory M.M. Videtic, Kevin L Stephans

      • Abstract

      Background

      Treatment of apical lung tumors with stereotactic body radiation therapy (SBRT) can be challenging due to proximity to the brachial plexus (BP). We retrospectively investigated outcomes after treatment of apical lung tumors to compare the rate of brachial plexopathy (BPX) with what would be estimated based on published protocol-derived BP constraints.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Apical lung tumors were defined in this analysis as those whose lung SBRT target had a planning-derived PTV edge <1cm from the anatomic BP. We surveyed an IRB-approved prospective registry of 1,462 patients treated with SBRT for the interval 2003-2017 and included all patients who received definitive or salvage SBRT using dose/fractionation schedules of 50 Gy/5 fx, 60 Gy/5 fx, or 48 Gy/4 fx. Salvage SBRT included patients with local recurrence after conventional fractionation radiotherapy. Per RTOG protocols, the subclavian vein (SCV) ipsilateral to target was contoured as the BP surrogate. In this study, the ipsilateral subclavian artery (SCA), and BP were also contoured to characterize dosimetric differences between structures. Statistical analysis involved repeated measures ANOVA.

      4c3880bb027f159e801041b1021e88e8 Result

      Sixty-four patients, which includes six patients (9.4%) receiving salvage SBRT, met inclusion criteria (median follow up of 21 months). No significant differences (p=0.77) were observed between maximum point doses to BP, SCV, and SCA. Within one year post-SBRT, two patients (3%) developed BPX (grade 2); both patients had exceeded 32 Gy to the BP and were treated with salvage SBRT. No patient treated with definitive SBRT (91%) developed BP, despite 17 of these exceeding recommended maximum doses.

      8eea62084ca7e541d918e823422bd82e Conclusion

      No BPX was observed for patients that exceeded a maximum dose of 32 Gy to the BP, unless they were treated as salvage SBRT. This suggests higher doses to the BP may be considered when clinically required for definitive SBRT. However, salvage SBRT may require more conservative BP constraints than used in the definitive setting.

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      P1.16-28 - The Impact of Spironolactone on the Lung Injury Induced by Concomitant Trastuzumab and Thoracic Radiotherapy

      16:45 - 18:00  |  Presenting Author(s): Guler Yavas  |  Author(s): Cagdas Yavas, Esin Celik, Erdem Sen, Ozlem Ata, Deniz Yuce, Rengin Elsurer-Afsar

      • Abstract

      Background

      Radiation-induced lung injury (RILI) is a potentially life-threatening and dose-limiting side effect of thoracic irradiation. Trastuzumab (T), a monoclonal antibody directed against HER2, improves overall survival in patients with HER2 positive breast cancer. T concurrently with radiation thus increases the antitumor effect of radiation. There are same clinical evidences in the literature that T also radiosensibilizes human healthy tissues and in this way it could increase the toxicity of the treatment. The incidence of T-induced pneumonitis is 0.4–0.6%. Although infrequent; pulmonary toxicity due to T may be life-threatening. Aldosterone, which is a physiological activator of MR, is partially responsible for increases in the extracellular matrix turnover, as observed in fibrosis of the cardiac, kidney and lung tissues, and exerts its effects primarily on lung epithelium. Spironolactone (S), an aldosterone receptor antagonist, may have the ability to ameliorate pulmonary fibrosis.We hypothesized that S would be effective in the treatment of both RT and T-induced lung injury by correcting pulmonary fibrosis

      a9ded1e5ce5d75814730bb4caaf49419 Method

      This study included 80 female Wistar-Albino rats (250-300 g); use of which was approved by the Ethical Committee. Rats were divided into eight groups: group (G) 1 was control group; G2, G3 and G4 were RT, S and T groups; G5, G6, G7 and G8 were RT+T, T+S, RT+S and RT+T+S groups respectively. RT was applied under general anesthesia with intraperitoneally administered 90 mg/kg ketamine hydrochloride and 10 mg/kg xylazine. A single dose of 15 Gy was applied to the both lungs. T (6 mg/kg) was administered intraperitoneally and S (80 mg/kg) was administered by oral gavage. Rats were sacrificed via cervical dislocation at 6th hour, 21st day and 100th day after RT and the lung samples were taken for microscopical examination.

      4c3880bb027f159e801041b1021e88e8 Result

      By 100th days of RT inflammation score, lung fibrosis score and TGF- expression were significantly different within study groups (p values were 0.002, 0.001 and 0.043 respectively). Inflammation score of G8 was significantly lower than inflammation scores of G2 and G5 (p values: G2-G8= 0.004, and G5-G8=0.022). Inflammation score of G2 was significantly higher than G7 (p=0.028). There were significant differences regarding to fibrosis scores between G2-G8 (p=0.015), G2-G7 (p=0.017) and G5-G8 (p=0.011). TGF-β expression was higher in both G2 and G5 when compared to G8 (p = 0.038).

      8eea62084ca7e541d918e823422bd82e Conclusion

      Our results suggested that S is an effective treatment option for improving radiation-induced pulmonary fibrosis. These findings should be clarified with further preclinical and clinical studies.

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      P1.16-29 - Accelerated Hypofractionated Radiotherapy for Central Lung Tumors Unsuitable for Stereotactic Body Radiotherapy Or Concurrent CRT

      16:45 - 18:00  |  Presenting Author(s): K. Liang Zeng  |  Author(s): Ian Poon, Yee Ung, Liying Zhang, Patrick Cheung

      • Abstract

      Background

      In our institution, accelerated hypofractionated radiotherapy is a treatment option for 1) stage I lung non-small cell lung cancer (NSCLC) patients whose tumors are too bulky or central for SBRT; and 2) select stage II-III NSCLC patients not candidates for concurrent CRT. The purpose of this project was to review the clinical outcomes of a large single institutional experience of treating such patients with a dose of 60 Gy in 15 fractions in an era when SBRT was routinely used in clinical practice for early stage lung cancer.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Central tumors were defined as the gross target volume being in contact with mainstem bronchi, trachea, esophagus, great vessels, or heart. All patients who received 60 Gy in 15 fractions treated between 2008 and 2017 were reviewed. Competing risk analysis was used to calculate the cumulative incidence of local failure (LF), regional failure (RF), and distant failure (DF). Kaplan-Meier methodology was used to calculate overall survival (OS). Univariate analyses were used to look for potential predictive factors.

      4c3880bb027f159e801041b1021e88e8 Result

      Eighty-nine patients were treated. Median follow-up was 24.0 months (range: 6.1-94.2 months). Median age was 79.4 years and most tumors were adenocarcinoma (n=47, 52.8%), followed by squamous cell carcinoma (n=31, 34.8%). Thirty patients (33.7%) had stage I disease, 47 patients (52.8%) had stage II-III disease, and 12 patients (13.5%) had stage 4 disease (mostly oligometastatic). Cumulative incidence of LF was 15.3% at 2 years. In those with stage I-III disease, cumulative incidence of RF and DF were 12.9%, and 28.5%, respectively at 2-years. OS was 74.9% at 2 years, with a median OS of 39.4 months for those with stage I-III disease. In the subset with stage II-III disease, median OS was 38.1 months and 2 year OS was 67.7%. Tumor stage, histology, EGFR mutation status, and location were not statistically significant predictors for any outcomes, although tumor size >3.5cm was borderline significant in predicting for a higher cumulative incidence of LF (subdistribution hazard ratio = 2.726; 95% confidence interval 0.995-7.469; p=0.051). The most common toxicity was radiation pneumonitis (n=6, 6.4%). The cumulative incidence of any grade 3 toxicity was 10.8% at ≥ 1 year. There were no deaths or hospitalizations directly attributed to treatment.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Accelerated hypofractionated radiotherapy to a dose of 60 Gy in 15 fractions resulted in favorable outcomes in NSCLC patients who were not suitable for SBRT or concurrent CRT. Patients with Stage II-III disease had good OS despite not receiving concurrent chemotherapy. Severe toxicities were uncommon.

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      P1.16-30 - Quality of Lymphadenectomy During Lobectomy for Non-small Cell Lung Cancer: VATS Versus Thoracotomy

      16:45 - 18:00  |  Presenting Author(s): Raquel Sâmia Gonzaga Alves  |  Author(s): Etienne Bourdages-Pageau, Charles-Antoine Paradis-Garneau, Arthur Vieira, Paula Ugalde

      • Abstract

      Background

      Lobectomy by video-assisted thoracoscopic surgery (VATS) is preferred over thoracotomy in patients with early-stage non-small cell lung cancer (NSCLC). However, controversy still exists regarding the quality of the lymph node dissection accomplished using VATS. This study analyzed the lymphadenectomy by surgical approach and applied the International Association of the Study of Lung Cancer (IASLC) criteria of lobe-guided lymphadenectomy.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We performed a retrospective review of patients with stage I or II NSCLC who underwent lobectomy via thoracotomy (2003-2007, n=408) or VATS (2014-2017, n=754) at our institution. We compared the lymph node stations dissected by lobe-specific and the outcomes between the two approaches.

      4c3880bb027f159e801041b1021e88e8 Result

      VATS was equal or superior to thoracotomy for dissection of all lymph node stations except stations 8R (p=0.0018) and 8L (p=0.0002) and was superior for subcarinal lymphadenectomy (p=<.0001). When examined by lung lobe(s), VATS was superior for lymphadenectomy during right upper lobectomies (p=<.0001) and at least equal to thoracotomy for all other lobes. Additionally, VATS was associated with less blood loss (p=<.0001), pneumonia (p=0.0008) and acute respiratory distress syndrome (p=0.0082), fewer air leaks (p=<.0001) and lower 30-day mortality (p=0.0308).

      results table.png

      8eea62084ca7e541d918e823422bd82e Conclusion

      At our institution, the transition from thoracotomy to VATS lobectomy for early-stage NSCLC did not negatively impact the quality of the lymph node dissection. Moreover, VATS significantly improved surgical outcomes.

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      P1.16-31 - Surgically Resected Acinar Adenocarcinoma of the Lung: Analysis of Different Prognostic Groups.

      16:45 - 18:00  |  Presenting Author(s): Pietro Bertoglio  |  Author(s): Andrea Viti, Giuseppe Salvatore Bogina, Carlo Pomari, Giuseppe Zamboni, Alberto Terzi

      • Abstract

      Background

      Adenocarcinoma has become the most frequently diagnosed histotype of Non-Small cell Lung Cancer (NSCLC). Nevertheless, the latest classification of lung adenocarcinoma issued by IASLC/ATS/ERS identified different subtypes with different prognostic impact; concurrently, different subtypes might mingle influencing biological features and behavior. We focused on surgically treated stage I and II predominantly acinar lung adenocarcinoma analyzing outcomes and prognostic factors according to the second main histological pattern.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We retrospectively collected all lung adenocarcinoma with a predominant acinar histological pattern operated on between October 2012 and September 2017 in our institution. We selected all patients in pathological stage I A-B and II A-B with full preoperative staging procedures performed at our institution. All clinical and pathological features were registered. We analyzed outcomes according to the histological sub pattern and we focused on main prognostic factors.

      4c3880bb027f159e801041b1021e88e8 Result

      During the study period we performed 153 lung resections for patients affected by NSCLC. Among them we found 93 adenocarcinoma and 55 had a predominant acinar pattern. Among selected patients, there were 33 female and the mean age was 68.2 (SD±9.3) years. The histology report showed a solely acinar pattern in 11 cases (20.0%), while a second main sub-pattern was seen in the remaining cases: papillary or micropapillary in 7 cases (12.7%); lepidic in 27 cases (49.1%) and solid in 10 (18.2%). Mean Overall Survival (OS) and Disease-Free Survival (DFS) of all the cohort of patients were 66.1 (CI 95% 59.7-72.4) and 51.9 (CI 95% 42.7-61.2) months respectively. According to the secondary histological pattern, papillary and micropapillary subtypes showed a significant worse OS (p=0.029) and DFS (p=0.015) compared to all the other subtypes; concurrently they showed a significant higher mean Standard Uptake Value of T component at the preoperative PET-CT (11.8 vs 6.4, p=0.007) and had a higher rate of vascular invasion at the specimen (P=0.002). Beyond papillary and micropapillary subtypes, vascular invasion showed to be a significant prognostic factor both for OS and DFS.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Lung adenocarcinoma encompasses different sub-histotypes. In our experience, stage I and II resected predominantly acinar adenocarcinoma with papillary or micropapillary component showed higher rate of vascular invasion in the specimen and worse long-term outcomes compared to other subtypes, which might be related with a higher aggressiveness. In conclusion, our results suggest that different postoperative management should be adopted according to adenocarcinoma histological subtypes pattern; histology patterns should also be considered as a prognostic factor to be included in the NSCLC staging system.

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      P1.16-32 - Lung Cancer Completeness of Resection in Uniportal Versus Multiportal Video-Assisted Thoracoscopic Surgery Lobectomy

      16:45 - 18:00  |  Presenting Author(s): Etienne Bourdages-Pageau  |  Author(s): Raquel Sâmia Gonzaga Alves, Arthur Vieira, Charles-Antoine Paradis-Garneau, Yves Lacasse, Paula Ugalde

      • Abstract

      Background

      In 2005, the International Association for the Study of Lung Cancer (IASLC) added a new category to complete and incomplete resection for residual tumor classification (R): uncertain resection (R(un)). R status has a major prognostic impact, and the prognosis of patients with a R(un) resection differs from that of patients with either complete (R0) or incomplete resection (R1 or R2). The aim of this study was to measure R status with the expanded classification system when performing lobectomy for non-small cell lung cancer (NSCLC) using a uniportal (U-VATS) or multiportal (M-VATS) video-assisted thoracoscopic surgery.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      From August 2014 through December 2017, 672 VATS lobectomies were performed for the primary treatment of clinical stage I and II NSCLC, 43 patients with ground glass opacity or complex cases were excluded. Patients were analyzed according to ports used (one or multiple), R status, lobe-specific lymphadenectomy, subcarinal lymphadenectomy, length of hospital stay and length of thoracic drainage. A propensity-matched analysis was planned however, all variables were evenly distributed in both groups.

      4c3880bb027f159e801041b1021e88e8 Result

      Of 629 VATS lobectomies, 234 (37%) were performed with U-VATS and 395 (63%) with M-VATS. Most resections were classified as R(un) (84%); 2% were incomplete. When compared with M-VATS, U-VATS was associated with superior completeness of resection (p=0.0159), superior lobe-specific lymphadenectomy (p=0.0004), and superior subcarinal lymphadenectomy (p=0.0064). The highest mediastinal lymph node station dissected was not different between the approaches. The patients who underwent U-VATS had shorter hospital stays (mean: 4.4 days vs 6.2 days, p=0.0001) and less thoracic drainage (mean: 4.7 days vs 5.8 days, p=0.0004). There was no difference in operative mortality (p=0.3024) (Table 1).

      results.png

      8eea62084ca7e541d918e823422bd82e Conclusion

      In our institution, most VATS lobectomies were uncertain resections due to the lymph node evaluation by IASLC definition. Using U-VATS is not inferior to M-VATS in accomplishing a complete oncologic resection thoracoscopically.

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      P1.16-33 - Occult Lymph Node Metastases in Early Stage NSCLC Patients: Where Do We Stand Now? A Proposal for a Preoperative Risk Model

      16:45 - 18:00  |  Presenting Author(s): Giuseppe Cipollone  |  Author(s): Mirko Barone, Decio Di Nuzzo, Massimo Ippoliti, Barbara Maggi, Luigi Guetti, Pierpaolo Camplese,