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Jhingook Kim
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OA 03 - Mediastinal and Esophageal Tumor: Insight and New Treatment (ID 654)
- Event: WCLC 2017
- Type: Oral
- Track: Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
- Presentations: 8
- Moderators:M. Chida, Jhingook Kim
- Coordinates: 10/16/2017, 11:00 - 12:30, Room 311 + 312
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OA 03.01 - Prevalence of Autoimmune Diseases in Thymic Epithelial Tumors (TET) Insights from RYTHMIC (ID 8745)
11:00 - 12:30 | Presenting Author(s): Marie-Eve Boucher | Author(s): E. Dansin, M. Kerjouan, Julien Mazieres, E. Pichon, F. Thillays, G. Massard, X. Quantin, O. Youssef, Virginie Westeel, L. Thiberville, C. Clement-Duchene, F. Morin, P. Thomas, Nicolas Girard, Benjamin Besse
- Abstract
- Presentation
Background:
TET have been associated with autoimmune disorders (AID) in up to 30 % of patients. However, there have been wide variations in the reported prevalence of TET associated disorders based mostly on small single center series. RYTHMIC (Réseau tumeurs THYMiques et Cancer) is a French network mandated to systematically discuss every case of TET. Using our database, we aimed to describe the prevalence of AID in a large French population with TET.
Method:
RYTHMIC database prospectively includes all consecutive patients with a diagnosis of TET discussed in our national tumor board. We calculated the prevalence and described epidemiologic, clinical and pathological characteristics of patients with TET’s related autoimmune diseases.
Result:
From January 2012 to May 2017, 1693 patients were included in the registry. Of these, 200 patients (11.8%) had autoimmune disorder. The mean age at diagnosis of TET was 54 years old and 52% were male. 149 had myasthenia gravis (75.3%), 15 Good syndrome (7.6%), 14 pure red cell aplasia (7.1%), 12 systemic erythematous lupus (6.1%) and 12 thyroiditis (6.1%). Some patients (14.5%) eventually developed more than 1 AID. Diagnosis of AID was mostly done at the same time of TET diagnosis (54.6%) but some patient had their AID diagnosed before (19.8%) or during follow up (13.4%). Masaoka Koga stages were overall well balanced with 16.5% stage III, 16% stage IIb, 13.5% stage I, 13% stage IIa and IV. Histologic subtype distribution was in order of frequency; B2 (37%), AB (14.5%), B3 (14%), B1 (10.5%), thymic carcinoma (4.5 %) and A (4%).
Conclusion:
In our registry of TET, the prevalence of autoimmune diseases was 11.8% and most diagnosis were established at the same time as TET. The extent of disease, measured by Masaoka Koga staging, does not seem correlated.
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OA 03.02 - Comprehensive Characterization of Thymic Epithelial Tumour Subtypes Through an Analysis of Somatic Mutations and Copy Number Alterations (ID 10322)
11:00 - 12:30 | Presenting Author(s): Spyridon Gennatas | Author(s): A. Mandal, Andrew G Nicholson, Sanjay Popat, A.M. Bowcock
- Abstract
- Presentation
Background:
Thymic epithelial tumours (TETs) are rare and under-researched intrathoracic cancers. So far the only significant finding is a recurrent (43%) missense mutation in GTF2I. In addition to validating this finding, we set out to expand our understanding of the molecular changes underlying TETs through whole exome sequencing (WES) and detection of copy number alterations (CNAs) following SNP genotyping.
Method:
WES was performed on 17 TETs (2AB, 1B1, 3B2, 2B3, 6CA and 3NETT) and matched normal tissue. Somatic single nucleotide variants (SNVs) were identified with the GATK HaplotypeCaller and annotated for impact prediction (SnpEff 3.6b and SnpSift 1.3.4b) and population frequency (SnpSift 1.3.4b). The frequency of the GTF2I mutation was assessed with Sanger sequencing with semi-nested primers on DNA from 144 TETs of all subtypes. SNP genotyping was performed on 100 TETs of all subtypes with matched normal tissue in most cases, to identify somatic CNAs. Analysis was performed with ASCAT (v2.4.4) and copy number segments were annotated with Bedtools (v2.26.0).
Result:
WES confirmed a low mutation burden for TETs. No highly recurrent mutations were found. Hotspot mutations in NRAS and KRAS were seen, as was a hotspot mutation in TP53 in a NETT. A high impact frameshift MSH6 somatic mutation was noted in one of the squamous cell carcinomas (SCCs). Another SCC had a germline BAP1 mutation and a family history of other cancers, suggesting a BAP1 familial cancer predisposition syndrome in this individual. The GTF2I mutation was seen in 48 of 141 evaluable TETs (34%) and was present more commonly in type A (90%) and AB (69%) thymomas. The frequency decreased to 16%, 6% and 13% in B1, B2 and B3 thymomas respectively and was not seen in any squamous (0/12) or neuroendocrine carcinomas (0/6). Overall, the most frequent copy number gains in TETs involved chromosomes 7q (22%), 1q (17%) and 11q (17%). The commonest gain was in a gene not previously found to be amplified in solid tumours. The most frequent copy number losses were in chromosomes 6p (40%), 2q (37%) and 7q (32%). Gains and losses demonstrated distinct patterns between aggressive versus indolent subtypes.
Conclusion:
The mutation in GTF2I remains the single most frequently recurrent mutation in TETs. We are in the process of establishing a clinical use for this finding. Results from WES and CNA through SNP genotyping have provided important insight into other potential key players in the aetiology of this intriguing malignancy.
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OA 03.03 - Phase II Trial of Cetuximab and Chemotherapy Followed by Surgical Resection for Locally Advanced Thymoma (ID 10288)
11:00 - 12:30 | Presenting Author(s): James Huang | Author(s): D.J. Raz, M. Cristea, Kay See Tan, K. Deonaraine, A. Starr, William D Travis, M.S. Ginsberg, D. Jones, Valerie W Rusch, Mark G Kris, Gregory J Riely
- Abstract
- Presentation
Background:
The mainstay of treatment for thymoma is surgery with neoadjuvant chemotherapy recommended to patients with locally advanced disease. EGFR is overexpressed in thymoma. Clinical responses to single-agent cetuximab have been reported in patients with advanced cetuximab. We conducted this two-site prospective phase II trial of cetuximab combined with a standard induction chemotherapy regimen of cisplatin, doxorubicin and cyclophosphamide (PAC) in patients with locally advanced thymoma prior to surgical resection.
Method:
Patients with clinical Masaoka stage III-IVA thymoma were treated with cetuximab (250mg/m[2] weekly x 4 weeks) followed by cetuximab (250 mg/m[2] weekly) combined with cisplatin (50mg/m[2]), doxorubicin (50 mg/m[2]) and cyclophosphamide (500mg/m[2]) 3 weeks x 4 cycles). Radiographic response was assessed by CT using RECIST 1.1 and FDG-PET using PERCIST. All patients went on to surgery after completion of induction therapy. The primary endpoint was major pathologic response (MPR, >90% treatment effect). Planned enrollment was 18 patients in first stage of a two stage design. If 1 MPR was observed, then enrollment would expand to 28 patients.
Result:
Eighteen patients were enrolled: 8 women, median age 53 (range 32-73). WHO Histologic subtype A: 2, AB: 3, B1: 3, B2: 7, B3: 3. Final Masaoka stage I: 2, II: 2, III: 5, IVA: 9. There were no responses to cetuximab alone by RECIST criteria, although 1 patient had a 25% reduction in indicator lesions. Response rate (CR+PR), in evaluable patients after complete treatment course was 50% (8/16, 95% CI 28-72%). Partial responses by PERCIST criteria were seen on PET in 11/18 (61%) evaluable patients. There were no MPRs. R0 resection was obtained in 7 patients; 5 had R1 and 6 had R2 resections.
Conclusion:
The addition of cetuximab to PAC chemotherapy did not lead to pathologic complete responses in the neoadjuvant setting. Cetuximab alone appears to have little effect during 4 weeks of treatment. There was no apparent increase in radiographic response rate with the addition of cetuximab to PAC chemotherapy compared to historical series.
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OA 03.04 - A Phase II Study of Pembrolizumab for Patients with Refractory or Relapsed Thymic Epithelial Tumor (ID 9689)
11:00 - 12:30 | Presenting Author(s): Jinhyun Cho | Author(s): K.H. Yoo, Hansang Lee, H.K. Kim, Y. Kim, J.H. Cho, S.W. Lim, Song Ee Park, Jong-Mu Sun, S. Lee, Jin Seok Ahn, Keunchil Park, Myung-Ju Ahn
- Abstract
- Presentation
Background:
No standard treatment exists for patients with thymic epithelial tumor (TET) who progress after platinum-containing chemotherapy. We conducted a phase II study of pembrolizumab in patients with refractory or relapsed TET to evaluate the efficacy and safety.
Method:
Between March 2016 and June 2017, patients with histologically confirmed TET who progressed after at least one platinum-containing chemotherapy were eligible. Patients were excluded if they had an active autoimmune disease requiring systemic treatment within the past one year or documented history of clinically severe autoimmune disease. Patients received 200mg of pembrolizumab intravenously every 3 weeks until tumor progression or unacceptable toxicity. Response was assessed every 9 weeks by investigator. The trial was registered with ClinicalTrials.gov, number NCT02607631.
Result:
Thirty-three patients were enrolled, 26 with thymic carcinoma and 7 with thymoma. 19 (57.3%) patients received two or more prior lines of systemic chemotherapy. Median number of cycles was 8 (ranges, 1-22) and median follow-up was 11.8 months (ranges, 1.6-14.9 months). Of 33 patients, eight (24.2%) achieved partial responses, 17 (51.5%) stable disease, and 8 (24.2%) progressive disease as best response, resulting in overall response rate of 24.2% (7 confirmed PR). The median progression-free survival was 6.1 months for both of thymoma and thymic carcinoma. The most common adverse events of any grade include dyspnea (11 [33.3%] of 33 patients), chest wall pain (10 [30.3%]), anorexia (7 [21.2%]) and fatigue (7 [21.2%]). Treatment-related adverse events ≥ grade 3 associated with immune related adverse events (irAE) include hepatitis (4 [12.1%]), myocarditis (3 [9.1%]), myasthenia gravis (2 [6.1%]), thyroiditis (1 [3.0%]), ANCA-associated rapidly progressive glomerulonephritis (1 [3.0%]), colitis (1 [3.0%]), and subacute myoclonus (1 [3.0%]) except anemia (1 [3.0%]). Eight (24.2%) patients (5 thymoma, 3 thymic carcinoma) discontinued study treatment due to irAE, whereas irAEs were manageable with immediate administration of high dose corticosteroid and other immunosuppressive agents in most of patients (7 of 8 [87.5%]). In 18 (54.5%) patients who had tumor specimens available for correlative biomarker analysis, all of four patients achieved partial response had 50% or more proportion score of PD-L1 immunostaining and higher PD-L1 RNA expression compared with non-responders (p=0.0471).
Conclusion:
Pembrolizumab showed promising antitumor activity in patients with refractory or relapsed TET. Given the relatively high incidence of irAEs especially in thymoma, early detection and management of autoimmune toxicity is essential to ensure feasibility of pembrolizumab treatment in patients with TET.
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OA 03.05 - Discussant - OA 03.01, OA 03.02, OA 03.03, OA 03.04 (ID 10852)
11:00 - 12:30 | Presenting Author(s): Masanori Tsuchida
- Abstract
- Presentation
Abstract not provided
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OA 03.06 - Clinicopathologic, Immunophenotypic and Genetic Studies of Mediastinal Paragangliomas (ID 8339)
11:00 - 12:30 | Presenting Author(s): Anja C Roden | Author(s): Y. Hsu, B. Kipp, S. Jenkins, W. Sukov, H. Schaff, S. Cassivi, J. Torres-Mora
- Abstract
- Presentation
Background:
Paragangliomas (PGLs) are rare neuroendocrine neoplasms arising from paraganglia of the autonomic nervous system. Only about 2% of all PGLs are found in the mediastinum; therefore they are not thoroughly investigated. Our study aims to characterize the clinicopathologic, immunophenotypic and genetic features of mediastinal PGLs.
Method:
Surgical files of Mayo Clinic Rochester and an institutional database (1973-2015) were searched for mediastinal PGLs. Thirteen patients were previously reported (Brown ML et al, Ann Thorac Surg 2008). All cases were reviewed by a thoracic pathologist to confirm the diagnosis. Immunohistochemistry was performed using antibodies to SDHB, Ki-67, ATRX, p53, PD-L1 (clone SP263) and ASCL1. Ki-67 labelling index (LI) was calculated as the mean percent Ki-67-positive cells per 3 HPF. Next generation sequencing (NGS) used a 50-gene neuro-oncology panel. Clinical data were retrieved from medical records. Statistical analysis was performed.
Result:
Twenty-four patients with mediastinal PGLs (7 men, 29.2%) had a median age at time of surgery of 44.6 years (19.8-72.2). Twenty-one (87.5%) paragangliomas were completely resected, 3 had an incomplete resection. The median tumor size was 5.1 cm (1.6-14). The median Ki-67 LI was 4.1% (0.5-29.7). PD-L1 was expressed in 10% (n=2), 1% (n=4) or 0% (n=17) of tumor cells. ASCL1 was focally expressed in 2 of 23 (8.7%) cases. Diffuse loss of SDHB expression was seen in 17 of 22 (77.3%) cases. ATRX was expressed in all 22 cases tested, but its expression was patchy in 1 case that showed ATRX duplication by NGS. NGS, performed in 19 cases, revealed a single pathogenic mutation in 10 cases including SDHB (n=3), SDHD (n=6) and ATRX (n=1); and two or more mutations in 2 cases including SDHC+TERT (n=1) and SDHB+ATRX+TP53 (n=1). Two additional patients were found to have an SDHB mutation. Ten of 21 patients with available SDHx mutation status (47.6%) had no SDHx mutation. Median follow up, available in 21 patients, was 4.7 years (0.8-11.5). Five patients (2 of which with SDHx mutation) developed metastases and/or recurrence; 4 patients (2 without SDHx mutation, 2 with unknown SDHx mutation status) died (1 perisurgically, 3 of unknown cause at 2.3, 5.8, and 10.6 years after surgery each). Statistical analysis of clinicopathologic features based upon SDHx mutation could not be performed due to the small number of cases.
Conclusion:
Our study demonstrates that the majority of mediastinal PGLs harbors an SDHx gene mutation. Alterations in ATRX gene might represent another genetic event in mediastinal PGLs.
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- Abstract
- Presentation
Background:
Nomogram has demonstrated its capability in individualized survival estimates. Some nomogram studies on esophageal squamous cell carcinoma (ESCC) have been reported, but accuracy of those nomograms is not high enough. Also, the role of ESCC nomogram in adjuvant chemotherapy remains unclear. Therefore, clinicopathological prognostic nomogram was developed and validated for patients with ESCC in this study. Its role in personalized adjuvant chemotherapy was investigated as well.
Method:
Data were retrieved about 1042 ESCC patients undergoing right transthoracic radical esophageactomy at Sun Yat-sen University Cancer Centre from January 1997 to December 2013. Of 1042 patients, 886 without adjuvant chemotherapy were divided into training set (Group A, n=590) and validation set (Group B, n=296) in a 2:1 ratio. Group C (the remaining 156 patients with adjuvant chemotherapy plus Group B, n=452) was used to evaluate the role of nomogram in personalized adjuvant chemotherapy. Cut-off points of continuous variables were established by X-tile. Survival and univariate analyses were calculated by Kaplan–Meier method. R software and "rms" package were used to perform Cox proportional hazard (CPH) regression model, plot nomogram, compute C-index, compare models, validate model, and plot calibration curve. The "survivalROC" package was used to plot time-dependent receiver operating curve (ROC).
Result:
The 1-, 3- and 5-year overall survival (OS) for the entire cohort was 88.3%, 64.5% and 54.8%, respectively. Univariate analyses were performed for 13 potential clinicopathological factors. Significant variables were analyzed for CPH regression model using R software and “rms” package. A prognostic nomogram including 8 factors (grade, location, T, N, resected negative nodes, length, gender, drinking history) was developed. C-index of the model was 0.739 (95% CI 0.719-0.759), higher than that of the 7[th] TNM staging system (0.696, 95% CI 0.676-0.716), p < 0.001. The calibration curve and time-dependent ROC showed this nomogram was superior to the 7[th] TNM staging system. The cut-off of prognostic score was 160, by which we grouped patients into low and high prognostic risk subgroup. In Group C, 209 patients belonged to high prognostic risk subgroup. Among them, patients receiving adjuvant chemotherapy had longer OS (p = 0.035). The remaining 243 patients belonged to low prognostic risk subgroup. Adjuvant chemotherapy didn’t improve OS (p = 0.799) in this subgroup.
Conclusion:
An accuracy clinicopathological prognostic nomogram was developed and validated for ESCC patients undergoing right transthoracic radical esophagectomy. The nomogram provided individual prediction of survival. Risk group stratification based on nomogram prognostic score successfully guided personalized adjuvant chemotherapy for ESCC patients.
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OA 03.08 - Discussant - OA 03.06, OA 03.07 (ID 10853)
11:00 - 12:30 | Presenting Author(s): Nicolas Girard
- Abstract
- Presentation
Abstract not provided
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Author of
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MS 23 - Management of N2 NSCLC: What “Operable” Means? (ID 545)
- Event: WCLC 2017
- Type: Mini Symposium
- Track: Locally Advanced NSCLC
- Presentations: 1
- Moderators:G. Lyons, Marc De Perrot
- Coordinates: 10/18/2017, 14:30 - 16:15, F203 + F204 (Annex Hall)
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MS 23.05 - What is Resectable N2 Disease, and What is Unresectable N2 Disease: A Surgeon's Viewpoint (ID 7753)
14:30 - 16:15 | Presenting Author(s): Jhingook Kim
- Abstract
- Presentation
Abstract:
What is Resectable N2 Disease, and What is Unresectable N2 Disease: A Surgeon's Viewpoint Jhingook Kim, MD (Samsung Medical Center, Sungkyunkwan University) The poor prognosis of N2 disease is related to the risk of occult systemic metastasis although N2 disease, by definition, is a localized disease. Therefore, multimodal treatment, including systemically chemotherapy and locally surgery or radiotherapy, is often required. However, the optimal multimodal approaches for N2 disease remain controversial. Although definitive concurrent chemoradiotherapy (CCRT) is considered the standard of care, its oncologic efficacy can be limited by the high rate of local failure. Adding surgical resection to this bimodal treatment as a neoadjuvant treatment setting or replacing the radiotherapy with surgery has been attempted and has achieved enhancement of local control and improved survival, but the main concern regarding this approach is the increased risk of postoperative mortality and morbidity. Since 1995, neoadjuvant CCRT followed by surgical resection has been the preferred treatment modality at our institution, and prospectively and consecutively performed for more than 800 medically fit patients with resectable NSCLC with N2 disease. Figure 1 Fig. 1. Summary of treatment scheme Based on the previous analysis of 574 patients (From 1997 to 2013, 59 years of mean age, 444 men), complete resection was obtained in 543 patients (95%) by lobectomy (418 patients; 73%), pneumonectomy (73 patients; 13%) and sleeve resection (25 patients; 4.3%). Postoperative complications and in-hospital mortality occurred in 199 patients (35%) and 21 (3.7%), respectively. Pathologic complete response was achieved in 72 patients (13%) and 304 (53%) experienced mediastinal clearance. The 5-year overall and recurrence-free survival rates were 47 and 29%, respectively, and the median overall survival and recurrence-free survival were 56 months and 18 months, respectively. The 5-year OS rates were 61% in ypN0, 49% in ypN1, and 35% in ypN2 (p = 0.001). The 5-year RFS rates were 45% in ypN0, 23% in ypN1, and 17% in ypN2 (p < 0.001). Older age, advanced pTstage, persistent N2, large cell carcinoma, and pneumonectomy were independent prognostic factors associated with worse OS and poorer RFS. Evidence such as acceptable early postoperative outcomes, satisfactory local control and encouraging long-term survival has supported the need to expand the indication or situation. When investigating the timing and patterns of recurrence after treatment, of 290 patients with recurrence, 25 (8.4%) experienced loco-regional recurrence, whereas 238 (80.4%) had distant metastases. The hazard rate function for overall recurrence revealed a peak at approximately 8 months after surgery and a marked decline after 2 years (figure 2). The peak recurrence frequency of distant metastasis differed at each site, with isolated brain metastases exhibiting the earliest peak (6 months) and a narrow recurrence interval (15 months). Interestingly, the dynamics of recurrence after trimodality therapy varies according to pathologic factors and response to induction therapy (not specifically related with pre-induction presentation), which may mean personalized consideration of the treatment including surgery. Figure 2 FIG 2. Comparison of the recurrence hazard rate according to the site of distant metastasis. Each organ has a different peak of recurrence, although the peaks and shapes of the hazard rate curves were similar between bone and supraclavicular lymph nodes. Therefore, in this session, we will discuss “resect or not to resect” in several specific situations such as 1) for the patients with invasive T3 or resectable T4 2) for the patients with multi-station, bulky lymph nodes (not every) 3) for the patients with central lung cancer with possible sleeve lobectomy 4) for the old patients (>75 year-old) with comorbidity By the rapid development of the medical sciences, especially in cancer medicine, there would be fundamental changes in the diagnosis and management of N2 disease. Especially, improvement in systemic treatment would have critical impact on the surgical role in locally-advanced lung cancer. Moreover, if systemic tumor burden or minimal residual disease could be assessed at the earliest, surgery would be applied with higher benefit, and thus, the survival outcome would be significantly improved. Therefore, there should be more studies of combined local control (surgery) and systemic control (chemo and/or immunotherapy); either as adjuvant, neoadjuvant or salvage purpose; either with or without radiotherapy; participated by thoracic surgeons, to maximize the survival of the patients from dreadful disease. References 1. Kim HK, Cho JH, Choi YS, et al. Outcomes of neoadjuvant concurrent chemotherapy followed by surgery for non-small cell lung cancer with N2 disease. Lung Cancer 2016; 96:56-92 2. Lee J, Kim HK, Park BJ, et al. Recurrence Dynamics after Trimodality Therapy (Neoadjuvant Concurrent Chemoradiotherapy and Surgery) in Patients with Stage IIIA (N2) Lung Cancer. Lung Cancer (submitted)
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P1.08 - Locally Advanced NSCLC (ID 694)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Locally Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.08-004 - Adjuvant Chemoradiotherapy vs. Chemotherapy for Completely Resected Unsuspected N2-Positive Non-Small Cell Lung Cancer (ID 8238)
09:30 - 16:00 | Author(s): Jhingook Kim
- Abstract
Background:
We investigated whether concurrent chemoradiotherapy (CCRT) would increase survival in patients with completely resected unsuspected N2-positive non-small cell lung cancer (NSCLC), compared with adjuvant chemotherapy alone.
Method:
Eligible patients were randomly assigned (1:1 ratio) to either the CCRT arm or the chemotherapy arm. In the CCRT arm, patients received concurrent thoracic radiotherapy (50 Gy in 25 fractions) with five cycles of weekly paclitaxel (50 mg/m[2]) and cisplatin (25 mg/m[2]), followed by two additional cycles of paclitaxel (175 mg/m[2]) plus cisplatin (80 mg/m[2]) at three-week intervals. In the chemotherapy arm, patients received four cycles of adjuvant paclitaxel (175 mg/m[2]) and carboplatin (AUC 5.5) every three weeks. The primary endpoint was disease-free survival.
Result:
We enrolled and analyzed 101 patients. The median disease-free survival of the CCRT arm was 24.7 months, which was not significantly different from that of the chemotherapy arm (21.9 months; hazard ratio [HR] 0.94, 95% CI: 0.58–1.52, P = 0.40). There was no difference in overall survival (CCRT: 74.3 months, chemotherapy: 83.5 months, HR: 1.33, 95% CI: 0.71–2.49). Subgroup analysis showed chemotherapy alone increased overall survival in never-smokers and multi-station N2-positive patients. The pattern of disease recurrence was similar between the two arms.
Conclusion:
There was no survival benefit from adjuvant CCRT compared with platinum-based chemotherapy alone for completely resected unsuspected N2-positive NSCLC.
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P2.02 - Biology/Pathology (ID 616)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.02-001 - Detection of Gene Fusions in NSCLC Using NGS Fusion Assay (ID 10033)
09:30 - 16:00 | Author(s): Jhingook Kim
- Abstract
Background:
ALK/RET/ROS and MET exon 14 skipping detection are important to guide of treatment in non-small cell lung cancer (NSCLC) patients. Next generation sequencing (NGS) platform has been implemented in the daily practice for the diagnosis. However, the validation of the NGS-based panel is still complicated and difficult.
Method:
We developed NGS-based fusion assay panel to detect 183 total fusion variants including ALK/RET/ROS as well as MET exon 14 skipping. The fusion call agreement between OCP-50 NGS assay and Nanostring was performed. The result was compared with the FISH and IHC results. This study describes the validation of the assay to define assay parameters, performance characteristics and reproducibility across laboratories.
Result:
For the 55 samples analyzed, the results are as follows;ALK Fusion ROS1 Fusion RET Fusion METD14 NGS(+) NGS(-) Total NGS(+) NGS(-) Total NGS(+) NGS(-) Total NGS(+) NGS(-) Total NS (+) 20 0 20 6 0 6 5 0 5 0 0 0 NS (-) 1 33 34 1 47 48 0 49 49 2 52 54 Total 21 33 54 7 47 54 5 49 54 2 52 54
Conclusion:
The results of our study will be of help in learning the process of establishing, validating and applying the fusion gene detection method in NSCLCs. Furthermore, NGS based OCP-50 assay for fusion detection is more accurate and reliable method for the diagnosis.
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P3.01 - Advanced NSCLC (ID 621)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.01-082 - Surgical Rebiopsy in Advanced Non-Small Cell Lung Cancer Resistant to Previous Chemotherapy (ID 10505)
09:30 - 16:00 | Author(s): Jhingook Kim
- Abstract
Background:
To optimize the personalized medicine for advanced non-small cell lung cancer (NSCLC), sufficient tumor tissue is mandatory to analyze molecular and genetic profile. The demand for repeat biopsy in NSCLC is increasing, it is more difficult to obtain specimen after initial treatment. The aim of this study was to evaluate the impact of surgical rebiopsy in advanced NSCLC.
Method:
From Jan 2014 to Mar 2017, 146 consecutive patients underwent surgical rebiopsy for NSCLC which was resistant to prior chemotherapy. Their medical record were reviewed retrospectively.
Result:
There were 60 male and 86 female patients with mean age of 57 years (range 30-83). Adenocarcinoma was most common histologic type (n=142, 93%). Among them, 107 patients represent EGFR mutation before chemotherapy, deletion in exon 19 (n=73) was most frequently observed. Before surgical rebiopsy, 121 patients (83%) were treated with EGFR-TKIs. The mean number of change in chemotherapy regimen was 2 (range 1-6) and 24% of patients underwent more than 3 different chemotherapy before rebiopsy. The median time between initial treatment and rebiopsy was 17.4 months (IQR 9-25). Surgical rebiopsy was possible in all cases. One hundred and seven patients (73%) underwent pleura biopsy, 22 underwent lung resection and 12 patients underwent both pleural and lung resection. Most procedure underwent video-assisted thoracic surgery (n=136, 93%), 10 patients required mini-thoracotomy. Median postoperative hospital stay was 4 days (IQR, 3-6) and the 30-day mortality was 2.7%. All specimens were confirmed as NSCLC and adequate for mutational and genetic analysis except 2 patients. One patient was failed to mutational analysis, other patients was failed to genetic sequencing due to low tumor volume. After surgery, 129 patients can resume chemotherapy. Of those, 85 patients were enrolled clinical trial or treated with new target agent. Thirty nine patients were treated with cytotoxic chemotherapy and 5 patients continued with prior target agent.
Conclusion:
Surgical rebiopsy can detect changes in cancer characteristics and may be used in therapeutic decision making in advanced NSCLC resistant to previous treatment.
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P3.02 - Biology/Pathology (ID 620)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.02-011 - A Prospective Study of Serial Circulating Tumor DNA Assessment in Detecting Recurrence of Resected Early-stage Lung Cancer (ID 10062)
09:30 - 16:00 | Author(s): Jhingook Kim
- Abstract
Background:
In advanced non-small cell lung cancer (NSCLC), circulating tumor DNA (ctDNA) can be used to identify clinically actionable mutations when tissue is insufficient or unobtainable for genotyping. In early-stage NSCLC, the persistence of ctDNA after complete resection may suggest the presence of minimal residual disease and predict an increased risk of recurrence; however, data on the longitudinal use of ctDNA is very limited. The aim of this study is to assess the clinical feasibility of ctDNA assessment for the prediction of lung cancer recurrence following surgical resection.
Method:
Patients undergoing curative-intent surgery for NSCLC were prospectively enrolled. Peripheral blood samples were collected at pre-specified time points immediately prior to surgery and 2-3 weeks after surgery. Plasma cell-free DNA samples were analyzed with a novel 21-gene Digital Sequencing NGS panel (Guardant Health, Inc.) with a theoretical genomic sensitivity of > 90% for NSCLC. For each patient, the identities and quantities of somatic alterations identified in ctDNA were correlated to clinical outcomes.
Result:
Of the 55 pair-matched patients, 33 were evaluable at the time of abstract submission. The median age was 61 (18 men). The histologic type was adenocarcinoma in 19 (58%), squamous cell carcinoma in 14 (42%), and small cell lung cancer in 2 (6%). The pathologic stage was I in 20 (61%), II in 3 (9%), and IIIA in 10 (30%). Median clinical follow up was 13 months. Of the 4 patients with detectable post-operative ctDNA, 3 recurred within the follow-up period. Of the 8 total recurrences observed, the most common site was the brain (4) and lung (3). One of 4 adenocarcinoma recurrences, 1 of 2 squamous cell carcinoma recurrences, and 1 of 2 small cell recurrences were associated with detectable post-operative ctDNA. By stage, post-operative ctDNA was detected in 1 of 1 stage II and 3 of 7 stage IIIA patients. Recurrences not associated with detectable post-operative ctDNA were enriched in oligometastatic recurrence (4 of 5 unpredicted recurrences were in isolated lymph nodes or the brain).
Conclusion:
In this small pilot cohort, ctDNA detected at 2 weeks post resection was associated with recurrence (RR 9.38, p=0.038), while the absence of detectable ctDNA was not significantly associated with lack of recurrence (RR 0.65, p=0.12). Oligometastatic disease, especially in the brain, was a primary risk factor for ctDNA-negative recurrence. These findings establish proof of concept for the use of ctDNA diagnostics as a risk stratification tool in resected lung cancer.
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P3.04 - Clinical Design, Statistics and Clinical Trials (ID 720)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Clinical Design, Statistics and Clinical Trials
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.04-011 - A Prospective Study to Optimize the Extent of Pulmonary Resection According to Decision-Making Algorithm in cStage IA NSCLC (ID 10047)
09:30 - 16:00 | Author(s): Jhingook Kim
- Abstract
Background:
Recent advances in imaging technology and the widespread use of low-dose computed tomography screening have greatly increased the chance of detecting small-sized non-small cell lung cancer (NSCLC) with indolent features (radiologically ground-glass opacity and histopathologically lepidic pattern adenocarcinoma). This change in the disease pattern of NSCLC has led to a resurgence of interest in sublobar resection. The purpose of this study is to determine the outcome of patients with clinical stage IA NSCLC treated by 3 types of surgical resection (wide wedge resection, segmentectomy, or lobectomy) according to the institutional decision-making algorithm.
Method:
In this study, we are planning to prospectively enroll 1,000 patients with clinical stage IA NSCLC undergoing curative-intent surgical resection. Our decision-making algorithm regarding the optimal extent of pulmonary resection has been developed based on our institutional consensus building meetings. We are planning to prospectively measure radiologic features such as tumor diameter and consolidation/tumor (CT) ratio. For ≤ 2cm tumors with CT ratio of ≤ 0.25, wide wedge resection needs to be performed. For ≤ 2cm tumors with CT ratio of 0.25 to 0.5 or 2-3cm tumors with CT ratio of ≤ 0.5, segmentectomy should be chosen. When CT ratio is larger than 0.5, lobectomy is required regardless of tumor size. When either parenchymal or bronchial resection margin is found to be insufficient during surgery, segmentectomy or lobectomy should be done even when a lesser resection was planned. Resection margins greater than the maximal tumor diameter (lesions less than 2cm) or at least 2cm gross margins (lesions larger than 2cm) should be achieved. Hilar and mediastinal lymph node dissection or at least systematic lymph node sampling is strongly recommended for any kind of pulmonary resection.
Result:
The primary objective is to determine disease-free survival following sublobar resection and lobectomy. The secondary objectives are (1) to determine overall survival following surgery, (2) to determine rates of loco-regional and systemic recurrence following surgery, (3) to compare postoperative pulmonary function between 3 different resection types, (4) to explore the relationship between radiologic parameters and pathologic subtypes, and (5) to determine the predictors of unexpected nodal involvement.
Conclusion:
This study is registered with ClinicalTrials.gov, number NCT03066297 (“OREX-IA” study) and we started recruiting patients in February, 2017 and will also be planning to follow up patients for at least 5 years to analyze their survival and recurrences.
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P3.05 - Early Stage NSCLC (ID 721)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Early Stage NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.05-012 - Clinicopathological Determinants of Circulating Tumor DNA Detection in Early-Stage Non-Small Cell Lung Cancer (ID 10329)
09:30 - 16:00 | Author(s): Jhingook Kim
- Abstract
Background:
Circulating tumor DNA (ctDNA)-based liquid biopsies have recently demonstrated substantial promise in the diagnosis and monitoring of advanced non-small cell lung cancer (NSCLC); however, data regarding utility in early-stage (operable) disease are very limited. The aim of this study is to define the clinical feasibility of ctDNA assessment in operable NSCLC.
Method:
We prospectively recruited 80 patients with clinical stage I-IIIa NSCLC undergoing cruative intent tumor resection. Pre-surgical plasma cell-free DNA (cfDNA) and matched tumor genomic DNA were collected and analyzed with a novel 21-gene Digital Sequencing NGS panel (Guardant Health, Inc.) with a theoretical genomic sensitivity of > 90% for NSCLC. Genomic results, including cfDNA yields, technical sequencing information, and identity and quantity of somatic variants, were correlated with various clinicopathological characteristics, including age, sex, smoking history, clinical and pathologic stage, histological tumor type, and preoperative treatment status.
Result:
[Cohort enrollment and sample collection is complete. Sequencing and analysis have been completed for the first 20 patients. The remaining patients will be completed within 1-2 months. Results from the complete cohort will be updated as directed by the Core Program Committee and will include the data elements described in the methods above. A preliminary review of the data is included below.] Of the 18 patients with somatic variants detected in tumor tissue (18/20, 90%), pre-operative ctDNA was detected in 12 (67%). Pre-operative ctDNA detection was high in squamous cell carcinoma (8/8), small cell lung cancer (1/1) and mixed histology (1/1) relative to adenocarcinoma (2/10, 20%). Clinical stage did not influence detection of small cell or squamous cell carcinoma; however, no ctDNA was detected in stage I or II adenocarcinoma samples (0/5). Detailed data from the complete cohort will be submitted as a late-breaking abstract.
Conclusion:
[Conclusion to be updated pending full cohort data.] ctDNA demonstrates sufficient pre-operative clinical sensitivity to be a feasible recurrence monitoring tool but appears to be influenced by tumor type.
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P3.08 - Locally Advanced Nsclc (ID 724)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Locally Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.08-006 - Treatment Response and Survival Outcomes Are Associated with Histologic Type in Non-Small Cell Lung Cancer Treated with Trimodal Treatment (ID 9972)
09:30 - 16:00 | Author(s): Jhingook Kim
- Abstract
Background:
Trimodal treatment incorporating neoadjuvant concurrent chemoradiotherapy (CCRT) and surgical resection is one of the treatment strategies for non-small cell lung cancer (NSCLC) patients with N2 disease. Although pathologic phenotypes as well as biological features might be different between adenocarcinoma (ADC) and squamous cell carcinoma (SqCC), histologic type has been rarely considered when selecting treatment strategy in patients with N2 disease. The aim of this study is to investigate if histologic type is associated with treatment response and survival outcomes in patients undergoing trimodal treatment for N2 disease.
Method:
A retrospective review of patients with N2 disease who underwent neoadjuvant CCRT followed by surgery at our institution was performed. Clinicopathologic features, response to CCRT, and survival outcomes were compared between ADC and SqCC.
Result:
From 2003 to 2013, 374 patients underwent curative-intent surgery after neoadjuvant CCRT for either ADC (n=233, 62.3%) or SqCC (n=141, 37.7%) with pathologically proven N2 disease. Sixty-nine patients (18.5%) had bulky and/or multi-stationed N2 diseases on pre-CCRT imaging tests. There were more male, more smokers, more advanced clinical T and N stages, and more bulky and/or multi-stationed N2 diseases in the SqCC group than in the ADC group. Conversely, the SqCC group had more radiologic responders, earlier pathologic T and N stages, more pathologic complete responders, and more frequent mediastinal downstaging than the ADC group. With a mean follow-up of 50.1 months, patients with SqCC showed significantly better 5-year recurrence-free survival than those with ADC (ADC, 22.8% vs. SqCC, 43%; p=0.001). However, there was no significant difference in the 5-year overall survival between the two groups (ADC, 57.5% vs. SqCC, 52.3%; p=0.366). This may be related to significantly better (p<0.001) post-recurrence survival in the ADC group (mean, 28 months) than in the SqCC group (mean, 14.5 months). In the ADC group, 164 patients developed recurrences and of those, 68 (41.5%) received targeted therapy. Patients who received targeted therapy for recurrences showed significant better 5-year overall survival than those who did not receive (61% vs. 45.6%, p=0.025).
Conclusion:
In this study, SqCC was associated with better treatment response and more favorable recurrence-free survival than ADC. Despite poor recurrence-free survival in ADC, its overall survival was improved by prolonged post-recurrence survival, which might be related to the use of targeted therapy for recurrence. Since treatment response and survival outcomes are different according to histologic type, individualized treatment strategy could be considered to improve outcomes of N2 disease.
