Virtual Library

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    EP1.01 - Advanced NSCLC (ID 150)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Advanced NSCLC
    • Presentations: 106
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.01-108 - EGFR Exon 18 Mutations in NSCLC: Frequent Co-Occurrence of Multiple EGFR Mutations and Assessment of Cis/Trans Status (ID 2747)

      08:00 - 18:00  |  Author(s): Christine M Lovly, Russell Madison, Benjamin Brown, Yun-Kai Zhang, Luke Juckett, Lee A Albacker, Jessica Lee, Sai-Hong Ignatius Ou, Vincent Miller, Brian Alexander, Siraj M Ali, Alexa Betzig Schrock

      • Abstract

      Background

      A subset of EGFR exon 18 (ex18) mutations including G719X are known drivers in NSCLC. However, the sensitivity profile of other ex18 mutations and frequently occurring dual ex18/ex18 and ex18/non-ex18 combinations has not been well described.

      Method

      Hybrid-capture based comprehensive genomic profiling was performed on 46,296 FFPE tissue samples from patients with NSCLC. Tumor mutational burden (TMB) was determined on 0.8-1.1 Mbp of sequenced DNA and reported as mut/Mb. Configuration was determined by analyzing sequencing reads that spanned both loci. The number of reads that harbored mutations at one or both positions was tabulated and used to infer cis or trans status. Patient ancestry was determined by single nucleotide polymorphism (SNP) microarray data, ancestry informative markers, and principal component analysis (PCA)..

      Result

      EGFR ex18 mutations (point mutations and indels) were identified in 1.1% (522/46,296) of NSCLCs. The median patient age was 67 years (range 30-96) and 67% of patients were female. This subset was also enriched for patients of East Asian descent when compared to EGFR wildtype NSCLC (17% v 3.9%; p < 0.001), similar to ex19del and L858R populations (19% and 24%, respectively). Median TMB was 4.35 mut/mb (range 0-70). Co-occurring EGFR mutations were identified in 69% (362/522) of cases, including most commonly S768I (20%, 103/522) and L858R (12%,61/522). T790M was detected in 6.1% (32/522) of ex18 cases. Multiple EGFR ex18 mutations occurred in 15% (76/522) of cases including 2 cases with 3 and a single case with 4 such mutations. The most commonly observed missense pairs were E709A/G719S (17/76) and E709A/G719A (16/76). Other combinations of E709X/G719X made up an additional 42% (32/76), with the remaining 14% of cases consisting of rare combinations (n<4 for all). All ex18 mutations in all cases (76/76) were in cis. Preliminary evidence from paired cases and assessment of mutant allele frequencies suggests that ex18 mutations found together in cis arise de novo. Results of in vitro studies to determine the sensitivity of single ex18 mutations as well as common pairs to all generations of EGFR inhibitors will be presented.

      Conclusion
      EGFR ex18 mutations co-occur at a high frequency with both ex18 and non-ex18 EGFR mutations, unlike classic EGFR mutations (L858R, ex19del). Female gender, East Asian ancestry, and low TMB were common in ex18 cases, similar to populations with classic EGFR mutations. In all cases with multiple EGFR ex18 mutations these mutations were always found to occur in cis. Further work to understand the evolution of these co-occurring EGFR mutations and to determine the best therapeutic strategy or strategies for this NSCLC patient population is warranted

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      EP1.01-01 - Atrial Resection Without Cardiopulmonary Bypass for Lung Cancer (Now Available) (ID 2778)

      08:00 - 18:00  |  Presenting Author(s): Domenico Galetta  |  Author(s): Lorenzo Spaggiari

      • Abstract
      • Slides

      Background

      Results of resection of lung cancer invading left atrium (T4atrium) without cardiopulmonary bypass (CPB) remain controversial. We reviewed our experience analyzing surgical results and postoperative outcomes.

      Method

      Patients who underwent extended lung resection for T4atrium without CPB between 1998 and 2018 were retrospectively reviewed using a prospective database.

      Result

      Forty-four patients were collected (34 men, median age, 63 years). Twenty-five patients underwent preoperative mediastinal staging and 27 received induction treatment (IT). Lung resection included 40 (90.9%) pneumonectomies, 3 (6.8%) lobectomies and one bilobectomy (2.3%). Pathological nodal status was N0 in 10 patients (22.7%), N1 in 18 (40.9%), and N2 in 16 (36.4%). Four patients receiving IT had complete pathological response (9.1%). Eight patients (18.2%) had microscopic tumor evidence on atrial resected margins. Mortality was nil. Major complication rate was 11.4%: one BPF, one cardiac herniation, and three hemothorax all requiring re-intervention. Minor complication rate was 25.5%. After a median survival of 37 months (range, 1-144 months), 20 patients (45.4%) were alive. Five-year survival and disease-free interval were 39% and 45.8%, respectively. Patients with N0 and R0 disease had a best prognosis (log-rank test: p=.03, and p=.01, respectively). IT neither influenced survival nor postoperative complications. At multivariate analysis, pN0 [p=.04 (95% CI: 0,65-9,66)] and negative atrial margins [p=.02 (95% CI: 0,96-8,35) were positive independent prognostic factors.

      Conclusion

      Resection of T4atrium is technically feasible without mortality and acceptable morbidity. Patients with N2 cancers should not be operated on. Lung cancer invading left atrium should not be systematically considered as a definitive contraindication to surgery.

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      EP1.01-03 - Real World Outcome of Crizotinib for Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer Patients (Now Available) (ID 141)

      08:00 - 18:00  |  Presenting Author(s): Yeon Joo Kim  |  Author(s): Chang-Min Choi, Jae Cheol Lee, Sang-we Kim, Dae Ho Lee, Shinkyo Yoon

      • Abstract
      • Slides

      Background

      Crizotinib has shown its superiority in clinical trials compared to conventional chemotherapy in patients with anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer (NSCLC) patient, but its use and outcomes in real-world settings are yet to be investigated. This study aimed to assess treatment patterns and outcomes of crizotinib therapy in ALK-positive NSCLC patients, as well as to seek factors associated with progression-free survival and overall survival of ALK-positive NSCLC patients.

      Method

      A retrospective medical record review of 176 patients who are diagnosed as metastatic or recurred NSCLC from January 1st, 2006 to June 30th, 2018 and treated with crizotinib was performed. Descriptive analyses were conducted to assess treatment patterns and objective response rate (ORR). Survival analysis to estimate progression-free survival (PFS) and overall survival (OS) was performed. Comparison of the treatment outcomes by the setting of crizotinib initiation was done. Cox regression analysis was used to find predictive factors associated with PFS and OS from initiation of crizotinib.

      Result

      Median age was 55.7 (ranged 20 to 84) years and 85 patients (48.3%) were male. Seventy-two (40.9%) patients died at the time of analysis. Seventy-eight patients initiated crizotinib as first-line therapy. Overall response rate was 54.5% (50.0% for first-line recipients, 58.2% for second-/later-line). Median (95% CI) PFS from crizotinib initiation and OS from first dose of chemotherapeutic agent were 14.3 (11.6-17.0) and 41.7 (25.4-58.1) months, respectively. No significant difference of ORR, OS, and PFS, according to the setting of crizotinib initiation was observed. Multivariate Cox analysis showed poor performance status (HR 3.472, p-value < 0.001) and number of metastatic organs (≥3, HR 1.648, p-value 0.017) were independently associated to shorter PFS and OS, while history of getting pemetrexed before use of crizotinib (HR 0.638, p-value 0.039) was independently related to longer OS.

      All patients

      Setting of Crizotinib Initiation

      (n = 176)

      First-Line

      (n = 78)

      Second- or Later-Line

      (n = 98)

      P value

      Progression-free survival

      0.699

      Mean (SE)

      25.0 (3.1)

      28.0 (6.4)

      16.6 (1.5)

      Median (95% CI)

      14.3 (11.6-17.0)

      15.8 (10.0-21.6)

      13.1 (9.1-17.0)

      Q1, Q3

      5, 27

      5, 22

      5, 27

      Overall survival

      0.137

      Mean (SE)

      54.1 (4.2)

      40.6 (6.1)

      57.8 (4.9)

      Median (95% CI)

      41.7 (25.4-58.1)

      26.3 (14.7-37.9)

      43.9 (25.7-62.1)

      Q1, Q3

      18, 109

      17, 77

      19, 109

      1- and 2-year survival rates

      Percent still alive at 1 year after diagnosis (95% CI)

      87.1 (86.7-87.5)

      85.4 (84.3-86.5)

      88.5 (87.8-89.2)

      0.483

      Percent still alive at 2 years after diagnosis (95% CI)

      65.7 (65.0-66.4)

      55.4 (51.9-58.9)

      69.0 (68.0-70.0)

      0.213

      Conclusion

      Outcomes for crizotinib recipients were in line with previous trials, with PFS and OS appearing more favorable. Poor performance status and number of metastatic organs correlated to worse PFS and OS, while history of previous use of pemetrexed before crizotinib correlated to better OS.

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      EP1.01-04 - Phase I/II Trial of Biweekly Nab-Paclitaxel in Patients with Previously Treated Advanced Non-Small Cell Lung Cancer: NJLCG1402 (Now Available) (ID 795)

      08:00 - 18:00  |  Presenting Author(s): Hisashi Tanaka  |  Author(s): Eisaku Miyauchi, Atsushi Nakamura, Toshiyuki Harada, Taku Nakagawa, Mami Morita, Daisuke Jingu, Kuda Tomoya, Shunichi Gamou, Ryota Saito, Akira Inoue

      • Abstract
      • Slides

      Background

      Nanoparticle albumin-bound paclitaxel (nab-PTX) is a cremophor-free formulation of paclitaxel that can be administered safely as a short infusion without dexamethasone or antihistamine premedication. NJLCG1402 consists of multiple, open-label, single arm, phase I/II trials designed to assess the benefit of biweekly nab-PTX treatment in patients (pts) with previously treated advanced NSCLC (UMIN 000014893).

      Method

      Eligible patients were aged ≥20 years; had histologically or cytologically confirmed, advanced-stage, previously treated NSCLC. Nab-PTX was administered biweekly at dose of 100 to 150 mg/m2 in a 28-day cycle. In the phase I part, we aim to determine the recommended phase II dose of nab-PTX. In the phase II part, pts were assessed for efficacy and tolerability. The primary endpoint for the phase II part is the objective response rate. Secondary endpoints were progression free survival, overall survival, disease control rate, and safety. Assuming an expected the objective response rate of 15% and threshold of 5%, a total of 18 pts were required to have 70% power at a two-tailed alpha of 0.2 at the phase II part.

      Result

      A total of 27 pts (median age 68 years, male 78%) were enrolled. The dose escalation cohort included 15 pts administered biweekly with 100 to 150 mg/m2 across 3 dose levels, and 12 patients in the phase II part were administered with 150mg. No dose-limiting toxicities were observed in the phase I part and 150mg was determined as recommend dose. Of the evaluable pts (n=18) at dose of 150mg/m2, the objective response rate was 22%(4 of 18 pts; 95% CI, 9.5 to 43.5), median progression free survival was 3.6 months (95% CI 1.4 to 5.9), and median overall survival was 7.2 months (95% CI, 0 to 15.0 months). Adverse events (AEs) of grade 3 or higher were observed in 39% of patients. The most common AEs were leukopenia (22%), anemia (22%), and rash (6%).

      Conclusion

      Biweekly nab-PTX monotherapy was well tolerated and exhibits promising systemic antitumor activity in previously treated NSCLC pts.

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      EP1.01-05 - EGFR-2013-CPHG, a Real-World Study of EGFR Mutant Advanced Non-Small-Cell Lung Cancer Patients Treated with Erlotinib (ID 892)

      08:00 - 18:00  |  Presenting Author(s): Didier Debieuvre  |  Author(s): Jean Tredaniel, Lionel Moreau, Sébastien Larivé, Jacques Le Treut, Cécilia Nocent, Stéphane Hominal, Valérie Grangeon, Jean-Louis Bizec, Olivier Molinier, Thibault Payen

      • Abstract
      • Slides

      Background

      Erlotinib (E) is a first-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor labelled in France and effective as a first-line treatment in advanced non-small-cell lung cancer (NSCLC). E has demonstrated a better efficacy than chemotherapy in EGFR mutant NSCLC in phase III trials.

      Method

      We undertook a multicentric study in 42 French Nonacademic Hospital Centres. Patients aged 18 years and older with histologically confirmed stage IIIB or IV NSCLC and harboring a confirmed activating mutation of EGFR received oral E (150 mg/day). We report here patient characteristics, progression-free survival (PFS), overall survival (OS), and safety data. Statistical analyses by R software were based on a Cox model and Kaplan-Meier method.

      Result

      Between April 1st, 2014 and March 31st, 2016, 184 patients were recruited: mean age = 72 years old, 125 (69.5%) female, 158 (90.8%) Caucasians, 112 (63.6%) non-smokers, 167 (94.9%) adenocarcinoma (21 stage IIIB and 156 stage IV), 127 (65.6%) ECOG 0-1, 40 (26%) brain metastasis at inclusion and 75 (42.4%) were treated by E in second- or latter line. 179 patients were included in the PFS and OS analysis. Median follow-up was 23.8 months, median PFS was 11.7 months and median OS was 25.8 months. Median survival rates at one year were 48.6% for PFS and 75% for OS. Risk of death was not correlated with brain metastasis (HR=1.15, IC95:0.67-1.97, p=0.296) but with ECOG = 2 (HR=4.55, IC95:2.05-10.10, p<0,001). E had a manageable safety profile (7.7% grade 3-4 adverse events at 6 months) and no new safety signals were identified.

      N %
      Patients 184
      Mean age (years) 72
      Sex

      Males

      Females

      59

      125

      30.5

      69.5

      Race
      Caucasians 158 90.8
      Smoking status
      Non-smokers 112 63.6
      Histological type
      Adenocarcinoma 167 94.9
      Staging

      Stade IIIB

      Stade IV

      21

      156

      ECOG
      0 or 1 127 65.7
      Brain metastases at inclusion 40 26
      Second-lind therapeutic strategy and more
      Erlotinib 75 42.4
      Progression-free survival and overall survival 179

      Median Progression-free survival (Months)

      Median Overall Survival (Months)

      11.7

      25.8

      Conclusion

      Data from EGFR-2013-CPHG real-world study are consistent with the efficacy and safety of E in EGFR mutant NSCLC patients seen in phase III clinical trials.

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      EP1.01-06 - Loss of Heterozygosity of Oncogene ERBB2 with an Activating Mutation Was Identified as Driver Eventin Leptomeningeal Metastasis of NSCLC (ID 1184)

      08:00 - 18:00  |  Presenting Author(s): Peng Wang  |  Author(s): Zengfeng Sun, Weihua Guo, Min Shi

      • Abstract

      Background

      Due to limited access to leptomeningeal lesions, cerebrospinal fluid (CSF) may be the most representative liquid biopsy to get genomic information from leptomeningeal metastases (LM) in non-small-cell lung cancer (NSCLC). Loss of heterozygosity (LOH) is a common genetic event during cancer tumorigenesis. LOH of tumor suppressor gene in which loss-of-function occurs on alternative allele serves as “second hit” and leads to loss of the remaining functional allele. LOH of tumor suppressor gene, such as TP53,in CSF had been reported for its associated with EGFR-TKI resistance in LM. Here, through CSF derived liquid biopsy, we report a LOH of oncogene ERBB2 in LM of NSCLC patient. To the best of our knowledge, this is the first report of LOH of oncogene, no matter in a primary or metastatic tumor.

      Method

      Three CSF biopsies and matched peripheral blood were collected within 6 months from one NSCLC patient with LM. Cell-free DNA (cfDNA) was extracted, and somatic mutations were examined using a designed lung cancer panel of 180 genes. SCNAs were further identified through 2x whole genome sequencing (WGS). Genomic alternations identified in all three matched biopsies were included in the subsequent analysis.

      Result

      A rare oncogene ERBB2 activating mutation (V659E) was identified in CSF but not in plasma. V659E lies within the transmembrane domain and results in constitutive activation of Src and Akt signaling. Extreme high variants allele fraction (96.8%) of ERBB2 V659E in CSF implied the LOH of ERBB2 in LM. SNPs heterozygosity analysis and low pass WGS were further carried out and confirmed the LOH of entire chromosome 17, but not limited to ERBB2 region. Furthermore, A consecutive an amplification was observed on the remaining copy of chromosome 17q, on which the activated oncogene ERBB2 located. The amplification, following ERBB2 LOH with a concomitant activating mutation, may enhance constitutively active ERBB2 expression and drive the evolution of LM. Besides, there were two more unique mutations in CSF, TP53 T256fs (45.31%) and JAK3 R582Q (32.85%). Relatively Low variants allele fraction indicated that they were subclonal mutation occurring after ERBB2 activating mutation and LOH of chromosome 17.

      Conclusion

      We first reported an oncogene ERBB2 LOH in CSF from one NSCLC patient with LM. Based on phylogeny inference, the ERBB2 activating mutation and LOH of chromosome 17 were likely to be the earliest driver event.

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      EP1.01-07 - Definitive Results of a Clinical and Molecular Multicentric Characterization of Long-Term Survivors with Advanced Non-Small Cell Lung Cancer  (Now Available) (ID 1191)

      08:00 - 18:00  |  Presenting Author(s): María Sereno  |  Author(s): Juan Moreno-Rubio, Santiago Ponce, Rosa Alvarez, María Eugenia Olmedo, Sandra Falagan, Xabier Mielgo Rubio, Fátima Navarro, Patricia Cruz, Luis Cabezon-Gutierrez, Marta Muñoz Fernandez De Leglaría, Ana Belen Enguita, Maria Cebollero, Amparo Benito, Isabel Alemany, Carolina Del Castillo, Ana Ramirez De Molina, Enrique Casado, Ricardo Ramos, Gonzalo Colmenarejo

      • Abstract
      • Slides

      Background

      Long survivors (LS) in non-small-cell lung cancer (NSCLC), defined as an overall survival (OS) greater than 2 years, are less than 10% in most series. Classical prognosis factors include stage, weight loss and ECOG, but more information is missing in the literature. Recently, EGFR, ALK and ROS 1 population (less than 20%) reach OS longer than 2 years. Immunotherapy has demonstrated very promising results with more LS compared to chemotherapy in first and second line setting. In this study, we focused in the analysis of LS patients with advanced NSCLC EGFR wt (wild type) and ALK nt (non-translocated), defined as those with OS greater than 36 months, in 7 hospitals in Madrid.

      Method

      In this serie, first of all, we will try to make a clinical, histopathological characterization collecting data from clinical reports according to a previously defined information. In a second step, we will carry out a genetic analysis of these patient samples comparing to an opposite extreme short survivors (SS) samples (OS less than 9 months). Initially, we used a NGS method of RNA-seq technology to identify differentiating profiles of gene expression between the two opposite populations. And finally, we confirmed this preliminary profile by RT-PCR in the rest of samples.

      Result

      Ninety-six patients were initially included. The majority were men, smokers or former with adenocarcinoma and ECOG 0- 1. We have obtained a differential transcriptome expression between samples from 6 LS and 6 SS, resulting 13 over-expressed and 42 down-expressed genes in LS comparing to SS transcriptome expression. Some of the genes involved in this initial profile belong to different cellular pathways: Secretin Receptor, Surfactant Protein, Trefoil Factor 1, Serpin Family, Ca-bindings Protein channel and Toll like Receptor family. Finally, we carried on by RT-PCR in 40 samples of SS and LS survivors and only four genes were significantly down-regulated in SS compared to LS in the multivariate analysis. These 4 genes were related to Surfactant Proteins: SFTPA1 (p = 0.023), SFTPA2 (p = 0.027), SFTPB (p = 0.02) and SFTPC (p = 0.047)

      Conclusion

      We present a sequential genetic analysis of a LS population with NSCLC EGFR wt (wild type) and ALK nt (non-translocated), obtaining a differential RNA seq- and RT-PCR gene profile based on different surfactant proteins expression. A further confirmation in a larger sample is ongoing.

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      EP1.01-08 - Efficacy of Osimertinib in Patients of Advanced Non-Small Cell Lung Cancer with Brain Metastasis: A Retrospective Analysis (Now Available) (ID 1656)

      08:00 - 18:00  |  Presenting Author(s): Jiexia Zhang  |  Author(s): lixuan Chen, meifeng Ye, honghao Li, Chengzhi Zhou, hui Pan

      • Abstract
      • Slides

      Background

      Osimertinib (AZD9291) is an oral, irreversible, third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that selectively inhibits both EGFR-TKI-sensitizing and EGFR T790M resistance mutations.The aim of this retrospective study was to evaluate the efficacy of AZD9291 for advanced non-small cell lung cancer(NSCLC) patients with brain metastasis.

      Method

      We followed up patients diagnosed with advanced non-small cell lung cancer who were detected with EGFR gene mutation and who received EGFR-TKI from 1st October 2006 to 1st June 2018.Patients finally collected were divided into two groups:One group comprised of 45 patients received first-generation or second-generation EGFR-TKI alone,while other group included 45 patients were given AZD9291.And the 95% confidence interval (CI)and the median progression-free survival (mPFS)were calculated by the Kaplan-Meier method.

      Result

      The median progression-free survival(mPFS) was longer with osimertinib than with standard EGFR-TKIs (14.0 months vs. 11.0 months; 95%Cl: 10.160-13.840, P=0.017). The mPFS of patients with brain metastasis was significantly longer with osimertinib than with standard EGFR-TKIs(13.0 months vs. 7.0 months; 95%CI: 6.087-11.913, P=0.020). The mPFS of patients with osimertinib was longer with combined radiotherapy than with not receive radiotherapy(18.0 months vs. 13.0 months; 95%CI:7.066-18.934, P=0.915).

      Conclusion

      In patients with non-small cell lung cancer with brain metastases, the median progression-free time of patients with osimertinib was longer than that of patients with first- or second-generation EGFR-TKIs alone, but osimertinib combined with radiotherapy showed no statistical significance compared with no radiotherapy.

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      EP1.01-09 - Clinical Efficacy of Circulating Tumor DNA Test in Advanced Non-Small-Cell Lung Cancer Patients Who Might Have T790M Mutation (Now Available) (ID 1673)

      08:00 - 18:00  |  Presenting Author(s): NamEun Kim

      • Abstract
      • Slides

      Background

      Using EGFR-tyrosine kinase inhibitors (TKIs) in patients with advanced lung cancer led to a significant improvement in survival. However, patients with these TKIs are ultimately resistant to disease, and about 50-60% patients showed EGFR T790M mutation. The purpose of this study was to evaluate the efficacy of tissue biopsy and liquid biopsy in patients undergoing re-biopsy after TKI use.

      Method

      We reviewed medical records of 85 NSCLC patients who had done both tissue rebiopsy and liquid sampling from december 2017 to december 2018, at Severance University Hospital, Seoul, Korea. In this patients, the degree of coincidence and an expression level of T790M were examined with rebiopsy tissue for EGFR and circulating tumor DNA (ct DNA). CtDNA in plasma requires 100 copies of EGFRT790M per milliliter of plasma, so allele-specific PCR and digital PCR method were used to increase sensitivity for detection..

      Result

      The mean age of the 85 patients was 62.9 ± 11.1 years, and 50 (58.8%) were female. The expression of T790M on rebiopsy was 17.6% (15/85) in ct DNA, and 23.5% (20/85) in tissue. The percentage of T790M from either liquid biopsy or tissue biopsy was 31.4% (27/85). The concordance between liquid biopsy and tissue biopsy was 72.9%. The sensitivity of liquid biopsy was 27%, specificity 72%, positive predictive value 22% and negative predictive value 77%.

      Conclusion

      Testing Circulating tumor DNA in patients with NSCLC after TKI use can help to find T790M mutation in addition to rebiopsy of tissue. Combination of liquid biopsy and tissue biopsy is complementary to find the subject of the third-generation TKI, osimertinib. Also, liquid biopsy is less invasive and repeatable than tissue biopsy, it is useful for group of negative finding at tissue biopsy initial

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      EP1.01-10 - Pembrolizumab in Combination with Chemotherapy as First-Line Treatment of Advanced Non-Small Cell Lung Cancer  (Now Available) (ID 1151)

      08:00 - 18:00  |  Presenting Author(s): Kyaw Zin Thein  |  Author(s): Nusrat Jahan, Sriman Swarup, Anita Sultan, Tun Win Naing, Francis Mogollon-Duffo, Somedeb Ball, Aung Myint Tun, Thura Win Htut, Akshar Dash, Nicholas D’cunha, Fred Hardwicke, Sanjay Awasthi, Lukman Tijani

      • Abstract
      • Slides

      Background

      Pembrolizumab, a monoclonal antibody directed against programmed death-1 (PD-1), has been established as preferred treatment as a monotherapy for advanced non-small cell lung cancer (NSCLC) with programmed death ligand 1 (PD-L1) expression of ≥ 50%. Combining immunotherapy with chemotherapy have shown synergistic anticancer activities and pembrolizumab has been studied in combination with various traditional chemotherapy regimens as first-line treatment for advanced NSCLC. Hence, we performed a systematic review and meta-analysis of currently available randomized controlled trials (RCTs) to evaluate the efficacy pembrolizumab in combination with chemotherapy as first-line treatment of advanced NSCLC.

      Method

      We conducted a comprehensive literature search using PUBMED, MEDLINE, EMBASE databases and meeting abstracts from inception through March 2019. RCTs utilizing first-line pembrolizumab chemoimmunotherapy in patients with advanced NSCLC were incorporated in the analysis. A generic inverse variance method was used to calculate the estimated pooled hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS) with 95% confidence interval (CI). Heterogeneity was assessed with Cochran’s Q-test. Random effects model was applied.

      Result

      3 RCTs (Keynote-021,189 and 407) including 1298 patients with advanced NSCLC were included in the analysis. The study arm used standard chemotherapy regimens in combination with pembrolizumab while control arm used only standard chemotherapy regimens. The randomization ratio was 2:1 in Keynote-189 study and 1:1 in other studies. The I2 statistic for heterogeneity was 0, suggesting homogeneity among RCTs. The pooled HR for PFS was statistically significant at 0.54 (95% CI: 0.47-0.62; P < 0.00001), including in PD-L1 tumor proportion score (TPS) of less than 1% cohort (HR: 0.72; 95% CI: 0.56-0.92; P = 0.010) and PD-L1 TPS ≥ 1% cohort (HR: 0.46; 95% CI: 0.39-0.56; P < 0.00001). The pooled HR for OS was 0.59 (95% CI: 0.45-0.76; P < 0.0001). Improvement in OS was also seen across all PD-L1 categories: in PD-L1 <1% group HR was 0.60 (95% CI: 0.43-0.83; P = 0.002) and in PD-L1 ≥ 1% group HR was 0.55 (95% CI: 0.40-0.75; P = 0.0002).

      Conclusion

      Our meta-analysis demonstrated that first-line chemoimmunotherapy with pembrolizumab significantly improved PFS and OS compared to standard chemotherapy in patients with advanced NSCLC. The improvement of PFS and OS were consistent across all PD-L1 expression categories.

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      EP1.01-11 - Prognosis of Lung Cancer in Patients with Interstitial Lung Disease; Comparison with NSIP and IPF (Now Available) (ID 1307)

      08:00 - 18:00  |  Presenting Author(s): Sehyun Kwak  |  Author(s): Myung Jin Song, Sang Hoon Lee, Yoon Soo Chang, Hee Yeong Kim

      • Abstract
      • Slides

      Background

      Lung cancer is the leading cause of death in worldwide. Some reports revealed that lung cancer with interstitial lung disease (ILD) is associated with poor prognosis. However, the prognosis of lung cancer according to the subtype of ILD is unclear. We analyzed the outcome of lung cancer according to CT findings of ILD.

      Method

      Among the non-small cell lung cancer (NSCLC) patients who visited Severance Hospital, Seoul, Korea from July 2005 to October 2018, patients with idiopathic pulmonary fibrosis (IPF) or non-specific interstitial pneumonia (NSIP) in chest CT image were enrolled in this study. Patients were divided into three groups according to CT findings; (1) definite + possible IPF, (2) intermediate, and (3) definite NISP + possible NSIP. All patients were diagnosed lung cancer NSCLC on biopsy. The characteristics of study population and prognosis of each group were examined

      Result

      A total of 151 patients were investigated in this study. Female was 4.6% and mean age was 70.2 years. 84 patients were definite + possible IPF group, 42 patients were intermediate, and 25 patients were definite NISP + possible NSIP group. The proportion of smokers who smoked once was significantly higher in definite + possible IPF group (p=0.006). Age, FVC, FEV1 and lung cancer stage were not different between the three groups. Median overall survival were 27.0 months in NSIP group, 15.3 months in intermediate group, and 9.5 months in IPF group (p=0.04). Additionally, 25% of patients in definite + possible IPF group experienced acute exacerbation.

      Conclusion

      CT findings of ILD in lung cancer patients could be helpful in predicting prognosis. Furthermore, acute exacerbation is more common in IPF patients. Therefore, careful attention should be paid to the treatment of lung cancer in patients with IPF pattern.

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      EP1.01-12 - SNPs of Organic Cation Transporter 6 Associate with the Efficacy of Platinum Combination Chemotherapy (Now Available) (ID 170)

      08:00 - 18:00  |  Presenting Author(s): Akira Takeuchi  |  Author(s): Tetsuya Oguri, Satoshi Fukuda, Yusuke Kagawa, Kazuki Sone, Osamu Takakuwa, Takehiro Uemura, Ken Maeno, Kensuke Fukumitsu, Yoshihiro Kanemitsu, Hirotsugu Ohkubo, Masaya Takemura, Yutaka Ito, Akio Niimi

      • Abstract
      • Slides

      Background

      Platinum derivatives (cisplatin or carboplatin) are key antitumor drugs to non-small cell lung cancer in combination therapy with not only other cytotoxic agents or vascular endothelial growth factor but also kinase inhibitors or immune checkpoint inhibitors. However, the predictive biomarker of effectiveness about platinum-based chemotherapy is still unclear.

      Organic cation transporter 6 (OCT6) is one of the solute carrier transporters (coded by SLC22A16) which transport substrates by facilitated diffusion or secondary active transport. We previously reported that OCT6 was involved in platinum drug resistance by mediating platinum drug influx in cancer cell. Single nucleotide polymorphisms (SNPs) in genome sequences bring about changes in the amino acid sequence, alter the protein structure, and result in individual differences.

      The aim of this study is to solve the association between the efficacy of cytotoxic chemotherapy including platinum derivatives and SNPs.

      Method

      We retrospectively screened 78 advanced non-squamous non-small cell lung cancer patients who received platinum derivatives (cisplatin or carboplatin) and pemetrexed combination therapy for the first line chemotherapy between October/2010 and May/2018. We investigated the association between SNPs (rs714368, rs723685, and rs12210538) of SLC22A16 or patients’ characteristics and clinical outcomes.

      Result

      The median age of patients was 67 years old. Sixty patients were male and 61 patients were current or former smokers. The historical features of Sixty-eight patients were adenocarcinoma, and 18 patients had positivity of EGFR mutation or ALK fusion. We excluded rs12210538 from covariable of this study as all patients had major homo allele about rs12210538.

      The clinical outcomes of this study were similar to those of previous clinical studies.

      We found the patients with phenotype “A” of rs714368 had higher disease control rate (DCR) and longer duration of progression free survival (PFS) compared to phenotype “G” [response rate (RR), 31.4 % vs 25%, p >0.99; DCR, 85.7% vs 37.5%, p<0.01; median PFS, 154 days vs 26,5 days, p<0.01; median overall survival (OS), 666 days vs 471 days, p=0.69, respectively]. On the other hand, genotype of rs723685 had no association with treatment outcomes [genotype “TT” vs “TC”, RR, 32.8% vs 18.2%, p=0.49; DCR, 83.6% vs 63.6%, p=0.21; PFS, 132 days vs 111 days, p=0.37; OS, 558 days vs 1014 days, p=0.46]. Phenotype A of rs714368 and earlier stage were good predictive factor about PFS in Cox proportional hazard model.

      Conclusion

      Gene polymorphisms of rs714368 may change the function of OCT6 and influence the efficacy of platinum combination chemotherapy.

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      EP1.01-13 - A Phase 2 Trial Assessing Osimertinib Activity Against Leptomeningeal Carcinomatosis in EGFR-Mutant Lung Cancer (Now Available) (ID 470)

      08:00 - 18:00  |  Presenting Author(s): Yuki Akazawa  |  Author(s): Shigeki Nanjo, Motohiro Tamiya, Akito Hata, Toshihiko Yamaguchi, Toru Kumagai, Masahide Mori, Nobuyuki Katakami

      • Abstract
      • Slides

      Background

      Leptomeningeal carcinomatosis (LMC) occurs in 10 % of EGFR-mutant lung adenocarcinoma (LA). Retrospective studies have suggeted a clinical benefit of osimertinib in treating LMC in patients with EGFR-mutant LA. We conducted a phase 2 prospective trial to demonstrate the clinical efficacy, activity, and LMC-specific mechanisms of resitance to osimertinib in EGFR-mutant LA patients.

      Method

      We performed gadalidium-enhanced brain MRIs at the time of enrollment, followed by scheduled brain imaging once every six weeks. Clinical neurological exams were performed every four weeks. Adverse Events (AEs) were assessed by NCI-CTCAE Ver. 4. Cerebral spinal fluid (CSF) and plasma was obtained on day 1 and 21 for all patients. The CSF osimertinib penetration rate was measured by liquid-chromatography mass spectrometry (LC-MSMS) and compared to plasma osimertinib levels. Targeted droplet digital PCR (ddPCR) was used to detect copy number changes of Met and the EGFR C797S mutation in patients CSF-DNA and plasma cell free (cf) DNA.

      Result

      We enrolled six pre EGFR-TKI treated EGFR mutant LA with LMC. We observed a LMC-specific progression free survival of 3.7 months and overall survival of 6.2 months or longer with osimertinib. Four and three of six patients showed neurological and radiological responses, respectively. No patients had any AEs greater than grade 3 and all patients continued osimertinib beyond PD. The osimertinib CSF penetration rate was 1.2±0.5%. Met copy number was normal in plasma, but increased in the CSF of 2/6 patients prior to progression. Met copy number was confirmed in 1/6 patients at the time of progression. An aquired EGFR C797S mutation was observed in 1/6 patients prior to progression.

      table1.jpgtable2.jpg

      Conclusion

      Osimertinib 80 mg is efficacious in the treatment of LMC in EGFR mutated LA. CSF-specific MET copy number gain and EGFR C797S mutations arise prior to progression in EGFR-mutant LA patients treated with osimeritinib.

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      EP1.01-14 - The Scour Using Pretreatment NLR, Liver Metastasis, PD-L1 Status and PS as a Marker of Outcomes in Nivolumab-Treated Patients with Advanced NSCLC (Now Available) (ID 884)

      08:00 - 18:00  |  Presenting Author(s): Akihiro Tamiya  |  Author(s): Motohiro Tamiya, Yoshihiko Taniguchi, Kenji Nakahama, Shun-ichi Isa, Takayuki Shiroyama, Takako Inoue, Hidekazu Suzuki, Kyoichi Okishio, Tomonori Hirashima, Fumio Imamura, Shinji Atagi

      • Abstract
      • Slides

      Background

      Although nivolumab showed the significantly longer overall survival (OS) compared with docetaxel for non-small cell lung cancer (NSCLC) based on two phase III randomized controlled trials, programed death ligand 1 (PD-L1) expression alone is not yet an adequate biomarker in treating nivolumab for NSCLC patients. Furthermore, some prior analyses indicated the liver metastasis, performance status (PS) and pretreatment neutrophil-to-lymphocyte ratio (NLR) is one of the candidates of effect predictors. This retrospective study aimed to analyze the score combining pretreatment patients’ status as a predictive marker in NSCLC patients treated with nivolumab.

      Method

      ne hundred and twenty-eight patients treated with Nivolumab who could examine the PD-L1 status from December 2015 to July 2016 were retrospectively reviewed. This study was multicenter study conducted by the three respiratory medical centers in Japan. We collected clinical data including age, sex, smoking history, histological types, PS, NLR, existence of Liver metastasis and PD-L1 status. We made the predictive score (PS2-4: 3 points, >NLR 4: 1 point, Liver metastasis +: 1 point, PD-L1 0%: 1 point and over 50%: -1 point) from pretreatment patients’ characteristics and evaluate the score (over 4 points is high risk group, 2-3 points is mediate risk group, and under 1 point is low risk group) as a marker of outcomes. The data cut off was on 31th October 2017.

      Result

      Median age was 67 years old, 86 patients were male, 101 patients had smoking history, 99 patients were PS 0-1 and 29 patients were PS 2-4, 26 patients were squamous carcinoma, >NLR 4 were 48 patients, and 16 patients had liver metastasis, respectively. Furthermore, PD-L1 expression 0% were 62 patients, 1-49% were 42 patients, and over 50% were 24 patients.

      Progression disease rate, median progression free survival (PFS) and median OS was 61.1%, 1.1 months, 2.4 months in high risk group; 60.6%, 1.4 months, 10.9 months in mediate risk group; and 36.4%, 4.6 months, 16.3 months in low risk group, respectively.

      Conclusion

      We could classify the three group which could predict an patients’ outcome according to the patients’ characteristics.

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      EP1.01-15 - Systemic Hyperinflammation Is a Strong Independent Predictor of Early Mortality in Advanced NSCLC (Now Available) (ID 1143)

      08:00 - 18:00  |  Presenting Author(s): Johan Isaksson  |  Author(s): Linda Willén, Eva Brandén, Hirsh Koyi, Sebastian Gagatek, Anders Berglund, Patrick Micke, Johan Botling

      • Abstract
      • Slides

      Background

      Prognostic tools in NSCLC are important for treatment decisions and evaluation of new treatment options. Ample evidence support inflammation as a marker of outcome in NSCLC. Our study explores outcome for a population-based real-life cohort of patients in the highest stratum of inflammatory activity.

      Method

      The source cohort comprised all patients diagnosed with NSCLC between January 2016 – May 2017 at Gävle County Hospital, Sweden (n=155, inclusion rate 95%). Following exclusion of patients with active infection, the subgroup (n=77) in stage IIIB-IV with complete available laboratory parameters were studied further. Blood parameters were examined individually, and cut-offs (ESR>60 mm, CRP>20 mg/L, WBC>10 x10e9/L, PLT>400 x10e9/L) for high inflammation were set with an aim to pin-point the top echelon of hyperinflamed patients. A prognostic score was developed by assigning one point for each parameter above cut-off (0-4 points).

      Result

      One year survival of patients with an inflammation score of ≥2 (n=23) was 0% compared to 50% and 33% among patients with a score of 0 (n=36) and 1 (n=18), respectively (figure 1). The effect of a high inflammation score on overall survival remained significant in multi-variate analysis adjusted for confounding factors (stage, gender, age, smoking status, ECOG PS). The hazard ratio of an inflammation score ≥2 in multi-variate analysis (HR 3.45, CI 1.62-7.34) was on par with a change of ECOG PS from 0 to 2 (HR 3.67, CI 1.44-9.4).

      Conclusion

      Inflammation is a well established marker for treatment outcome in solid tumours. Our results show that high level inflammation is a strong independent marker for poor survival in patients with advanced stage NSCLC. This observation may indicate a need to stratify and subgroup patients in clinical studies with regard to systemic hyperinflammation and warrants further research on underlying mechanisms linked to tumour progression.

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      EP1.01-16 - Characteristics of Stage III Lung Cancer Patients in the Period 2014-2016 in Vietnam (Now Available) (ID 1231)

      08:00 - 18:00  |  Presenting Author(s): Voc Tai Dang  |  Author(s): Khac Dung Nguyen, Thi Oanh Bui, Phuong Thao Tran, Van Tu Dao

      • Abstract
      • Slides

      Background

      Despite lung cancer is the leading cause of cancer-related mortality around the world, data and impact on health systems related to characteristics of the diseases is not fully understood in developing countries. The study aims to describe and evaluate the characteristics stage III lung cancer patients in Vietnam.

      Method

      Medical records of patient with diagnosis of stage III lung cancer hospitalized in the period 2012-2015 in the National Cancer Hospital (Vietnam) were retrospectively analyzed. Patients were followed up about the survival information in April 2019 to identify overall survival (OS) rates. We compared the efficacy of treatments between 2 patient groups: surgery and/or radio-chemotherapy (group 1) and radiotherapy only or chemotherapy only or supportive care only (group 2).

      Result

      From a total of 5220 lung cancer patient hospitalized in the National Cancer Hospital over 3-year period, we reviewed 600 original medical records, of which 70 stage III lung cancer patients having valid survival information were identified (11.7%). We found 60 patients with death outcome (85.7%) and median OS and its 95% confidence interval were 9.80 [5.39, 19.70]. Patients were mainly men (54, 77.1%) with mean age (SD) was 65.96 (8.62). We found 14 patients with surgery and/or radio-chemotherapy in group 1 (4 surgery and 10 radio-chemotherapy). In group 2, 34 patients were treated with chemotherapy or radiotherapy alone, and 22 patients were provided supportive care only. The estimated 1-year, 3-year and 5-year survival probabilities were 40.7 (30.6 - 54.1) %, 15.5 (08.8 - 27.1)% and 10.3 (04.64 - 22.9)% correspondingly. We estimated 3-year survival probability of patients in group 1 was 34.3 (16.24 - 72.4 %) was higher than group 2 which was 10.6 (4.89 - 23.2)% (p=0.055).

      Conclusion

      Our results showed a benefit of surgery and/or radio-chemotherapy treatment on stage III lung cancer patients in Vietnam. Further research is required.

      rplot02.png

      table1.png

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      EP1.01-17 - Predictors of Survival Outcomes with Chemotherapy in Advanced NSCLC Patients with Performance Status 2 and Above and Without Driver Mutation (Now Available) (ID 1287)

      08:00 - 18:00  |  Presenting Author(s): Harish Kancharla  |  Author(s): Prabhat Singh Malik, SACHIN Khurana, Deepali Jain, SUNIL Kumar, Sushmita Pathy

      • Abstract
      • Slides

      Background

      Platinum-based combination chemotherapy is recommended as the standard treatment for patients with advanced non-small-cell lung cancer (NSCLC), but its benefit is limited to patientswith performance status (PS) of 0 or 1. However, it is not clear whether these benefits apply to patients with poor performance status (PS 2 and above) and there are no predictors of outcome to suggest whom to treat .This population accounts for a significant portion (up to 30%) of patients of our practice and some of them have been treated with systemic chemotherapy based on clinician’s discretion.We have analyzed the outcome of these patientswho have been treated with chemotherapy despite poor performance status.

      Method

      We performed a retrospective analysis of patients of advanced NSCLC with poor PS (ECOG PS 2 or more) registered at our lung cancer clinic between January 2016 and December 2017 and treated with systemic chemotherapy. Patients with driver mutations who were treated with first line TKIs were excluded. Hospital case records were reviewed for baseline characteristics, treatment details and outcome data. Patients who haven’t come to the hospital in last 3 months were contacted on phone.

      Result

      A total of 95 patients were found to be eligible for this analysis. Median age was 62 years (30-84 years, including 23(24%) patients 70 years or above. At presentation out of these 95 patients, 63(66%) were smokers,31(32%) had cytological proven pleural/pericardial effusion, 10(10.5%) patients had brain metastasis and 34(35.5%) had extra thoracic metastasis (≥2 sites).Majority(64%) patients had ECOGPS 2 but 36 % had PS 3 or 4 also and 44(46%) had one or more associated comorbidities. The most common chemotherapy regimen used was weekly paclitaxel and carboplatin(57.8%) followed by pemetrexed and carboplatin (16.8%).Majority (64%) patients could complete 4or more cycles of chemotherapy however 15 patients (15.7%) could receive only one cycle and 20(21%) patients even received maintenance chemotherapy. Chemotherapy was interrupted due to poor tolerance in 20(21%) patients and grade ¾ toxicity seen in 22(23%) % patients. At least one point improvement in ECOG PS from baseline was observed in 43 patients (45%) after 4 cycles of chemotherapy. Objective response and disease control rates were 20 % and 48.42% % respectively.Aftera median follows up of 8.6 months, median progression free survival was 6.2 months (95%CI 5-10.33).On univariate analysis ,neutrophil –lymphocytic ratio (<5 vs >5 )and induction regimen (weekly Taxol+Platinum vs rest) were significantly associated(p=0.02 and p= 0.04 respectively) with better median PFS

      Conclusion

      Systemic chemotherapy in modified doses and schedules in advanced NSCLC patients with PS 2 and above is feasible and may be associated with better symptom palliation with clinical benefit and improvement in survival.neutrophil –lymphocytic ratio (<5 vs >5 )and induction regimen (weekly Taxol+Platinum vs rest) are predictors of better median PFS . Further studies addressing this neglected subgroup are indicated.

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      EP1.01-18 - Clinical Features of Locally Advanced Lung Cancer Patients with Radiation Pneumonitis After Induction Chemoradiotherapy (Now Available) (ID 2199)

      08:00 - 18:00  |  Presenting Author(s): Kota Araki  |  Author(s): Ken Suzawa, Shunsaku Miyauchi, Akihiro Miura, Kei Namba, Shinji Otani, Hiromasa Yamamoto, Mikio Okazaki, Seiichiro Sugimoto, Masaomi Yamane, Shinichi Toyooka

      • Abstract
      • Slides

      Background

      The therapeutic management of locally advanced non-small cell lung cancer (NSCLC), such as those in the N2-3, bulky N1, or T3-4 stage, remains controversial. Induction chemoradiotherapy (CRT) followed by surgery is one of the potential therapeutic options for locally advanced NSCLC, however, sometimes develops radiation pneumonitis (RP). Severe RP induce remarkable respiratory disfunction, resulting in a delay of next treatment. The purpose of this study is to reveal the clinical features of NSCLC patients with RP after induction CRT.

      Method

      The clinical data of NSCLC patients who underwent surgical resection of lung cancer after induction CRT between 1999 to 2017 at our institution were analyzed. We compared NSCLC patients who had RP with those who didn’t, regarding patient’s and therapeutic factors, and their prognosis. RP of our cases was defined as RP which occurred between the administration of induction CRT and 30 days after surgery.

      Result

      A total of 172 data of NSCLC patients who underwent surgical resection of NSCLC of stage IIB–IIIC after induction CRT was collected. Among them, 34 NSCLC patients had RP, and 15 NSCLC patients received steroid therapy in 30 NSCLC patients, able to be assessed retrospectively. Non-smoking status was significantly associated with RP in univariate analysis (p = 0.006) and in multivariate analysis (odds ratio: 3.70, 95% confidence interval: 1.05-13.10, p = 0.042). Duration between completion of RT and surgery was longer in NSCLC patients with RP than those without RP (range [median]: 14-141 [45.5] vs 23-91 [40.0], p = 0.029). Adjuvant therapy was more frequently given to the patients without RP (p = 0.019). No significant difference in overall survival (OS) was observed between the 2 groups.

      Conclusion

      Non-smoking status was the risk factor of RP of NSCLC patients who received induction CRT followed by surgery. The frequency of adjuvant therapy was more in NSCLC patients without RP than those with RP while OS was not different in the 2 groups.

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      EP1.01-19 - Updated Statistics of Never-Smoker Female Lung Cancer in Korea (ID 1330)

      08:00 - 18:00  |  Presenting Author(s): Seung Joon Kim  |  Author(s): Chan Kwon Park, Young Kyoon Kim

      • Abstract
      • Slides

      Background

      The clinical characteristics and prognostic factors of patients with lung cancer are expected to differ with respect to geographical differences from the past to the future. According to epidemiological, clinical and biological characteristics, lung cancer in never-smokers is a different disease from lung cancer in smokers.

      Method

      To investigate the updated statistics of never-smoker female lung cancer in Korea, we analyzed data from the Korean Statistical Information Service and the Korea Central Cancer Registry in 2014.

      Result

      According to the Korean Statistical Information Service, lung cancer deaths in the Korean population have been increasing in both men and women since the early 1980s. Among the total of 17,980 deaths due to lung cancer in 2017, men accounted for 13,272 and women accounted for 4,708. Of a total of 25,780 incidences of lung cancer in 2016, men accounted for 17,790 and women accounted for 7,990. Considering that the lung cancer incidence in Korean women was 3,592 in 2000, it increased by more than 2-fold in 16 years. However, after age-standardized adjustment, the lung cancer incidence has recently been stable in women. The smoking rate in Korean women was 6.0% in 2017, which has remained stable since 1998. The passive smoking rate in non-smoking women was 6.3% in 2017, which has been decreasing since 2005.

      Among the total of 6,460 Korean female patients with lung cancer in 2014, 745 patients were investigated from the Korea Central Cancer Registry. Most Korean women who developed lung cancer were never-smokers (87.5%). According to smoking status, female lung cancer characteristics such as symptoms, stage, histopathology, EGFR mutation positivity, and initial treatment modality were significantly different. Never-smoker female patients with lung cancer showed an increase in asymptomatic disease, stage I lung cancer, histology of adenocarcinoma, EGFR mutation positivity, and curative resection compared to ever-smoker female patients.

      Conclusion

      The trends in epidemiology and clinical characteristics of lung cancer in Korea have changed over time. The never-smoker lung cancer incidence was estimated to increase in Korea. The reason for the stable incidence after the age adjustment could be growth in the Korean elderly population. Further research is needed to guide patient management, as well as future therapeutic strategies for lung cancer.

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      EP1.01-20 - A Single-Arm Phase II Trial of Weekly Nanoparticle Albumin-Bound Paclitaxel Monotherapy After Standard Therapy for Advanced NSCLC (Now Available) (ID 370)

      08:00 - 18:00  |  Presenting Author(s): yasuhiro Kato  |  Author(s): Yusuke Okuma, Yukio Hosomi

      • Abstract
      • Slides

      Background

      Few studies have investigated the clinical efficacy of later-line treatments after standard therapy for advanced non-small cell lung cancer (NSCLC). Nanoparticle albumin-bound paclitaxel was one of the useful option for treatment of NSCLC. We conducted PII trial for evaluating the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) following standard therapy for advanced NSCLC.

      Method

      The eligible patients having adequate organ functions with performance status 0−2 were enrolled after completing standard therapy. Standarad therapy defined as chemotherapy including docetaxel and pemetrexed in patients with non-squamous cell lung cancer or docetaxel in patients with squamous cell lung cancer. After the ICI nivolumab was approved by the Ministry of Health, Labor and Welfare of Japan in December 2015, standard therapy was defined as including ICIs treatment. They received weekly nab-paclitaxel 100 mg/m2 intravenously on days 1, 8, and 15 every 3 weeks. The primary end point was objective response rate (ORR). Median progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were evaluated as secondary end points.

      Result

      This trial was discontinued because of late accrual. Twenty-two patients were enrolled from April 2013 and February 2019. All patients recieved chemotherapy including docetaxel and Six patients recieved ICIs tretment. Median follow-up interval was 6.7 months. The total ORR was 22.7% [95% CI: 7.8−45.4] and disease control rate (DCR) was 81.8% [95% CI: 59.7−94.8]. Median PFS was 3.4 months [95% CI: 2.3−4.1] and median OS was 7.4 months [95% CI: 4.2−10.7]. Hematological AEs of Grade 3/4 included anemia (18%), leukopenia (18%), and neutropenia (32%), and the most frequent nonhematological AEs were fatigue (50%) and peripheral neuropathy (36.4%). Severe AEs related to treatment were observed in only one patient.

      Conclusion

      Although all patients recieved chemotherapy including docetaxel before protocol tretment, our tral suggested nab-paclitaxel may be a safe and effective later-line chemotherapeutic option for previously treated advanced NSCLC after standard of chemotherapies based on other trials.

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      EP1.01-21 - Time on Treatment of First-Line PD-1 Inhibitor Monotherapy for Metastatic Non-Small Cell Lung Cancer Patients: Real-World Experience Data (Now Available) (ID 764)

      08:00 - 18:00  |  Presenting Author(s): Nava Siegelmann-Danieli  |  Author(s): Lior Apter, Sarah Sharman Moser, Sheenu Chandwani, Xin Chen, Varda Shalev, Gabriel Chodick

      • Abstract
      • Slides

      Background

      Clinical trials have established the role of immune checkpoint inhibitors for metastatic NSCLC treatment, but real-world data are limited. We describe the first report of a prospective study on real-world time on treatment (rwTOT) for first-line (1L) anti-PD-1 monotherapy in metastatic NSCLC in a 2.3 million member public health provider in Israel.

      Method

      Newly diagnosed stage IV NSCLC patients who initiated 1L anti-PD-1 therapy in 2017 were identified from the national cancer registry. rwTOT was defined as the length of time between first and last administration date of anti-PD-1 therapy. Patients were considered discontinued if they had a record of next line of therapy, or death, or whose last activity date was ≥120 days from the last administration date; others were censored. The Kaplan-Meier (KM) median and restricted mean (rMean) rwToT were estimated. Jun 2018 data cutoff was utilized to allow minimum 6 months follow-up.

      Result

      A total of 63 patients initiated 1L anti-PD-1 monotherapy; of these, 59 were PD-L1 TPS≥50%, one was TPS<50% and 3 unknown. This cohort comprised of 97% pembrolizumab monotherapy, 65% males, median age=59 yrs, 76% ever smokers, 71% adenocarcinomas, 11% brain metastases, and 62%/14%/24% with 0-1/2-4/unknown ECOG status. The median rwToT was 4.6 (95% CI 2.8-12.8) mo and estimated rMean at 24 months using parametric extrapolation was 10.9 mo (4.3-16.8). Patients with ECOG 0-1, n=39, had a median rwTOT of 10.6 mo (1.9-19.2).

      Time on treatment for anti-PD-1 monotherapy

      1L anti-PD-1 Monotherapy

      N=63

      1L Pembrolizumab Monotherapy

      N=61

      N discontinued (%)

      38 (60.3)

      36 (59.0)

      KM Median rwToT (95% CI)

      4.6 (2.8-12.8)

      5.0 (3.5-NE)

      rMean rwToT @ 12 months (95% CI)

      6.5 (5.3-7.7)

      6.7 (5.4-7.9)

      Parametric (extrapolated) rMean rwToT @ 24 months (95% CI)

      10.9 (4.3-16.8)

      [Gompertz]

      11.2 (4.4-17.1)

      [Gompertz]

      6 months on treatment rate, % (95% CI)

      44.1 (31.6-55.9)

      45.5 (32.7-57.5)

      12 months on treatment rate, % (95% CI)

      39.7 (27.3-51.9)

      41.0 (28.3-53.4)

      Conclusion

      The results of this unselected real-world cohort of metastatic NSCLC patients treated with 1L anti PD-1 monotherapy show that rwTOT rates compare favorably with published data from clinical trials and other real-world studies.

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      EP1.01-22 - Liquid Biopsy in the Detection of EGFR Activating and Resistance Mutations in Advanced Pulmonary Adenocarcinoma (Now Available) (ID 1761)

      08:00 - 18:00  |  Presenting Author(s): Varsha Singh  |  Author(s): Prabhat Singh Malik, Pranay Tanwar, Anant Mohan, Deepali Jain

      • Abstract
      • Slides

      Background

      Approximately 30% of the advanced pulmonary adenocarcinoma (PADC) patients are found to be mutated with epidermal growth factor receptor (EGFR). Nearly 60% of EGFR mutated patients develop T790M resistance mutation against which third generation TKIs are available. Detection of T790M mutation is a challenge due to non availability of enough tumour tissues in patients receiving first-generation EGFR-TKI treatment. Liquid biopsies (cell- free DNA) are promising for detection of EGFR activating and resistance mutations. The current study focuses on detection of EGFR mutations in cell-free DNA from patients with histologically confirmed EGFR mutation status.

      Method

      50 PADC patients (22 males; 28 females with mean age 63 years) were studied for EGFR mutations. Out of them 40 were TKI naïve and 10 patients were treated with EGFR-TKIs. Follow up biopsy from TKI treated patients was not available for resistant mutation studies. Real-time PCR and Digital droplet PCR techniques were adopted for studying EGFR exon 19 (deletions), 20 (T790M) and 21 (L858R) mutations in tissue and plasma samples respectively.

      Result

      Clinically all patients were in stage III-IV and 52% were never smokers. Out of 40 TKI naive cases, 20 cases were positive for EGFR activating mutations in tissue and 17 in plasma. Twenty cases were negative for EGFR mutations in both tissue and plasma. In 10 EGFR-TKI treated patients, founder activating mutation was still present in plasma of 7 cases and 3 of them also showed T790M resistance mutation. Two patients carrying this resistant mutation died subsequently. Remaining three TKI treated patients did not harbour even founder activating mutation in the plasma.

      Conclusion

      We observed a concordance of 88% (44/50) between liquid biopsy and tumour tissue. Our study highlights role of liquid biopsy as an alternative for detecting EGFR activating and resistance mutations in advanced PADC. EGFR mutation analysis in liquid biopsy can be helpful in those patients where the tissue biopsy is not possible.

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      EP1.01-23 - SRC Inhibition with Bosutinib as a Potential Approach for Restoring Pemetrexed Responsiveness (Now Available) (ID 2843)

      08:00 - 18:00  |  Presenting Author(s): Nagla Abdel Karim  |  Author(s): Ola Gaber, ihab Eldessouki, John C. Morris

      • Abstract
      • Slides

      Background

      One of the principle approaches in malignant mesothelioma andnon-squamousnon-smallcelllung cancer management is cellular folate-dependentpathways inhibition with pemetrexed(PEM) combined with platinum-basedchemotherapy. Despite the promising activity of PEM, drug resistance demands new approaches allowing for abolishing resistance and better outcomes. In lung cancer, there is an association betweenin vitroPEMresistance, SRC over-expression, and thymidylatesynthase(TS) overexpression.

      Method

      We treated lung cancer cell line (A549) and mesothelioma cell line (MSTO) with PEM and bosutinib (a small molecule tyrosine kinase inhibitor (TKI)) which is also an SCR inhibitor. Increasing dose regimen was adopted with these drugs. Then we conducted cellviability assays (MTT tetrazolium), detection of SRC andTS expression by western blot and apoptotic assays (AnnexinV) for drug effect evaluation.

      Result

      Data showed that sequential treatment with bosutinib then PEM lowered the IC50 of PEM of both cell lines as indicated by cellviability and apoptosis assays. There was a 9% increase in apoptosis with combination regimen compared to PEM only regimen. Nevertheless, a decrease in TS expression was found, with correlation to the decrease in SRC expression.

      Conclusion

      Combining bosutinib’s SCR inhibition to PEM activity may improve the latter’s therapeutic response due to synergism. Further in vivo evaluation for these results are needed to better understand these effects on tumor response

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      EP1.01-24 - Lung Adenocarcinoma: Mutational Profile in Ever Smokers and Non-Smokers Patients (ID 2847)

      08:00 - 18:00  |  Presenting Author(s): Daniel Oliveira Reis  |  Author(s): Catarina Marques, Daniel Coutinho, Eloísa Silva, Margarida Dias, Telma Costa, Sérgio Campainha, Sara Conde, Luís Cirnes, Ana Barroso

      • Abstract
      • Slides

      Background

      Lung cancer occurring in never-smokers had become a distinct entity. This study aims to evaluate the mutational profile in ever smokers and non-smokers patients with pulmonary adenocarcinoma.

      Method

      Retrospective analysis (Oct-2016 to Aug-2017) of patients diagnosed with pulmonary adenocarcinoma in our pulmonology department.

      Next generation sequencing (NGS) was used to identify different mutations and translocations. Pathological variants of genes and variants of uncertain clinical significance were included.

      Result

      60 patients were enrolled in this study: 18 (30%) non-smokers and 42 (70%) ever smokers.

      In 72.2% of non-smokers and 57.1% of ever smokers were identified at least one mutation. Despite this, ever smokers had an overall higher frequency of mutations (72.6% vs 27.4%) because many patients had concomitant mutations.

      Although not statistically significant, ever smokers had more mutations that are variants of uncertain clinical significance (40% vs 23.5%; p=0,227)

      Table 1. Frequency of mutations

      ___ Non-smoker Ever smokers
      Mutated gene

      Pathological variants

      (n)

      Variants of uncertain clinical significance (n)

      Pathological variants

      (n)

      Variants of uncertain clinical significance (n)
      KRAS 3 0 18 0
      EGFR 5 0 4 5
      ERBB4 0 0 0 1
      MET 0 1 0 3
      PTEN 0 0 1 1
      HER2 1 2 0 7
      PI3KCA 0 1 1 1
      BRAF 0 0 1 0
      ROS 1 0 1 0
      ALK 3 0 1 0
      Total 13 4 27 18
      Conclusion

      Although not statistically significant, smokers and non-smokers appear to have a different mutational profile. Smokers have a higher rate of concomitant mutations, although some of them are variants of uncertain clinical significance. NGS will help to increase knowledge about the mutational profile in these patients.

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      EP1.01-25 - An Interactive Interface for Prediction of Anti-PD-1 Efficacy in Lung Cancer Patients (ID 2460)

      08:00 - 18:00  |  Presenting Author(s): Corentin Richard  |  Author(s): Jean-David Fumet, Sandy Chevrier, Valentine Derangere, Romain Boidot, Caroline Truntzer, Francois Ghiringhelli

      • Abstract

      Background

      The past decade has seen a new field of promising treatments for non-small cell lung cancer patients (NSCLC) with immune checkpoint inhibitors (ICI). Medicine community embarks on a biomarker race to identify the one-quarter of responders and potential hyper-progressors. The assessment of PD-L1 tumor expression by IHC is used to select responder patients and is considered as the gold standard biomarker in many studies but it does not predict the absence of anti-PD-1 efficacy. Recent review from Keenan TE et al. summaries all potential studied markers in literature as intratumoral T cell infiltration, tumor neoantigens or else mismatch repair deficiency. Despite this abundance of potential markers, recommendations only rely on high PD-L1 expression and more recently on high tumor mutational burden (TMB). In this study, we propose estimations of response probability based on the different data that may be available for clinicians according their molecular biology and material means.

      Method

      Based on a cohort of 100 patients with advanced NSCLC treated with nivolumab in second line of treatment, we developed an algorithm enabling the calculation of the probability of survival without progression at 6 or 12 months when treated with ICI. Using Cox proportional hazards multiple regression, we adjusted these three stages of information to estimate the probability of response of a patient based on the type of available data: only clinical data and/or exome analysis and/or RNA sequencing. Stability and predictive ability of these models where evaluated internally and externally through bootstrap procedure.

      Result

      Among the 100 patients, 90 had both somatic and constitutional exome sequencings available and 50 had an RNA sequencing. We built a main model based on clinical and pathological data easily available for clinicians. As mandatory criteria, the age, sex, performance status, tumor histology, routine mutational status and PD-L1 immunohistochimical expression were first included in the predictive model. In addition, RECIST response to previous chemotherapy line and antibiotics usage were added into the initial model as they were described significantly associated with respectively good and poor survival to ICI in previous publications. Additional criterion were obtained thanks to extensive DNA tumor analysis such as TMB, mutations in DNA repair pathways, the number of large deletions and intratumoral TCR clones. A third stage of data was added with CD8A and CD274 RNA expressions obtained by RNA sequencing. Thus, several models are available for clinicians to estimate the probability of survival without progression at 6 or 12 months for their patients according to the type of available data. An interactive on-line interface based on R Shiny enables the questioning of all these models for further predictions.

      Conclusion

      Altogether, these data provide validated and more complex biomarkers according to the type of available data to predict probability of survival without progression to anti-PD-1 in patients with advanced NLCSC. Further predictions can be obtained thanks to a shiny R free and interactive interface available on-line.

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      EP1.01-26 - Non-Small Cellular Pulmon Cancer ALK Positive in Pediatrics (Now Available) (ID 506)

      08:00 - 18:00  |  Presenting Author(s): Alvaro Jaime Guerrero Villota  |  Author(s): Lisbeth Patricia Ramirez, Juan Manuel Herrera Parga, Margarita Maria Velasco, Jorge Ivan Lòpez

      • Abstract
      • Slides

      Background

      For 2018 the American Cáncer Society reports 234.030 new cases of lung cáncer, 154.050 people will die from this cause, the average age of diagnosis is approximately 70 years old. Lung cáncer in children and adolescents is extremely rare, in Colombia the incidence in children under 18 is less than 1%. The 85% of lung cancers are classified as non-small cell lung cáncer, there are recent advances in treatment with Anaplastic lymphoma kinase (ALK) inhibitors Crizotinib, Alectinib, Brigatinib for non-small cell lung cáncer ALK positive. This case report is from a 14-year-old adolescent patient treated in our institution with an ALK inhibitor.

      ALK disease is 3% to 5% of all non-cell lung cancers small adenocarcinoma type, more frequent in young people, women, nonsmokers, and with advanced disease.

      Method

      Case report and literature review.

      Result

      Male patient 14 years with respiratory symptoms productive cough. Tomography computed tomography: injury to the middle lobe and right lower lobe, biopsy: Adenocarcinoma poorly differentiated, immunohistochemistry: positive for cytokeratin 7, napsin-a, MUC-1, CK1E1 / AE3 positive and transcription factor -1 (TTF-1) and cytokeratin 20 negative, EGFR-KRAS wild type, ALK (EML-4 with clone D5F3) positive. Treatment was started with Crizotinib 250mg every 12 hours, obtaining partial response and with PFS of 36 months, gastrointestinal toxicity, hematological I grade.

      Conclusion

      We report the experience of a case with excellent tolerability to an inhibitor of ALK, and its clinical benefit, (partial response and stable disease). Patients under 18 years, are excluded in most clinical trials and can benefit from treatment, increase in progression-free survival, overall survival, avoiding the toxicity of chemotherapy.

      imagenes caso .gif

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      EP1.01-27 - Preliminary Study on Immune Checkpoint and EMT Feature of CTCs in Advanced Non-Small Cell Lung Cancer Patients (ID 625)

      08:00 - 18:00  |  Presenting Author(s): Lina Zhang  |  Author(s): Jinjing Tan, Mei Jiang, Xiaoting Zhao, Yu Teng, Weiying Li, Tongmei Zhang

      • Abstract
      • Slides

      Background

      Non-small cell lung cancer (NSCLC) is the most common malignant tumor with high morbidity and mortality. Platinum-containing chemotherapy is the standard first-line chemotherapy regimen for patients with advanced NSCLC. However, 65-75% patients would progress after a few weeks of chemotherapy treatment. The programmed cell death 1 (PD-1)/PD-1 ligand 1(PD-L1) has become the rising star of cancer research only because their development of PD-1/PD-L1 inhibitors has bring cancer patient new hope and changed the landscape of NSCLC therapy. Nevertheless, the high degree of non-responders demonstrates that we are still far from completely understanding the events underlying tumor immune resistance. Circulating tumor cells (CTCs), as an accessible source of tumor for biologic characterization that can be serially obtained with minimally invasive procedure. Studies have shown that presence of PD-L1 on CTC might predict resistance to anti-PD-1 therapy, and PD-L1 positive CTCs usually present an elongated morphology, which was associated with epithelia-mesenchymal transition (EMT). Those research provided evidence that CTC might be a promising object to predict whether the patient could be benefit from the second-line checkpoint inhibitor treatment. In this prospective cohort study, we aimed to describe the molecular background of CTCs from patients with disease progress after first-line chemotherapy.

      Method

      We consecutive enroll patients who have been treated with platinum-containing chemotherapy in our hospital from May 2018 to the present, and have been assessed for disease progression (PD) by RECIST version 1.1. 6.5ml of peripheral blood was collected before further treatment. Then we enriched the CTCs and performed in situ co-detection of PD-L1 and EMT marker (Vimentin) using SE-iFISH technology.

      Result

      To date we have recruited 13 eligible patients. Detectable CTCs counts range from 1 to 22 in 6.5ml blood. Among them, 4 samples presented PD-L1 positive, 4 samples presented Vimentin positive. Only 1 sample has co-expression of PD-L1 and Vimentin.

      Conclusion

      Above results proved that SE-iFISH method could be used for CTC enrichment and detection. Next step, we will wait for those patients’ checkpoint inhibitor treatment outcome, analysis the correlation between PD-L1 and Vimentin co-expression and patient response. At the same time, we will continue to include cases, collect CTC samples and evaluate the expression of PD-L1 and Vimentin on CTCs.

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      EP1.01-28 - Real World Use of Afatinib in NSCLC EGFRm+ Patients Outside Clinical Trials: A FAETT Experience (Now Available) (ID 655)

      08:00 - 18:00  |  Presenting Author(s): Inmaculada Ramos García  |  Author(s): Amparo Sánchez, Ana Laura Ortega, José Fuentes Pradera, Manuel Cobo, Mª Ángeles Moreno, Isidoro Barneto, Sofía Ruiz, Inmaculada Fernández, Teresa García, Fatima Toscano, Jose Manuel Trigo Perez

      • Abstract
      • Slides

      Background

      Epidermal growth factor receptor (EGFR) tyrosine kynase inhibitors (TKIs) remain the standard of care as first-line therapy for patients with non-small cell lung cancer (NSCLC) harboring an EGFR mutation. These drugs have been associated with improvements in both clinical outcomes and tolerability, compared with platinum-based chemotherapy.

      Three generations of TKIs are currently approved in the first-line setting, though only first (erlotinib and gefitinib) and second generation blockers (mainly afatinib, but also dacomitinib) have been extensively used in clinical practice nowadays.

      Method

      We reviewed 105 patients with NSCLC with advanced or recurrent stages that harbour EGFR mutations, treated with afatinib as first´line therapy among the academic hospitals adhered to the FAETT network.
      The information of clinical, pathological and treatment characteristics of the patients was collected retrospectively and the statistical analysis was performed with the software SPSS software version 21.0, considering the statistical significance if p-value <0.05.

      Result

      The characteristics of the patients are reflected in Table 1.
      The mean age at the beginning of treatment with afatinib was 61 (37-81) years. 48.6% of the patients were older than 65 years. 27.6% were older than 70 years. With a median follow-up of 15 months (0-82), the median progression-free survival was 14 months (10.74-17.26) Fig 1, and the median overall survival was 31 months (24.00) -37.99).
      The median PFS and OS among patients older than 65 years, and even those older than 70 years, is not statistically significant (14 vs 13 and 30 vs 31 months, repectively. P-value:0,83 and 0,78
      On the other hand, the toxicities between both groups remain similar, with diarrhea and skin rash standing out as the most frequent, as reflected in the data published to date. Table 2

      tablas2.jpg

      tabla3.jpg

      Conclusion

      This retrospective study shows no differences in the use of afatinib among older patients in terms of both efficacy and tolerability.

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      EP1.01-29 - Lung Adenocarcinoma Harboring EGFR-19del/C797S/T790M Triple Mutations Responds to Brigatinib and Anti-EGFR Antibody Combination Therapy (Now Available) (ID 674)

      08:00 - 18:00  |  Presenting Author(s): Xiaofei Wang  |  Author(s): Beili Gao

      • Abstract
      • Slides

      Background

      Treatment of non-small-cell lung cancers (NSCLCs) harboring primary EGFR oncogenic mutations such as L858R and exon 19 deletion delE746_A750 (Del-19) using gefitinib/erlotinib ultimately fails due to the emergence of T790M mutation. Though Osimertinib is effective in overcoming EGFR T790M by targeting Cys797 via covalent bonding, their efficacy is again limited due to the emergence of C797S mutation.

      Method

      The study showed one patient with advanced NSCLC treated with targeted therapy, who developed acquired drug resistance to 1st to 3rd generation of EGFR-TKIs. The medical records and imaging studies of the patient were retrospectively reviewed under the approval of the institutional review board and the waiver the informed consent. The study was conducted with agreement of the patient herself.

      Result

      This is one of the earliest report which describe cis mutations of T790 and C797s as the resistance mechanism observed in circulating tumor DNA (ctDNA) from a patient with initial response followed by progression on osimertinib and sucesesfuly treated with Brigatinib + Erbitux.brigatinib+egfrab_fig 1.jpgbrigatinib+egfrab_fig 2.jpg

      Conclusion

      This case report,as to our knoweledge, is the first clinical evidence of efficacy using a combination of brigatinib and cetuximab to target concomitant EGFR-T790M and C797S in cis.

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      EP1.01-30 - Clinico-Pathological Profile of Adenocarcinoma of the Lung – A Prospective Study in a Nepalese Population (Now Available) (ID 722)

      08:00 - 18:00  |  Presenting Author(s): Natasha B Leighl  |  Author(s): Soniya Dulal, Bishnu Dutta Paudel, Aarati Shah, Prakash Neupane, Bibek Acharya, Sandhya Chapagain, Asmita Rayamajhi, Rameej Revanta Thapa, Odd Terje Brustugun

      • Abstract
      • Slides

      Background

      Lung cancer represents the most common cause of cancer related mortality in developing countries including Nepal where patients (pts) often present in advanced stage. The purpose of this study was to determine the incidence and clinico-pathological profile of pts with adenocarcinoma of the lung (ACL) presented to a tertiary care center of Nepal.

      Method

      An IRB approved prospective study was conducted in pts with ACL over a period of 15 months from April 2017 to July 2018 at a tertiary care center, Bir Hospital, Kathmandu. Demographic data, history of smoking, histological type, presence and type of epidermal growth factor receptor (EGFR) mutations were studied. EGFR-analysis was performed using TheraScreen EGFR mutation kit.

      Result

      A total of 253 pts were diagnosed with lung cancer in the period. Of the 83 (33%) diagnosed with ACL, 45 (54%) were males and 38 (46%) females. The mean age at diagnosis was 59.4 years, and 74 (89%) were in stage III/IV. Forty eight (58%) pts were smoker of whom 30 (63%) pts had less than 10 pack years. Sixty one percent (61%) were illiterate. Eighteen (22%) pts had wrongly received anti-tuberculosis treatment before the diagnosis of ACL was made. All ACL pts were tested for EGFR-mutations which were found in 24 (29%) pts, the most common mutation being exon 21 (L858R) (42%) followed by exon 19 deletion (38%). Exon 18 and exon 20 (T790M) mutation were found in 2 pts (8%) each. One pt had dual mutation in exon 20 (T790M) and exon 21 (L858R).

      Conclusion

      The frequency of EGFR-mutations in ACL in this Nepalese cohort was lower than in Eastern Asian studies, but higher than in western population. EGFR mutation testing of ACL has to be encouraged in developing countries like Nepal as presence of these mutations predict durable response to oral tyrosine kinase inhibitors. Interestingly, lung cancer is often mistreated as tuberculosis leading to delay in diagnosis and treatment.

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      EP1.01-31 - PET CT Radiogenomic Depiction in PDL1 Expression in Lung Cancer in Indian Population (Now Available) (ID 1230)

      08:00 - 18:00  |  Presenting Author(s): Venkata Pradeep Babu Koyyala  |  Author(s): RUPAL Tripathi, Ankush Jajodia, Arvind Chaturvedi, Sunil Pasricha, Sumit Goyal, Ullas Batra, Anurag Mehta, Helmut Prosch

      • Abstract
      • Slides

      Background

      Non small cell lung cancer (NSCLC) represents an area of paramount importance wherein patients undergo testing for targetable genetic alterations. Association between the imaging and molecular phenotypes needs to be explored highlighting the growing importance of classifications based on radio genomic characterization. This study was conducted to evaluate the correlations between the radiologic and molecular phenotypes in patients with NSCLC.

      Method

      211 patients with lung cancers during the study period of one year from October 2017 till November 2018 in our institution and undergoing both radiologic (PET-CT) and molecular investigations [Programmed death ligand 1 (PDL1)] were included in the study. Both quantitative and qualitative CT findings were evaluated and correlated with the molecular findings. Quantitative data included SUV max obtained from PET component of CT and maximum diameter of lesion according to the RECIST criteria. Qualitative data recorded included location, pleural tail, pleural effusion, pericardial effusion, opacity, margins, calcifications, obstructive changes, pleural nodules, lung nodules, invasion, air bronchogram, emphysema, pulmonary fibrosis, mediastinal lymph nodes and distant metastasis. Statistical analysis was performed to evaluate the association of the qualitative features with the molecular expression. Receiver operating characteristic curves (ROC) were drawn and the corresponding area under curve (AUC) was calculated. P-values <0.05 were considered significant.

      Result

      PDL1 expression was observed in 69 patients and 13/14 females and 29/34 non-smokers showed the expression (p-value <0.0001). A total of 1, 19, 22 and 27 patients had <1%, 1-10%, 10-50% and >50% PDL1 expression. SUV max was 11.7+3.7 in the group with PDL1 expression. Correlations were observed between PDL1 expression and location (p-value <0.0001), pleural tail (p-value <0.0001), pleural effusion (p-value <0.0001), obstructive changes (p-value 0.001), pleural nodule (p-value 0.001), lung nodules (p-value <0.0001), air bronchogram (p-value <0.0001), emphysema (p-value <0.0001), mediastinal nodes (p-value <0.0001) and distant metastasis (p-value <0.0001). PDL1 expression correlated with pulmonary fibrosis (p-value 0.001). In ROC curves, in case of PDL1 expression, the AUC was 0.728 on the basis of length.

      Conclusion

      The correlation between CT findings and molecular findings highlights the importance of newer radio genomic based characterization for patients with NSCLC for better diagnostic and prognostic approaches.

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      EP1.01-32 - Improving the Prognosis of Non-Small Cell Lung Cancer After the Approval of Immune Checkpoint Inhibitors: A Retrospective Analysis (Now Available) (ID 1276)

      08:00 - 18:00  |  Presenting Author(s): Teppei Yamaguchi  |  Author(s): Yuko Oya, Hiromi Furuta, Naohiro Watanabe, Takehiro Uemura, Junichi Shimizu, Yoshitsugu Horio, Toyoaki Hida

      • Abstract
      • Slides

      Background

      Anti-programmed death-1/programmed death-ligand-1 (PD-1/PD-L1) blockade represents a revolutionary breakthrough in the treatment of advanced non-small-cell lung cancer (NSCLC). However, it remains unclear whether the immunotherapy for PD-1 axis are associated with overall survival (OS) in real world patients.

      Method

      We retrospectively analyzed consecutive 246 patients with stage IIIB or IV NSCLC who underwent at least 1 regimen of chemotherapy. Patients who have EGFR mutations, ALK/ROS1 rearrangements, or received curative thoracic radiotherapy were excluded. Besides, patients administered any immune checkpoint inhibitors in clinical trials were also excluded. Treatment outcomes were compared between patients who started chemotherapy from January 2012 to December 2014 (cohort A; n=135) and those who started it from January 2016 to December 2017 (cohort B; n=111). Baseline characteristics were balanced using propensity score matching, including variables such as age, sex, performance status (PS), histology, clinical stage, bone metastases, central nervous system (CNS) metastases, liver metastases, pulmonary metastases, and pleural dissemination.

      Result

      Median OS was 11.4months in cohort A and 16.6mo in cohort B (HR 0.68, 95%CI 0.50-0.93, P=0.016). In 111 propensity-score matching pairs, median OS was 11.2months in cohort A and 16.6months in cohort B (HR 0.68, 95%CI 0.49-0.94, P=0.021), and the 12-month OS rate was 48.7% in cohort A versus 59.9% in cohort B, respectively. PD-1 axis inhibitors were received 13.5% in cohort A and 64.9% in cohort B. Forest plot for the propensity-matched patient analysis demonstrated a significantly better outcome in cohort B, for patients with PS 0 to 1, smokers, number of metastases ≤1, no bone metastases, no CNS metastases, no liver metastases, no pulmonary metastases, pleural metastases, and squamous histology.

      Conclusion

      This result indicates the appearance of immunity checkpoint inhibitors improved the prognosis of driver-mutation negative NSCLC in real world.

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      EP1.01-33 - Extracellular Medium of Senescent Lung Cancer Cells Promoted Tumor Progression Through Activation of YAP and PD-L1 (Now Available) (ID 1335)

      08:00 - 18:00  |  Presenting Author(s): Jiewei Liu  |  Author(s): Lingling Zhu, Dan Pu, Liyuan Yin, Yanyang Liu, Qinghua Zhou

      • Abstract
      • Slides

      Background

      Cellular senescence has been perceived as a barrier against carcinogenesis. However, the senescence-associated secretory phenotype (SASP) of senescent cells can promote tumorigenesis. Our previous researches revealed that the secretary cytokines from senescent cancer cells induced by bleomycin promoted migration and invasion of associated non-senescent cells, while the impact of hydrogen peroxide (H2O2)-induced senescent epithelial originated tumor cells on associated non-senescent tumor cells was rarely reported and the underlying mechanisms has not been discerned.

      Method

      Senescence was induced in human lung adenocarcinoma cancer cells (A549 and NCI-H1299) by Oxidative DNA damage chemical, hydrogen peroxide (H2O2), and verified by senescence-associated β-galactosidase (SA-β gal) staining and flow cytometry. A549 and NCI-H1299 cells were treated with condition medium of senescent/non-senescent A549 and NCI-H1299 (senescent vs. non-senescent group), and their protumorigenic roles were tested by cell viability assay, colony formation assay and cell invasion and migration assay. Label-free quantitative proteomics was performed to detect the expression of cytokines in culture medium of senescent/non-senescent A549 and NCI-H1299. To determine whether the YAP and programmed cell death ligand 1 (PD-L1) were involved in the tumorigenic roles, the protein and mRNA expression levels of PD-L1, YAP, CYR61, c-Myc and CTGF in A549 and NCI-H1299 were assessed by Western blot (WB) and quantitative reverse transcriptase PCR (qRT-PCR). To characterize senescent cells in lung cancer patients, we performed SA-β-Gal staining using fresh-frozen tissue sections from 20 normal lung samples and 40 lung adenocarcinoma cancer samples. To elucidate the relationship between YAP and PD-L1 in the same tumor tissue, immunohistochemistry detected the expression of both YAP and PD-L1.

      Result

      A549 and NCI-H1299 could be steadily induced senescence with an induced rate of more than 90% at a dose of 200uM and 100uM of H2O2, respectively. The proliferation and migration ability of cells was significantly higher in senescent than in non-senescent group. Senescent condition medium significantly promoted cell proliferation and migration in both PD-L1 high-expressing NCI-H1299 and PD-L1 low-expressing A549. However, the presence of senescent condition medium increased the proliferation and invasion of co-cultured cells was significantly less in PD-L1 low-expression A549 than that seen in PD-L1 high-expressing NCI-1299. The secrete proteins identified following H2O2 treatment included extracellular matrix protein, inflammatory cytokines, growth factors, chemokines etc. Further mechanistic investigations revealed that mRNA level of target genes of YAP (CYR61, c-Myc, CTGF) and PD-L1 were increased after H2O2 treatment and their expression were positively correlated. Besides, in senescent lung adenocarcinoma cancer tissue, PD-L1 positive lung adenocarcinoma cancer samples showed significantly higher nuclear YAP positive ratios compared to PD-L1 negative samples.

      Conclusion

      H2O2 successfully induced senescence on epithelial tumor cells A549 and NCI-H1299, whose secretary phenotype significantly promoted the proliferation and invasion of associated PD-L1 high-expressing non-senescent lung adenocarcinoma cancer cells compared with PD-L1 low-expressing NSCLC cells in vitro. PD-L1 and nuclear YAP are co-expressed in senescent lung adenocarcinoma cancer tissues, enlightening a therapeutic target of the combination of Hippo/YAP signaling pathway with immune checkpoint PD-L1/PD-1 inhibitors.

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      EP1.01-34 - A Retrospective Study of the Pattern of Lymph Node Metastasis in Superior Sulcus Non-Small-Cell Lung Cancers (Now Available) (ID 1742)

      08:00 - 18:00  |  Presenting Author(s): Hongxuan Li  |  Author(s): Jun Liu, Xiaolong Fu

      • Abstract
      • Slides

      Background

      By comparing the probability of lymph node metastasis between superior sulcus non–small-cell lung cancers (SS NSCLC) and non-SS NSCLC located in the pulmonary apex, we hope to find out whether there is a unique pattern of lymph node metastasis in SS NSCLC.

      Method

      During 2008-2014, a retrospective study was performed on NSCLC patients with lesions located in the pulmonary apex. Patients with lesions invading the peripheral tissue structure were enrolled in the SS NSCLC group, while those without lesions invading the peripheral structure were enrolled in the non-SS NSCLC group. A total of 65 patients in the SS NSCLC group received surgery, and all patients in the non-SS NSCLC group received surgery. According to postoperative pathology and enhanced CT before treatment, the location and number of lymph node metastasis were determined. The chi-square test was used to statistically analyze the difference in the probability of N1, N2 and distant metastasis (DM) between the two groups.

      Result

      Compared with the non-SS NSCLC group, the T staging of SS NSCLC group was advanced, but the rate of N1 lymph node metastasis was similar. However, the N2 lymph node metastasis rate of the SS NSCLC was significantly lower than that of the non-SS NSCLC, which was 25.3% and 39.8% respectively (P=0.048). Distant metastasis rates were similar at lower levels in both groups,which was 9.3% and 6.4% respectively (P=0.471).

      Table Basic information and results
      SS NSCLC N0n-SS NSCLC P value Chi-square
      Gender male 67 65
      female 8 28
      Median age 61(37-87) 62(42-82)
      ad 27 67
      Pathology squ 32 16
      others 16 10
      T stage T3+T4 75(100%) 3(3.2%) 0.000* 156.328
      N1 25(33.3%) 33(35.8%) 0.771 0.085
      N2 19(25.3%) 37(39.8%) 0.048* 3.902
      DM 7(9.3%) 6(6.4%) 0.471 0.519

      Ad:adenocarcinoma squ: squamous carcinoma DM:distant metastasis

      * P<0.05. There were significant differences between the two groups.

      Conclusion

      Although T staging was very late in SS NSCLC, the N2 lymph node metastasis rate and distant metastasis rate did not increase correspondingly. Therefore, enhanced local treatment, such as neoadjuvant concurrent chemoradiotherapy combined with surgery, may lead to better survival benefits.

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      EP1.01-35 - Concurrent Use of Low Dose Aspirin and Vitamin D in ALK, ROS and EGFR Mutant NSCLC: A Single Institution Retrospective Analysis (Now Available) (ID 2434)

      08:00 - 18:00  |  Presenting Author(s): Carolina Bernabe  |  Author(s): Sandhya Sharma, Jose G. Sanchez, Kevin Sullivan, Nagashree Seetharamu

      • Abstract
      • Slides

      Background

      Tyrosine kinase inhibitors (TKI) are the backbone therapy for EGFR, ALK and ROS positive (pos) non-small cell lung cancer (NSCLC). Pre-clinical data suggest that low vitamin D level facilitates the growth of mutant EGFR NSCLC through Vitamin D receptor (VDR). VDR is highly expressed in EGFR lung cancer cells, and its interaction with activated 1,25 vitamin D3 (1,25D3) promotes epithelial differentiation and apoptosis while inhibiting cellular proliferation and angiogenesis. Thus vitamin D3 supplementation may potentially add anti-cancer activity to conventional therapy in this population. On the other hand, murine models have shown that prolonged use of aspirin reduces the incidence of distant metastases. It is postulated that biosynthesis of prostaglandins generate a permissive intravascular metastatic niche, through platelet aggregation and endothelial activation.

      Recent meta-analysis published by Feng et al. analyzed seventeen studies and reported statistically significant reduction in risk of lung cancer by 8% when circulating 25-VD is at 10 nmol/L, this benefit was seen in both Caucasian and Asian population. To our knowledge, there have been no studies looking at influence of concurrent vitamin D or aspirin intake on outcomes in ALK, ROS and EGFR pos NSCLC treated with tyrosine kinase inhibitors. We performed a retrospective single institution analysis to study this association.

      Method

      Patients (pts) with ALK, ROS EGFR pos NSCLC treated with first line TKI from January 2014 to June 2017 were included. Information on concurrent use and doses of aspirin and vitamin D supplements were studied. Patients were dichotomized based on use of these individual supportive medications. Two sample t-test was used to compare mean PFS and chi-square test to compare proportions of disease control rate (DCR) at 3 months between groups.

      Result

      74 patients were included. PFS in Vitamin D supplementation (n=41, 55%) group was 11 months compared to 10.2 m in those not on Vitamin D (p = 0.21, CI 1.9). For those on aspirin (n=23, 35%), mean PFS was 16m vs 12.5 m (p = 0.7213; 95% CI -5.5812 to 3.8812). DCR for aspirin use was 50% vs 65% (p = 0.1796) and for vitamin D 48.6% vs 43.7% (p= 0.6989).

      Conclusion

      Our study did not show any differences in PFS or DCR in EGFR, ROS and ALK positive NSCLC patients who were concurrently taking vitamin D or aspirin compared with those who were not. Our study was small and was not powered to pick up any significant differences. Given the strong pre-clinical background, further prospective studies would be interesting to evaluate the synergistic benefit of vitamin D and aspirin with concurrent TKI use.

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      EP1.01-36 - Quality of Life in Advanced Lung Cancer Patients in a Dutch Population (Now Available) (ID 2623)

      08:00 - 18:00  |  Presenting Author(s): Romina Sluga  |  Author(s): Elisabeth A Kastelijn, Ben E.E.M van den Borne Beem, Bas J.M Peters, Pieter Zanen, Angelique Dernison, Franz Schramel

      • Abstract
      • Slides

      Background

      In advanced lung cancer chemotherapy is associated with a statistically significant improvement in overall survival (OS) compared to best-supportive care (BSC) alone. The palliative benefit of systemic therapy in incurable cancers cannot be deduced from response rates and survival benefits, but needs to be assessed directly, through validated patient reported tools. Studies have suggested that systemic therapy also improves quality of life (OoL) due to better overall physical functioning and alleviation of cancer-related symptoms. We aimed to investigate the QoL of patients with advanced lung cancer treated with systemic therapy or best-supportive care (BSC) alone in real-world practice.

      Method

      The European Organisation for Research and Treatment of Cancer (EORTC) QOL questionnaire (QLQ-C30) and the EORTC QLQ-LC13 were used to assess patients reported outcome measures (PROMs) at baseline, 3, 6 and 12 months in 235 patients with stage IIIb and IV NSCLC or SCLC diagnosed and treated between Janury 2013 and September 2017 in four large teaching hospitals in the Netherlands. Demographic and baseline data were compared with unpaired T- or c2-tests. Cox proportional hazard model was used to compare survival among these two groups and investigate the influence of age at diagnosis (continuous variable), gender and performance status. The change over time in raw questionnaire scores were analysed by using linear mixed modelling.

      Result

      Systemically treated patients (n=177) had a significantly prolonged OS compared to BSC (median OS of 691 vs 219 days (p<0.0001)) and a higher number of patients in the BSC arm (n= 58) died during the observation period (62.1% vs 44.6%, p=0.02). ‘Physical functioning’, ‘role functioning’, ‘shortness of breath’ and ‘bothered by shortness of breath’ were significantly different between the PST/BSC groups (p<0.001, p=0.025, p=0.017 and p=0.031 resp.) at baseline. Over time there was no significant time-treatment interaction in global health, functional or symptom scores between systemic therapy and BSC (p >0.09 in all cases). Patients deceased during observation had significantly worse global health and functional status and experienced more disease and treatment related symptoms.

      Conclusion

      Treatment with systemic therapy in advanced lung cancer led as expected to longer OS than BSC alone. However, unlike the evidence obtained from clinical trials, the QoL of patients in real-world practice, decreased in both groups equally over time.

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      EP1.01-37 - Platinum-Based Chemotherapy (CT) Rechallenge in Advanced Non Small Cell Lung Cancer (NSCLC) Patients (p): A Single Institution Experience (ID 2689)

      08:00 - 18:00  |  Presenting Author(s): Enric Carcereny  |  Author(s): Ana M Esteve, Anna Estival, Marta Domenech, Laura Angelats, Carlos Erasun, Andrea Gonzalez, Andrea Plaja, Natalia Garcia, Sofia España, Marc Cucurull, Angelica Ferrando, Anna Pous, Lucia Notario, Silvia Sanchez Martin, Claudia Villacorta Garcia, Teresa Moran

      • Abstract
      • Slides

      Background

      No phase III trials have been carried out to prove the value of a platinum-doublet rechallenge in p with NSCLC. Currently, the availability of different effective drugs makes the platinum-based salvage therapy unusual. Moreover, the potential cumulative toxicity related to cisplatin or carboplatin can be an issue. However, retreatment with platinum-based CT could be hypothetically proposed for p with a long time to progression (TTP) from the last platinum treatment, in p with a good performance status, who may be symptomatic and with no formal contraindication to receive such treatment We have retrospectively reviewed experience at our institution of platinum-based chemotherapy rechallenge in stage III and IV NSCLC p

      Method

      A cohort of 376 p with stage III and IV NSCLC treated with first-line platinum doublets from January 2012 to December 2017 were included. We extracted information on clinical and molecular characteristics, as well as treatment details. Time to progression was evaluated by Kaplan-Meier curves and groups were compared using Log-rank test.

      Result

      Overall, 57 p were rechallenged with platinum-based CT (group A). Median age was 57 years (51.5-65) for rechallenged p versus (vs) 62 (56.2-68.8) for the entire cohort (group B)[p=0.001]. Group A include more p with stage III p( 54.4% vs. 30.7%; p=0.001), as well as more p with better ECOG Performance Status (PS) (PS 0 70.2% vs. 44.5%; p=0.001). No differences in gender, smoking status, histology and comorbidities were observed between both groups (20.7% and 29.8% were women and 38.6% and 53.9% were smokers in groups A and B, respectively).

      No differences in molecular profile (EGFR, ALK, ROS1, KRAS, BRAF) were observed. The most common platinum doublet administered in first line setting was cisplatin plus pemetrexed. Group A received more frequently carboplatin plus gemcitabine or vinorelbine. Disease Control Rate (DCR) was 57.9% in p included in group A. No differences in DCR were observed in first line between both groups. Time to progression or death was 9.6 m for gropuo B(5-18.1) vs 20.5 m (14.6-37.3) p <0,001 for p in group A.

      Conclusion

      Rechallenge with platinum-based CT doublets could represent an option for NSCLC p with good PS and no contraindications for such therapy.

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      EP1.01-38 - Real World Experience of 1st Line Pembrolizumab in Patients with Metastatic Non-Small Cell Lung Cancer (NSCLC) (Now Available) (ID 90)

      08:00 - 18:00  |  Presenting Author(s): Nicola Steele  |  Author(s): Sonam Ansel, Philip McLoone

      • Abstract
      • Slides

      Background

      In July 2017, Pembrolizumab, a Programmed Cell Death protein-1 (PD-1) inhibitor was approved in Scotland for first-line treatment of metastatic NSCLC in patients with tumours expressing PD-L1 with tumour proportion score (TPS) of ≥50% and no targetable genetic alterations. Approval was based on findings of the KEYNOTE-024 study. We investigated the survival and toxicities experienced by patients receiving Pembrolizumab in the West of Scotland.

      Method

      We identified patients with tumours expressing PD-L1 at TPS ≥ 50% from pathology records from August 2017 to August 2018 and subsequently identified 83 patients receiving first-line Pembrolizumab. We collected baseline and treatment characteristics using electronic patient records. Survival was estimated using the Kaplan Meier method.

      Result

      Baseline and treatment characteristics are shown in table 1. Thirty patients had pre-treatment CT head and 8 of them had untreated brain metastases, this would have prohibited KEYNOTE-024 trial entry. Furthermore, there were 10 patients (12%) with active autoimmune co-morbidities which would have been excluded from the trial.

      After 9.4 months median follow-up, 32 (38.6%) patients had died. Survival at 6 months was 69.6% (95% CI: 58.3 to 78.3%) and 57.1% (95% CI: 42.1 to 69.6%) at 12 months.

      39 patients (47%) experienced treatment toxicities, 15 (18.1%) experienced ≥ 2 toxicities. Diarrhoea was commonest (14 patients; 16.9%) followed by hypothyroidism (8 patients; 9.6%), pneumonitis (6 patients; 7.2%) and rash (5 patients; 6%).

      Table 1: baseline and treatment characteristics
      n=83

      Median age (range)

      68 years (range: 39-86 years)

      Gender

      Male: 42 (51%) Female: 41 (49%)

      Stage of disease

      Stage 4

      - untreated brain metastases*

      Stage 3

      68 (81.9%)

      - 8 (11.8%)

      15 (18.1%)

      Histology

      Adenocarcinoma

      Squamous carcinoma

      Undifferentiated NSCLC

      Other histology

      54 (65.1%)

      17 (20.5%)

      9 (10.8%)

      3 (3.6%)

      Performance status

      0

      1

      2

      12 (14.5%)

      69 (83.1%)

      2 (2.4%)

      Active autoimmune

      co-morbidities*

      Psoriasis

      Interstitial lung disease

      Fibromyalgia

      Raynauds phenomenon

      Rheumatoid arthritis

      Post-polio syndrome

      Multiple sclerosis

      3 (3.6%)

      2 (2.4%)

      1 (1.2%)

      1 (1.2%)

      1 (1.2%)

      1 (1.2%)

      1 (1.2%)
      Median number of cycles = 6 (range: 1-24); 31 patients (37.3%) still continuing treatment**

      Reason for discontinuing

      treatment (n=52; 62.7%)

      Poor PS

      Disease progression

      Treatment toxicity:

      - Colitis

      - Pneumonitis

      Death:

      - NSCLC

      - Unknown cause

      Patient choice

      19 (22.9%)

      14 (16.9%)

      10 (12%)

      - 7 (8.4%)

      - 3 (3.6%)

      7 (8.4%)

      - 5 (6%)

      - 2 (2.4%)

      2 (2.4%)

      *These patients would have been ineligible for KEYNOTE-024 trial

      ** At time of data analysis - 21 February 2019

      Conclusion

      Survival at 6 months for our cohort was less than in the KEYNOTE-024 study (69.6% vs 80.2%) however fewer patients were PS 0 (14.5% vs 35.1%) and several had co-morbidities which would have precluded trial entry. The median number of treatment cycles in our cohort was 6 (range: 1-24) vs 10.5 (range: 1 to 26) trial. Toxicity was more common in this real life cohort with 12% discontinuing treatment due to toxicity vs 7.1% in the pivotal trial.

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      EP1.01-39 - A Randomised Phase II Trial of Vitamin C Synergy with Hyperthermia in Patients with Advanced Non-Small-Cell Lung Cancer (Now Available) (ID 120)

      08:00 - 18:00  |  Presenting Author(s): Junwen Ou  |  Author(s): Xinyu Zhu, Pengfei Chen, Yanping Du, Yimin Lu, Xiufan Peng, Shuang Bao, Junhua Wang, Xinting Zhang, Tao Zhang, Clifford L.K. Pang

      • Abstract
      • Slides

      Background

      Intravenous vitamin C (IVC) and modulated electrohyperthermia (mEHT) are widely used by integrative cancer practitioners for many years. However, there are no sufficient data in quality of life (QoL) ,clinical response and survival time of the above treatments in patients with stage III-IV Non-Small Cell Lung Cancer (NSCLC). Our phase I clinical trial proved that IVC simultaneously with mEHT were safe for NSCLC patients.

      Method

      A randomised phase II controlled trial was performed to compare supportive care with and without IVC + mEHT concomitant treatment (In the active arm: patients were allocated into 1 g/kg d, 1.2 g/kg d, 1.5 g/kg d dosage groups simultaneously with mEHT, three times a week for 25 treatments in total)on tumour size, progression-free survival (PFS) and overall survival (OS) in advanced Chinese NSCLC patients.Subsequently, 97 patients were analysed at the data cut-off (17th July, 2018). Enhanced chest and abdomen CT scans, brain MRI and bone scans were carried out at baseline, and every 4 weeks for the first 12 weeks from the start of the study. Response measurements were carried out according to RECIST 1.1. 3 month disease control rate(DCR) was measured 3 months after the therapy and defined as the percentage of subjects with complete response (CR), partial response (PR) or stable disease (SD) at 3 months relative to all randomly assigned patients.

      Result

      After a median follow up of 10 months, both the PFS and OS were significantly improved by IVC + mEHT compared to control (PFS: 3 month vs. 1.85 months, P<0.05; OS: 12 months vs. 7.5 months, P<0.05). The average scores for the functioning scales increased continuously, so that the QoL improved in the active arm despite the advanced stage of the disease(P<0.05). 3-month DCR after treatment was 42.9% in the active arm and 16.7% in the control arm (P<0.05). Both interleukin-6 and c-reactive protein were significantly decrease after treatments in active arm in comparison with control arm (P<0.05). However,there were no significant differences in 3 month DCR, PFS and OS between the three groups with different applied dosages of vitamin C. No significant differences were observed between parameters of adenocarcinoma and squamous cell carcinoma and between EGFR(+) and EGFR(–).

      Conclusion

      IVC + mEHT treatment significantly improves QoL, prolongs PFS and OS, and moderates cancer-related inflammation, and so is a feasible treatment for patients with advanced NSCLC. This trial is registered in ClinicalTrials.gov (ID: NCT02655913).

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      EP1.01-40 - Outcome of EGFR-Mutated and Non-Mutated Lung Adenocarcinoma Receiving Standard Therapy - A Nepalese Cohort (Now Available) (ID 941)

      08:00 - 18:00  |  Presenting Author(s): Natasha B Leighl  |  Author(s): Soniya Dulal, Bishnu Dutta Paudel, Aarati Shah, Prakash Neupane, Bibek Acharya, Sandhya Chapagain, Ambuj Karn, Ramila Shilpakar, Rameej Revanta Thapa, Balram Gautam, Odd Terje Brustugun

      • Abstract
      • Slides

      Background

      Lung cancer represents major health challenges worldwide including Nepal where patients (pts) often present in advanced stage. The purpose of this study was to compare the objective response rates (ORR), progression free survival (PFS), and quality of life (QoL) of EGFR-mutated (EGFR-mut) and non-mutated (EGFR-wt) pts with adenocarcinoma of the lung (ACL) receiving standard therapy.

      Method

      An IRB approved comparative analytical study was performed in pts with ACL. Newly diagnosed stage IV ACL pts were enrolled and ORR, PFS and QoL was compared between EGFR-mut and EGFR-wt (33 pts in each arm) pts. EGFR-mut pts were given gefitinib and EGFR-wt pts were given systemic chemotherapy (pemetrexed/cisplatin or cisplatin/etoposide). Response evaluation was done using RECIST criteria in both arms. PFS was calculated from the date of starting treatment to the date of progression and QoL was evaluated using EORTC QLQ-C30 (version 3) questionnaire and compared between two arms. Adverse effects were assessed using CTCAE criteria. Pts were followed for 1 year.

      Result

      Complete response (CR) was achieved in 9.1% vs 3.0 % (p=0.46), and ORR was 27.3% vs 15.2% (p=0.23) in EGFR-mut vs EGFR-wt. The median PFS was 11 and 9 months for EGFR-mut and EGFR-wt respectively (p = 0.045). The mean score of global health status from EORTC QLQ-C30 was 68.1 vs 61.6 in EGFR-mut pts vs EGFR-wt pts (p = 0.036). Skin toxicities were more common in pts receiving gefitinib. One pt had grade 3 skin toxicity. Febrile neutropenia and peripheral neuropathy (either grade 1 or grade 2) were the most common toxicities in pts receiving standard chemotherapy.

      kaplan meier-pfs.jpg

      Conclusion

      EGFR-mut pts treated with EGFR-TKI had improved ORR, PFS and QoL in comparison with EGFR-wt pts treated with chemotherapy. EGFR-mutational analysis and EGFR-directed therapy is feasible and provides survival benefit, also in developing countries as Nepal.

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      EP1.01-41 - Feasibility of EBUS-TBNA Cytologies for an Extensive Assessment of Predictive Biomarkers in Lung Cancer (Now Available) (ID 1640)

      08:00 - 18:00  |  Presenting Author(s): Roberto Martin-Deleon  |  Author(s): Cristina Teixido, Roxana Reyes, Carlos Cabrera, Ainhoa Fontana, Sara Castillo, Ramon Mª Marrades, Nuria Viñolas, Daniel Martinez, Jose Ramirez, Ivan Vollmer, Pedro Jares, Carmen Mª Lucena, Noemi Reguart, Carlos Agusti

      • Abstract
      • Slides

      Background

      Clinical guidelines support the determination of several driver genes as well as PD-L1 to drive treatment decisions in non-small cell lung cancer (NSCLC). Endobronchial-ultrasound transbronchial needle aspiration (EBUS-TBNA) cytology specimens are useful for the initial diagnosis of NSCLC, although its capacity to provide enough material for a complete genotyping remains controversial. The aim of this study is to determine the yield of EBUS for a comprehensive multiplex genotyping in patients (pts) with suspected NSCLC.

      Method

      In this single-center, ongoing, prospective study, samples from mediastinal lymph nodes were obtained from pts undergoing EBUS-TBNA for lung cancer diagnosis/staging. Following malignant confirmation and appropriate cell content by rapid on-site evaluation, the study sample was obtained and formalin-fixed paraffin-embedded (FFPE). Three analytes were evaluated (DNA/RNA/protein). DNA and RNA were extracted and analyzed by Oncomine Solid Tumour panel (22 genes) and a customized nCounter panel (ALK, ROS; RET, NTRK, METDe14). Tumor Proportion Score (TPS) for PD-L1 protein expression was evaluated by an expert pathologist and scored into <1% (negative), 1-49% (weakly positive) and 50% (high).

      Result

      Twenty-five pts with NSCLC have been included and cytology samples of 20 of them molecularly characterized (5 still in progress). Overall, cytological analysis of EBUS-TBNA yield a complete characterization for the three analytes (DNA/RNA/protein) in 15 pts (75%). EBUS-TBNA sampling was sufficient for both, Nanostring and Oncomine evaluation, in a total of 18 pts (90%): 15 patients (83%) had any alteration detected by oncomine (TP53 61% [11/18],KRAS 44% [8/18], EGFRe 195.5% [1/18], BRAF V600E 5,5% [1/18], DDR2 5.5% [1/18], STK11 11% [2/18]) and 1 pt (5.5 %) by nanostring (METDex14). A total of 19 samples were sufficient for PD-L1 expression scoring (95%). TPS for PD-L1 expression was negative in 8 pts (42%), week in 4 (21%) and high in 7 pts (37%). Overall, half of the pts evaluated (10/20) would be potential candidates for an upfront personalized treatment strategy using targeted agents or immunotherapy.

      Conclusion

      EBUS-TBNA is a promising alternative source of material for NSCLC genotyping and allows the identification of pts candidates for personalized therapies.

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      EP1.01-42 - Is Serum Lymphocyte Count Predictive Biomarker to Identify Lung Cancer Patients Who May Benefit from an Immunotherapy? (Now Available) (ID 2039)

      08:00 - 18:00  |  Presenting Author(s): Eun Young Heo  |  Author(s): Ye Jin Lee, Seo Young Yun, Tae Yun Park, Deog Keom Kim, Hee Soon Chung, Jung Kyu Lee

      • Abstract
      • Slides

      Background

      Programmed death ligand 1 (PD-L1) expression is not truly reflected response of immunotherapy. Thus, tumor mutational burden is new biomarker for predict response of immunotherapy. However, sufficient quantity or quality tumor samples must be obtained, so this is limitation. Therefore, we investigated whether high serum lymphocyte is predictive biomarker for immunotherapy response regardless of PD-L1 immunohistochemistry stain among lung cancer patients.

      Method

      We retrospectively analyzed the medical charts of lung cancer patients who treated with immunotherapy (pembrolizumab, nivoluamb, ipilimumab, atezolizumab) at Seoul National University Hospital between April 2016 and March 2019. We evaluated correlation the serum lymphocyte count (SLC) with the progression free survival (PFS) using multivariable linear regression. SLC was evaluated when patients

      Result

      Total 236 patients treated with immunotherapy for lung cancer. SLC at baseline was not significantly associated with progression free survival (Coeff = -0.00, p = 0.478) after adjustment age, sex, ECOG status, histology and PD L-1 expression status. The 1-year progression free survival rate was 14.8% and patients who survived over 1 year were not revealed difference of SLC compared with those who didn’t survive over 1 year. When we divided two group according lymphocyte count as 5000/uL, among patients who were over 5000/uL of lymphocyte related with increased progression probability (hazard ratio for disease progression, 1.68; 95 % CI, 1.03 to 2.77; P=0.04).

      figure1..jpg

      Conclusion

      In this study, we revealed that increased serum lymphocyte count over 5000/uL at baseline when immunotherapy start is associated with decreased progression free survival among lung cancer patients who treated with immunotherapy.

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      EP1.01-43 - Immunotherapy and Radiotherapy - A Useful Combination? (Now Available) (ID 2984)

      08:00 - 18:00  |  Presenting Author(s): Stephan Eisenmann  |  Author(s): Filiz Oezkan, IRIS Vogt, NINA Lambrecht

      • Abstract
      • Slides

      Background

      Immunotherapy has emerged as a major and effective therapeutic modality in non-small cell lung cancer (NSCLC). With expanding indications for immunotherapy, therapeutic modalities in progressive disease under immunotherapy are needed.

      Method

      In a retrospective single center analysis patients treated with immunotherapy and radiation for progressive lesions were identified. Both patients with acquired and primary resistance to immunotherapy were included in the analysis.

      Result

      In eight patients (2 adenocarcinoma, 6 SCC) immunotherapy was continued (5 Nivolumab, 1 Pembrolizumab, 2 Atezolizumab) despite disease progression due to good tolerance and missing therapeutic alternatives because of multiple pretreatment regimens and their toxicities. We observed that all 8 patients had a clinical benefit without developing a disseminating disease, we only observed a growth in the previously existing lesions. In 5/8 patients the disease could be stabilized. An abscopal effect could be excluded.

      In five patients local metastatic growth was treated with radiation to manage pain and local complications. Three additional patients with asymptomatic, progressive lesions were treated with radiotherapy to prevent organ complications.

      Conclusion

      Immunotherapy has revolutionized NSCLC treatment. However there are therapeutic modalities questioned in progressive disease under immunotherapy. By maintaining immunotherapy during and after radiotherapy localized progression might be effectively treated.

      Therefore we summarize that in a number of patients further metastatic evolution might be preventable. Whether peritumoral or systemic prognostic determinants can be identified should be a matter of further research.

      Either benefits of local ablative techniques or perpetuation of immunotherapy despite of disease progression were recently reported (Gandara et al. 2018, Gettinger et al. 2018). This also suggests a differentiative perspective of local ablative therapy in metastatic NSCLC.

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      EP1.01-44 - Early and Long-Term Results of Tracheal Sleeve Pneumonectomy for Lung Cancer After Induction Therapy (Now Available) (ID 2794)

      08:00 - 18:00  |  Presenting Author(s): Domenico Galetta  |  Author(s): Lorenzo Spaggiari

      • Abstract
      • Slides

      Background

      The role of induction therapy (IT) and its effects on morbidity and mortality of patients receiving tracheal sleeve pneumonectomy (TSP) are unclear. We evaluated early and long-term outcomes of patients who underwent TSP after IT.

      Method

      From 1998 to 2018, 32 patients (26 men; median age, 63 years) underwent TSP. Twenty-two patients (69%) received IT (cisplatin-based chemotherapy). The TSPs were all right sided and included three completion pneumonectomies. Superior vena cava resection was combined with TSP in 15 cases. Diaphragmatic and vertebral resection was also associated in 1 case each.

      Result

      Operative mortality was nil. Thirty-day mortality was 9% (n = 3). Major complications occurred in 7 patients (21.8%): bronchopleural fistulas in 3; acute respiratory distress syndrome in 2; cardiac hernia in 1; and empyema in 1. The IT had no significant effects on morbidity and mortality. Resection was complete in 31 patients (97%). Pathologic N status was N0 in 2 cases, N1 in 17, and N2 in 13. Nodal downstaging was diagnosed in 13 of 22 patients (59.1%) who received IT (11 passed from N2 to N1, and 2 to N0). Mean survival was 36 months (range, 1 to 181). Overall 5-year survival and disease-free survival were 30.3% and 27.7%, respectively. Patients receiving IT had a poor survival (p = 0.03). At multivariate analysis, nodal downstaging and adjuvant treatment significantly affected survival (p = 0.035 and p = 0.007, respectively).

      Conclusion

      Tracheal sleeve pneumonectomy is a feasible but technically challenging surgical procedure and provides acceptable results in terms of early and long-term outcomes. Induction therapy did not significantly affect morbidity and mortality.

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      EP1.01-45 - Cisplatin Plus Gemcitabine Therapy Followed by Maintenance Gemcitabine for Advanced Squamous Cell Lung Cancer (KTORG1302) (Now Available) (ID 514)

      08:00 - 18:00  |  Presenting Author(s): Toshihiko Kaneda  |  Author(s): Satoshi Ikeda, Hiroshige Yoshioka, Toshihide Yokoyama, Takashi Niwa, Naoyuki Sone, Tadashi Ishida, Mitsunori Morita, Hiromi Tomioka, Chihito Komaki, Masataka Hirabayashi, Yoshinori Hasegawa, Tetsuo Noguchi, Yasutaka Nakano, Chikara Sakaguchi, Kenichi Yoshimura, Toyohiro Hirai

      • Abstract
      • Slides

      Background

      One of the standard treatments in chemo-naïve patients with advanced non-small cell lung cancer (NSCLC) is platinum-containing doublet chemotherapy. Moreover non-squamous NSCLC, patients benefit from pemetrexed maintenance therapy following induction therapy with cisplatin (CDDP) plus pemetrexed. However, no large-scale trial showing the efficacy of maintenance therapy has been reported in squamous cell lung cancer. We evaluated the efficacy and the safety of continuation maintenance therapy with gemcitabine (GEM) after induction chemotherapy with CDDP plus GEM in advanced squamous cell lung cancer.

      Method

      This study was a single-arm, multicenter and phase II trial. Main eligibility criteria included Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1, and the aged of 20 to 74 years old. Patients received an induction phase which consisted of 4 cycles of CDDP (80mg/m2, day 1, q3w) plus GEM (1000mg/m2, day 1, 8, q3w). Patients who did not progress after completion of 4 cycles of induction received continuation maintenance therapy with GEM (1000mg/m2, day 1, 8, q3w) until disease progression. The primary endpoint was progression-free survival (PFS) in the intention-to-treat population.

      Result

      Between June 2013 and October 2018, 26 patients were enrolled in this study. Although the scheduled numbers were 60, this study was ended early for poor accrual.

      The mean age was 65.7 years (range, 47 – 74 years). 18 patients (69.2%) completed 4 cycles of CDDP plus GEM, and 16 patients (61.5%) received continuation maintenance therapy with GEM. At the cutoff date of December 31, 2018, overall response rate was 46.2%, median PFS from induction therapy was 5.3 months (95% confidence interval [CI]: 2.9-7.3), and median PFS from continuation maintenance therapy was 3.8 months (95% CI: 2.3-5.2). Median overall survival from induction therapy was 11.9 months (95% CI: 7.5-26.5). The most common grade 4 adverse events were neutropenia (16%) and thrombocytopenia (12%). Pneumonitis ware seen in 3 cases (grade 1: 1, grade 2: 1, grade 3: 1 case). Adverse events except for hematotoxicity were generally well tolerated. There were no treatment-related deaths.

      Conclusion

      This study terminated early because of poor accrual and did not meet its primary endpoint. However, this study indicated continuation maintenance therapy with GEM can be well-tolerated treatment option for patients with advanced squamous NSCLC.

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      EP1.01-46 - Acute Esophageal Damage in Patients with Inoperable Non-Small Cell Lung Cancer Treated with Concurrent and Sequential Chemoradiotherapy (Now Available) (ID 234)

      08:00 - 18:00  |  Presenting Author(s): Simonida Crvenkova

      • Abstract
      • Slides

      Background

      Acute esophageal damage may be dose-limitation factor for application of the full planning radiotherapy dose in patients with inoperable Non Small Lung Cancer-NSCLC. Combination of chemotherapy and radiotherapy may increase esophageal toxicity, however three-dimensional conformal radiotherapy offers better spearing.

      Method

      To evaluate the treatment results, study of 75 patients was randomly assigned to one of the two treatment arms. In the sequential arm, 26 (34.7%) patients had previously received sequential chemotherapy with 4 cycles of carboplatin and etoposide followed by conformal radiotherapy (RT). In the second concurrent arm, 49 (65.3%) patients received concurrent chemotherapy of cisplatine and etoposide and conformal RT. We described all phases of the conformal RT. Treatment-related toxicities were assessed according RTOG/EORTC criteria.

      Result

      From 2010 to 2013, 73 patients were enrolled in this study. From all included patients, 43 (57.3%) did not present any grade of esophagitis during the treatment. In sequential group 73.1% presented no esophagitis and in concurrent group 49%, respectively. Although there were differences between the two groups, none was statistically significant. The median survival was 13 months for the patients in the sequential arm and 17 months for those in the concurrent treatment arm. The differences were statistically significant (log-rank test p=0.0039). Table 1 and 2 present grade of ezophagitis and the needs of analgesia in the patients of sequential and concurrent treatment arm.

      The risk of esophagitis was 22%, in patients whose esophageal volume (V50) recieved less than 30% of prescribed dose in comparation, the risk of esophagitis was 71%, in patients whose V50 recieved dose higher than 30% (p=0.0009).

      barcelona 1.jpgbarcelona 2.jpg

      Conclusion

      The reason for good tolerability of the combination of chemotherapy and radiotherapy for patients in this study is using three-dimensional conformal radiotherapy. Further improvements may be obtained with more sophisticated radiotherapy techniques or by using radio protective drags.

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      EP1.01-47 - Thyroid Related Adverse Events Predict Survival in NSCLC Patients Receiving Anti-PD-1/ PD-L1 Therapy (Now Available) (ID 279)

      08:00 - 18:00  |  Presenting Author(s): Yasar Ahmed  |  Author(s): J Lee, P Calvert

      • Abstract
      • Slides

      Background

      Immune checkpoint inhibitors (ICI) have altered the therapeutic paradigm of advanced non-small cell lung cancer (NSCLC) and produce antitumor effects by activating host immunity, which also causes immune-related adverse events (irAEs).

      Thyroid irAE is the second most common irAEs after dermatological irAEs following ICI and present in 2%-21% of patients s depending upon the immune checkpoint inhibitors used.

      It has been reported that irAEs induced by ICI may be associated with possible improvement in survival and better therapeutic outcomes.

      The aim of this study is to analyze the relationship between PD-1 inhibitors -induced Thyroid irAE and clinical efficacy in advanced NSCLC patients treated at three regional cancer centres.

      Method

      Retrospective study was conducted using the Hospitals’ Inpatient Enquiry (HIPE) to identify patients with NSCLC stage IV or inoperable stage IIIB who received at least one dose of PD-1 inhibitors (Nivolumab or pembrolizumab) between Januarys 2017 and December 2018.

      Patients who had no baseline Thyroid function tests (TFTs) , abnormal baseline TFT or had a history of thyroid disorder were excluded.

      Thyroid irAE were identified and classified according to TSH and free T4 (fT4)

      Efficacy was evaluated with progression free survival (PFS) and median overall survival (OS) according to the development Thyroid IrAEs

      Result

      One hundred and eighty-five patients were included, 120 male [64.9%] ,65 female [35.1%] and the median age was median age 66(38-88) years.

      A total of 38 (20.5 %) patients on PD-1 inhibitors (nivolumab or pembrolizumab) had new-onset Thyroid IrAEs. 76.3% (29/38) of those patients manifested initially with thyrotoxicosis. The remaining 22.6% (9/38) of patients presented with hypothyroidism as the initial presentation.

      The median times to new-onset Thyroid IrAEs was 46 days.

      Kaplan Meier survival analysis showed that patients with Thyroid IrAEs had a statistically significant longer median PFS of 9.0 months (95% CI, 9.3–17.1) compared to patients with without Thyroid IrAEs who had a median PFS of 2.0 months (95% CI, 2.0–13.5), hazard ratio = 0.38, (95% CI, 0.20–0.71; P = 0.002). For entire cohort, Thyroid IrAEs was associated with superior survival (median OS 16.0 months for those who developed Thyroid IrAEs compared to 2.9 months of those without Thyroid irAEs (p < 0.0001)

      Conclusion

      The result of this study emphasizes the association between irAEs and better survival outcomes from anti-PD1 therapy.

      Development of grade 2 Thyroid IrAEs was a useful predictor of survival outcomes in NSCLC patients treated with ICI.

      These results support previously published retrospective data.

      Further prospective studies are required to thoroughly underline the association between ICI induced irAEs, tumor response and long term survival.

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      EP1.01-48 - Invasive Mucinous Adenocarcinoma of the Lung: Serial CT Findings, Clinical Features, and Treatment Outcomes (Now Available) (ID 1203)

      08:00 - 18:00  |  Presenting Author(s): Kyongmin Sarah Beck  |  Author(s): Kyo Young Lee, Dae Hee Han

      • Abstract
      • Slides

      Background

      Invasive mucinous adenocarcinoma of the lung is a rare and distinct subtype of adenocarcinoma, previously described as bronchoalveolar carcinoma (BAC). In our daily practice, we have sometimes encountered spontaneous regression without treatment in patients with invasive mucinous adenocarcinomas, but serial CT findings of this cancer have not been described in the literature. We performed an analysis to describe the serial chest CT findings, clinical features, and treatment outcomes of patients with invasive mucinous adenocarcinoma of the lung.

      rsna abstract figure.jpg

      Method

      From January 2013 to June 2018, 49 cases of pathology-confirmed invasive mucinous adenocarcinoma of the lung were identified. Initial chest CT and follow-up CTs were available for 48 patients (23 men and 25 women; median age, 69.5 years; range, 26-82 years). Median follow-up period was 19.0 months (range, 0-110 months). Serial CT scans were reviewed, with emphasis on changes over time and in relation to medical or surgical treatment. Patients were classified as either nodule/mass type or consolidation type according to the initial CT. Clinical, radiological, and treatment outcomes were compared between nodule/mass and consolidation types by adopting the χ2 test, Mann-Whitney U test, and Kaplan-Meier analysis with log-rank tests.

      Result

      There were 33 nodule/mass type and 15 consolidation type at initial CT scan. Of 15 consolidation type, 9 patients showed combined GGO. Consolidation type presented with significantly larger lesion size (p<0.001), higher stage (p<0.001), and multifocality (p=0.001) on initial CT and showed spontaneous regression without treatment during follow-up (p<0.001) compared to the nodule/mass type. Six patients died during follow-up, and they were all from the consolidation group (p<0.001). 33 patients underwent surgery and 11 patients received chemotherapy. Patients with the consolidation type showed reduced progression-free survival (PFS) (mean 9.5 months) compared with those with the nodule/mass type (mean 63.9 months) (p<0.001).

      Conclusion

      Invasive mucinous adenocarcinomas of the lung appearing as consolidation on initial CT are larger and multifocal, have higher stage, higher mortality, and reduced PFS, and can show spontaneous regression.

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      EP1.01-49 - Histology-Depended Pattern of Patho-Histological Response After Induction Therapy in Locally Advanced Non-Small Cell Lung Cancer (Now Available) (ID 2251)

      08:00 - 18:00  |  Presenting Author(s): Waldemar Schreiner  |  Author(s): Wojciech Dudek, Ralf Joachim Rieker, Rainer Fietkau, Horia Sirbu

      • Abstract
      • Slides

      Background

      Pathological response after induction therapy (IT) is expected to be associated with favorable outcome in locally advanced non-small cell lung cancer (NSCLC). The pathologic response pattern remains unpredictable. Aim of this retrospective study was to analyze the patho-histologic response according to tumor histology, in order to identify the potential correlation and prognostic impact.

      Method

      In 57 patients with locally advanced NSCLC the patho-histologic response to IT were assessed and compared for adenocarcinoma vs. squamous cell lung cancer after curative lung resection. The prognostic differences were estimated by Kaplan-Meier method and compared using log-rank test.

      Result

      The IT included chemo-radiation with 50.4Gy (range 45-56.4 Gy) combined with platin-based chemotherapy in 54 patients (94.7%) or only platin-based chemotherapy in 3 patients (4.3%). Perioperative morbidity and 30-days-mortality was 36% and 3.5%, respectively. Complete resection was achieved in 93% patients. Significantly improved long-term survival and recurrence-free survival were associated with <15% viable squamous cells and with <60% viable adenocarcinoma cells (long rank 0.013 and 0.012, 0.04 and 0.05, respectively). The median long-term survival for <15% viable squamous cells was 35.2 months, recurrence-free survival was not achieved; for <60% viable adenocarcinoma cells the median long-term and recurrence-free survival were 87.9 and 35.9 months, respectively.

      Conclusion

      The patho-histologic response pattern to IT is correlated to tumor histology and has potential implication on pathologic assessment. Distinct prognostic impact can be further reflected in the clinical practice and multimodal treatment strategies.

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      EP1.01-50 - Quantitative Assessment of Subsegmental Bronchi on Thin-Section CT for Pulmonary Lymphangitis Carcinomatosa (Now Available) (ID 2290)

      08:00 - 18:00  |  Presenting Author(s): Daisuke Takenaka  |  Author(s): Yoshiharu Ohno, Chika Tanaka, Erika Matsushiro, Ayumi Higashida, Tomohisa Hashimoto, Hiroaki Maeda, Setsu Sakamoto, Miyako Satouchi

      • Abstract
      • Slides

      Background

      CT is the main modality to measure the of the tumor and/or metastasis of solid malignancies to evaluate the change over time due to conservative therapy, especially in chemotherapy. However, the change of lymphangitis carcinomatosa which appears at advanced stage could be evaluated quantitatively, only. The purpose of this study was to evaluate the availability of CT to quantify the lymphangitis carcinomatosa of lung cancer.

      Method

      Fifteen consecutive patients (12 males, three females; 51-76 y.o.) with pulmonary lung cancer who were diagnosed as lung cancer with lymphangitis carcinomatosa by CT were enrolled retrospectively. Each patient’s lung cancer was diagnosed by using bronchoscope or CT guided biopsy. All patients underwent CT examination before and after the chemotherapy. All CT studies were performed by using MDCT machine (Aquilion Prime or Aquilion Precision; Canon Medical Systems, Otawara, Japan). All CT examinations were performed with 80 or 160-detector row CT scanner with contrast media. CT images were reconstructed with 1mm slice, 1mm interval, 512 x 512 matrix. The long axis diameters of primary tumors were measured on CT before and after the therapy. The wall area of the sub-segmental bronchus affected by lymphangitis carcinomatosa was defined by Synapse Vincent (Fujifilm Medical; Tokyo, Japan) before and after the therapy. The correlation coefficient of tumor reduction rates between the primary tumor diameter and wall area of the affected sub-segmental bronchus was statistically assessed. P value less than 0.05 was considered as significant in statistical analyses.

      Result

      The correlation coefficient of tumor reduction rates between the primary tumor diameter and wall area of the affected sub-segmental bronchus was 0.533 (p = 0.041).

      Conclusion

      The positive correlation of tumor reduction rates was significant between the primary tumor diameter and wall area of the affected sub-segmental bronchus. The measurement of wall area of affected sub-segmental bronchus on thin-slice CT has the availability to evaluate the quantitative change of lymphangitis carcinomatosa of lung cancer patients.

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      EP1.01-51 - Efficacy Impact of Serum VEGF for Elderly or Poor PS Patients Receiving Anti-PD-1 Antibody with Advanced Non-Small Cell Lung Cancer (ID 1691)

      08:00 - 18:00  |  Presenting Author(s): Ryota Shibaki  |  Author(s): Shuji Murakami, Yuki Shinno, Yuji Matsumoto, Tatsuya Yoshida, Yasushi Goto, Shintaro Kanda, Hidehito Horinouchi, Noboru Yamamoto, Yuichiro Ohe

      • Abstract
      • Slides

      Background

      Anti-programmed cell death (PD)-1 antibody therapies have shown durable clinical efficacy and manageable toxicity profiles, and have become a standard therapy in advanced non-small cell lung cancer (NSCLC). Because of manageable toxicity profiles, extensive interest in the potential benefits of anti-PD-1 antibody has expanded to high-risk patients such as the elderly or poor performance status (PS) patients. Here, we aimed to investigate predictive markers for the efficacy of anti-PD-1 antibody in elderly patients and poor PS patients.

      Method

      The medical records of 75≥ years old or PS2 NSCLC patients treated with anti-PD-1 antibody (e.g., nivolumab and pembrolizumab) at the National Cancer Center Japan between December 1, 2015, and May 31, 2018, were reviewed retrospectively. We evaluated the association between efficacy for anti-PD-1 antibody and gender, smoking status, histology, PD-ligand 1(PD-L1) expression on tumor cells, white blood cell counts, lymphocyte counts, albumin, lactate dehydrogenase, c-reactive protein, and serum vascular endothelial growth factor (VEGF). We divided patients into two groups with the median values.

      Result

      A total of 235 patients with advanced NSCLC treated with anti-PD-1 antibody were reviewed. Of these patients, 31 patients were ≥ 75 years old, and 22 patients were PS2. The median PFS was 6.9 months in patients aged ≥ 75 years and 2.1 months in PS2 patients. Cox proportional hazard regression analysis showed that only the low-VEGF was significantly associated with longer PFS in patients aged ≥ 75 years (HR, 0.35; 95% CI, 0.13-0.88; P = 0.025) and in PS2 patients (HR, 0.31; 95% CI, 0.10-0.85; P = 0.023). The overall response rate of patients with low-VEGF was tend to be higher than that with high-VEGF among patients aged ≥ 75 years (43% vs. 20%; P = 0.18) and PS2 patients (20% vs. 0%; P = 0.084).

      Conclusion

      Low-VEGF in patients aged ≥ 75 years and PS2 patients was associated with longer PFS. Serum VEGF may thus be a biomarker for the efficacy of anti-PD-1 antibody therapy.

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      EP1.01-52 - Preferable Intracranial Chemotherapy for Lung Cancer Patients with Meningeal Metastasis Harboring CIN in CSF (ID 2262)

      08:00 - 18:00  |  Presenting Author(s): Peng Wang  |  Author(s): Henghui Zhang, HuaiBo Sun, JingJie Li, Lei Zhang, Peng Chen

      • Abstract

      Background

      Brain metastases occur in about half of the NSCLC patients throughout the course of disease, including brain parenchymal metastasis and meningeal metastasis. It has been reported that compared with plasma detection, next-generation sequencing (NGS) of circulating tumor DNA (ctDNA) from cerebrospinal fluid (CSF) is capable of more comprehensively characterizing the genomic alterations of brain tumor, so as to identify actionable variants.

      Method

      We conducted a small sample study consisting of 7 patients with brain metastasis, including 3 lung cancer patients with meningeal metastasis (P314, P316, P318), a lung cancer patient with brain parenchymal metastasis (P323), 2 breast cancer patients with meningeal metastasis (P324 and P328) as well as a gastric cancer patient with meningeal metastasis (P326). Profiling of the specimens from CSF, brain parenchyma and plasma of these 7 patients was performed using NGS along with bioinformatics analysis.

      Result

      Among the three patients P314, P316 and P318, high-frequency driver mutations including ERBB2 p.V659E, EGFR p.L858R & MET amplification, EGFR 19del were detected in the CSF respectively, but all of these variants were not observed in the plasma. Notably, these three patients’ brain lesions continued to progress after receiving corresponding targeted agents, while their conditions remained stable in the presence of switching to intracranial chemotherapy. Following bioinformatic analysis revealed the occurrence of chromosome instability (CIN). We wonder if it is a special case or a common phenomenon. To further explore whether there is similar phenomenon in brain parenchymal metastasis, we examined the patient P323. The detection results of his brain parenchyma, CSF and plasma showed that there was no variation of CIN in brain parenchyma and CSF. In view of this, we hypothesized that CIN variants might exist only in lung cancer patients with meningeal metastasis. In addition, our results displayed that no chromosome instability was identified in the CSF of patients P324, P328 and P326.

      Conclusion

      In summary, CIN is likely an important genomic feature of lung cancer with meningeal metastasis and is apt to be detected in the CSF. According to our observation, NGS of CSF specimen rather than plasma sample may be more favorable to the selection of appropriate treatment options for lung cancer patients with meningeal metastasis. For such patients with CIN variation, intracranial chemotherapy possibly offers more significant clinical benefit than other treatments such as targeted therapy. It still requires more investigations to verify above hypothesis.

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      EP1.01-53 - Update of Mutation Status in Lung Cancer. A Multicenter Local Study (Now Available) (ID 2466)

      08:00 - 18:00  |  Presenting Author(s): Norma Graciela Pilnik  |  Author(s): Veronica Bengio, Maximiliano Franco Canigiani

      • Abstract
      • Slides

      Background

      Advances have been made in the understanding of the biology of NSCLC in relation to the characterization of molecular features such as activations of oncogenes by mutations, translocations and amplifications, which are being used as a targets and predictive biomarkers. Molecular analysis of NSCLC, adenocarcinoma (AC) is now the standard of care for therapy selection.

      Method

      We determined the molecular alterations in EGFR , and gene fusion ALK in our Caucasian and Hispanic populations

      169 small samples and resection specimens of patients with NSCLC in different institutions of Cordoba were studied during a period (2014 - 2019).

      In addition to Histopathology Type, we analyzed immunohistochemistry (IHC) characteristics, molecular profiles , and several clinical variables were studied.

      Different tests were used to detect alterations of EGFR and fusion gene EML4-ALK expression, with the aim to identify our own profile. EGFR mutation was studied by therascreen kit, PCR, in order to detect genetic alterations in exons 18, 19, 20 and 21. ALK translocations were analyzed by FISH (Vysis- Break Apart, Abbott) and IHC (clon D5F3, ventana, Roche). We correlated the molecular profile with different clinical variables (age, gender, and tobacco habits). The statistical method used was the multiple regression logistic model.

      Result

      169 samples were tested for EGFR expression and alk alterations 64% of subjects were men and 89% were smokers. Smoking habit was associated with sex (33% and 67% of smokers were women and men respectively, p=0.009). Smokers were older than non-smokers (p=0.011); to 64.4 (0.98) and 57.5 (2.35) years old for smokers and non-smokers.

      EGFR alterations were associated with sex (p=0.002, Fig 1). Women had more chance of having positive alterations of the gene (OR 3.57, 95CI:2.04-7.55). Age and smoking habit of patients did not show significant effects (p=0.44, Fig.2 , and p=0.09, respectively).

      Only 1.7% of subjects reported ALK alterations, and were not related to sex (p=0.42), age (p=0.965) and smoking habit (p=0.281).

      Conclusion

      Our results showed a comparable frequency in EGFR mutations and gene fusion ALK in relation to the data published in western population. These results allowed a proper diagnosis to provide the most adequate therapy.

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      EP1.01-54 - Implementation of Fine Needle Aspiration of Supraclavicular Lymph Node as a Novel Medium for Genomic Profiling in NSCLC (Now Available) (ID 1171)

      08:00 - 18:00  |  Presenting Author(s): Zhengfei Zhu  |  Author(s): Ying Cheng, xun Zhang, Jianjiao Ni, Bing Li, Hao Liu

      • Abstract
      • Slides

      Background

      Supraclavicular lymph node (SLN) metastasis is not rare in non-small cell lung cancer (NSCLC). Palpation or B-ultrasound guided fine needle aspiration (FNA) of SLN is a very simple, rapid, and minimally invasive tool for diagnosis of these patients. With the development next generation sequencing (NGS) which has been widely used to catalogue genetic mutations in cancer, uncertainty remains if FNA of lymph node could be combined with NGS and applied in clinical practice. The aim of this study was to evaluate the clinical utility of FNA of SLN in patients with NSCLC

      Method

      FNA of SLN samples (stored in 10% neutral buffered formalin) and matched plasma samples from 30 patients with NSCLC were collected. Twenty-three patients (both FNA and plasma samples) were sequenced using a panel covering whole exons and critical introns of 520 cancer-related genes and seven patients (both FNA and plasma samples) were profiled using a panel of 168 lung cancer-related genes.

      Result

      During the procedure of next-generation sequencing library construction, the amount of extracted DNA and qualification percentage of FNA samples (n=30) from lymph nodes were similar to those of punctured lung biopsy samples (n=100, randomly selected from burning Rock database). Comparative analysis of mutation spectrums revealed that mutations were positively identified in 93.3% (28/30) FNA samples and 90.0% (27/30) plasma samples, while mutations of eight well-established lung cancer-related genes (EGFR, ERBB2, MET, BRAF, KRAS, ROS1, ALK and RET) were detected in 83.3% (25/30) FNA samples, which was higher than that in plasma samples (63.3%, 19/30). Moreover, FNA was significantly superior to plasma in detecting copy number variation (CNV) (detection frequencies, 88.9% vs 0.9%, p<0.001), both for CNVs of all genes in NGS panel (99.5% vs 10.0%) and eight well-established genes (96.0% vs 20.0%).

      Conclusion

      Samples from FNA of SLNs were found to be equivalent to plasma during NGS library construction. Moreover, FNA of SLNs was superior to plasma in detecting mutations of eight lung cancer-related genes, as well as CNVs in both all genes of NGS panel and the 8 key genes. This study provides knowledge for the potential use of FNA of lymph nodes in sequencing genomic profiles of patients with lung cancer, and further support its utility in clinical practice.

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      EP1.01-55 - Neoantigen Deletion Leads to Hyperprogressive Disease (HPD) in Non-Small Cell Lung Cancer (NSCLC) Treated with PD-1/PD-L1 Inhibitors (Now Available) (ID 1179)

      08:00 - 18:00  |  Presenting Author(s): Di Wu  |  Author(s): Xiaohua Hong, Yiying Liu, Kai Zhang, Yue Hu, Feifei Gu, Yuting Liu, Zhikun Zhao, Jun Liu, Li Liu

      • Abstract
      • Slides

      Background

      Hyperprogressive disease (HPD) is a distinct pattern of progression described in patients with cancer treated with PD-1/PD-L1 inhibitors. The incidence of HPD is reported to be 13.8% in advanced NSCLC. Recently multiple characteristics have been recognized to predict the risk of HPD, however the mechanism underlying have not been systemically studied.

      Method

      We report a Chinese patient who developed hyperprogressive disease after 4 cycles of PD-1 blockade treatment. Clinical and demographic data was collected from electronic records. Whole exome sequencing (WES) of the primary tumor was performed to identify tumor mutation burden (TMB) and tumor neoantigen burden (TNB) following the restricted pipeline. Liquid biopsy targeting ctDNA and T cell receptor (TCR) was constructed to monitor the efficacy of immunotherapy.

      Result

      A 70-year-old male with smoking history underwent chest CT scan in February 2018 and was found to have a right upper lobe mass with intrapulmonary metastasis in different lobes and multiple lymph nodes. Resection of right lower lung by video-assisted thoracic surgery (VATS) revealed poorly differentiated, squamous cell carcinoma. In July 2018, he progressed after two cycle of chemotherapy and radiation therapy targeting newly bone metastasis of lumbar spine, then he was screened to start Nivolumab at dose of 240mg daily/2 weeks. After four cycle of Nivolumab, he obtained PD and was assigned to palliative thoracic radiation therapy. The PD-L1 expression level of our patient was 1%≤TC<5%, next generation sequencing (NGS) didn’t show alteration in genes related to HPD, such as MDM2/MDM4 or EGFR. Blood sample retrieved before and after immunotherapy revealed the increase in bTMB (from 7.70 Muts/Mb to 18.00 Muts/Mb), however TNB truly expressed as neoantigens were rather lower compared to TMB, indicating the low immunogenicity of tumor. We also found a sharp fluctuate in the detection of driver genes mutations in ctDNA (TP53,CDKN2A,ERBB3,FBXW7), and the majority of high-frequency TCR dropped significantly during immunotharapy.

      Conclusion

      It is reported that NSCLC with a high tumor mutation burden (TMB) may benefit from PD-1/PD-L1 inhibitors treatment, and TMB is considered as the surrogate of tumor neoantigen burden (TNB). However the deletion of neoantigen may occur at different level, including copy number variation at the DNA level, down-regulation of transcription level and inherited variation at the epigenetic level, resulting in the low immunogenicity of primary tumor. Deletion of neoantigen may provide a mechanism of immune evasion which leads to the resistance to PD-1/PD-L1 inhibitors. In this case, treatment of checkpoint inhibitors may activate certain signaling pathway of driver genes to support the hyperprogression disease (HPD). This case report focusing on neoantigen provides a new approach to predict the presence of hyperprogressive disease (HPD) before immunotherapy, and explains the potential mechanism of HPD.

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      EP1.01-56 - Co-Presentation of Adenocarcinoma and Squamous Cell Lung Carcinoma Harbouring ALK Rearrangement in Different Sites  (Now Available) (ID 1416)

      08:00 - 18:00  |  Presenting Author(s): Domenico Galetta  |  Author(s): Vito Longo, Annamaria Catino, Gabriella Del Bene, Rosanna Lacalamita, Michele Montrone, Francesco Pesola, Daniela Petriella, Pamela Pizzutilo, Stefania Tommasi

      • Abstract
      • Slides

      Background

      Approximately 4% to 9 % of NonSmallCellLungCarcinoma (NSCLC) contain mixed adenomatous on squamous pathologies (adenosquamous cell carcinoma). The lung ADC to SCC transdifferentiation as a drug-resistance mechanism has been recently described. While the histological transformation mainly described in ALK-positive patients is from NSCLC entity to SCLC, only one case of histologic transformation of ALK rearranged ADC to SCC after treatment with an ALK inhibitor has been reported. Importantly, transformed samples retain the initial genomic alteration, supporting the lineage transition as a novel resistance mechanism.We describe an unique case of co-presentation of ADC and SCC in two different disease sites, both harbouring ALK rearrangement.

      Method

      A 57-year-old male never smoker presented with a left adrenal mass. CT Scan showed a right superior lobe mass, bilateral pulmonary nodules (Fig. 1 A), and bone metastases. The lung biopsy documented ADC with moderate differentiation and ALK rearrangement by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC).

      ct.jpgihc.png

      Result

      The patient was treated with Crizotinib but, after 4 months, the CT showed a near complete response of the pulmonary disease (Fig. 1 B), while a progression of the left adrenal metastasis was observed. (Fig. 2 A, Fig. 2B). A left adrenal biopsy showed a SCC histology, with ALK rearrangement confirmed both by IHC and FISH. The treatment was switched to alectinib without respoinse so the patient received chemotherapy.

      Conclusion

      The absence of an initial biopsy of the adrenal mass doesn't allow to distinguish between a lung ADC to SCC transdifferentiation with a consequence of the treatment-induced selection pressure, so a preexisting SCC at the time of diagnosis would exhibit tumor dominance after elimination of the ADC. However, the presence of the ALK rearrangement in the adrenal biopsy suggest a possible ADC to SCC transdifferentiation in the early phase of metastases development as a new potential mechanism of drug resistance

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      EP1.01-57 - Clinical Profile and Treatment Outcomes of NSCLC in Elderly Subjects with Poor Performance Status from India (ID 1577)

      08:00 - 18:00  |  Presenting Author(s): Digambar Behera  |  Author(s): Valliappan Muthu, Navneet Singh, Kuruswamy Thurai Prasad

      • Abstract
      • Slides

      Background

      Background: Elderly population and subjects with poor performance status (PS) are generally excluded from Lung cancer (LC) trials evaluating various treatment modalities, and their outcome is unclear. Herein, we report the clinical profile, treatment and overall survival (OS) of elderly non-small cell LC (NSCLC) subjects with poor PS.

      Method

      Methods: We retrospectively reviewed our database (from Jan 2016-Dec 2017) to identify NSCLC subjects aged ≥65 years and having an Eastern cooperative oncology group PS (ECOG-PS) ≥2 at presentation. Demographic profile, treatment details, PS after treatment and OS (as on 15th November 2018) were retrieved. We also report the incidence of grade 3 or 4 adverse events (AE) following chemotherapy.

      Result

      Results: 122 patients with a median (interquartile range [IQR]) age of 72.5 (65-88) years were included. Majority were men (86.1%) and smokers (79.5%). ECOG-PS was 2, 3 and 4 in 64.8%, 27.9% and 7.4% patients. Squamous cell carcinoma (53, 43.4%) and adenocarcinoma (51, 41.8%) were the most common histologic subtypes. 69% had TNM (8th edition) stage IV (A in 41%, B in 28%) and 26% had stage III (IIIA 8%, IIIB 10% and IIIC in 8%). Chemotherapy with or without radiotherapy (86%), tyrosine kinase inhibitors (6%) and immunotherapy (1%) were the common treatment modalities, while 10 patients did not receive any treatment. In whom response could be assessed (n=61), the best response achieved was partial response in 38%, stable disease in 49%, complete response in 5% and progressive disease in 8%. Of the subjects undergoing chemotherapy (n=102), 33 experienced grade 3 or 4 AE and 14 subjects had to discontinue chemotherapy before 4 cycles. ECOG PS improved to 0/1 in 22 (19.6%) subjects who underwent any form of treatment. The median survival of the study cohort was 250 days. On a multivariate analysis, the presence of brain metastases was associated with poor OS (HR [95% CI] 7.6 [1.4-41.6])

      Conclusion

      Conclusions: Most of the Elderly patients with NSCLC and poor PS had an advanced stage at presentation. Majority tolerate chemotherapy well and some have an improvement in their PS. The presence of brain metastases is associated with a poor survival.

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      EP1.01-58 - Impact of Tumour Size on the Management and Outcome of Stage III Non-Small Cell Lung Cancer (NSCLC) (Now Available) (ID 1940)

      08:00 - 18:00  |  Presenting Author(s): Kaouther Herbegue  |  Author(s): Nesrine Mejri, Houda El Benna, haifa Rachdi, nouha Daoud, Soumaya Labidi, hamouda Boussen

      • Abstract
      • Slides

      Background

      We aimed to evaluate the difference in clinical/radiological presentation and patient management according to tumour size in stage III NSCLC. We also reported its impact on patient’s outcome.

      Method

      We retrospectively studied 88 patients with stage III NSCLC treated between 2010 and mid-2017 in our oncology department. Various cut-off values for tumour diameter were evaluated. We selected a cut-off value of 4 cm, and considered two groups: tumour size≤4 cm and >4 cm. Epidemiological, anatomo-clinical parameters were collected and compared. Kaplan-Meier method was used to evaluate survival.

      Result

      Differences in characteristics of the two groups were described in table 1.

      Initial therapeutic strategy was significantly correlated with tumour size; in tumour≤4 cm therapy was concurrent chemoradiation in 0%, neoadjuvant chemotherapy in 53%, upfront surgery 47% vs 25%, 61%, and 14% respectively for tumour size>4 cm group (p=0.003).

      Among patients receiving neoadjuvant chemotherapy, response was not correlated to tumour size; in≤4 cm group we observed (Partial response (PR) 89%, stable disease (SD)11%, Progressive disease(PD) 0%), in >4cm group response was (PR 39%, SD 36%, PD 25%)(p=0.6). Surgery (upfront or after neoadjuvant chemotherapy) was significantly higher in tumour ≤4cm (65% vs 20%) (p=0.0001). Definitive chemoradiation was more indicated in larger tumours, without statistical significance (75% vs 46%)(p=0.4). Therapeutic discordance between the planned and the administered treatment was significantly higher in larger tumours (68% vs 18%) (p=0.0001). Progression free survival was longer in smaller tumours (18±9.3 vs 11±12.1 months) without being statistically significant. However, median overall survival was significantly correlated with tumour size (41.7± 5.1 in ≤4 cm, 32.8±4.6 months in > 4 cm) (p=0.04). The pattern of recurrence was not correlated to tumour size; it was locoregional in 30%, distant in 20% and both locoregional/distant in 50% in≤4 cm group vs 42%, 24%, and 34% respectively in tumour size> 4 cm (p=0.6).

      Table 1: Characteristics of patients in the two preselected groups.

      Patient characteristics

      Tumour size ≤4 cm

      (n=17)

      Tumour size> 4 cm

      (n=71)

      P

      Age at diagnosis

      Median ± SD (years)

      Elderly (≥70 years),%

      Young (<70 years),%

      .

      59±9.1

      6%

      94%

      .

      62.27±10.8

      28%

      72%

      0.25

      0.05

      Gender, %

      Male

      Female

      .

      59%

      41%

      .

      87%

      13%

      0.006

      Performance Status, %

      0

      1

      2

      .

      6%

      94%

      0%

      .

      1%

      83%

      16%

      0.02

      Weight loss, %

      18%

      42%

      0.06

      Histological type, %

      Adenocarcinoma

      Squamous cell carcinoma

      large cell carcinoma

      .

      88%

      12%

      0%

      .

      47%

      52%

      1%

      0.008

      Histological grade, %

      Well differentiated

      Moderately differentiated

      Poorly differentiated

      .

      18%

      76%

      6%

      .

      24%

      48%

      28%

      0.075

      T Status, %

      T1

      T2

      T3

      T4

      .

      24%

      29%

      29%

      18%

      .

      0%

      7%

      18%

      75%

      0.0001

      N Status,%

      N0

      N1

      N2

      N3

      .

      6%

      6%

      71%

      17%

      .

      10%

      15%

      58%

      17%

      0.67

      Stage,%

      IIIA

      IIIB

      .

      77%

      23%

      .

      44%

      56%

      0.015

      Conclusion

      When taking 4 cm as a cut-off value, tumour size influenced clinical presentation and management modalities. It may be considered as a prognostic factor in stage III NSCLC.

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      EP1.01-59 - The Effectiveness of Osimertinib in a NSCLC Patient with Complex Uncommon EGFR Mutations of G719X and S768I: A Case Report (Now Available) (ID 2535)

      08:00 - 18:00  |  Presenting Author(s): Kewei Ma  |  Author(s): Xu Wang, Yangyang Cai, Yinghui Xu, Ye Guo, Chao Sun

      • Abstract
      • Slides

      Background

      With the deeper and wider application of gene detection technology in lung cancer, an increasing number of genetic alterations have been identified, especially in the epidermal growth factor receptor (EGFR) gene, including uncommon and complex types of EGFR gene mutations; however, the efficacy of the targeted therapy in these gene mutation types is not clear.

      Method

      We report the genetic test results from the analysis of postoperative specimens from a lung adenocarcinoma patient that suggest complex EGFR mutations of G719X and S768I.

      Result

      After tumor recurrence, the patient was treated with osimertinib and achieved an excellent and long-lasting clinical response. The patient has taken osimertinib for 18.2 months with an efficacy evaluation partial response (PR), and her follow-up is still ongoing.

      figure 1.png

      Conclusion

      Complex uncommon EGFR mutations of G719X and S768I have a good response to osimertinib.

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      EP1.01-60 - LENT Prognostic Score for Lung Cancer in the Presence of Malignant Pleural Effusion (ID 2556)

      08:00 - 18:00  |  Presenting Author(s): Giedre Cincileviciute  |  Author(s): Rolandas Zablockis, Edvardas Danila

      • Abstract
      • Slides

      Background

      LENT scoring system is the first validated prognostic score in non-selected malignant pleural effusion (MPE), although its significance in MPE secondary to lung cancer remains unclear.

      Method

      85 consecutive patients (59% male, mean age 67±12yrs) with MPE secondary to lung cancer were enrolled. First episode of MPE presented a new cancer diagnosis in 71% of cases, 29% of MPE were diagnosed on disease progression. Histology types were: adenocarcinoma – 71 (83.5%), small cell carcinoma – 10 (11.8%), NOS – 4 (4.7%). LENT score was calculated on the day of MPE diagnosis confirmed.

      Result

      53 (62%) patients presented moderate risk category by LENT score, and 32 (38%) – high risk category. Mean LENT score was 4 (2–6), median (IQR) survival – 70 (32–281) days.

      The patients with a moderate risk LENT score had a median (IQR) survival of 147 (70–423) days, those with high risk LENT score – 34 (31–41) days.

      The ROC analysis showed no significant difference between LENT score and ECOG PS at 1, 3 and 6 months at predicting survival time (p>0.05).

      MPE group that presented primary cancer diagnosis had a median (IQR) survival of 75 (31-318) days and MPE group that presented disease progression had a median (IQR) survival of 63 (37–185) days, there were no significant difference between these groups.

      Conclusion

      Our study meets literature data for LENT score predicting survival prognosis in malignant pleural effusion. However, our study showed no superiority of LENT score over ECOG PS.

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      EP1.01-61 - iSEND Model as a Predictor of Efficacy in Immune Checkpoint Inhibitors for Non-Small Cell Lung Cancer: Fukushima Cohort (Now Available) (ID 1689)

      08:00 - 18:00  |  Presenting Author(s): NAOYUKI Okabe  |  Author(s): Hayato Mine, Hironori Takagi, Masayuki Watanabe, Satoshi Muto, Takeo Hasegawa, Yutaka Shio, Wungki Park, Gilberto Lopes, Hiroyuki Suzuki

      • Abstract
      • Slides

      Background

      The expression of PD-L1 in tumor tissue and the number of gene mutations (TMB) in tumor tissue have been investigated as predictors of the efficacy of PD-1/PD-L1 inhibitors in non-small cell lung cancer. However. In actual clinical practice, it is difficult to perform these tests in all cases.

      Therefore, we are searching for an effect prediction marker that can be done easily and inexpensively. Wungki Park et al. constructed the iSEND model as a therapeutic effect predictor and showed its usefulness. We examined the usefulness of iSEND model for non-small cell lung cancer patients who received PD-1 / PD-L1 inhibitor at our institution.

      Method

      We retrospectively examined the usefulness of the iSEND model in 56 patients with non-small cell lung cancer who were treated with PD-1/PD-L1 inhibitor in our department after the second treatment. The iSEND model uses patient background and blood tests. Calculated and scored using gender, ECOG performance status, NLR before treatment and after treatment (Neutrophi-to-Lymphocyte Ratios), and divided into three group. For each group, we statistically compared the clinical course such as overall survival and recurrence-free survival.

      Result

      In the analysis by Wungki Park et al. , The iSEND Poor group has a median overall survival of 4.0 months and 15.9 months, respectively, compared with the iSEND Good group (p = 0.0002), and the median recurrence free period is 1.6 months and 2.6 months, respectively. Months (p = 0.0045), and each showed a significant difference. In our study, no statistically significant difference was found, but a trend similar to the analysis of Wungki Park et al.

      Conclusion

      In this study, it is suggested that the iSEND model may be useful as a predictor of the effect of PD-1/PD-L1 inhibitor.

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      EP1.01-62 - The Safety Profile and Preliminary Efficacy of Ceritinib 450mg with Food in Chinese ALK/ROS-1 Positive NSCLC Patients (Now Available) (ID 1881)

      08:00 - 18:00  |  Presenting Author(s): Juan Li  |  Author(s): Yuke Tian, Ping Yu, Xude Yin, Ke Wang, Meijuan Huang, Yongsheng Wang, Youling Gong

      • Abstract
      • Slides

      Background

      Ceritinib have shown potent efficacy in both ALK and ROS-1 rearranged NSCLC. However, high rate of treatment interruption was suffered due to gastrointestinal or liver toxicity using Ceritinib 750mg fasting in previous study. Recently, ASCEND-8 study reported an improved tolerance and a trend to better efficacy with 450mg with food, but little data is available in Chinese patients. This first-time real-world study aims to assess the safety profile and preliminary efficacy of Ceritinib 450mg with food in Chinese patients.

      Method

      From Oct 2018 to March 2019, 51 ALK or ROS1 positive NSCLC patients received ceritinib were enrolled from 8 centers in Sichuan province. Safety profile and preliminary efficacy were retrospectively analyzed. The follow-up was to 31st March 2019.

      Result

      The baseline characteristics of enrolled patients are listed in Table 1. The median time from diagnosis to Ceritinib treatment is 15.93 months(Range:1.37- 89.97), the median treatment duration is 2.63 months (Range:0.2-5.73)by the time of data cut off.

      50 out of 51 patients were assessable for toxicity. The adverse event (AE) rate is 76%, majority of which are grade 1/2. Only 2 patients reduced to 300mg due to AE and no patient dead or terminated treatment due to Ceritinib related AEs. Details are in the Table 2. By the data cut-off, 15 patients have stopped treatment due to disease progression(33.3%),death (53.3%) or other reasons(13.3%)。Among the 39 patients underwent radiological assessment,the ORR was 41.0% and DCR was 87.2%。

      table 1.jpg

      table 2.jpg

      Conclusion

      Ceritinib 450mg with food demonstrated a good safety profile and efficacy with lower AE incidence rate and better compliance rate compare to ASCEND-8 data for Chinese patients in real-world setting.

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      EP1.01-63 - The Usefulness of “Serum” Samples to Detect EGFR T790M Mutation in EGFR-TKI-Resistant Non-Small Cell Lung Cancer (Now Available) (ID 562)

      08:00 - 18:00  |  Presenting Author(s): Keigo Kobayashi  |  Author(s): Katsuhiko Naoki, Shinnosuke Ikemura, Hiroyuki Yasuda, Ichiro Kawada, Kenzo Soejima

      • Abstract
      • Slides

      Background

      Osimertinib, a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor, exerts remarkable effects against EGFR T790M resistance mutation-positive NSCLC. Identifying T790M mutation by re-biopsy is essential before prescribing osimertinib. Tissue biopsy is the golden standard for this purpose, but several factors limit its success rate. The liquid biopsy with blood, using circulating tumor DNA, has been an alternative method. However, the true biological meaning and equivalence of liquid biopsy and tumor biopsy are still under investigation. Especially, the usefulness of serum samples to detect T790M mutation is not yet been known.

      Method

      We prospectively evaluated the sensitivity, specificity, and parallelism of the detection of EGFR mutations in tissue re-biopsy and liquid biopsy (plasma and serum), simultaneously, from June 2016 to May 2017. EGFR-mutations in tumor re-biopsy were evaluated by COBAS ver2 and peptide nucleic acid/locked nucleic acid PCR clamp method, and those in liquid biopsy were evaluated with COBAS ver2.

      Result

      Fifteen patients were enrolled. In ten patients whose EGFR mutation was detected in liquid biopsy, the original EGFR mutation (exon 19 del or L858R) was detected in all patients. The detection rate of T790M was lower than that of the original EGFR mutation in liquid biopsy compared to that in tissue re-biopsy. The detection of T790M in serum exhibited a higher specificity (67%) and positive predictive value (50%) than that in plasma (50% and 40%, respectively). The detection sensitivity was similar in plasma and serum. Nine patients were treated with osimertinib. The RR was 77.8% and DCR was 100%. One patient who presented a response was positive for T790M in liquid biopsy (both plasma and serum) and negative in tissue re-biopsy.

      Conclusion

      We suggest serum samples to be more useful than plasma samples for determining the effectiveness of osimertinib against relapse tumor sites because they were more reliable in the detection of T790M mutation at the relapse tumor tissue sites. Repeated tests with different samples and different methods may improve accuracy of T790M detection and will lead to the maximum benefit for the patient.

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      EP1.01-64 - Effect of Amrubicin in Patients with Previously Treated Non-Small-Cell Lung Cancer (Now Available) (ID 599)

      08:00 - 18:00  |  Presenting Author(s): Shin Takayama  |  Author(s): Tomoki Tamura, Tomoka Kawajiri, Tatsuya Nishi, Kenichiro Kudo, Shoichi Kuyama, Keita Kawakado

      • Abstract
      • Slides

      Background

      Although the prognosis of non-small cell lung cancer (NSCLC) has been rapidly improved due to the appearance of various tyrosine kinase inhibitors and immune checkpoint inhibitors, cytotoxic chemotherapy are still important treatment for patients who can’t receive these drugs or are ineffective for these drugs. Amrubicin (AMR) couldn’t significantly improve the progression free survival compared with docetaxel in a randomized phase III trial of Japanese previously treated NSCLC patients, but median progression free survival (PFS) and overall survival (OS)were comparable in the amrubicin and docetaxel groups. The purpose of this study is to clarify the use of amrubicin in clinical practice.

      Method

      From January 2014 to March 2019, 479 progressive or recurrent NSCLC patients received chemotherapy or radiotherapy. Only 27 patients received AMR. We retrospectively evaluated these 27 patients.

      Result

      None of the NSCLC patients who received AMR had epidermal growth factor recepter gene mutations nor anaplastic lymphoma kinase gene translocations. Median number of prior chemotherapy regimens was four, and median PFS was 62 days and OS was 229 days. Overall response rate was 7.4% and disease control rate was 37.0%.

      Conclusion

      AMR was often used for patients considered to have a poor prognosis, and its effect was limited.

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      EP1.01-65 - The Relationship Between Preliminary Efficacy and Prognosis After First-Line EGFR-TKI Treatment of Advanced NSCLC (Now Available) (ID 711)

      08:00 - 18:00  |  Presenting Author(s): Yanwei Zhang  |  Author(s): Dongfang Chen, Tianqing Chu, Qing Chang, Liwen Xiong, Rong Qiao, Jiajun Teng, Baohui Han, Runbo Zhong

      • Abstract
      • Slides

      Background

      Nowadays, patients with EGFR-TKI-sensitive advanced non-small cell lung cancer (NSCLC) receive EGFR tyrosine kinase inhibitors (EGFR-TKIs) as first-line treatment. We aimed to analyze the relationship between preliminary efficacy (tumor shrinkage within 1 month) and progression-free survival (PFS) after first-line EGFR-TKI treatment.

      Method

      A total of 82 patients with EGFR-TKI-sensitive advanced NSCLC confirmed by histopathology from January 2013 to January 2017 were retrospectively analyzed. All patients received first-line EGFR-TKI treatment and follow-up at Shanghai Chest Hospital.

      Result

      Of 82 patients, 42 (51.2%) patients achieved partial response (PR) within 1 month, and 40 (48.8%) patients achieved stable disease (SD: -30%~0) within 1 month. The median PFS among all patients was 10 months. The median PFS in patients achieving PR within 1 month was 10 months. The median PFS in patients achieving SD (-30%~0) within 1 month was 9.3 months. There was no statistically significant difference between PR within 1 month and SD (-30%~0) within 1 month (P=0.620). In the EGFR-sensitive mutation subgroup, there was also no statistically significant difference between PR within 1 month and SD (-30%~0) within 1 month. Univariate and multivariate analysis of first-line EGFR-TKI treatment showed that age, EGFR mutation type, and T staging had effects on PFS. Patients who were more than 65 years old, had EGFR 19del mutation, along with a T staging less than 4, had a longer PFS; these differences were statistically significant. Liver metastasis, bone metastasis, and brain metastasis were not shown to be related to PFS.

      Conclusion

      For patients with EGFR-TKI-sensitive advanced NSCLC, there is no correlation between preliminary efficacy (tumor shrinkage within 1 month) and PFS after first-line EGFR-TKI treatment.

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      EP1.01-66 - Detection of Genomic Mutations in Blood and Urine ctDNA in Lung Adenocarcinoma with EGFR Mutation on Tissue – An Interim Progress Report (Now Available) (ID 2766)

      08:00 - 18:00  |  Presenting Author(s): Helen Brooks  |  Author(s): Alfredo Addeo, Charles Comins, Megan Stevens, Ling Li, Louise Wade, Sebastian Oltean

      • Abstract
      • Slides

      Background

      Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are effective therapy for stage IIIB/IV EGFR-mutation positive (EGFRm+) NSCLC. Despite initial response, clinical progression occurs, often with development of a second TK mutation.

      Mutation analysis is performed at time of diagnosis usually on single tissue biopsy. Samples can be difficult to obtain and may not represent neoplastic tissue at other sites due to heterogeneity. On progression, patients rarely undergo repeat tissue biopsy. Therapy is no longer truly personalised.

      CtDNA may be an alternative to tissue biopsy for mutation analysis. It may be more representative, and provide real time assessment of disease status, maintaining individualised therapy.

      Published retrospective data are available on detection of EGFR mutations in plasma ctDNA, and evidence that urine can be used is emerging. Clinical use has been limited by lack of evidence for detection methods and concordance with tissue.

      Retrospective data suggest that on response to TKI, TK mutation load reduces, and on progression, mutation load increases and/or a new mutation emerges. This has not been validated prospectively.

      Method

      A prospective pilot study: 20 patients, 2 UK sites; with stage IIIB/IV EGFRm+ NSCLC on tissue sample, TKI-treatment naïve. Plasma and urine collected prior to TKI treatment and monthly on treatment. CtDNA is extracted from plasma and urine using Quigen kit, and analysed using digital droplet PCR for the 3 most common EGFR mutations – del19, L858R and T790M.

      Objective: To investigate if urine/plasma ctDNA may be used to prospectively detect and monitor EGFR mutational status at baseline and during TKI therapy

      Primary Endpoint: To assess if ctDNA from urine/plasma could be a reliable source of EGFR testing

      Secondary Endpoint: To assess if changes in levels of baseline mutation or development of new mutations in ctDNA correlates with disease response/progression during TKI therapy

      Outcome: To inform development of a larger study to further investigate and validate the role of liquid biopsy in treatment of EGFRm+ NSCLC

      Result

      CtDNA analysis performed on samples from 14patients to date. On baseline tissue, 8 (57%) had del19 mutation, 5 (36%) had L858R mutation, and 1 (7%) had L861Q mutation. Representative of population distribution of EGFR mutations.

      In those with tissue del19 mutation, del19 mutation was identified on baseline ctDNA in 8/8 (100%) plasma samples and 6/7 (86%) urine samples (one patient did not provide baseline urine sample). None had L858R mutation in plasma/urine. In one plasma ctDNA sample, very low levels of T790M mutation were identified, but no T790M mutations were found in urine ctDNA.

      In those with tissue L858R mutation, L858R mutation was identified on baseline ctDNA in 3/5 (60%) plasma samples and 4/5 (80%) urine samples. All were found to have del19 mutation on baseline plasma ctDNA, 3/5 had del19 mutation in urine ctDNA. None had T790M mutations in plasma/urine ctDNA.

      Conclusion

      Sensitivity is high for identifying baseline EGFR mutations in plasma/urine ctDNA.

      Very hard to comment on specificity. It's known that del19 and L858R mutations can co-exist. It's possible that mutation analysis performed on DNA extracted away from primary tumour site may carry additional mutations due to heterogeneity.

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      EP1.01-67 - Molecular Profiling of K-Ras and Its Subtypes in NSCLC Patients with Liver Metastasis (Now Available) (ID 2802)

      08:00 - 18:00  |  Presenting Author(s): Nagla Abdel Karim  |  Author(s): Daniel Chandra, ihab Eldessouki, Hirva Mamdani, Misako Nagasaka

      • Abstract
      • Slides

      Background

      Non-small cell lung cancer (NSCLC) tend to have a poor prognosis in the presence of liver metastasis. Molecular profiling of NSCLC has played a major role in identifying a number of oncogenic targets that have led to novel targeted therapies. KRAS is a frequently mutated gene in NSCLC, occurring in approximately 30% of lung adenocarcinomas and most commonly manifesting as the transversion mutations G12C, G12V, G12A. there are presently no targeted therapies approved for KRAS-mutant NSCLC. Immunotherapy has emerged as a standard of care for first-line treatment of advanced NSCLC, specifically through targeting the programmed cell death protein-1 (PD-1/PD-L1). Given the aggressive nature of KRAS-mutant NSCLC with liver metastases and the lack of approved therapies targeting the KRAS pathway, checkpoint blockade immunotherapy may represent an impactful primary therapeutic option for these patients.

      Method

      The CARIS database from 2016 - 2018 was queried and patients with NSCLC were identified. PD-L1 antibody 22c3 ≥1% was considered positive. PD-L1 expression as well as k-ras and TP53 mutation status were analyzed and correlation between different variables were identified using ANOVA

      Result

      We identified 361 patients with NSCLC having Liver metastasis. Median age was 67. Gender distribution was equal (51.4% males, 49.7% females). Of the 361 patients, we identified 74 patients with mutated K-ras. Thirty nine out of the 74 patients had PD-L1 expression (52.7%). Twenty one patients had the G12C sub-type (28%) with 14 patients (66%) having positive PD-L1 expression.Of the 287 patients with wild type K-ras, 115 patients had PD-L1 positive expression (40%) with no statistical significance (P=0.134) in comparison to the k-ras mutant population.We also studied 2237 K-ras mutant patients without liver metastases where 882 patients had the G12C subtype (39.4%). On the other hand, only 21 patients were positive for G12C k-ras subtype out of the 74 k-ras mutant patients with liver metastases.Among patients with liver metastases, adenocarcinoma was the most common histological subtype (223 patients), Carcinoma NOS was the second common histological subtype (61 patients).Patients with no liver metastasis had median age of 68. Gender distribution was equivocal.

      Conclusion

      Patients with k-ras mutant G12C subtype were associated with more frequent PD-L1 expression and less occurrence of liver metastases.

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      EP1.01-68 - Impact of EGFR Genotype on the Efficacy of Osimertinib in Patients with Non-Small Cell Lung Cancer: A Prospective Observational Study (ID 271)

      08:00 - 18:00  |  Presenting Author(s): Satoshi Igawa  |  Author(s): Taihei Ono, Takahiro Ozawa, Hideyuki Sone, Seiichiro Kusuhara, Shinya Harada, Mikiko Ishihara, Masashi Kasajima, Yasuhiro Hiyoshi, Tomoya Fukui, Masaru Kubota, Jiichiro Sasaki, Hisashi Mitsufuji, Katsuhiko Naoki

      • Abstract
      • Slides

      Background

      A T790M of the epidermal growth factor receptor (EGFR) is the most frequently encountered mutation occurring acquired resistance to EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC). The aim of this study was to assess the differential clinical outcomes of osimertinib therapy in NSCLC patients with T790M according to the type of active EGFR mutation, i.e. exon 19 deletion or L858R point mutation.

      Method

      We conducted a prospective observational cohort study to evaluate the efficacy and safety of osimertinib in patients with major EGFR mutation and T790M-positive advanced NSCLC who had disease progression after first-line EGFR-TKI therapy. The efficacy of osimertinib was evaluated according to the type of EGFR mutation.

      Result

      A total of 51 patients were included in this study. The exon 19 deletion was found in 33 (65%) patients, and the L858R point mutation in 18 patients (35%). An objective response was obtained in 29 patients, indicating an objective response rate of 58.8%. The response rate was 69.7% in patients with exon 19 deletion and 38.9% in patients with L858R point mutation, indicating a statistically significant difference (P =0.033). The median progression-free survival (PFS) and overall survival (OS) of the entire patient population were 7.8 and 15.5 months, respectively. Median PFS in the exon 19 deletion and L858R point mutation groups was 8.0 months and 5.2 months, respectively, indicating a statistically significant difference (P =0.045). Median OS in the exon 19 deletion and L858R point mutation groups was 19.8 months and 12.9 months, respectively, indicating a statistically significant difference (P =0.0015). Multivariate analysis identified exon 19 deletion as a favorable independent predictor of PFS and OS.

      Conclusion

      Investigators should consider the proportions of sensitive EGFR mutation types as a stratification factor in designing or reviewing clinical studies involving osimertinib.

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      EP1.01-69 - Safety and Efficacy of Percutaneous Computed Tomography-Guided Thermal Ablation of Non-Small Cell Lung Cancer Metastases (Now Available) (ID 1147)

      08:00 - 18:00  |  Presenting Author(s): Ioannis Gkiozos  |  Author(s): Kyriaki Tavernaraki, Dimitra Grapsa, Andriani Charpidou, Panagiotis Nikolopoulos, Eleni Kokkotou, Ilias Kotteas, Loukas Thanos, Konstantinos Syrigos

      • Abstract
      • Slides

      Background

      Percutaneous computed tomography-guided (CT-guided) thermal ablation is a minimally invasive method for the treatment of adrenal metastases, painful bone metastases and liver metastases originating from non-small cell lung cancer (NSCLC). We aimed to further evaluate the safety and efficacy of CT-guided radiofrequency ablation (RFA) and microwave ablation (MWA) in the management of metastases in a real-life cohort of NSCLC patients.

      Method

      The medical records of 142 patients with metastatic NSCLC (71, 32 and 40 patients with adrenal metastases, painful bone metastases and liver metastases, respectively) treated with CT-guided RFA or MWA were retrospectively studied. The efficacy of thermal ablation was evaluated by post-ablation imaging. For painful bone metastases, palliation was assessed by the Brief Pain Inventory (BPI) score.

      Result

      Technical success of CT-guided thermal ablation was 100%. No major complications occurred. Among patients with adrenal metastases treated with RFA or MWA, local recurrence was observed in 17.1% and 19.4% of cases at 1-year follow up, respectively. In patients with painful bone metastases, significant pain relief was noted after thermal ablation (p<0,001). Local recurrence was observed in 3.3% of cases with liver metastases at 1-year follow-up.

      Conclusion

      CT-guided RF and MW ablation is a safe and effective local treatment for the management of adrenal, bone and liver metastases from NSCLC. For painful bone metastases RF ablation provides significant pain relief.

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      EP1.01-70 - Reirradiation for Locoregionally Recurrent Lung Cancer: Outcomes in Non-Small Cell Lung Carcinoma (Now Available) (ID 1848)

      08:00 - 18:00  |  Presenting Author(s): Niketa Thakur  |  Author(s): Rajan Yadav, Parag Roy

      • Abstract
      • Slides

      Background

      Locoregional failure in non-small cell lung cancer (NSCLC) remains high often leading to symptoms like hemoptysis and chest pain and the management for recurrent disease in the setting of prior radiotherapy is difficult. We retrospectively analyzed the outcomes for re-irradiation (reRT) for locoregionally recurrent lung cancer when used with intention of symptomatic relief in NSCLC.

      Method

      This is a retrospective analysis of treatment of thirty-four patients of NSCLC who received re-irradiation to the thorax. All received re-irradiation by intensity-modulated radiotherapy. Palliative responses, survival outcomes, and prognostic factors were analyzed.

      Result

      Median age of the group was 63 years, all but seven patients were males. All patients received a dose of 30.6 Gy in 17 fractions. Median survival of the group was 4.7 months, median KPS was 70. Relief of haemoptysis could be obtained in 31/34 assessable cases (91%), treatment was less effective for coughing 19/34 (56%) and dyspnoea 11/34 (32%). However, acute toxicities and new disease symptoms limited the duration of palliative benefit in the symptomatic NSCLC patients to a median of 2.3 months. No fatal complications were noted . Grade 2 or greater esophagitis was seen in 3/34(8%) cases.

      Conclusion

      Reirradiation to the thorax for locoregionally recurrent NSCLC can provide palliative benefit. Select patients may experience meaningful survival prolongation after reirradiation. Careful selection of patients is necessary to avoid acute toxicity in already symptomatic patients. This experience demonstrates that repeated courses of radiotherapy can be given successfully and safely despite previous radical dosage.

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      EP1.01-71 - Thymidylate Synthase and Folate Receptor Alpha Expression as Potential Biomarkers for Efficacy of Pemetrexed in NSCLC (Now Available) (ID 1878)

      08:00 - 18:00  |  Presenting Author(s): Saurav Verma  |  Author(s): Prabhat Singh Malik, Ajay Yadav, Deepali Jain, SACHIN Khurana, Sachin Kumar

      • Abstract
      • Slides

      Background

      Predictive biomarkers for chemotherapy in advanced non-squamous NSCLC are lacking. Thymidylate synthase (TS) and folate receptor alpha (FRA) are target enzymes for pemetrexed. Here we investigated TS and FRA expression and their role as a prognostic and predictive biomarker for efficacy of pemetrexed-based chemotherapy.

      Method

      We performed immunohistochemistry on pre-treatment tumour specimens for TS and FRA expression and correlated it with patient’s demographic and clinical characteristics, treatment responses and survivals in a retrospective training cohort of patients with advanced non-squamous NSCLC treated with pemetrexed-based chemotherapy. Similar analysis for validation was performed in a prospective cohort of patients participating in a randomized control trial “to compare efficacy and safety of pemetrexed-carboplatin versus paclitaxel-carboplatin as induction regimen in advanced non-squamous NSCLC”. Chi-square test was used to co-relate TS and FRA expression with clinico-pathological characteristics. Kaplan-Meier methods, Log-rank test and Cox proportional-hazards model were used for survival analysis.

      Result

      In the retrospective training cohort median age was 57 (26-70) years with male predominance (ratio=2:1). TS and FRA expression were evaluable in 55 and 47 patients respectively. In this cohort TS and FRA expression didn’t co-relate with best overall response rates (ORR), however, low TS expression and positive FRA expression were associated with improved progression free survival (PFS), albeit non-significant. In the prospective validation cohort median age was 52 (28-65) years with 70% males. In this cohort TS and FRA expression were analysed in 113 and 97 patients respectively. High TS expression was significantly associated with better ORR in patients treated with paclitaxel-carboplatin (p=0.04) but there was no co-relation of TS expression with response rates in pemetrexed-carboplatin group. Younger patients (age<40 years) had more TS ‘low or negative’ status (p=0.04). High TS expression was associated with ALK positivity (p=0.02), bone metastases (p=0.01) and brain metastases (p=0.002). Positive FRA expression was associated with EGFR positivity (p=0.004) and liver metastases (p=0.020). Positive FRA expression was associated with improved PFS in patients treated with pemetrexed-carboplatin (median: 9.23 versus 4.27 months, p=0.01), paclitaxel-carboplatin (median: 10.87 versus 6.47 months, p=0.08) as well as improved OS (median: OS not reached versus 10.13 months, p=0.01), especially in patients treated with pemetrexed-carboplatin (median: 18.73 versus 10.46 months, p=0.08).

      Conclusion

      In conclusion, the results from this study suggest that TS or FRA expression doesn’t predict efficacy of Pemetrexed, however, high TS expression may predict better ORR in patients receiving paclitaxel-carboplatin. FRA expression may serve as a prognostic factor in patients receiving chemotherapy irrespective of the regimen.

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      EP1.01-72 - Treatment Outcome of 2nd Generation EGFR-TKI for Non-Small Cell Lung Cancer (Now Available) (ID 1988)

      08:00 - 18:00  |  Presenting Author(s): Tetsuro Kondo  |  Author(s): Yoshiro Nakahara, Ryo Usui, Shuji Murakami, Terufumi Kato, Haruhiro Saito, Kouzo Yamada

      • Abstract
      • Slides

      Background

      Efficacy of EGFR-TKI has been demonstrated in 1st line treatment for EGFR mutation positive NSCLC. Afatinib, 2nd generation EGFR-TKI inhibits HER2 (ErbB2) or ErbB4 in addition to the EGFR (ErbB1), is expected more effective compared to the 1st generation EGFR-TKI. In this study, we investigated retrospectively on the treatment outcome of the cases that received 2nd generation EGFR-TKI treatment at our institution.

      Method

      The subjects were 70 patients treated with a 2nd generation EGFR-TKI afatinib for the period from May 2014 to April 2018. Age, gender, smoking history, performance status (ECOG), EGFR mutation type, starting dose, dose reduction during treatment period, objective response, presence of brain metastasis, EGFR-TKI treatment line and T790M mutation result were retrospectively analyzed the association with the time to treatment failure and survival.

      Result

      Among the 70 patients, male 28 cases and female 42 cases, and 42 never smoker included. Median age was 65 years old (43-88 years old). EGFR mutation type included exon 19 deletion 42 cases, exon 21 L858R 13 cases, uncommon mutation 13 cases and compound mutation 2 cases. 18 cases were administered with 40mg initial dose, 28 cases were 30mg and 24 cases were 20mg. 68 cases were good performance status (0 or 1), and 33 (47%) cases had brain metastasis. Dose reduction were performed in 43 (61%) cases, and partial response were observed in 34 (49%) cases. 36 (51%) cases were no pretreatment with EGFR-TKI (afatinib as first EGFR-TKI). Of the 70 cases, 33 (47%) cases were performed re-biopsy, and 15 cases of those were proved T790M acquired resistant mutation.

      Conclusion

      Good performance status, dose reduction, good objective response, no brain metastasis, early EGFR-TKI treatment line and T790M mutation positivity were significantly associated with prolongation of the time to treatment failure, but no significant characteristics were associated with prolongation of the survival.

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      EP1.01-73 - Trousseau's Syndrome Associated with Pulmonary Pleomorphic Carcinoma Showing Aggressive Features: A Case Report (Now Available) (ID 3122)

      08:00 - 18:00  |  Presenting Author(s): Satoru Okada  |  Author(s): Aya Miyagawa-Hayashino, Jun Fujinami, Kenji Kameyama, Shuta Kitaoka, Narumi Ishikawa, Tatsuo Furuya, Satoshi Ikebe, Shunta Ishihara, Hiroaki Tsunezuka, Masanori Shimomura, Junichi Shimada, Masayoshi Inoue

      • Abstract
      • Slides

      Background

      Trousseau's syndrome is characterized as an unexpected cancer-related thrombotic event, such as a cerebral infarction or a deep vein thrombosis/pulmonary embolism. The histology of most reported cases of lung cancer with Trousseau's syndrome involves adenocarcinoma. We describe the first reported case of Trousseau's syndrome with pulmonary pleomorphic carcinoma and aggressive features.

      Method

      A 74-year-old man, a current heavy smoker (38 pack-years), presented with a well-circumscribed peripheral mass (diameter: 38 mm) in the lower lobe of the left lung. A fluorine-18-fluorodeoxyglucose (FDG) positron-emission tomography scan showed a strong accumulation of FDG in the mass. Serum carcinoembryonic antigen (CEA) and D-dimer levels were 16.0 ng/mL and 0.6 µg/mL, respectively. A left lower lobectomy with systemic mediastinal lymph node dissection revealed the tumor was pleomorphic carcinoma with extensive lymph node involvement and was graded as pT3N2M0, pStage IIIB (pm1, pl1, ly1, v1, br+). The tumor mainly comprised giant cells with high-grade pleomorphism, admixed with a solid adenocarcinoma component and papillary growth pattern. The adenocarcinoma component was positive for periodic acid-Schiff (PAS) stain and resistant to diastase, suggesting mucin production. Moreover, most of the tumor cells were strongly positive for tissue factor (clone TF (H-9)).

      Result

      Three months postoperatively, diffuse infiltration rapidly appeared in plain chest radiographs of the left lung, which was identified as lymphangitic carcinomatosis via bronchoscopy. Prior to treatment for cancer recurrence, the patient suddenly presented with dysarthria and left hemiplegia. Magnetic resonance imaging revealed acute ischemic stroke in the right hemisphere accompanied with subacute small infarcts in the left hemisphere and bilateral cerebellum. Magnetic resonance angiography revealed a right middle cerebral artery M2 segment occlusion. An echography and a chest CT showed no evidence of atherosclerotic thrombus or cardiac thrombus in the left atrium or in the stump of the resected pulmonary vein. Plasma D-dimer level was elevated at 17.6 µg/mL, as were the CEA and carbohydrate antigen 125 (CA125) levels (73.4 ng/mL and 331 U/mL), respectively. He underwent mechanical thrombectomy with a stent retriever, and partial recanalization was achieved. The pathology of the retrieved thrombus showed that almost all parts consisted of fibrin without red blood cells. These findings and pathological findings of the primary lung cancer suggested Trousseau’s syndrome as the etiology of the cerebral infarction.

      Conclusion

      A hypercoagulable state, due to aggressive recurrence of pulmonary pleomorphic carcinoma accompanying with cancer cell production of mucin and tissue factor, may be a potential mechanism for cancer-related thrombosis.

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      EP1.01-74 - Implantation of Permanent Pleural Catheter (PPC) for Malignant Pleural Effusion (PE) in Advanced Non Small Cell Lung Cancer (NSCLC) (ID 65)

      08:00 - 18:00  |  Presenting Author(s): Mireia Martinez-Kareaga  |  Author(s): Iratxe Intxaurbe-Etxebarria, Beatriz Mareque, Nuria Torrego, Laura Tomás-López, Cristina Sánchez-Vieco, Alicia Narro, Laura Puntí, Garbiñe García-Gómez, Nerea Urbieta

      • Abstract
      • Slides

      Background

      Pleural effusion (PE) is a frequent complication in patients (p) with advanced NSCLC that causes refractory symptoms such as pain and dyspnea. These patients frequently need repeated thoracocentesis to relieve symptoms. Implantation of PPC can avoid repeated thoracocentesis.

      Method

      Thirty consecutive patients of our hospital with advanced NSCLC who overwent to PPC implantation from May 2008 to September 2018 were retrospectively evaluated. Baseline characteristics, acute and late complications and outcome were retrospectively collected. Overall survival (OS) was calculated from the date of the PPC implantation to the date of death.

      Result

      Thirty patients were evaluated, 20 were male and 10 female. All the patients were death at the cut-off date, the 1st October 2018. Median age at PPC implantation was 66y (range: 47-91) and 80% presented ECOG PS 2. Adenocarcinoma was the most frequent histology (22p). Mean hospital stay was 7 days (range 1-28). Average catheter duration was 60 days (range 3-181). Four patients (13%) suffered an acute complication: 1 pleuro-cutaneus fistula, 1 empyema, 1 hematoma and 1 needed surgical intervention because the catheter guided was at pleural cavity. After hospital discharge, one patient presented a complication, with pleural liquid exit from pericatheter. Tweny-five patients (83%) presented clinical relief and 11p (37%) received chemotherapy after PPC implantation. Citology of pleural liquid was performed in 23p (77%) and resulted positive for malignancy in 14p. Median OS was calculated from PPC implantation to death and resulted of 14.3 weeks (IC 95%, range 1.3-59.1).

      Conclusion

      PPC implantation is a safe technique that can cause symptomatic relief in selected patients with malignant pleural effusion. However, average catheter duration and median survival after PPC implantation are low. Therefore a better selection of patients is mandatory in our centre.

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      EP1.01-75 - Palliative Thoracic Radiotherapy for Lung Cancer: What Is the Most Appropriate Fractionation? (Now Available) (ID 325)

      08:00 - 18:00  |  Presenting Author(s): Niketa Thakur  |  Author(s): Rajan Yadav

      • Abstract
      • Slides

      Background

      Radiotherapy is the one of the most effective modalities to palliate the symptoms ( hemoptysis, pain, breathlessness) of poor-prognosis patients with advanced non-small-cell lung cancer. Most appropriate dose schedule however remains debatable. We conducted a retrospective analysis that compared the efficacy of radiotherapy schedules consisting of 5 fractions of 4 Gy (5 x 4 Gy) versus 10 fractions of 3Gy (10 x 3 Gy) in advanced Non Small Cell Lung Cancer (NSCLC). The end point evaluated was symptomatic relief.

      Method

      Between July 2016 and September 2017, 60 patients with advanced NSCLC were randomised to either 5 fractions of 4 Gy (5 x 4 Gy):Arm A or 10 fractions of 3Gy (10 x 3 Gy):Arm B. The eligibility criteria was histologically or cytologically confirmed NSCLC, age > 30, stage III or IV disease, Karnofsky performance status (PS) > 40, expected survival > 3 months. The quality-of-life was assessed using the patient records :European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 and the lung cancer–specific module QLQ-LC13. The primary study end points was control of symptoms viz cough, hemoptysis, pain and dyspnea, and the secondary end point was to evaluate Overall Survival (OS).

      Result

      52 out of 60 patients were males,18/60 had lost to follow up. Majority of patients presented in 5th and 6th decade of their lives, mean age of presentation was 58.87 (Range31-80). Majority (69%) of patients had presented with poor KPS 70 or less. Most common presenting symptom was cough with expectoration (74.66%) followed by hemoptysis (47.33%). Post treatment 36% reported reduced cough, 44% reported reduced dyspnea, 57% reported reduced pain and 90% reported reduced hemoptysis within 20 weeks from start of treatment, with no statistical difference among the groups. Except for improved hemoptysis at week 5 in Arm A (P =0.03), there was no difference among the groups. Furthermore, the palliative effect of symptoms seemed to last throughout the planned follow-up period. Overall survival for all patients (n=42) revealed no significant survival difference among the treatment groups (P = 0.2). The median survival was 6.2 and 6.7 months in arm A and B, respectively.

      Conclusion

      Hypofractionated regimen of 20Gy/5 fractions is atleast as effective at providing symptomatic relief and yields equivalent survival as 30Gy/10 fractions in patients with advanced non-small cell lung cancer and thoracic symptoms besides having the advantage of fewer visits to hospital as well.

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      EP1.01-76 - Oncomine Tumor Mutation Load Assay in NSCLC Patients from Argentina: Study Design and Feasibility (Now Available) (ID 2733)

      08:00 - 18:00  |  Presenting Author(s): Gonzalo Recondo Jr.  |  Author(s): Valeria Cecilia Denninghoff, Vanesa Romano, Romina Cabrerizo, Alejandro Daniel Kuzminin, Vanina Wainsztein

      • Abstract
      • Slides

      Background

      High throughput next generation sequencing has improved the understanding of the genomic landscape of cancer. Somatic mutations throughout the exome derive in novel peptide sequences that can be recognized by the host immune system and drive immune responses in patients. The tumor mutational load (TML) is the number of somatic mutations per megabase of DNA and is an emerging biomarker to predict response to immune checkpoint inhibitors.

      Method

      The objective of this study was to evaluate the feasibility of assessing TML in tumors from patients with advanced NSCLC, treated with Nivolumab in second with Ion Torrent™ Oncomine™ TML Assay and compare it with TML from WES. The Oncomine TML is a targeted NGS assay that provides quantification of somatic mutations, from limited formalin-fixed, paraffin-embedded (FFPE) samples.

      Result

      DNA was purified with QIAamp DNA FFPE Tissue Kit (QIAGEN). We used a new Ion AmpliSeq targeted panel, derived from the Comprehensive Cancer Panel which covers approximately 1.7 Mb of genomic DNA and 409 genes, OTML in S5, Ion Proton (Life Technologies); and WES were performed in NovaSeq 6000 Sequencing System (Illumina). We included 40 patients with advanced NSCLC. 27 (68%) of patients had both, tumor and normal tissue to perform WES. FFPE samples were obtained from lungs (N=21), lymph nodes (N=11), pleura (N= 3), brain (N=1), skin (N= 1), bone marrow (N = 1), soft tissue (N=1). We used 20 ng of DNA to develop the manual library and templating. We covered a large genomic footprint to accurately measure somatic mutations, replacing the need for whole-exome sequencing (WES). Pipeline for analysis of the NGS output will be presented.

      Conclusion

      TML estimation with low DNA input requirements from FFPE samples is feasible. Up to 8 samples can be sequenced in a Ion 540™ Chip. Mutation load assessment can be done within 2–3 days. This assay was highly reproducible in FFPE samples. A detailed report provides normalized mutation count per MB as well as mutation signatures.

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      EP1.01-77 - Locally Advanced Non Small Cell Lung Cancer - Treatment Outcome in Real World Setting (Now Available) (ID 1626)

      08:00 - 18:00  |  Presenting Author(s): Arun Thimmarayappa  |  Author(s): Sushmita Pathy, Prabhat Singh Malik

      • Abstract
      • Slides

      Background

      Lung cancer is one of the leading cancers in India. About two-thirds present in advanced /metastatic stage. The mainstay therapy for advanced non small cell lung cancer (NSCLC) is concurrent chemoradiation. Locoregional failure constitutes the predominant failure pattern.

      A larger proportion of the patients are treated with palliative intent. The current study evaluates the demographic profile, treatment pattern, and outcome and radiation practice for palliative treatment at a tertiary care academic medical institution.

      Method

      Medical records of patients treated between June 2016- June 2018 were evaluated Clinical presentation, treatment details and outcome was recorded. Case records with incomplete workup or treatment was excluded.

      Result

      A total of 181 patients of NSCLC were registered of which 108 were metastatic at presentation 96 patients received palliative radiotherapy and are analysed. 11 patients has pulmonary metastasis and 85 had extrapulmonary metastasis of which 21 patients had multiple extrapulmonary disease.

      Ninety-six patients received palliative radiotherapy. 84 patients had ≤ 1comorbidity. Most of the patients were aged ≤65years (80%) with a female preponderance. Cough, chest pain and dyspnea each were present in one-third of patients. Twenty-six patients had bony pain, 18 had symptoms of raised intracranial pressure and 7 patients had SVCO.

      Adenocarcinoma was the commonest histology observed in 86.4% patients. Bone was the most common site of metastasis, seen in 65(65.7%) patients; followed by brain in 23(24%).

      Palliative radiotherapy was given to primary in 13(13.5%), brain in 27(28%), bone in 56(58%). Palliative radiotherapy to weight bearing sites was treated with 8Gy in single fraction. Whole brain radiotherapy was treated with 20Gy in 5 fractions. 65% of patients received palliative chemotherapy. Platinum- taxane and platinum- pemetrexed regimens were the most common regimen practiced for among squamous and adenocarcinoma histology respectively. Median follow up was 6.6 months (2 to 37 months). Median time for oncological intervention was 1.2 months (0.1 to 5.4months). Median PFS was 6months (IQR 3- 11.2months)

      Conclusion

      The study concludes that a large proportion of patients present in advanced/metastatic disease. In the metastatic setting bone metastasis was the most common site followed by brain. The outcome is dismal and newer treatment techniques /modalities may result in improved outcome in this group of patients.

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      EP1.01-78 - T4 Lung Cancer Invading the Descending Thoracic Aorta: A Case Successfully Treated with Surgery by a Multidisciplinary Team (Now Available) (ID 2555)

      08:00 - 18:00  |  Presenting Author(s): Angela 3355399488 De Palma  |  Author(s): Giulia Nex, Giulia De Iaco, Debora Brascia, Marcella Schiavone, Rosatea Quercia, Raffaele Pulli, Domenico Angiletta, Giuseppe Marulli

      • Abstract
      • Slides

      Background

      T4 lung cancer invading the great vessels was usually considered a relative contraindication for radical surgery, because of technical difficulties and intra/postoperative bleeding complications. Recent studies have proved radical pneumonectomy or lobectomy together with aorta endograft positioning to have low mortality and morbidity rate and fairly good overall survival; however, only few cases have been reported in the literature. We report a case of T4 lung cancer invading the descending thoracic aorta (DTA) successfully treated with surgery by a multidisciplinary thoracic and vascular team.

      Method

      A 60-year old male patient was admitted to our Department with a left upper lobe pulmonary tumor of 9 cm invading the DTA, as shown by preoperative computed tomography (CT) scan and magnetic resonance imaging (MRI). 18F-fluorodeoxyglucose positron emission tomography (FDG-PET)/CT total body scan revealed an uptake only at tumor site (SUV max 26.28) with no lymph nodes positivity. Preoperative spirometry values were FEV1 79%, FVC 82% and DLCO 72.5%. Pulmonary perfusion scintigraphy showed 65% for the right lung and 35% for the left one. We performed left pneumonectomy and hilar-mediastinal lymphadenectomy by posterolateral thoracothomy approach, observing about 5 cm long abventitial infiltration of DTA, 3 cm after left subclavian artery origin. An aortic endograft (GORE TAG Comformable Thoracic Stent Graft with ACTIVE CONTROL System) via left femoral artery was disposed 2 cm distal to the subclavian artery origin, then the infiltrated abventitial aortic wall (40% of the aortic circumference) was removed, leaving only the macroscopic healthy endothelium and protecting it with a Goretex mesh (BARD COMPOSIX E/X MESH).

      Result

      The patient spent one night in intensive care unit (ICU), transfusing blood once. The only postoperative complication was a transitory atrial fibrillation pharmacologically treated. He was discharged 9 days after surgery. Pathologic analysis showed a non-mucinous lung adenocarcinoma invading the visceral pleura with a metastatic bronchial lymph node (pT4N1M0), with margins free of tumor. Chemotherapy and radiotherapy were administered and the patient is alive and in good condition 6 months after surgery, free of relapse.

      Conclusion

      In selected cases, in young patients with good performance status, surgery for T4 lung cancer invading the DTA can successfully be accomplished, without complications, by an experienced multidisciplinary thoracic and vascular surgeons team, in high volume centers.

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      EP1.01-79 - Chemoradiotherapy in Advanced Non Small Cell Lung Cancer (Now Available) (ID 2557)

      08:00 - 18:00  |  Presenting Author(s): Mohamed Ait Erraisse  |  Author(s): Fatima zahra Abboud, khaled Hassouni

      • Abstract
      • Slides

      Background

      Advanced NSCLC is a frequent cancer among our patients. Delay in diagnosis and treatment leads to advanced stages that require complex treatment modalities and poor prognosis. We report our experience in term of epidemiological, diagnostic, therapeutic and prognostic aspects of this disease in our department.

      Method

      This is a retrospective study of 38 cases of advanced NSCLC treated with concurrent chemoradiotherapy, collected in the radiotherapy department in the University Hospital Hassan II in Fez, between January 2012 and January 2017. All cancers were prooved histologically by biopsy. The standard treatment was concurrent chemoradiotherapy alone or after induction chemotherapy mostly due to a large tumor volume where radiotherapy is not feasible upfront. Chemotherapy drugs were mainly cisplatin-based with vinorelbine or paclitaxel and in some cases carboplatin if renal function is not correct. Radiotherapy was delivered through 3D conformal technique after CT-simulation and image fusion with CT or in rare cases PET-CT. After completion of treatment, no patient received adjuvant chemotherapy. Immune therapy was not affordable due to the high price. Follow-up was done clinically and with control CTscan. Tobacco control counseling was recommended to all our patients.

      Result

      The average age was 59 years (38 to 81 years). The patients were all males and chronic smokers. Significant clinical symptoms were mainly chest pain, dyspnea and hemoptysis. There were 21 cases of adenocarcinoma, 17 cases of squamous cell carcinoma. 18 cases were classified as stage IIIA, 20 cases as stage IIIB.

      Neoadjuvant chemotherapy was received in 23 cases from 2 to 4 cycles. All patients received radiotherapy with doses to PTV between 60-70Gy with concomitant chemotherapy including cisplatin or carboplatin.
      After an average follow-up of 12 months, the evolution was marked by the occurrence of 2 deaths, distant metastasis in 14 patients (6 cases of cerebral metastasis and 8 cases of bone metastasis), 2 cases of progressive disease, 14 patients in complete clinical remission and are always followed, and 6 patients were lost to follow-up,

      Conclusion

      It is now proven that the survival of patients with locally advanced lung cancer is better if chemotherapy is combined with radiotherapy. The survival gain obtained is essentially related to better control of micro-metastases even though the local control remains very poor. Some irradiation techniques seem to be able to improve this local control: conformal radiotherapy with intensity modulation, hypofractionation. Immue therapy concomitant to radiation might be the future but still needs randomized clinical trials to approve it.

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      EP1.01-80 - Progressive Disease with T790M Mutation vs Non-T790M Mutation in EGFR Positive Patients Treated with Tyrosine Kinase Inhibitors (ID 2781)

      08:00 - 18:00  |  Presenting Author(s): Daniel Oliveira Reis  |  Author(s): Nuno China, Margarida Dias, Daniel Coutinho, Eloísa Silva, Sérgio Campainha, Telma Costa, Sara Conde, Luís Cirnes, Ana Barroso

      • Abstract
      • Slides

      Background

      Patients with metastatic non-small cell lung cancer (NSCLC) with a sensitizing EGFR mutation are candidates for treatment with a tyrosine kinase inhibitor (TKI), but acquired resistance is inevitable. The most frequent mechanism of acquired resistance to TKI is the T790M mutation.

      Method

      Retrospective analysis of patients with EGFR mutation treated with TKI who progressed from November 2016 to July 2018, for whom the T790M mutation testing was done through liquid or tissue biopsy.

      Result

      Progression disease was observed in 18 patients. The mean age was 67.1 ± 14.4 years. Twelve patients (66.7%) were female. Ten patients (55.5%) presented the T790M mutation as a resistance mechanism to TKI.

      T790M positive T790M negative p value

      Non-smokers

      Ever smokers

      9 (90%)

      1 (10%)

      2 (25 %)

      6 (75 %)

      0.005

      EGFR mutation

      Exon 18

      Exon 19

      Exon 21

      0 (0%)

      8 (80%)

      2 (20%)

      1(12.5%)

      5(62.5%)

      2 (25%)

      0.604

      Initial TKI

      Gefitinib

      Afatinib

      Erlotinib

      2 (20%)

      0 (0%)

      8 (80%)

      2 (25%)

      3(37.5%)

      3(37.5%)

      0.146

      Response evaluation

      Stable disease

      Partial response

      3 (30%)

      7 (70%)

      6 (75%)

      2 (25%)

      0.119
      PFS with initial TKI - months (mean ± SD) 11 ± 5.3 10 ± 6.9 0.586
      Months treated with initial TKI after disease progression due to clinical benefit (median - IQR) 2 - 5 4 - 3 0.409

      Progressive disease

      Increase of primary lesion size

      Increase of metastasis size

      New intrathoracic lesions

      New extrathoracic ± intrathoracic lesions

      3 (30%)

      3 (30%)

      2 (20%)

      2 (20%)

      3(37.5%)

      2 (25%)

      0 (0%)

      3(37.5%)

      0.465

      Conclusion

      The T790M mutation was the most frequent mechanism of TKI resistance. Non-smokers developed the mutation more often than ex-smokers, although this result was not statistically significant. In the other analyzed variables there were no statistically significant differences.

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      EP1.01-81 - Resection of Tumors with Carinal Involvement After Induction Therapy (Now Available) (ID 2790)

      08:00 - 18:00  |  Presenting Author(s): Domenico Galetta  |  Author(s): Lorenzo Spaggiari

      • Abstract
      • Slides

      Background

      Tumors involving the carina may be treated with resection of trachea-bronchial bifurcation with or without lung resection. The role of induction therapy (IT) and its effects on morbidity/mortality are unclear. We evaluated surgical and long-term outcomes of patients who underwent carinal resection after IT.

      Method

      From 1998 to 2018, 45 patients (35 men; median age, 62 years) underwent carinal resection. Twenty-nine patients (64.4%) received IT (24 chemotherapy and 5 chemo-radiation). Histology included 41 non-small cell lung cancers, 3 adenoid cystic carcinomas, 1 carcinoid. Carinal pneumonectomy was performed in 32 cases (all right sided), carinal resection plus right upper lobectomy in 9, carinal resection plus upper bilobectomy in 1, and carinal resection without pulmonary resection in 3. Superior vena cava resection was associated in 22 cases.

      Result

      Operative mortality was nil. Thirty-day mortality was 8.8% (n=4). Major complications occurred in 9 patients (20%): 5 bronchopleural fistulas, 2 ARDS, 2 cardiac hernias. IT did not influence morbidity rate (p=.7371). Pathological N status included 6 N0, 22 N1, and 17 N2. Follow-up was completed for all patients. Median survival was 16 months (range, 1 to 181 months). Overall 5-year survival rates was 35.8%. Overall, 5-year freedom from recurrence was 49.8%. Patients receiving IT had a poor survival (22.6% versus 60%) but it was not statistically significant (p=.0596). Histology, extended resection, and N status, did not influence survival.

      Conclusion

      Carinal resection is a feasible but challenging procedure providing acceptable mortality and long-term outcomes. IT did not influence morbidity, mortality, and overall survival.

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      EP1.01-82 - 10 Years Single Center Experience with Resection of the Superior Vena Cava in Locally Advanced Non-Small Cell Lung Cancer (Now Available) (ID 2814)

      08:00 - 18:00  |  Presenting Author(s): Mir Alireza Hoda  |  Author(s): Thomas Klikovits, Elisabeth Gschwandtner, Katharina Sinn, Richard Hritcu, Walter Klepetko

      • Abstract
      • Slides

      Background

      In patients with locally advanced T4 non-small cell lung cancer (NSCLC) invading the superior vena cava (SVC), combined multimodality treatment including surgery is indicated. However, this treatment approach warrants careful patient selection and adequate postoperative management. We aim to review our institutional experience with SVC resection in advanced NSCLC.

      Method

      Between 2006 and 2017, surgery for NSCLC including SVC resection has been performed in 21 patients at our department. We defined “SVC resection” as resection of the SVC and replacement with ring-enforced tube grafts and “SVC reconstruction” as partial resection with direct closure or reconstruction with a bovine pericardial patch. Clinical parameters and long-term outcome were analyzed.

      Result

      Overall, 15 male and 6 female patients have been included. Induction treatment was performed in 16 patients, 8 patients received chemoradiation therapy and the other 8 patients had chemotherapy alone. Pulmonary resection included 8 sleeve pneumonectomies, 4 pneumonectomies, 3 lobectomies and 4 sleeve-lobectomies of the right upper lobe, 1 extraanatomical resection of the right upper lobe and one mediastinal tumor debulking. Two patients required cardiopulmonary bypass during surgery. An additional extended resection including chest wall (n=1), phrenic nerve (n=3), pericardium or right atrium (n=4) was performed in 8 patients. Overall 5 patients underwent SVC reconstruction whereas 16 patients had complete SVC resection and replacement. The 90-day-mortality rate was 4.8% (n=1). Major complications occurred in 8 patients (38%) with no difference between patients undergoing SVC resection or reconstruction. Oncological long-term outcome will be presented at the conference.

      Conclusion

      Our results suggest that an extended resection including SVC replacement or reconstruction is a feasible and safe procedure for carefully selected patients with NSCLC and SVC involvement with acceptable postoperative morbidity and mortality rates.

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      EP1.01-83 - Efficacy and Safety of EGFR-TKI Rechallenge Treatment in Elderly Patients with Advanced NSCLC Harboring Sensitive EGFR Mutations (Now Available) (ID 81)

      08:00 - 18:00  |  Presenting Author(s): Yutaka Yamada  |  Author(s): Hisao Imai, Hiroyuki Minemura, Tomohide Sugiyama, Kyoichi Kaira, Kenya Kanazawa, Takashi Kasai, Koichi Minato, Takayuki Kaburagi

      • Abstract
      • Slides

      Background

      Epidermal growth factor receptor–tyrosine kinase inhibitor (EGFR–TKI) is effective as first-line chemotherapy for patients with advanced non-small-cell lung cancer (NSCLC) harboring sensitive EGFR mutations. However, whether the efficacy of second-line EGFR–TKI treatment after first-line EGFR–TKI treatment was poorly studied in elderly patients aged ≥ 75 years harboring sensitive EGFR mutations. Therefore, we aimed to investigate the efficacy and safety of EGFR-TKI re-administration after first-line EGFR–TKI treatment in elderly patients with NSCLC harboring sensitive EGFR mutations.

      Method

      Between October 2002 and December 2015, 22 elderly patients with advanced NSCLC harboring sensitive EGFR mutations who were initiated on EGFR–TKI Rechallenge at four Japanese institutions were included in this study.

      The eligibility criteria were histologically or cytologically confirmed NSCLC, unresectable stage III/IV disease, and a drug-sensitive EGFR mutation (exon 19 deletion or exon 21 L858R).

      All patients were initially treated with gefitinib (250 mg/day) or erlotinib (150 mg/day) and after recurrence, re-administration of EGFR-TKIs (gefitinib, erlotinib, afatinib) was performed as a secondary chemotherapy

      Result

      Ultimately, 22 cases of this study were studied. The median age was 77.5 years (range 75-87 years).

      Although it was a retrospective analysis, even with re-administration of EGFR-TKI rechallenge, the response rate was 23%, PFS 5.26 months, OS (after EGFR-TKI rechallenge) 14.4 months (the administration lines were 2, 3 and 4 lines ).

      Conclusion

      Until now it was said that EGFR-TKI rechallenge does not contribute to OS in LUX-LUNG 1 and so on.

      On the other hand, there are also reports on the usefulness of EGFR-TKI rechallenge.

      From the results of this study it can be said that it can be one of the options among the limited treatment options for elderly EGFR positive lung cancer.

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      EP1.01-84 - Second Line Treatment with Docetaxel/Nintedanib in Patients with Metastatic Non Small Cell Lung Adenocarcinoma-Preliminary Results (Now Available) (ID 2302)

      08:00 - 18:00  |  Presenting Author(s): Michael M. Vaslamatzis  |  Author(s): Theodoros Tegos, Nektarios Alevizopoulos, Konstantinos Christos Folinas, Michael George Pavlakis, Katerina Gioti, Vasili Edvin, Vasiliki Nikolaidou, Charalabos Stathopoulos, Varvara Sioufi

      • Abstract
      • Slides

      Background

      The treatment landscape of non small cell lung cancer (NSCLC) has changed dramatically during the last years involving targeted therapy, chemotherapy ± immunotherapy or/and antiangiogenic agents, based mainly on patients’ molecular characteristics. Not all patients respond well to immunotherapy, so there is an essential need for other effective treatments.

      Method

      The aim of this prospective study is to estimate and record, the efficacy of the combination of Docetaxel with Nintedanib as a second line therapy in metastatic NSCLC. There were 20 patients, 16(80%) men, 4(20%) women, median age 62(52-73) years and median ECOG 1(0-3), without driver mutations, consecutively admitted in Evangelismos Oncology Department in Athens, Greece from 27/11/2017- 23/02/2019.

      Result

      All patients had received Cisplatin/Pemetrexed/Bevacizumab as first line treatment for their disease, with a median duration of 104(45-255) days. Progressive disease sites were found in lung, liver, and bones in :18/20(90%), 8/20(40%) and 4/20(20%) patients respectively. All received as second line treatment Docetaxel 75mg/m2 q3weeks plus Nintedanib 400mg p.o., d 2-20 in 21 days cycles. CEA, CA125, NSE, CA19.9, CA72-4 and Cyfra 21.1 tumor markers were monitored according to our clinical protocol. Increased values of these markers were documented at initiation of therapy in 18, 14, 10, 14 ,0, 2 patients respectively.

      After 3 cycles of treatment all patients were reevaluated and in 2 of them partial response (P.R.) was documented, with 40-50% reduction of CEA, CA125, CA19.9 και Cyfra 21.1, while 12 patients had stable disease (S.D.) with no more than 20% change in the aforementioned tumor markers. Six patients with progressive disease (P.D.) showed significant increase of CEA, CA 125, NSE, CA 19.9 and CA 72-4. The responders (P.R.+ S.D.) continued therapy for a median of 5(3-8) cycles.

      Among 96 cycles of chemotherapy, any toxicity grade ≥ ΙΙ occurred in 14 (7%) of them. Anaemia in 7(50%), stomatitis in 4(28.5%), diarrhea in 5(36%) and AST/ALT elevation of >2.5 fold in 3(21%) cycles respectively. All patients were treated symptomatically, without dose reduction in any patients

      Conclusion

      The combination of Docetaxel/Nintedanib in metastatic NSCLC adenocarcinoma, following progressive disease post Cisplatin/ Pemetrexed/ Bevacizumab treatment, showed 70% response rate. Although the number of the patients included in the study is small, we concluded that the tumor markers examined, had a clear correlation with the disease outcome. No major toxicity issues were documented. Larger studies are needed in order to make more solid conclusions.

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      EP1.01-86 - Comprehensive Next-Generation Sequencing-Guided Targeted Therapy Correlates with Survival in Non-Small-Cell Lung Cancer (Now Available) (ID 2455)

      08:00 - 18:00  |  Presenting Author(s): Zhenyao Chen  |  Author(s): Zhaoxia Wang, Binbin Lu, Guojian Liu, Tianwei Xu, Lihua Jiang

      • Abstract
      • Slides

      Background

      Although increasingly common in clinical practice, whether genetic testing confers a survival benefit remains to be firmly established.

      Method

      We performed retrospective analysis of 82 lung adenocarcinoma patients who were diagnosed at the Second Affiliated Hospital of Nanjing Medical University from 2013 to 2018. We evaluated progression-free survival (PFS) with respect to genetic testing status.

      Result

      63 (77%) patients received targeted next-generation sequencing. Of these, 43 (69%) patients received tailored targeted TKI therapies. No significant difference in mPFS was observed between patients with and without genetic testing (Fig.1). However, an increase in PFS started to manifest at later times in patients who received genetic testing. In patients treated with osimertinib, PFS was longer in those who received genetic testing and had EGFR T790M mutation status confirmed (Fig.2 and Table 1). A cis-C797S mutation was identified in a patient who progressed on osimertinib treatment. Patient 6 with EGFR L858R responded poorly to osimertinib. We found that genetic testing was conducted using a 139-gene panel, and more comprehensive testing may be necessary to uncover potential resistance mechanism(s) to osimertinib in this patient.

      2019 wclc figure 1.png2019 wclc figure 2.png

      Table 1. NSCLC patients treated with osimertinib
      Patient ID Age/Gender Sample Type Previous Targeted Therapy Mutations PFS (months after osimertinib
      1 65 / F Blood Gefitinib

      EGFR p.745_750del

      EGFR p.T790M

      20
      2 59 / F Blood/Tissue Gefitinib

      EGFR p.746_751del

      EGFR p.T790M

      30
      3 54 / M Blood Erlotinib

      EGFR p.L747_T752del

      MAP2K1 p. C121S

      NF1 p.L732X

      0.3
      4 48 / M Blood Osimertinib

      EGFR p.L858R

      EGFR p.T790M

      EGFR p.C797S

      4
      5 87 / M Tissue Osimertinib EGFR p.745_750del 10
      6 48 / M Blood Osimertinib EGFR p.L858R 4
      7 77 / M Blood/Tissue No EGFR p.L861Q 18
      8 60 / F Blood Gefitinib

      EGFR p.L858R

      EGFR p.T790M

      15
      9 77 / M Tissue Gefitinib KRAS 7
      10 50 / M Blood/Tissue Osimertinib No 18
      11 79 / M Blood/Tissue Osimertinib EGFR p.L858R 5

      Conclusion

      Routine genetic tests should implemented in treating patients with advanced NSCLC, particularly in those who developed resistance to first-generation TKIs.

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      EP1.01-87 - Cutaneous Metastasis in Lung Cancer – A Retrospective Study in a Local Health Unit in Guarda, Portugal (Now Available) (ID 2841)

      08:00 - 18:00  |  Presenting Author(s): Rebeca Martins Natal  |  Author(s): João Fernandes Costa, Marcos Oliveira, Adelino Amaral, Fátima Cabral, Rita Gomes, Luís Ferreira

      • Abstract
      • Slides

      Background

      Cutaneous metastasis from lung cancer is rare, occurring in 0.22-12% of cases. Their presence has generally been considered a sign of an already disseminated, poor-prognosis and non-surgical disease. Current data suggest lung cancer is the second most frequent cause of cutaneous metastasis in men, behind malignant melanoma.

      Method

      We conducted a retrospective analysis of patients diagnosed with lung cancer and cutaneous metastasis, submitted to skin biopsy to confirmation, from November 2010 to March 2019, in our local health unit. Data regarding demographic characteristics, smoking history; location and histology and of the primary tumor; staging; number, location and type of skin lesion; overall survival and survival after detection of cutaneous metastasis were collected from clinical records.

      Result

      Five patients were included, 4 were of male gender (80.0%), with median age of 79 years (range, 56-88). Three patients (60.0%) were former smokers, 1 current smoker and 1 non-smoker. The location of the primary tumor was right upper lobe (3 cases, 60.0%) and left lower lobe (2 cases, 40.0%); histology of adenocarcinoma in 3 patients (60.0%), 1 patient with squamous cell carcinoma and another with neuroendocrine carcinoma. All cases of lung cancer were diagnosed with an initial stage IV disease. Most of them had a unique skin lesion, mainly a nodule, located either in the upper abdominal wall or dorsal region. From the 5 cases, 4 had died, with a median overall survival 0.5 months (range, 0-1) and survival after cutaneous metastasis 15.5 days (range, 12-82).

      Conclusion

      According to data, also in our study men had more cutaneous metastasis from lung cancer than women. Previous or active smoking history was present in almost all patients, the main histology type was adenocarcinoma and primary lung cancer was frequently located in right upper lobe, consistent with reported data. In all cases, lung cancer was diagnosed in an advanced stage and survival after diagnosis of cutaneous metastasis was extremely low.

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      EP1.01-88 - Next-Generation Sequencing in Hispanic Patients with Advanced Lung Cancer and Correlation with Response to Immunotherapy (Now Available) (ID 2784)

      08:00 - 18:00  |  Presenting Author(s): Diana Saravia  |  Author(s): Luis Raez, Daniel Sumarriva, Jared Cotta, Dino Fanfan, Gilberto Lopes

      • Abstract
      • Slides

      Background

      Cancer is a leading cause of death among Hispanics (HISP); the largest ethnic minority in the United States (17% of the total population). With the approvals of checkpoint immunotherapy in advanced lung cancer, many patients (pts) are starting to see long-lasting remissions and longer survival rates. However, response to a given treatment often depends on the tumor’s genomic profile. Our aim was to analyze NGS results for HISP pts living in the US in an effort to better understand this population’s genomic profile and prognosis.

      Method

      Retrospective analysis on pts with biopsy proven advanced NSCLC who received checkpoint immunotherapy at two large institutions in the US. Patient charts were reviewed to obtain data on demographic characteristics including race, gender, age, and smoking history. Next generation sequencing (NGS) results were obtained from Guardant Health and Foundation One testing in blood and in tissue, respectively. We assessed progression-free survival (PFS) and overall survival (OS) associated with outcome.

      Result

      Seventy HISP pts receiving immunotherapy underwent NGS testing from 10/2013 to 4/2018. 46% were male, 76% were smokers, 89% had adenocarcinoma, and 39% were PD-L1 positive (with 67% of those having TPS ≥ 50%). Thirty pts (43%) had one genetic aberration (GA), and 15 pts (22%) had >5 GA. The most frequent actionable GA was EGFR mutation (26%) and nonactionable mutation was KRAS (40%). Other less common GA were BRAF (10%), MET (10%), and STK11 (9%).

      Survival

      1 Genetic Aberration

      >5 Genetic Aberrations

      P value

      Median PFS

      3.57m

      3m

      0.2767

      Median OS

      14.96m

      3.8m

      0.0117

      Conclusion

      The presence of >5 GA (actionable and nonactionable) on NGS testing was associated with worse OS when compared to pts with one GA. There was no difference in PFS. In addition, PD-L1 incidence in HISP pts is high with a larger proportion of pts expressing ≥ 50% TPS compared to what is reported for NHW. Given the numerous nonactionable GA encountered, it is clear that continued development of targeted therapies would keep benefitting pts. Increased NGS profiling in HISP pts could potentially broaden treatment and clinical trial options to serve this purpose.

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      EP1.01-89 - Retroperitoneal Metastasis with Marked Fibrosis from Lung Adenocarcinoma: An Autopsy Case Report (Now Available) (ID 606)

      08:00 - 18:00  |  Presenting Author(s): Hiroki Ota  |  Author(s): Eriko Narisawa, Hideyuki Chiba, Hiroshi Nakayama, Yoko Tsukumo, Atsuhiko Sakamoto, Naoko Honma, Tomohiro Ota

      • Abstract
      • Slides

      Background

      Retroperitoneal metastasis of lung cancer is rare. Here we report a unique case of retroperitoneal metastasis with fibrosis from lung adenocarcinoma. Case: A 73-year-old woman was admitted to the hospital in June 2018 because of nausea and vomiting of a few days' duration. In February 2018 she had received a diagnosis of lung adenocarcinoma (clinical T3N3M1a stage IVA, epidermal growth factor receptor [EGFR] mutation positive, exon 19 deletion) in the right lower lung and was taking afatinib 20 mg once daily. On admission, chest radiography and computed tomography (CT) showed that the primary tumor was smaller than at the time of diagnosis; however, abdominal CT showed a new retroperitoneal lesion and right hydronephrosis. Contrast-enhanced CT and MRI scan revealed poorly marginated soft tissue around the duodenum and inferior vena cava. She underwent gastrojejunostomy and biopsy of the peritoneum after duodenal obstruction was revealed by examination of the upper gastrointestinal tract (Figure 1). Analysis of the biopsy specimen revealed EGFR mutation–positive adenocarcinoma with exon 19 deletion, which was consistent with retroperitoneal metastasis of the lung adenocarcinoma. She was treated with CBDCA/PEM and CBDCA/PEM/BV each one cool [DK1] but developed cerebral infarction and died 104 days after admission.

      figure1.jpg

      Method

      Section not applicable

      Result

      Autopsy showed that right ureteral obstruction and hydronephrosis were caused by markedly sclerotic retroperitoneum. Histopathologic examination revealed marked fibrosis with scattered adenocarcinoma (Figure 2).

      figure 2.jpg

      Conclusion

      Although rare, metastasis of non–small lung cancer should be considered in patients with doudenal obstruction or hydronephrosis.

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      EP1.01-90 - The Prognostic Role of Mean Platelet Volume in Patients with Advanced Non-Small Cell Lung Cancer (Now Available) (ID 1039)

      08:00 - 18:00  |  Presenting Author(s): Ioannis Gkiozos  |  Author(s): Kyriaki Cholidou, Nektarios Anagnostopoulos, Dimitra Grapsa, Eleni Kokkotou, Rodoula Trigidou, Antonis Vassias, Sofia Tsagouli, Petros Bakakos, Ilias Kotteas

      • Abstract
      • Slides

      Background

      Previous studies suggest the potential correlation between increased mean platelet volume (MPV) and survival in non-small cell lung cancer (NSCLC), but results are often contradictory. We herein aimed to further evaluate the prognostic value of MPV in patients with advanced-stage NSCLC in the real-world setting of a tertiary referral oncology center.

      Method

      Demographic, clinicopathological and laboratory data (including complete blood count parameters) of 30 patients with stage IIIB or IV NSCLC were retrieved from the Lung Cancer registry of the Oncology Clinic of Sotiria Athens General Hospital and analyzed. All the above variables (including MPV) were correlated to each other, as well as with overall survival (OS) and progression-free survival (PFS).

      Result

      Mean patients’ age was 68,5 (SD=7,5) years. The majority of patients were male (76.7%), had positive smoking history (90%), squamous cell carcinoma (53.3%), and stage IV disease (76.7%). No statistically significant correlations between survival and sex, age, smoking history or tumor histology (squamous cell carcinoma versus adenocarcinoma), or between MPV and histology were noted. Worse performance status (p=0.004) and higher white blood cell count (p=0.01) were correlated with reduced OS, while increased MPV was strongly correlated both with OS and PFS (p<0.0001 in both cases).

      Conclusion

      Increased MPV may correlate with improved survival of patients with NSCLC, thus potentially representing a marker of favorable prognosis. Our study findings warrant confirmation in larger prospective series

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      EP1.01-91 - Outcomes with Systemic Chemotherapy with Weekly Regimen in Advanced NSCLC Patients with PS 2 and Above and Without Driver Mutation (Now Available) (ID 1173)

      08:00 - 18:00  |  Presenting Author(s): Harish Kancharla  |  Author(s): Prabhat Singh Malik, SACHIN Khurana, Deepali Jain, SUNIL Kumar, Sushmita Pathy

      • Abstract
      • Slides

      Background

      Platinum-based combination chemotherapy is recommended as the standard treatment for patients with advanced NSCLC, but its benefit is limited to patientswith performance status (PS) of 0 or 1. However, it is not clear whether these benefits apply to patients with poor PS( 2 and above)). These patients have inferior outcomes and have been excluded from clinical trials. We have analyzed the outcome of these patients who have been treated with weekly chemotherapy despite poor performance status.

      Method

      We performed a retrospective analysis of patients of advanced NSCLC with poor PS (ECOG PS 2 or more) registered at our lung cancer clinic between January 2016 and December 2017 and treated with weekly chemotherapy. Patients with driver mutations who were treated with first line TKIs were excluded. Hospital case records were reviewed for baseline characteristics, treatment details and outcome data.

      Result

      A total of 68 patients were found to be eligible for this analysis. Median age was 63.5 years (30-77 years, including 17(25%) patients 70 years or above. At presentation out of these 68 patients, 50(73.5%) were smokers,22(32%) had cytological proven pleural/pericardial effusion, 7(10.2%) patients had brain metastasis and 35(51.5%) had extra thoracic metastasis (≥2 sites). Majority(61%) patients had ECOGPS 2 but 39 % had PS 3 or 4 also and 29(42%) had one or more associated comorbidities. The most common chemotherapy regimen used was weekly paclitaxel and carboplatin(82.8%) followed by single agent paclitaxel(17.8%).Majority (63%) patients could complete 4 or more cycles of chemotherapy however 9 patients (13.2%) could receive only one cycle and 16(23%) patients even received maintenance chemotherapy. Chemotherapy was interrupted due to poor tolerance in 10(14.7%) patients and grade ¾ toxicity seen in 16(23%) % patients. At least one point improvement in ECOG PS from baseline was observed in 33 patients (48.5%) after 4 cycles of chemotherapy and objective response and disease control rates were 23.5 % and 50% % respectively. After a median follows up of 13 months, median progression free survival was 7.3 months.

      Conclusion

      Systemic chemotherapy in modified doses and schedules in advanced NSCLC patients with PS 2 and above is feasible and may be associated with better symptom palliation with clinical benefit and improvement in survival. Further studies addressing this neglected subgroup are indicated.

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      EP1.01-92 - Effectiveness of Second-Line Treatment with Nintedanib + Docetaxel (ND) in Patients with Metastatic Lung Adenocarcinoma (Now Available) (ID 1815)

      08:00 - 18:00  |  Presenting Author(s): Joel Veas  |  Author(s): Juan Felipe Cordoba Ortega, Christina Adaniel, SERAFIN Morales, Ariadna Gasol, Alvaro Rodriguez, Antonio Calles Blanco, Antonieta Salud

      • Abstract
      • Slides

      Background

      Nintedanib is an oral angiokinase inhibitor directed against VEGFR 3, FGFR 1-3, and PDGFR alpha and beta. It is approved by the European Medicines Agency in combination with docetaxel for the treatment of metastatic lung adenocarcinoma previously treated with platinum-doublet chemotherapy. Given the efficacy of checkpoint inhibitors in the second-line treatment of advanced lung cancer, we evaluated the outcomes of ND in this setting

      Method

      Patients diagnosed with advanced lung cancer between July 2015 to October 2017 at the University Hospital Arnau de Vilanova (Lleida, Spain) and treated with ND were included. The clinical history, tumor pathology, tumor biologic characteristics, treatments prior and posterior to ND were reviewed. Statistical analysis was realized using IBM SPSS Statistics 23.0 software. Overall survival (OS) was calculated by Kaplan-Meier curve, determining a median OS with 95% confidence interval and estimated mortality rates during each year of follow-up

      Result

      Thirteen of 357 patients with advanced lung cancer during the time period specified were treated with ND and included in the analysis. Median follow-up was 14.4 months (range: 7.3 – 41.2 months). Median age at diagnosis was 62.1 years (range: 46-73 years). Never-smokers comprised 15.4% of the patients, ex-smokers 46.2% and active smokers 38.5%. Bone metastases were present in 23.1% of patients, while 15.4% and 15.3% had central nervous system and hepatic metastases, respectively. The majority, 69.2%, received a platinum-doublet first-line and 46.2% received pemetrexed maintenance. The median number of ND cycles was four. Responses to ND were 53.8% partial response (PR), 23.2% stable disease (SD), and 23% progressive disease, with a disease control rate (DCR) of 77%. 53.8% of patients continued with nintedanib maintenance with the following responses: 43% PR, 14.3% SD, and 42.7% progressive disease (DCR 57.3%). There were no grade 2 or greater toxicities in the nintedanib maintenance group. Fifty-four percent of ND patients received third-line therapy: 50% atezolizumab, 16.7% carboplatin + vinorelbine, 16.7% nivolumab, and 16.7% oral vinorelbine. Eleven percent of patients received fourth-line therapy. Median OS was 14.4 months (CI 95%: 11.7 – 17.1 months). OS rates at 2 and 3 years were 69.2% (CI 95%: 44,1% - 94,3%) and 23.1% (CI 95%: 0,2 - 46%), respectively

      Conclusion

      ND is an effective second-line treatment for patients with advanced lung adenocarcinoma. In this descriptive analysis, the median OS associated with ND was superior to the results of Lume-Lung 1 and Checkmate 057, although the study is limited by sample size

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      EP1.01-93 - Rare Immune Related Adverse Events by Immune Checkpoint Inhibitors in Clinical Practice (Now Available) (ID 1721)

      08:00 - 18:00  |  Presenting Author(s): Takamoto Saijo  |  Author(s): Akihiko Tanaka, Norihiko Ikeda

      • Abstract
      • Slides

      Background

      Immune checkpoint inhibitors (ICIs) such as anti-PD-1 and PD-L1 antibodies including nivolumab/pembrolizumab and atezolizumab are available practically in Japan. While ICIs produce excellent antitumor activity and long-term survival, unexpected immune related adverse events (irAEs), which are different from those for cytotoxic drugs, have been reported. We experienced varieties of irAEs which have successfully been treated.

      Method

      We retrospectively analyzed irAEs in 50 NSCLC patients treated with ICIs as clinical practice from January 2016 to November 2018 in TODA Central General hospital.

      Result

      Nivolumab, pembrolizumab and atezolizumab was given in 27, 11 and 12 patients, respectively. The median age was 69 (43-84). Male/female: 40/10 patients, adenocarcinoma/squamous cell carcinoma/unclassified non-small cell carcinoma: 30/15/5 patients. Tissue proportional score for PD-L1 antibody was strongly positive/weakly positive/negative/unknown in 12/4/12/22 patients, respectively. The treatment response was CR/PR/SD/PD/NE in 3/14/2/22/9 patients, respectively. Various types of irAEs have been observed, exacerbation of rheumatoid arthritis: 1, hypothyroidism: 3, secondary adrenocortical insufficiency with ACTH isolated deficiency: 1, pneumonitis: 6, liver dysfunction: 1, neutropenia: 1, diarrhea: 1, rash: 3, infusion reaction: 1. Each irAEs had been basically managed according to algorism, such as treatment discontinuation, irritative treatment, steroid therapy, hormone replacement therapy etc. One patient, who developed multiple irAEs, diarrhea, liver dysfunction and neutropenia at same time, recovered from irAEs quickly by supportive care including steroid pulse therapy.

      Conclusion

      A variety of unexpected irAEs have been experienced in NSCLC patients treated with ICIs, however, excellent tumor response was observed in 10 of 13 patients who developed irAEs. In patient who showed multiple irAEs, tumor size was decreased significantly by nivolumab therapy and tumor progression was not observed 33 months after the final nivolumab administration. IrAEs associated with ICIs are diverse and difficult to predict, so safety management and early detection are important.

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      EP1.01-94 - The Role of Neoadjuvant Chemo-Immunotherapy in Unresectable Non-Small Cell Lung Cancer (Now Available) (ID 2873)

      08:00 - 18:00  |  Presenting Author(s): Young Kwang Chae  |  Author(s): Michael S Oh, Andrew A. Davis, Robert Lentz, Neil Peterman, Alex Robertson, Rohith Srivas, Nicole Lambert, Timothy Wilson, Haluk Tezcan, Ankit Bharat

      • Abstract
      • Slides

      Background

      Current practices and guidelines invoke a limited role for neoadjuvant therapies in NSCLC. These strategies are not considered for use in advanced, unresectable disease. However, the development of immune checkpoint inhibitors has drastically improved the efficacy of systemic treatments for NSCLC.

      Method

      We describe the case of a patient who was diagnosed with squamous cell carcinoma of the lung.

      Result

      Imaging demonstrated a 7.9-cm right lower lobe lesion, a 1.8-cm satellite right middle lobe nodule, and ipsilateral mediastinal lymphadenopathy, consistent with stage IIIB disease. The tumor biopsy exhibited 5% PD-L1 positivity in tumor cells. Tissue next generation sequencing (NGS) revealed loss-of-function mutations in RB1, TP53, and EP300, copy number gain in PIK3CA, and tumor mutational burden of 4.3/Mb. Analysis of circulating tumor DNA (ctDNA) demonstrated a highest allele fraction of 4.1% (TP53 mutant clone). As the tumor was deemed unresectable, the patient was started on carboplatin, nab-paclitaxel, and pembrolizumab. Follow-up imaging at 12 weeks after 4 cycles showed partial response, with significant reduction in tumor size and improvement in lymphadenopathy. After tumor board discussion, the decision was made to proceed with surgical resection. A right thoracotomy with bilobectomy was successfully performed. Resected tumor demonstrated major pathologic response with less than 5% viable cancer cells. Whole-genome sequencing of plasma was also carried out on blood collected over the course of treatment. The observable cancer signal shrank to less than 5% of the baseline as early as 25 days after treatment start. Finally, repeat ctDNA analysis 6 weeks after the surgery showed no detectable somatic variants.

      Conclusion

      Conversion of unresectable tumors in NSCLC may be more feasible with modern treatment regimens. The potential efficacy of neoadjuvant strategies using chemoimmunotherapy warrants further clinical investigation.

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      EP1.01-95 - Up-Regulation of c-Met by Cox-2 Promotes Resistance of Gefitinib in NSCLC Patients (ID 3049)

      08:00 - 18:00  |  Presenting Author(s): Fei Wang

      • Abstract
      • Slides

      Background

      c-Met amplification is one of the reasons for Gefitinib resistance in NSCLC patients.

      Method

      1.Explore the mechanism of the up-regulation of c-Met by Cox-2; 2.Combination of Cox-2 inhibitor and Gefitinib can overcome Gefitinib resistance in cells or animal study; 3.Test the expression pattern or activity of Cox-2 in NSCLC patients, and evaluate the possibility of Cox-2 serving as biomarker for Gefitinib resistance and prognosis for NSCLC patients.

      Result

      1.Both c-met and Cox-2 are highly expressed in Gefitinib resistant lung cancer cell lines; 2.Cox-2 is highly expressed in malignant lung adenocarcinoma than in matched normal tissues; 3.Inhibition of Cox-2 can decrease c-Met expression, and promote apoptosis induced by Gefitinib in Gefitinib resistant cells.

      Conclusion

      Up-regulation of c-Met by Cox-2 promotes resistance of Gefitinib in NSCLC patients

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      EP1.01-96 - Metastatic Lymphoepithelial Lung Cancer (Now Available) (ID 244)

      08:00 - 18:00  |  Presenting Author(s): AbdelNasir Nourallah  |  Author(s): Sarah Nazimuddin Qureshi

      • Abstract
      • Slides

      Background

      NSCLC remains the leading cause of cancer deaths globally. Lymphoepithelial-like carcinoma (LELC) of the lung, (EBV)-driven tumor; mostly found in East Asian population; is not only one of the rarest subtypes of non-small cell lung cancer (NSCLC) but is also quaint to have a good prognosis. Advanced or metastatic Lymphoepithelial lung cancer is even rarer. LELC of the lung is traditionally considered be chemo-sensitive; although recurrences common lending to chemo-related toxicity and increased morbidity. High predilection of LELC for Programmed Death Ligand-1 (PDL-l) positivity and its long established association with EBV, led to the exploration of the role of PD- 1/PDL- 1 inhibitors in its management.

      Method

      poster / case report

      Result

      There have been only 4 cases reported in literature highlighting the use of PDL/PDL-1 inhibitors in LELC of lung and that too in recurrent/relapsed setting; out of which three had a favorable outcome and only one patient was treated with Pembrolizumab . We report the first case of a young Pilipino female who presented with metastatic LELC of the lung with vertebral metastases causing severe lower backache; initially treated with chemotherapy, followed by Pembrolizumab alone due to high PDL-I expression in her tumor, resulting in complete remission of symptoms and radiological evidence of complete metabolic resolution of multiple metastatic bony lesions. This case not only necessitates the need for larger prospective trials to assess the role or PD- 1/PDL- 1 inhibitors in this rare kind or lung cancer but also reiterates the long-brewing dilemma regarding the duration of treatment with these agents after achievement of complete remission.

      Conclusion

      Pembrolizumab used alone in high PDL-I expression, results in complete remission of symptoms and radiological evidence of complete metabolic resolution of multiple metastatic bony lesions in patients with NCSLC Lymphoepithelial-like carcinoma (LELC)

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      EP1.01-97 - Is Surgical Treatment Suitable for Stage III or IV Primary Lung Cancer? (Now Available) (ID 1269)

      08:00 - 18:00  |  Presenting Author(s): Yoshifumi Sano  |  Author(s): Hisayuki Shigematsu, Ryujiro Sugimoto, Nobuhiko Sakao, Tatsuya Hayashi, Tomohisa Sakaue

      • Abstract
      • Slides

      Background

      Background: It is generally known that advanced lung cancer is not an indication for surgical treatment, whereas it is an indication for chemotherapy and/or immunotherapy. We examined cases in which surgery was performed for clinical stage III or IV lung cancer and investigated whether this treatment was effective or not.

      Method

      Methods: We retrospectively reviewed 34 patients who underwent radical resection for stage III or IV primary lung cancer at Ehime University Medical Hospital from October 2010 to February 2019.

      Result

      Results: In this series, 23, 5, and 6 patients had stage IIIA, stage IIIB, and stage IV disease, respectively. Following were the histological types: adenocarcinoma, 14; squamous cell carcinoma, 9; large-cell carcinoma, 5 (large-cell neuroendocrine carcinoma [LCNEC], 1); adenosquamous carcinoma, 1; pleomorphic carcinoma, 1; LCNEC + adenocarcinoma, 1; LCNEC + squamous cell carcinoma, 1; and LCNEC + small-cell carcinoma, 1. As preoperative treatment, 8 and 7 patients received full-dose chemoradiotherapy (salvage surgery) and induction chemoradiotherapy, respectively. We also included 2 cases involving salvage surgery after only chemotherapy and 1 case involving salvage surgery after chemotherapy and brain metastasis resection. The remaining 16 patients underwent surgery without any pre-surgical treatment. In addition, adjuvant chemotherapy was administered in 17 cases. In a mean observation period of approximately 4 years, the overall 3-year and 5-year survival rates were 57.2% and 30.6%, respectively. In patients with clinical stage IIIA disease, the 3-year and 5-year survival rates were 55.9% and 21.7%, respectively. In patients with clinical stage IIIB disease, the 3-year and 5-year survival rates were 75% and 50%, respectively. In patients with stage IV disease, the 3-year and 5-year survival rates were 50% and 33.3%, respectively. In patients without any multimodal treatments (n = 16), the 3-year and 5-year survival rates were 55.0% and 23.6%, respectively. In patients who underwent surgery after induction chemoradiotherapy (n = 7), the 3-year and 5-year survival rates were 85.8% and 42.9%, respectively. In patients who underwent salvage surgery (n = 11), the 3-year and 5-year survival rates were 41.7% and 41.7%, respectively.

      Conclusion

      Conclusion: Long-term survival can be achieved even in stage III or IV lung cancer patients by combining multimodal treatment with surgery in appropriate cases.

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      EP1.01-98 - Outcomes of Non-Small Cell Lung Cancer Patients with Brain Metastasis Treated by Whole Brain Radiotherapy, a Single Institution Experience (Now Available) (ID 116)

      08:00 - 18:00  |  Presenting Author(s): Apurna Jegannathen  |  Author(s): Selvaraj Giridharan, salil Vengalil, shahid Gilani, Homayemem Weli

      • Abstract
      • Slides

      Background

      Whole brain radiotherapy (WBRT) is predominantly used in the treatment of brain metastasis but recent data suggests that it does not significantly contribute to improved overall survival in patients. This study was carried out to review our practice by assessing the survival outcome for NSCLC patients with brain metastasis treated with WBRT in relation to the QUARTZ trial data (Mulvena et al, 2016).

      Method

      A retrospective study of such patients over a period of 12 months was carried by obtaining data from

      electronic record systems and radiotherapy records. Data demographics and analysis of overall survival were

      calculated and comparison was made with literature findings.

      Result

      Over 12 months 39 patients with brain metastasis had received WBRT (30G in 10# or 20G in 5#). 68% (n=29) were of NSCLC origin with a gender ratio of 1:1. The average age at diagnosis of NSCLC was 67.8 and 70 years for males and females respectively. Majority of NSCLCC patients treated with WBRT had a WHO performance status (PS) of 1(41.3%, n=12) or 0 (27.5%, n=8). Mean survival following treatment with WBRT was 16.7 weeks. The median survival was 10 weeks and average ages of death in the female and male patients were 67.8 and 70 years respectively. An incidental finding of longer survival (31.8 weeks) was noted in patients treated with 30Gray and 10 fractions compared with those treated with 20Gray and 5# (9.5 weeks). 43.8% of those receiving 30Gray and 10 fractions were of PS 0 in contrast with 14.2% of those receiving 20G in 5#.

      Conclusion

      The median survival in our patients treated with WBRT was comparable to that obtained in the QUARTZ study (9.2 weeks in those who received WBRT and optimal supportive care). Although a retrospective study, it is suggestive of an above average survival outcome in our practice when compared to the multinational QUARTZ study. The incidental observation of higher survival in the group who received higher RT dose and fraction may be explained by clinical decision influencing RT categorisation due to the fact that patients with better performance status are more likely to tolerate higher doses of RT and be given same.

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      EP1.01-99 - Effect of Immune Checkpoint Inhibitors Re-Administration in Non-Small-Cell Lung Cancer Patients (Now Available) (ID 236)

      08:00 - 18:00  |  Presenting Author(s): Tomoka Kawajiri  |  Author(s): Tomoki Tamura, Tatsuya Nishi, Kenichiro Kudo, Shoichi Kuyama

      • Abstract
      • Slides

      Background

      Immune checkpoint inhibitors, drugs targeting the programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) pathways, are approved for the treatment of patients with non-small-cell lung cancer (NSCLC) with impressive clinical activity and durable responses in some patients. But the re-administration of immune checkpoint inhibitors have not be clarified.

      Method

      From December 2015 to December 2018, 93 NSCLC patients received immune checkpoint inhibitor monotherapy. We retrospectively evaluated these 93 patients.

      Result

      6 patients received re-administration of immune checkpoint inhibitors. Median progression free survival of immune checkpoint inhibitors initial treatment and re-administration were 98 and 55 (p = 0.139). Overall response rate was 24.7% and 0% (p = 0.331) and disease control rate was 53.7% and 16.7% (p = 0.105). There was no significant difference between initial treatment and re-administration. The effect of re-administration of immune checkpoint inhibitor is not so high, but one patient received more than 6months.

      Conclusion

      The effect of re-administration of immune checkpoint inhibitors are not high, but few patients can receive long term of therapy.

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      EP1.01-100 - Evaluation of the Clinicopathological Features of Patients in Whom Residual Carcinoma in Bronchial Stump After Surgery for Lung Cancer (Now Available) (ID 372)

      08:00 - 18:00  |  Presenting Author(s): Yohei Kameda  |  Author(s): Takao Morohoshi, Hiroyasu Koga, Kohei Ando, Yukio Tsuura, Munetaka Masuda

      • Abstract
      • Slides

      Background

      Operation for lung cancer should be carried out with no residual carcinoma at bronchial stump. Rarely, we encounter unexpected microscopic residual carcinoma at surgical bronchial stump after surgery. Additional therapy for these patients is still controversial.

      Method

      From January, 2008 to December, 2018, 812 consecutive patients with non-small lung cancer underwent surgery (99 of segmentectomy, 694 of lobectomy, and 19 of pneumonectomy) in our institution. Among them, there were 7 cases (0.9%) which had bronchial stump with residual cancer cells. We investigated the clinicopathological characteristics and outcomes of these patients retrospectively.

      Result

      The procedures for the 7 cases consist of 5 lobectomy, 1 segmentectomy, and 1 pneumonectomy. In 3 cases, frozen diagnosis were done and in 2 of 3 cases additional resection were done. Histologically, there were 4 case of adenocarcinomas and 2 of squamous cell carcinomas, and 1 of adenosquamous cell carcinoma. 3 cases were stage B(pT4N2M0, pT3N2M0), and 3 cases were A (pT2bN2M0, pT4N1M0), 1 case was stage B (pT1bN1M0) respectively. All cases had lymphatic invasion microscopically.

      6 cases developed recurrence or distant metastasis. 2 had local recurrence at bronchial stump and 4 had distant metastasis (1 was in brain, 1 was at lymph nodes, 1 was at vertebrae, 1 was at bilateral lungs).

      5 cases were received postoperative additional therapies. 4 cases were received cytotoxic chemotherapy only, and another case was recieved cytotoxic chemotherapy and TKI. None of them were received radiotherapy for bronchial stump. 5 cases passed away because of cancer progression and 1 case was because chronic heart failier. Another case is alive with lung metastases taking TKI therapy.

      In all cases, preoperative CT scan didn’t show bronchial wall thickning, and preoperative bronchoscopic findings showed normal bronchial mucosa.

      Conclusion

      In surgical cases of non-small cell lung cancer, 1.2% had microscopic residual cancer at surgical bronchial stump. Our study revealed that such cases tended to have a relapse as distant metastasis rather than local recurrence. Preoperative evaluation whether bronchial invasion exists or not is difficult and post-operative additional treatment strategy is still uncertain. In postoperative follow-up, systemic survey for not only local region but distant organs is necessary.

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      EP1.01-101 - Transposition of the Pulmonary Veins for Mobilization of Rt-Middle and Lower Lobes for Safe Reconstruction After Carinal Rt-Upper Lobectomy (Now Available) (ID 1320)

      08:00 - 18:00  |  Presenting Author(s): Takeshi Shiraishi  |  Author(s): Toshihiko Sato, Shin-ichi Yamashita, Akinori Iwasaki

      • Abstract
      • Slides

      Background

      A variety of techniques for reconstruction of the carina after carnal or carinal right upper lobe resection have been proposed. The most important point to accomplish this complex surgery is to achieve safe tension free airway anastomosis. Here we report a case of carinal right upper lobectomy, in whom transposition of the middle and lower pulmonary veins to the opening of the right superior pulmonary vein was performed to achieve safe tension free anastomosis between the trachea and right intermediate bronchus (RIB).

      Method

      A 70-year-old female was admitted with severe cough. Bronchoscopy and CT scan revealed an intraluminal tumor obstructing the right main bronchus. A biopsy returned a diagnosis of adenoid cystic carcinoma. After tumor debulking by rigid-bronchoscope, extension of the tumor to the RIB and left main bronchus (LMB) was clarified and it was judged that complete resection of the lesion is possible by carinal right upper lobectomy.

      Result

      A standard posterolateral thoracotomy was performed. Firstly, the trachea and LMB were transected at 2 cartilage rings above and below the carina respectively, and end-to-end anastomosis was safely performed. Then the RIB was transected immediately after the tumor invasion and the carinal right upper lobectomy was completed. Because the patient's LMB was narrow, side-to-end anastomosis of the RIB to the lateral wall of LMB was considered to be at high-risk for anastomotic stenosis. Thus the most desirable reconstruction procedure of the RIB was thought to be the side-to-end anastomosis to the lateral wall of the trachea. However, the opening of the RIB was far apart from the desirable anastomosis point of the trachea despite mobilization procedures such as right hilar release. The right middle and lower pulmonary veins were thus resected and transferred to the opening of the superior pulmonary vein and anastomosed by the double-barrel fashion. The opening of the RIB was then elevated and implanted to the lateral wall of the trachea. プレゼンテーション1.png

      Conclusion

      The technique of pulmonary venous transposition can be an excellent airway release maneuvers to achieve safe tension free anastomosis between trachea and RIB in case of carinal right upper lobectomy.

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      EP1.01-102 - Efficacy and Toxicity of Erlotinib and Gefitinib in Moroccan Patients with Advanced Non-Small Cell Lung Cancer with EGFR Mutation (Now Available) (ID 1926)

      08:00 - 18:00  |  Presenting Author(s): nadia Benchakroun  |  Author(s): Nicolas Minoungou, Zineb Bouchbika, Hassan Jouhadi, Nezha Tawfik, Souha Sahraoui, Abdellatif Benider, Abdelkader Acharki, Madiha Lemzah

      • Abstract
      • Slides

      Background

      BACKGROUND

      Lung cancer, the second most common cancer in Morocco, is a public health problem.

      It is also the leading cause of cancer death in the world because its prognosis is poor and the diagnosis is often made at a metastatic stage.

      The advent of tyrosine kinase inhibitors has improved survival in patients with epidermal growth factor receptor mutation (EGFR)

      There are few studies in Morocco, the aim of this study was to evaluate the efficacy and safety of anti-EGFR in patients with non-small cell lung cancer with EGFR mutated in Morocco.

      Method

      METHODS

      We had collected twenty-three patients followed for metastatic non-small cell lung cancer with EGFR mutation and management in the onco-radiotherapy department of the IBN ROCHD University Hospital of Casablanca (MOROCCO)

      Result

      RESULTS

      Of the twenty-three patients collected, the sex ratio was 7 men to 16 women, the average age was 59 years, only one case had a history of smoking, all cases had adenocarcinoma, the mutation on exon 19 was found in 87%.

      The median progression-free survival was 4 months and the median overall survival was 12 months,

      For tolerance; diarrhea and folliculitis were found in all patients with 50% grade II.

      Conclusion

      CONCLUSIONS

      The EGFR mutation appears to be more frequent in women and non-smokers, and anti-EGFR treatment improves survival with a particular tolerance profile that should be known.

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      EP1.01-103 - Long-Term Response to Second-Line Afatinib for the Treatment of Advanced Lung Squamous Cell Carcinoma (Now Available) (ID 2962)

      08:00 - 18:00  |  Presenting Author(s): Ye Guo  |  Author(s): Kewei Ma, Xu Wang, Mengyao Sun, Yinghui Xu, Chao Sun, Shi Qiu

      • Abstract
      • Slides

      Background

      Lung squamous cell carcinoma (SqCC) with large heterogeneity and complex genetic map accounts for 25–30% of non-small-cell lung cancer (NSCLC) cases. SqCC is lack of defined molecular targets and often diagnosed at a advanced stage, which contribute to poor prognosis. Afatinib is an irreversible ErbB family inhibitor that is approved for the second-line treatment of patients with advanced SqCC who progressed after platinum-based chemotherapy based on the significant clinical benefits in Lux-Lung8.

      Method

      We presented a case of a 56-year-old male with a 30-year history of smoking was diagnosed as SqCC of the left lung (cT2N3M0, IIIB). After neoadjuvant chemotherapy +sugery + adjuvant chemotherapy, CT scans showed disease progressed with disease-free survival (DFS) of 12 months. Thus, continuous chemoradiotherapy was administered. Seven months later, chest CT suggested that the disease progresssed again. Subsequently, the patient was enrolled into LUX-Lung 8 study and began the second-line therapy of afatinib (40 mg/day).

      Result

      The patient remaining in stable disease (SD) after 8 weeks and achieving complete response(CR) after 12 weeks treatment.The patient is still alive and the disease has not progressed more than 5 years since initiation of treatment. There‘s no obvious side effects during the treatment.

      Conclusion

      We found that the patient had a favorable progosis with the overall survial of more than five years treated with afatinib. Long-term response to afatinib in this case provides an important reference for the treatment of patients with advanced SqCC.

      wclc 阿法替尼.png

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      EP1.01-104 - Denosumab Experience in Lung Cancer Patients with Bone Metastases (Now Available) (ID 1005)

      08:00 - 18:00  |  Presenting Author(s): Dilek Erdem

      • Abstract
      • Slides

      Background

      Denosumab, is a monoclonal antibody against receptor activator nuclear factor kappa B ligand (RANKL). It inhibits the bone resorbtion and therefore decreases skeletal related events (SRE). It is practically used instead of zoledronic acid in the tumors with bone metastasis. This study aims to reveal general characteristics and adverse event profile of lung cancer patients with bone metastasis.

      Method

      This study includes 17 patients referred to outpatient clinic who have lung cancer with bone metastasis between July 2014 and July 2018. We retrospectively analyzed the data. The patients who were on denosumab treatment at least 2 months were included.

      Result

      All of the patients were men (n=17). The median age was 66,8 years old (range 34-84 years). All of the patients had non small cell lung cancer histology. Six patients (35,2 %) had squamous cell carcinoma and eleven patients were with adenocarcinoma histology. Except for two patients, all had metastatic disease. 3 had bone metastasis after the cancer diagnosis while others had bone metastasis initially. Seven patients had another metastatic sites besides bone metastasis and the most common metastatic site was lung (57,1 %). Among eleven adenocarcinoma patients, 4 had EGFR mutation (36 %): 2 with exon 19 deletion and 2 with exon 21 mutation. These 4 patients had anti-EGFR treatment. The patients had denosumab in the range of 2-33 months, with the median 6,5 months. 10 patients had radiation therapy besides denosumab treatment. Six patients (35,2 %) were switched from zoledronic acid therapy to denosumab because of renal failure. There was no hypocalcemic status because all the patients had laboratory checks for calcium, vitamin D and albümin and treated according to the deficiency before denosumab therapy. Also during denosumab treatment we did not see any osteonecrosis because all had undergone dentist examination before the initiation of the drug. 29,4 % (five patients) died during the therapy. All of the patients passed on because of the disease progression.

      Conclusion

      Bone is the most common metastatic site of lung cancer. Bone metastasis cause morbidities like pain, fracture, hypercalcemia and spinal cord compression. In our study, unlike the literatüre, there were no hypocalcemia or osteonecrosis. This outcome may be connected not only the shortness of the follow-up but also the initial replacement of calcium and vitamin D. Because of being effective and with less toxicity, denosumab may be a positive option in lung cancer patients with bone metastasis.

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      EP1.01-105 - Experience in Treating Recurrent Non-Small Lung Cancer Patients After Surgery with Immune-Checkpoint Inhibitor (Now Available) (ID 1148)

      08:00 - 18:00  |  Presenting Author(s): Masafumi Yamaguchi  |  Author(s): Taichi Matsubara, Shinkichi Takamori, Naoki Haratake, Ryo Toyozawa, Naoko Miura, Takashi Seto, Mitsuhiro Takenoyama

      • Abstract
      • Slides

      Background

      Recent rapid advancements in the development of chemotherapy, including immune checkpoint inhibitors (ICIs), such as program death-1 (PD-1) inhibitor or program death-ligand 1 (PD-L1) inhibitors, in the field of non-small cell lung cancer (NSCLC) have remarkably prolonged patients’ survival.

      Several clinical trials currently underway are assessing the efficacy of ICIs in adjuvant chemotherapy (AC) following complete resection of Stage I-IIIA NSCLC. One of the issues with AC for completely resected NSCLC is the limited proportion of patients who benefit from such treatment, as some patients will experience recurrence despite AC while others will not experience recurrence even without AC.

      Given the emergence of adverse events (AEs), including immune-related AEs at a constant rate, the appropriate timing of treatment with ICI remains unclear whether AC or at the time of recurrence.

      Method

      In this single-institutional retrospective study, to clarify the treatment effect of ICIs in terms of the survival or response, we reviewed 21 patients treated with ICIs for recurrent NSCLC who had undergone complete surgical resection between March 2016 and October 2018.

      Result

      The median age was 61 years old (range: 47-75 years old). There were 16 men and 5 women. Thirteen patients had adenocarcinoma, 5 had squamous cell carcinoma, and 3 had others. The PD-L1 expression by 22C3 antibody was <1% in 7 patients, 1%-50% in 3 patients, >50% in 5 patients and not done in 6 patients, and the treatment lines of ICIs was first- to second-line in 8 patients and third-line or later in 13 patients. The response was partial response (PR) in 3 patients, stable disease (SD )in 10 patients, progressive disease (PD) in 6 patients and not evaluable in 2 patients. The median overall survival time from the initial administration of ICIs was 22.8 (2.0-80.1) months, while that from surgical resection was 63.7 (9.5-109.7) months.

      Conclusion

      The efficacy of administering ICIs after recurrence should be compared with that of AC with ICIs.

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      EP1.01-106 - A Special Case of Synchronous Multiple Primary Lung Cancer with Mediastinal Lymph Node Metastases of Unknown Primary Origin (Now Available) (ID 2101)

      08:00 - 18:00  |  Presenting Author(s): Kewei Ma  |  Author(s): Mengyao Sun, Yinghui Xu, Xu Wang, Chao Sun, Ye Guo, Shi Qiu

      • Abstract
      • Slides

      Background

      Coexisting lung cancers that are independent of each other and have either different or the same histology type are designated synchronous multiple primary lung cancer (sMPLC). The incidence of sMPLC is 0.2%-8% and has been increasing due to the recent development of early detection technology. Cancer of unknown primary site (CUP) accounts for 3%-5% of cancers, it rarely occurs in mediastinal lymph nodes and accounts for only 1.0−1.5% of all CUP cases.

      Method

      We presented a 61-year-old man with a history of smoking and old tuberculosis. The image data showed a large mass (2.4 cm*2.3 cm*2.0 cm) in the left lower lobe, and the 5th group of mediastinum lymph nodes was enlarged, suggesting peripheral lung cancer with lymph node metastasis. Multiple GGNs had been found in both lungs and the tuberculosis in the upper lobes of both lungs was identified. No other distant metastases were detected from other image data. Left lower lobe resection and lymph node dissection were performed on the patient.

      Result

      Intraoperative pathology revealed squamous cell carcinoma with no driver mutations in the left lower lobe. Adenocarcinoma harbouring the EGFR gene exon 18 mutation (G719A/G719C) was diagnosed in the mediastinum lymph node dissection. Multiple gene sequencing showed that there’s no relationship was between two primary sites. The hypothesis of the primary origin of the metastatic mediastinal lymph nodes is scar cancer from tuberculosis or multiple GGNs. Chemotherapy consisting of four cycles of gemcitabine plus cisplatin were prescribed for this patient after the operation. The current status of the patient was evaluated as stable disease (SD) with a PFS of more than 12 months.

      wclc.png

      Conclusion

      We found a sMPLC patient with different pathological types between the lung and lymph node lesions. Lung scar cancer or GGNs is highly suspected to be the origin of the metastatic mediastinal lymph node.

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      • Abstract
      • Slides

      Background

      The extent to which treatment response to immunotherapy translates into quality-adjusted survival time in NSCLC pts is worthwhile. We aimed to evaluate survival outcomes adjusted to quality of life (QoL) in NSCLC pts who are responders (Rs) and nonresponders (nRs) to nivolumab (Nivo) as 2+ line treatment within expanded access program and in a real-world practice.

      Method

      Adult pts with advanced platinum refractory NSCLC were enrolled in 11 centers in RF. All the pts received Nivo 3 mg/kg q2w. Tumor response was assessed using RECIST v. 1.1, adverse events (AEs) – NCI CTCAE v3.0. Pts with complete/partial response or disease stabilization (CR/PR or SD) at first tumor evaluation were considered as Rs, with progression or early death due to disease – as nRs. For QoL assessment pts filled out RAND SF-36 at different times during Nivo treatment. Overall survival (OS) and progressive-free survival (PFS) curves were evaluated by the Kaplan-Meyer method and compared by the log-rank test. Quality-adjusted outcomes in Rs and nRs were compared using Q-TWiST method. UTWiST and UREL were calculated on the basis of SF6D.

      Result

      Overall, 200 pts were included in the analysis: 65% – males; median age – 62 y.o.; ECOG 0-1 – 81%; former/current smokers – 70.5%; non squamous NSCLC – 64%; ≥2 lines of previous treatment – 53%. Median follow-up – 7.5 mos; 195 pts completed Nivo treatment at cut-off. Out of 200 pts response was not evaluated in 7 pts; among 193 pts 58% were categorized as Rs, 42% – nRs (the median evaluation time – 2.1 mos). Responder status was not significantly associated with demographics, smoking status, or baseline ECOG. Median duration of PR/SD in Rs – 4.4 mos (CI 95% 0.7-33.4). Median follow-up in nRs – 1.8 mos (CI 95% 0.26-4.21). As compared with nRs, Rs had longer median OS (18.7 vs 3.5 mos, p<0.001) and PFS (9.1 vs 1.8 mos, p<0.001) as well as longer TWiST (mean 12.5 vs 1.9 mos, 95%CI of difference 8.4–12.9). Mean Q-TWiST in Rs was 11.8 mos vs 4.8 mos in nRs with 7.0 mos gain. Relative Q-TWiST gain is 88%.

      Conclusion
      The results obtained in this observational study demonstrate acceptable treatment outcomes of Nivo in advanced refractory NSCLC pts. Response to Nivo treatment is significantly associated with better median PFS and OS and accompanied with better quality-adjusted survival outcomes in this difficult patient cohort. The Q-TWiST provides a comprehensive assessment of the benefit of response to immunotherapy into quality-adjusted survival in NCSLC pts.

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    EP1.02 - Advocacy (ID 289)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Advocacy
    • Presentations: 2
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.02-01 - Prospects of Cancer Patients and Patient Association from the Viewpoint of Live Survey at Participatory Symposium (Now Available) (ID 1746)

      08:00 - 18:00  |  Presenting Author(s): Toshiyuki Sawa  |  Author(s): Kazuko Hamanaka, Yoko Yamada, Yuki Yamamoto, Chizuko Sakashita

      • Abstract
      • Slides

      Background

      At the Japan Cancer Patient Meeting, which is held once a year in November 2018, a live Internet survey was conducted for the symposium "Let's talk together, patient strength". Based on the results, we discussed the status of
      support for cancer patients and the problems that cancer patients have.
      And as a patient groups, we put together requests to the government and the medical association.

      Method

      We conducted an online questionnaire using the survey-monkey system immediately before the symposium, targeting participants in the cancer patient association (including online viewers). While presenting the results of the questionnaire at
      the symposium, we exchanged opinions with the panelists and the participants,
      and summarized the contents of the request.

      Result

      The total number of responses was 257 people in total, including net and documents, including 85% of cancer patients and families. At the time of cancer diagnosis, 59.5% had someone to
      consult, and 16.6% of those who consulted cancer survivors showed the spread of
      peer support activities.
      On the other hand, 12..6% were not available for
      consultation.
      The information that helped to get over the cancer was in order of website, patient's association, and medical staff. 95.1% of the participants felt that they could receive
      support and livelihood from the words of the cancer experienced person.
      Conversely, 90% wanted to make use of their own cancer experiences. The requests for medical institutions were in the order of palliative care, collaboration with the patient association, and home care.

      Conclusion

      While the patient association activities play a role in making the most of "patient strength" through questionnaires and discussions, the place of activity, funding, and aging of the patient association officers were regarded as important issues in the future.

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      EP1.02-02 - The Path of a Survivor (Now Available) (ID 357)

      08:00 - 18:00  |  Presenting Author(s): Diane Mary Colton

      • Abstract
      • Slides

      Background

      Being diagnosed with lung cancer was both the worst and best day in my life. Dying was not on my agenda but then again I lived my life the way so many do. Without thought going through the motions of living. I truly started to live after my diagnosis. Funny when you think you have a finite amount of time you live differently. From deep down; at least in some of us comes a strength and determination be change and enact change in the world around us. I found that strength and the deep feeling that I could be the pebble to start the avalanche of change and acknowledgement that seems to be so lacking for lung cancer and those affected by it. Another patient who has a bigger battle then I would ever have put it aptly. We are the invisible cancer, masked behind stigma that is difficult to shake off, myths, misinformation; finally the lack of knowledge people have relating to lung cancer. This means most patients have two fronts to fight; the disease and the stigma. One saps the life out of a person, the other takes their self-respect leaving them having to defend themselves on being diagnosed with lung cancer. I on the other hand had a rather short fight with lung cancer which leaves me the ability and the wherewithal to speak up and bring the world of lung cancer out from behind the mask into the open through dialogue, events, sharing and hopefully supporting others who hqve to endure a much harder, longer battle.

      Each one of us personally and with organizations need to keep our eye on the end of the road. We are all working for the same outcomes. Each has their own way of doing, presenting the knowledge, sharing. What we should have is the support of each other. A united front; each working in their own manner to achieve results. Creating a safer environment for those diagnosed to speak and be seen without the censor of stigma. Those diagnosed with lung cancer and their caregiver families belong in the world, embraced and supported throughout their ordeal. Not feeling like they need to be hidden away.

      Every person deserves to be the best and live the best

      Method

      As an advocate and patient I continue to speak whenever opportunities present themselves. I have spearheaded and will continue to expand events bringing lung cancer to the forefront. The more it is in the public realm the easier it will be over time.

      Result

      Bringing lung cancer into the light; even if one person has a better understanding then we are achieving something.

      Conclusion

      not applicable

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    EP1.03 - Biology (ID 193)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Biology
    • Presentations: 35
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.03-01 - Molecular Spectrum of Patients with JAK1 Mutations in East Asian Non-Small Cell Lung Cancer (ID 188)

      08:00 - 18:00  |  Presenting Author(s): Chunwei Xu  |  Author(s): Xiuyi Yu, Wenxian Wang, Quxia Zhang, Wu Zhuang, Youcai Zhu, Yunjian Huang, Gang Chen, Meiyu Fang, Tangfeng Lv, Yong Song

      • Abstract

      Background

      JAK1 is a critical effector of pro-inflammatory cytokine signaling and plays important roles in immune function, while abnormal JAK1 activity has been linked to immunological and neoplastic diseases. The aim of this study is to investigate mutations and prognosis of non-small cell lung cancer (NSCLC) harboring JAK1 mutations.

      Method

      A total of 933 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of JAK1 mutations and other genes were detected by next generation sequencing.

      Result

      JAK1 gene mutation rate was 1.50% (14/933) in non-small cell lung cancer, including D660G (2 patients), Q499E (1 patient), L954P (1 patient), C16* (1 patient), R239W (1 patient), S295* (1 patient), I359T (1 patient), E791K (1 patient), Q207L (1 patient), R69H (1 patient), H434Y (1 patient), K218N (1 patient) and E662Q (1 patient), and median overall survival (OS) for these patients was 13.0 months. Among them, all patients were JAK1 gene with co-occurring mutations. Briefly, patients with (n=3) or without (n=10) co-occurring EGFR mutations had a median OS of 14.5 months and 13.0 months respectively (P=0.70); patients with (n=13) or without (n=1) co-occurring TP53 mutations had a median OS of 15.0 months and 13.0 months respectively (P=0.64); patients with (n=5) or without (n=8) co-occurring KRAS mutations had a median OS of 11.0 months and 15.0 months respectively (P=0.79); patients with (n=3) or without (n=11) co-occurring NF1 mutations had a median OS of 11.0 months and 20.0 months respectively (P=0.11).

      Conclusion

      Althoght EGFR, TP53, KRAS, NF1 gene accompanied may have less correlation with JAK1 mutation in NSCLC patients, predict which patients may harbor JAK1 mutations, could have implications in triaging toward JAK1 variant identification for potential future targeted therapy. These data have implications for the identification of therapeutic target candidates.

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      EP1.03-02 - Frequency of Microsatellite Instability in Patients with Primary Non Small Lung Cancer in a Single Institution from Colombia (Now Available) (ID 322)

      08:00 - 18:00  |  Presenting Author(s): Luis Eduardo Pino  |  Author(s): Maria Mercedes Mendoza, Gina Paola Saavedra, Juan Sebastian Lozano, Claudia Liliana Echevarria, Juan Pablo Pino, Felipe Canro, Marcela Botero

      • Abstract
      • Slides

      Background

      Lung carcinogenesis is a focus of research for prognosis and development of possible therapeutic objectives. The microsatellite instability (MSI) has been described as a potential mechanism of cancer development mainly in colorectal cancer as a marker of prognosis and treatment response. In lung cancer is not known the precise frequency of MSI and its possible implications for precision therapeutics. Past trials reported a low incidence of this biological signature, but this finding could improve some immune characterization of lung cancer focused in immunotherapeutics. Is very important to know the incidence of MSI in lung cancer in a sample of latin patients to know its indicence y relation with some clinical features.

      Method

      The present study is a case series were we describe microsatellite instability (MSI) in patients with primary non small cell lung cancer. First, the patients with non-small cell lung carcinomas of the Hospital Militar Central diagnosed between january 2010 and january 2016 were included, then the clinical charts of each patient were reviewed to identify clinical and socio-demographic variables. The immunohistochemical staining were realized in the paraffin blocks using the Ventana Benchmark Ultra and GX equipment allowing the identification of the mismatch repair proteins (MMRP) MLH1, PMS2, MSH2 y MSH6; defining microsatellite instability with the negativity for any of these markers. We reviewed other molecular biology signatures : EGFR mutation and KRAS in some cases were this finding could be avaliable. In Colombia there´s no health system coverage for this mutations.

      Result

      33 patients with non-small cell lung carcinoma were included in the study. Of this patients we can identify 69.7% with lung adenocarcinoma and 30.3% with squamous cell lung carcinoma. 54.5% of the total of patients were diagnosed in stage IV (TNM 7th edition). We identified a history of tobacco exposition in 45.5% of this patients. In the immunohistochemical staining, we identify that 9.1% of all the patients had microsatellite instability (MSI high); with negativity for the expression for MHL1 gene in 2 patients and for MSH6 gene in 3 patients, all of this patients were diagnosed with lung adenocarcinoma and all of this patients were EGFR wild type, in 1 of this patients we found a registry of KRAS mutated tumor. For the MHL1-negative patients, one of them had tobacco exposition history (heavy smoker) and for the MSH6-negative patients 2 of 3 had a tobacco exposition history. Unfortunately we didn´t found any of this patients treated with immunooncology agents.

      Conclusion

      In a small latin population at a single institution the present study found a frequency of 9.1% in 33 patients with non-small cell lung cancer with microsatellite instability (MSI-High). All of this patients were adenocarcinoma subtype, non related with EGFR mutations and with a correlation with tobacco exposure. Unfortunately this is a small case series and we could not establish a response to immunooncology agents because in Colombia we have this medications available since 2018. The frequency of this finding is higher than previous reports and must be confirmed in a multiinstitutional registry from latin population in development.

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      EP1.03-03 - Association Between Molecular Spectrum of EZH2 Variants and Prognosis in Patients with Non-Small-Cell Lung Cancer in Chinese Patients (ID 93)

      08:00 - 18:00  |  Presenting Author(s): Chunwei Xu  |  Author(s): Hong Wang, Wenxian Wang, Quxia Zhang, Wu Zhuang, Youcai Zhu, Zhangzhou Huang, Gang Chen, Meiyu Fang, Tangfeng Lv, Yong Song

      • Abstract

      Background

      Enhancer of zeste homolog 2 (EZH2) shows upregulated expression in tumors and is an important driver of tumor development and progression. However, the mechanism underlying the mediation of tumor aggressiveness in non-small-cell lung cancer (NSCLC) by EZH2 remains unclear. The aim of this study is to investigate mutations and prognosis of NSCLC harboring EZH2 mutations.

      Method

      A total of 1122 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of EZH2 mutations and other genes were detected by next generation sequencing.

      Result

      EZH2 gene mutation rate was 0.62% (7/1122) in non-small cell lung cancer, including K515R (1 patient), I55M (1 patient), D142H (1 patient), K222N (1 patient), Q66R (1 patient), P486S (1 patient), and S652C (1 patient), and median overall survival (OS) for these patients was 20.0 months. Among them, all patients were EZH2 gene with co-occurring mutations. Briefly, patients with (n=2) or without (n=5) co-occurring EGFR mutations had a median OS of 16.0 months and 20.0 months respectively (P=0.88); patients with (n=6) or without (n=1) co-occurring TP53 mutations had a median OS of not up to now and 20.0 months respectively (P=0.79); patients with (n=2) or without (n=5) co-occurring BRAF mutations had a median OS of 14.0 months and 20.0 months respectively (P=0.45); patients with (n=2) or without (n=5) co-occurring SMARCA4 mutations had a median OS of 20.0 months and not up to now respectively (P=0.88).

      Conclusion

      EZH2 mutation may predict a worse prognosis of NSCLC. Methyltransferase inhibitor may be beneficial for NSCLC patients with specific EZH2 mutations. EGFR, TP53, BRAF, SMARCA4 gene accompanied may have less correlation with EZH2 mutation in NSCLC patients. The findings of this study could facilitate both clinical trial design and therapeutic strategies.

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      EP1.03-04 - Analysis of Post-Surgical Systemic Inflammatory Indexes After Non-Small Cell Lung Cancer Surgical Intervention (ID 1135)

      08:00 - 18:00  |  Presenting Author(s): Lucia Milla Collado  |  Author(s): Carlos Alfredo Fraile Olivero, Mario Mecho Carratala, Carlos Cerdan Santacruz, Javier Trujillano Cabello, Amaia Ojanguren Arranz, Mario Montesinos, Carlos Rombolá

      • Abstract
      • Slides

      Background

      High NSCLC´s mortality rates pushes the research of new prognostic indexes further tan TNM staging and could help in better treatment´s selection. Neutrophil-Lymphocyte Ratio (NLR) preoperatively determined has demonstrated its relation with the immunologic status of the patient prior to the intervention and its capacity of “beating” tumor growing and its prognostic influence.

      OBJECTIVE: Evaluate the prognosis influence of NLR, Lymphocyte-Monocyte Ratio (LMR) and Platelet-Lymphocyte Ratio (PLR) in patients who underwent surgery for NSCLC with R0 resection and abscence of neoadjuvant treatment in peripheric blood determinations after surgery.

      Method

      A retrospective review of all consecutive patients operated on stage I to IIIA NSCLC from may 2014 – october 2018, completely resected and with no neoadjuvant treatment. Patients with previous oncologic history, haematologic neoplasms, perioperatory blood transfussion, perioperative infections or corticosteroids treatment were excluded. Peripheral blood determinations were taken during the first 6-months follow-up period.

      NLR, LMR and PLR were calculated.

      A descriptive analysis of demographic, tumor and surgical details is done.
      Overall survival (OS) was calculated since the date of surgery to date of death or last follow-up date. Disease-free survival (DFS) was calculated since the date of surgery to the date of recurrence. The discrimination capacity of the ratios was assessed with the calculation of the area under the ROC curve [AUC (CI 95%)].

      The relationship among relevant clinico-pathological variables, DFS and OS was calculated. Analysis of recurrence risk factors with univariate and multivariate binary logistic regression (LR) OR(95%CI) was performed.

      Result

      86 patients were included in the analysis. Median follow-up time was 45.7 months. Median OS and DFS were 27 and 24 months respectively. The AUC values of NLR [0.59(0,44-0,74)] and PLR [0,61(0,45-0,76] were not statistically significant, but value of LMR was significant with [0,70(0,57-0,83)].

      The LR model found as factors associated with a higher probability of recurrence adjusted by sex and age: the value of LMR with OR=0,38 (0,20-0,73) and a higher stage than the OR=11,3 (1,89-67.5).

      Conclusion

      Conversely to other publications, in our study the results showed the only relationship between LMR, tumor stage and risk of recurrence.

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      EP1.03-05 - A Meta-Analysis of Association Between Serum Iron Levels and Lung Cancer Risk (ID 94)

      08:00 - 18:00  |  Presenting Author(s): Chunwei Xu  |  Author(s): Huafei Chen, Lixin Wu, Xiaofeng Li, Youcai Zhu, Kaiqi Du, Wenxian Wang

      • Abstract

      Background

      Many studies conducted on the relationship between serum iron levels and lung cancer risk had produced inconsistent results. We therefore conducted a meta-analysis to determine whether serum iron levels were lower in lung cancer patients compared to those in controls.

      Method

      A literature survey was conducted by searching the PubMed, WanFang, CNKI, and SinoMed databases for articles published as of Mar 1, 2018. Standard mean differences (SMD) with the corresponding 95% confidence intervals (CI) were executed by Stata 12.0 software.

      Result

      A total of 13 publications involving 1118 lung cancer patients and 832 controls were included in our study. The combined results showed that serum iron levels in lung cancer cases had no significantly lower when compared to those in controls [summary SMD = -0.125, 95%CI= -0.439, 0.189, Z = 0.78, p for Z test= 0.435], with high heterogeneity (I2= 89.9%, P< 0.001) found. In the stratified analysis by geographic locations, consistent results were found for serum iron levels between lung cancer patients and controls both in Asian populations [summary SMD = -0.113, 95%CI= -0.471, 0.245] and European populations [summary SMD = -0.215, 95%CI= -0.835, 0.404].

      Conclusion

      Publication bias was not found when evaluated by Begg’s funnel plot and Egger’s regression asymmetry test.In summary, the current study showed that serum iron levels had no significant association on lung cancer risk.

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      EP1.03-06 - POLD1 Mutations Define a Unique Molecular Class of Non-Small Cell Lung Cancer in Chinese Patients (ID 198)

      08:00 - 18:00  |  Presenting Author(s): Chunwei Xu  |  Author(s): Wenxian Wang, Quxia Zhang, Wu Zhuang, Youcai Zhu, Yunjian Huang, Gang Chen, Meiyu Fang, Tangfeng Lv, Yong Song

      • Abstract

      Background

      Somatic POLE mutations have been found in a subset of non-small cell lung cancer (NSCLC) while POLD1 mutations are reportedly rare in NSCLC. The aim of this study is to investigate mutations and prognosis of NSCLC harboring POLD1 mutations.

      Method

      A total of 833 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of POLD1 mutations and other genes were detected by next generation sequencing.

      Result

      POLD1 gene mutation rate was 1.20% (10/833) in non-small cell lung cancer, including L357Rfs*36 (1 patient), R225H (1 patient), D76H (1 patient), I659M (1 patient), T582R (1 patient), A930T (1 patient), A749S (1 patient), G178V (1 patient), V455L (1 patient) and D102N (1 patient), and median overall survival (OS) for these patients was 13.0 months. Among them, all patients were POLD1 gene with co-occurring mutations. Briefly, patients with (n=4) or without (n=6) co-occurring EGFR mutations had a median OS of not up to now and 11.0 months respectively (P=0.11); patients with (n=8) or without (n=2) co-occurring TP53 mutations had a median OS of 13.0 months and 12.6 months respectively (P=0.80); patients with (n=2) or without (n=8) co-occurring NRAS mutations had a median OS of 15.0 months and 13.0 months respectively (P=0.61); patients with (n=3) or without (n=7) co-occurring PTPRD mutations had a median OS of not up to now and 13.0 months respectively (P=0.79).

      Conclusion

      POLD1 mutations represents an uncommon phenotype in NSCLC and may thus reprensent a candidate biomarker for response to immunotherapy in patients with NSCLC.

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      EP1.03-07 - Prevalence and Clinicopathological Characteristics of EIF1AX Mutations in Chinese Patients with Non-Small Cell Lung Cancer (ID 127)

      08:00 - 18:00  |  Presenting Author(s): Chunwei Xu  |  Author(s): Wenxian Wang, Quxia Zhang, Wu Zhuang, Youcai Zhu, Yunjian Huang, Gang Chen, Meiyu Fang, Tangfeng Lv, Yong Song

      • Abstract

      Background

      The EIF1AX gene was recently described as a new thyroid cancer-related gene. Its mutations were mainly reported in poorly differentiated (PDTC) and anaplastic thyroid cancers (ATC), but also in well-differentiated thyroid cancer (WDTC) and in benign thyroid lesions, although less frequently. The prevalence of these mutations in non-small-cell lung cancer (NSCLC) is unknown. The aim of this study is to investigate mutations and prognosis of NSCLC harboring EIF1AX mutations.

      Method

      A total of 923 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of EIF1AX mutations and other genes were detected by next generation sequencing.

      Result

      EIF1AX gene mutation rate was 1.30% (12/923) in non-small cell lung cancer, including D125N (1 patient), G6D (1 patient), R14G (1 patient), G15D (1 patient), W70C (1 patient), K3N (1 patient), G9D (1 patient), R13P (1 patient), R14S (1 patient), R57G (1 patient), G135E (1 patient), and P2L (1 patient), and median overall survival (OS) for these patients was 20.0 months. Among them, all patients were EIF1AX gene with co-occurring mutations. Among them, 11 patients with co-occurring mutations had a median OS of 20.0 months, and OS of one patient without complex mutations was 19.8 months. No statistically significant difference was found between the two groups (P=0.84). Briefly, patients with (n=2) or without (n=10) co-occurring TP53 mutations had a median OS of 14.0 months and 20.0 months respectively (P=0.87); patients with (n=2) or without (n=10) co-occurring STK11 mutations had a median OS of 4.0 months and 20.0 months respectively (P=0.02); patients with (n=3) or without (n=9) co-occurring NRAS mutations had a median OS of 4.0 months and 20.0 months respectively (P=0.17); patients with (n=3) or without (n=9) co-occurring KRAS mutations had a median OS of not up to now and 20.0 months respectively (P=0.88).

      Conclusion

      There is no significant difference of molecular features in EIF1AX gene mutations in NSCLC. Patients with complex mutations benefited more from therapy than those with single mutations. Next generation sequencing provides a simplified strategy and reasonably high detection rate for EIF1AX mutation, which suggested application of the strategies into clinical molecular diagnostics.

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      EP1.03-08 - MiR-744 Facilitates Non-Small Cell Lung Cancer Progression by Transcriptional Regulation of c-FOS (Now Available) (ID 1806)

      08:00 - 18:00  |  Presenting Author(s): Xiaoxia Zhu  |  Author(s): Shangbiao Li, Xiaotong Duan

      • Abstract
      • Slides

      Background

      Metastasis is the leading cause of lung cancer associated death. Here, we focused on the function and downstream molecular mechanism of miR-744 and its potential clinical application in non-small cell lung cancer (NSCLC) progression.

      Method

      The clinical cohort and data from TCGA were analyzed for the correlation of miR-744 and clinical outcomes. Multiple NSCLC cell lines and a NSCLC xenograft model were applied for the functional studies in vitro and in vivo respectively. Reporter assays were used for transcriptional regulatory mechanism study.

      Result

      It was confirmed that the overexpression of miR-744 was significantly correlated with lymph node metastasis and poor prognosis in NSCLC. It was an independent prognostic molecular marker for NSCLC. Both in vitro and in vivo studies revealed that miR-744 overexpression aggravated the invasion and metastasis of NSCLC cells. MiR-744 positively regulated c-FOS by directly binding to the promoter of c-FOS. We also identified -358 to -332 bp and -221 to -192 bp upstream of c-FOS gene as the direct and efficient miR-744 binding site in c-FOS promoter region. MicroRNA-744 could regulate MAPK signaling and enhanced the resistance of lung cancer cells to radiotherapy and paclitaxel.

      Conclusion

      Our findings uncover the function of miR-744 in NSCLC and reveal a novel mechanism of miR-744 in mediating growth and metastasis of NSCLC cells. Our data suggests that miR-744 may serve as a possible therapeutic target for NSCLC. Support: 81572279, 2016J004, LC2016PY016, 2018CR033.

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      EP1.03-09 - Epidemiological Study of TSC1 Mutations Among Non-Small Cell Lung Cancer Patients in China (ID 115)

      08:00 - 18:00  |  Presenting Author(s): Chunwei Xu  |  Author(s): Yong Fang, Wenxian Wang, Hongming Pan, Quxia Zhang, Wu Zhuang, Youcai Zhu, Zhangzhou Huang, Gang Chen, Meiyu Fang, Tangfeng Lv, Yong Song

      • Abstract

      Background

      The tuberous sclerosis complex 1 (TSC1) is an endogenous regulator of the mechanistic target of rapamycin (mTOR). While mTOR has been shown to play an important role in neoplasm. The aim of this study is to investigate mutations and prognosis of NSCLC harboring TSC1 mutations.

      Method

      A total of 1106 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of TSC1 mutations and other genes were detected by next generation sequencing.

      Result

      TSC1 gene mutation rate was 1.90% (21/1106) in non-small cell lung cancer, including Q654E (2 patients), R429K (2 patients), A1072D (1 patient), R850S (1 patient), E625K (1 patient), R715Q (1 patient), A84T (1 patient), S1038G (1 patient), M1090I (1 patient), D903H (1 patient), I143N (1 patient), Q3H (1 patient), L134F (1 patient), T1065M (1 patient), V407M (1 patient), S673F (1 patient), D675Y (1 patient), Q149H (1 patient) and T1144P plus L916M (1 patient), and median overall survival (OS) for these patients was 14.0 months. Among them, all patients were TSC1 gene with co-occurring mutations. Briefly, patients with (n=12) or without (n=9) co-occurring TP53 mutations had a median OS of 14.0 months and 15.0 months respectively (P=0.58); patients with (n=9) or without (n=12) co-occurring KRAS mutations had a median OS of not up to now and 14.0 months respectively (P=0.56); patients with (n=2) or without (n=19) co-occurring BRAF mutations had a median OS of 18.5 months and 12.0 months respectively (P=0.71); patients with (n=4) or without (n=17) co-occurring CDKN2A mutations had a median OS of 8.0 months and 18.0 months respectively (P=0.47).

      Conclusion

      Accompanied gene has not well been connected with TSC1 gene mutations. Our finding expands the mutant spectrum of TSC1 gene and adds new understanding of the phenotype.

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      EP1.03-10 - Expression of Anti-Aging Gene, Klotho Is a Surrogate Marker of Pemetrexed for Lung Cancer Treatment (Now Available) (ID 296)

      08:00 - 18:00  |  Presenting Author(s): Kyoshiro Takegahara  |  Author(s): Jitsuo Usuda

      • Abstract
      • Slides

      Background

      Adjuvant chemotherapy using cisplatin is recommended for patients with lung cancer p-stage IB-IIIA, who were received surgical resection completely. In order to improve the prognosis of the patients with lung cancers, we need to find a new predictive factor for anti-cancer agents and establish a new regimen for the adjuvant chemotherapy. We have previously reported that anti-aging gene Klotho expression was a prognostic factor for small cell lung cancer and LCNEC so far. Therefore, in this study, we investigate the association between the expression of Klotho and the sensitivity against anti-cancer agents, and we examined the anti-tumor tumor effect of Klotho expression.

      Method

      We established a cell line, A549/Klotho, which stably overexpress Klotho, and then examined the association between the expression of Klotho and Epithelial-Mesenchymal Transition related proteins such as N-cadherin, E-cadherin, Snail, Vimentin, etc. Next, we performed the sensitivity test for various anticancer agents including pemetrexed, CDDP, paclitaxel, gefitinib, etc, using A549 cells and A549/Klotho cells. Moreover, we evaluated the role of Klotho expression against anti-tumor effect.

      Result

      By western blot analysis, the expression of N-cadherin was completely inhibited in A549/Klotho cells, but in A549 cells. This result suggested that Klotho expression may regulate the expression of N-cadherin and Klotho can play an important role in cancer metastasis/invasion by regulating EMT. Moreover, we clarified that miR145 was related to the inhibition of N-cadherin in analysis of A549/Klotho cells but not miR218, miR67. A549/Klotho cells were more sensitive seven times against pemetrexed compared to A549 cells (IC50; 0.1 micro M) by MTT assay. There is no difference of sensitivity between A549/Klotho cells and A549 cells against molecular target drugs such as gefitinib, other kinds of TKI.

      Conclusion

      From these results, we conclude that overexpression of Klotho may regulate the sensitivity against pemetrexed through the inhibition of expression of mir145 and N-cadherin. In the future, we may establish a new strategy of chemotherapy for patients with advanced lung cancer based on the expression of anti-aging gene Klotho.

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      EP1.03-11 - Mechanisms of Gefitinib Plus Pemetrexed on Human Non-Small Cell Lung Cancer (Now Available) (ID 1402)

      08:00 - 18:00  |  Presenting Author(s): Yuqing Lou  |  Author(s): Jianlin Xu, Yanwei Zhang, Jun Lu, Xueyan Zhang, Huimin Wang, Wei Zhang, Baohui Han

      • Abstract
      • Slides

      Background

      Resistance to EGFR tyrosine kinase inhibitors (EGFR-TKI) is often acquired in non-small cell lung cancer (NSCLC) patients during treatment. We previously demonstrated that combined treatment with EGFR-TKI gefitinib plus chemotherapy improved progression-free survival (PFS) in NSCLC patients carrying sensitive EGFR mutations.

      Method

      Pharmacological interaction between gefitinib and pemetrexed was evaluated in NSCLC cell line PC-9 using MTT assay. The influence of combined treatment with gefitinib plus pemetrexed on gene expression profiles and signaling pathways has been investigated using microarray and Ingenuity Pathway Analysis (IPA).

      Result

      Synergistic inhibitory effect between gefitinib and pemetrexed was observed in NSCLC cell line PC-9. Figure 1A suggested representative proliferation inhibitory effects of gefitinib, pemetrexed and combined treatment for 48 hours. Figure 1B showed CI values of concurrent gefitinib-pemetrexed treatment in PC-9 NSCLC cell line. CI values at ED50, ED75 and ED90 were shown.

      Furthermore, widespread gene expression changes and critical signaling pathways were induced significantly by combined treatment in PC-9 cells. Figure 2A was heatmap of gene expression prolifes in human NSCLC PC-9 cell line treated with gefitinib (blue), pemetrexed (purple) or gefitinib-pemetrexed combination (orange) with the criteria P<0.05 and ▏fold change ▏>1.5. Genes and samples were listed in rows and columns, respectively. A colour standard for data normalization was shown at the bottom with green representing downregulated genes while red representing upregulated genes. In Figure 2B, pathway enrichment of differential expressed genes was analysed using Ingenuity Pathway Analysis (IPA). Signaling pathways shown here were based on a P<0.0001. Figure 2C showed heatmap of critical pathways affected by combined treatment as compared to gefitinib single treatment. Heatmap colour represented the Z-score of signalling pathways. Z-score>0 meant the signalling pathway was stimulated by related treatment while Z-score<0 meant the signalling pathway was inhibited by related treatment.

      figure 1.jpg

      figure 2.jpg

      Conclusion

      Gene expression profiles revealed potential signaling pathways contributing to the synergism.

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      EP1.03-12 - IL-10 Promotes Tumor Aggressiveness in Non-Small Cell Lung Cancer via Down-Regulated the Expression Level of miR-125b (Now Available) (ID 1776)

      08:00 - 18:00  |  Presenting Author(s): Yanwei Zhang  |  Author(s): Baohui Han

      • Abstract
      • Slides

      Background

      IL-10 is an anti-inflammatory factor with bi-directional regulation of tumor immunity. While, the role and mechanism of IL-10 in lung cancer is not clear. The aim of the present study was to identify the potential mechanisms of IL-10 in lung carcinogenesis.

      Method

      RT-PCR was used to detect the expression of miRNAs and mRNAs. CKK8 and flow cytometry assays was performed for the function experiments. Microarray analysis and IPA analysis were used to predict the potential signal pathway.

      Result

      IL-10 was found significantly associated with the risk of non-small cell lung cancer (NSCLC). Meanwhile, the expression level of miR-125b in NSCLC cell line was dramatically decreased when stimulated by IL-10. The results of cell function experiments showed that miR-125b inhibited the tumor promoting effects of IL-10 in NSCLC. Then, microarray and IPA analysis found that IGF-1 signaling pathway was significantly activated after down-regulated the expression of miR-125b.2.jpg

      Conclusion

      IL-10 promotes tumor aggressiveness via down-regulated the expression level of miR-125b in lung cancer.

      3.jpg

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      EP1.03-13 - Molecular Characteristics of East Asian Patients with VHL-Mutated Non-Small-Cell Lung Cancer: A Retrospective Study (ID 113)

      08:00 - 18:00  |  Presenting Author(s): Chunwei Xu  |  Author(s): Jinluan Li, Wenxian Wang, Quxia Zhang, Wu Zhuang, Youcai Zhu, Zhangzhou Huang, Gang Chen, Meiyu Fang, Tangfeng Lv, Yong Song

      • Abstract

      Background

      The von Hippel-Lindau (VHL) gene is inactivated frequently in sporadic clear-cell renal cell carcinomas (ccRCCs) by genetic alteration. However, the pathological or prognostic significance of VHL gene alteration has not been well defined in the other cancers, especially non-small cell lung cancer (NSCLC). The aim of this study is to investigate mutations and prognosis of NSCLC harboring VHL mutations.

      Method

      A total of 972 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of VHL mutations and other genes were detected by next generation sequencing.

      Result

      VHL gene mutation rate was 0.72% (7/972) in non-small cell lung cancer, including W117fs*15 (1 patient), G44A (1 patient), G44V (1 patient), P81S (1 patient), R120T (1 patient), E51K (1 patient) and T100A (1 patient), and median overall survival (OS) for these patients was 22.0 months. Among them, all patients were VHL gene with co-occurring mutations. Briefly, patients with (n=2) or without (n=5) co-occurring EGFR mutations had a median OS of 22.0months and 12.0 months respectively (P=0.16); patients with (n=3) or without (n=4) co-occurring TP53 mutations had a median OS of not up to now and 12.0 months respectively (P=0.23); patients with (n=3) or without (n=4) co-occurring KRAS mutations had a median OS of 3.0 months and 22.0 months respectively (P=0.07); patients with (n=2) or without (n=5) co-occurring SETD2 mutations had a median OS of 3.0 months and 22.0 months respectively (P=0.01).

      Conclusion

      The present study expanded the database on VHL gene mutations in NSCLC and enriched the spectrum of known somatic mutations of the VHL gene. Chemotherapy may be considered as a possible treatment for carriers of the mutation. SETD2 mutated accompanied mutations might play a poor prognosis in VHL gene mutation NSCLC.

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      EP1.03-14 - Clinicopathologic Characteristics and Outcomes of Chinese Patients with Non-Small-Cell Lung Cancer and INPP4B Mutations (ID 109)

      08:00 - 18:00  |  Presenting Author(s): Chunwei Xu  |  Author(s): Dongyong Yang, Wenxian Wang, Quxia Zhang, Wu Zhuang, Youcai Zhu, Zhangzhou Huang, Gang Chen, Meiyu Fang, Tangfeng Lv, Yong Song

      • Abstract

      Background

      Inositol polyphosphate 4-phosphatase B (INPP4B) has been identified as a tumour suppressor in different human cancers. However, the role of INPP4B in the angiogenesis of human non-small cell lung cancer (NSCLC) remains unclear. The aim of this study is to investigate mutations and prognosis of NSCLC harboring INPP4B mutations.

      Method

      A total of 750 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of INPP4B mutations and other genes were detected by next generation sequencing.

      Result

      INPP4B gene mutation rate was 2.80% (21/750) in non-small cell lung cancer, including p.R623K (2 patients), p.N378S (1 patient), p.G187W (1 patient), p.V117I (1 patient), c.1721-1G>T (1 patient), p.R818* (1 patient), p.T829R (1 patient), p.Q753H (1 patient), p.L542M (1 patient), p.I68M (1 patient), p.Q814E (1 patient), p.K448N (1 patient), p.C617F (1 patient), p.Q600H (1 patient), p.G479* (1 patient), p.L155Q (1 patient), p.P572A (1 patient), p.L16V (1 patient), p.F652Y (1 patient), and p.T671S plus p.N228K (1 patient), and median overall survival (OS) for these patients was 15.0 months. Among them, all patients were INPP4B gene with co-occurring mutations. Briefly, patients with (n=2) or without (n=19) co-occurring EGFR mutations had a median OS of 20.0 months and 5.5 months respectively (P=0.01); patients with (n=17) or without (n=4) co-occurring TP53 mutations had a median OS of 15.0 months and 14.4 months respectively (P=0.68); patients with (n=7) or without (n=14) co-occurring PTPRD mutations had a median OS of not up to now and 15.0 months respectively (P=0.48); patients with (n=8) or without (n=13) co-occurring KRAS mutations had a median OS of 17.0 months and 15.0 months respectively (P=0.68).

      Conclusion

      INPP4B mutations were observed in 2.80 % of cases of NSCLC. INPP4B-mutated NSCLC can exhibit other driver gene alterations. No clinical characteristics were significantly associated with INPP4B mutation.

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      EP1.03-15 - Comparison of Plasma Expression of Drosha and Dicer mRNAs in Early and Advanced Stages of NSCLC Patients (Now Available) (ID 628)

      08:00 - 18:00  |  Presenting Author(s): Paweł Krawczyk  |  Author(s): Anna Grenda, Michał Szczyrek, Barbara Kuźnar-Kamińska, Grażyna Balicka, Monika Jakimiec, Halina Batura-Gabryel, Marek Sawicki, Janusz Milanowski

      • Abstract
      • Slides

      Background

      Drosha and Dicer are the enzymes necessary during the miRNA biogenesis. They have the same effect on all microRNAs. Many studies have focused on profiling the expression of selected miRNAs or whole miRNom’s analysis in serum or plasma, as potential tool for early detection of diseases. We would like to check, whether the expression of Drosha and Dicer mRNA is detectable in plasma of NSCLC patients, and whether it can differentiate early and advanced stages of this disease.

      Method

      We enrolled 59 (43.1%) NSCLC patients in early (I-IIIA) stages and 78 (56.9%) in locally advanced or advanced (IIIB-IV) stages. We isolated total mRNA and reverse transcription PCR (RT-PCR) was performed. RT-PCR was made using High-Capacity cDNA Reverse Transcription Kit (Applied Biosystems). Real-time PCR (qPCR) was performed for assessment of Drosha and Dicer mRNA expression on Eco Illumina Real-Time PCR system device (Illumina Inc.). We used TaqMan probe Hs00203008_m1 (Applied Biosystems) for Drosha and Hs00229023_ m1 (Applied Biosystems) for Dicer mRNA expression measurement. GAPDH was used a housekeeping gene. Statistical analysis were performed with use of Statistica 13.1 software (Tibco).

      Result

      Drosha mRNA expression was detectable in plasma of 57 (41.6%) patients. 17 (28.8%) patients with Drosha mRNA expression were in early stages and 40 (51.3%) patients were in stages IIIB or IV (χ2=6.98, p=0.008).

      Expression of Dicer mRNA was detectable in plasma of 71 (57.8%) patients. 15 (25.4%) of patients from this group were in early stages and 56 (71.8%) – in IIIB or IV stages (χ2=28.93, p<0.0001).

      Significant higher expression of Drosha mRNA was observed in group of patients with lymph node involvement compared with group of patients without lymph node metastases (p=0.001).

      Moreover, significantly higher expression of Dicer mRNA was observed in group of patients with distant metastases compared with group without metastases (p=0.0002).

      Furthermore, we found statistically nonsignificant (p=0.07) lower expression of Drosha mRNA in stages IIIB-IV compared with early stages.

      We did not find any differences between Drosha or Dicer mRNAs expression in patients stratified by age, tumor size or histopathological diagnosis (p<0.1).

      Conclusion

      Plasma expression of Drosha and Dicer mRNAs is detected more often in advanced stages of NSCLC. Probably, different mRNAs from more damaged tumor cells in more advanced disease stages are present in higher expression in blood stream. However, this proves that free mRNAs of Drosha and Dicer are mainly produced by cancer cells in NSCLC patients. indirectly, it can be concluded that cancer cells have disturbed production of microRNAs. There are necessity to use more sensitive tools (i.e. Next Generation Sequencing method) to asses expression of Dicer and Drosha mRNAs in early stages of NSCLC.

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      EP1.03-16 - Lysimachia Capillipes Capilliposide C Restores Radiation Sensitivity in Radiation Resistant Lung Cancer Cells by Enhancing ERRFI1 Expression (ID 810)

      08:00 - 18:00  |  Presenting Author(s): Kan Wu  |  Author(s): Bing Wang, Yasi Xu, Jianguo Feng, Lucheng Zhu, Xueqin Chen, Bing Xia, Shirong Zhang, Xufeng Chen, Shenglin Ma

      • Abstract
      • Slides

      Background

      Radiation therapy is used as the primary treatment for lung cancer. Unfortunately, radiation resistance and local failure remain to be the major clinic problems for lung cancer patients. It is therefore crucial to find new therapeutic targets and/or drugs to enhance the effects of radiation without increasing the adverse effects. Lysimachia capillipes capilliposide C (LC-C) extracts from LC Hemsl. show anti-cancer effects both in vitro and in vivo. The purpose of this study is to investigate a potential therapeutic impact of LC-C as a radiation sensitizer in lung cancer cells.

      Method

      Non small cell lung cancer (NSCLC) cell line A549 was initially irradiated with a total dose of 60 Gy (3 Gy/Fx, 20 Fx, 2-3 Fx/week) to generate radiation-resistant cancer cell line A549-IR. RNA-seq analysis was used to examine the whole-transcriptome alteration in A549-IR cells treated with or without LC-C, and the differentially expressed genes with most significance were verified by RT-qPCR. Colony formation assays were performed to determine the effect of the target gene ErbB receptor feedback inhibitor 1 ( ERRFI1) on radiosensitivity of A549-IR cells. In addition, effects of ERRFI1 on cell cycle distribution, DNA damage repair activity were assessed by flow cytometry and γ-H2AX immunofluorescence staining respectively. Western blot was performed to identify the activation of related signaling pathways. Tumor xenograft experiments were conducted to observe the effect of LC-C and ERRFI1 on radiosensitivity of A549-IR cells in vivo.

      Result

      ERRFI1 was significantly up-regulated in A549-IR cells when cells were treated with LC-C (IC20=3.5 μM). With irradiation treatment, clonogenic formation decreased in the ERRFI1 overexpressed cells when comparing to the parental cells, with reduced survival fraction-2 value from 0.54±0.07 to 0.24±0.06 (p<0.01). The sensitizing enhancement ratio for LC-C was 1.667. Furthermore, ERRFI1 overexpression may enhance radiosensitivity of A549-IR cells in vitro by inducing G2/M phase arrest and inhibiting DNA damage repair. Overexpression of the ERRF11 decreased the activation of EGFR and STAT3 signaling pathways in A549-IR cells. Knocking down ERRFI1 expression in A549-IR cells attenuated the radiosensitization effect of LC-C. Moreover, in a A549-IR cells-derived xenograft model, combination treatment with LC-C (25 mg·kg−1·d−1, qod, ig) and irradiation (6Gy) dramatically enhanced tumor growth suppression comparing with LC-C or radiation alone.

      Conclusion

      LC-C can restore the cells' sensitivity to irradiation through regulation of ERRFI1 expression in lung cancer cells. Combination treatment of LC-C and irradiation may serve as a promising therapeutic strategy to overcome the radiation resistance and ERRFI1 may be a poteintal therapeutic target to improve radiosensitivity in NSCLCs.

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      EP1.03-17 - Outcomes of Molecular Characteristics in Chinese BAP1-Mutant Non-Small Cell Lung Cancer Patients (ID 140)

      08:00 - 18:00  |  Presenting Author(s): Chunwei Xu  |  Author(s): Honggang Ke, Wenxian Wang, Quxia Zhang, Wu Zhuang, Youcai Zhu, Yunjian Huang, Gang Chen, Meiyu Fang, Tangfeng Lv, Yong Song

      • Abstract

      Background

      BRCA1-Associated-Protein 1 (BAP1) is a dynamic tumor suppressor which, when mutated, has been associated with an increased risk of uveal melanoma, cutaneous melanoma, mesothelioma, and several other cancers. There is some clinical evidence for the use of BAP1 mutations as prognostic and predictive biomarker. The aim of this study is to investigate mutations and prognosis of non-small-cell lung cancer (NSCLC) harboring BAP1 mutations.

      Method

      A total of 851 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of BAP1 mutations and other genes were detected by next generation sequencing.

      Result

      BAP1 gene mutation rate was 1.88% (16/851) in non-small cell lung cancer, including H94Y (1 patient), T177P (1 patient), E198Gfs*45 (1 patient), R238K (1 patient), D34Y (1 patient), Y173C (1 patient), E450K (1 patient), G41C (1 patient), S325F (1 patient), P293L (1 patient), Q28* (1 patient), E498K (1 patient), E631Q (1 patient), H144D (1 patient), Q280* (1 patient), (1 patient) and R518L (1 patient), and median overall survival (OS) for these patients was 24.0 months. Among them, all patients were BAP1 gene with co-occurring mutations. Briefly, patients with (n=4) or without (n=12) co-occurring EGFR mutations had a median OS of 14.5 months and not up to now respectively (P=0.35); patients with (n=9) or without (n=7) co-occurring TP53 mutations had a median OS of not up to now and 24.0 months respectively (P=0.79); patients with (n=3) or without (n=13) co-occurring CDKN2A mutations had a median OS of 24.0 months and not up to now respectively (P=0.57); patients with (n=4) or without (n=12) co-occurring KEAP1 mutations had a median OS of 5.0 months and 24.0 months respectively (P=0.07).

      Conclusion

      BAP1 genetic alter occurs in a subset of NSCLC, and improved understanding of the implications of BAP1 aberrations is critical for the identification of therapeutic target candidates.

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      EP1.03-18 - Analysis of IDH1 Mutation Spectrum from Non-Small-Cell Lung Cancer in East Asian Patients (ID 95)

      08:00 - 18:00  |  Presenting Author(s): Chunwei Xu  |  Author(s): Liping Wang, Wenxian Wang, Quxia Zhang, Wu Zhuang, Youcai Zhu, Zhangzhou Huang, Gang Chen, Meiyu Fang, Tangfeng Lv, Yong Song

      • Abstract

      Background

      Isocitrate dehydrogenase 1 (IDH1) is a metabolic enzyme that converts isocitrate to alpha-ketoglutarate. IDH1 mutations are associated with the accumulation of the oncometabolite D-2-hydroxyglutarate, which acts as an epigenetic modifier, and the development of multiple malignancies. Previous studies uncovered mutations in IDH1 in several malignancies, with the most frequent mutation being IDH1 R132H. It has been demonstrated that IDH1 expression is induced in non-small-cell lung cancer (NSCLC). The aim of this study is to investigate mutations and prognosis of NSCLC harboring IDH1 mutations.

      Method

      A total of 893 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of IDH1 mutations and other genes were detected by next generation sequencing.

      Result

      IDH1 gene mutation rate was 1.23% (11/893) in non-small cell lung cancer, including Q138S (1 patient), D79V (1 patient), T373N (1 patient), C114* (1 patient), W336L (1 patient), I99M (1 patient), G104R (1 patient), R132C (1 patient), A193S (1 patient), Y34C (1 patient) and H67R (1 patient), and median overall survival (OS) for these patients was 11.0 months. Among them, all patients were IDH1 gene with co-occurring mutations. Briefly, patients with (n=9) or without (n=2) co-occurring TP53 mutations had a median OS of not up to now months and 8.5 months respectively (P=0.32); patients with (n=2) or without (n=9) co-occurring KMT2D mutations had a median OS of 11.5 months and 11.0 months respectively (P=0.80); patients with (n=5) or without (n=6) co-occurring KRAS mutations had a median OS of not up to now months and 8.0 months respectively (P=0.22); patients with (n=2) or without (n=9) co-occurring CREBBP mutations had a median OS of 15.5 months and 8.0 months respectively (P=0.67).

      Conclusion

      Our results demonstrated that decreased IDH1 gene mutation correlated with poor overall survival in NSCLC patients. IDH1 gene mutation may define a subset of patients with lung cancer appropriate for investigational therapeutic strategies.

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      EP1.03-19 - The Frequency and Prognosis of MDM2 Mutations in East Asian Non-Small-Cell Lung Cancer Patients (ID 107)

      08:00 - 18:00  |  Presenting Author(s): Chunwei Xu  |  Author(s): Bing Wan, Wenxian Wang, Xiuwei Zhang, Quxia Zhang, Wu Zhuang, Youcai Zhu, Zhangzhou Huang, Gang Chen, Meiyu Fang, Tangfeng Lv, Yong Song

      • Abstract

      Background

      In neoplasm, the mouse double minute 2 (MDM2) is an oncoprotein that contributes to the promotion of cell growth, survival, invasion, and therapeutic resistance. The aim of this study is to investigate mutations and prognosis of non-small cell lung cancer (NSCLC) harboring MDM2 mutations.

      Method

      A total of 1152 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of MDM2 mutations and other genes were detected by next generation sequencing.

      Result

      MDM2 gene mutation rate was 0.52% (6/1152) in non-small cell lung cancer, including D179N (1 patient), S84L (1 patient), T195M (1 patient), V234L (1 patient), A471S (1 patient) and E184Q (1 patient), and median overall survival (OS) for these patients was 24.0 months. Among them, all patients were MDM2 gene with co-occurring mutations. Briefly, patients with (n=2) or without (n=4) co-occurring EGFR mutations had a median OS of 18.5 months and 24.0 months respectively (P=0.89); patients with (n=4) or without (n=2) co-occurring TP53 mutations had a median OS of 24.0 months and 7.0 months respectively (P=0.05); patients with (n=2) or without (n=4) co-occurring BRCA1 mutations had a median OS of 24.0 months and 13.0 months respectively (P=0.20); patients with (n=2) or without (n=4) co-occurring KEAP1 mutations had a median OS of 15.5 months and 24.0 months respectively (P=0.59).

      Conclusion

      MDM2 mutations represent a distinct subset of NSCLC. Next generation sequencing showed that MDM2 mutations commonly co-existed with other driver genes. Our results show that MDM2 mutations delineate an aggressive subtype of lung cancer for which a targeted treatment through MDM2 inhibition might offer new opportunities.

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      EP1.03-20 - Diagnostic and Prognostic Utility of Differentially Expressed Circulating MicroRNAs in Indian NSCLC Patients (Now Available) (ID 875)

      08:00 - 18:00  |  Presenting Author(s): Sachin Kumar  |  Author(s): Surender Kumar Sharawat, Ashraf Ali, Prabhat Singh Malik, Anant Mohan, Randeep Guleria

      • Abstract
      • Slides

      Background

      The presence of circulating tumour DNA, mRNA and non-coding RNAs, such as microRNA (miRNA), in the serum and plasma of cancer patients has sparked great interest because conventional diagnostic tests tend to be imperfect and more invasive, posing logistic difficulties for serial tumour sampling. Hence, identification of differentially expressed circulating miRNAs in the serum of non-small cell lung cancer (NSCLC) patients may have potential as cancer biomarkers for diagnosis, prognosis and predicting therapeutic response.

      Method

      For the identification of differentially expressed miRNAs in the serum of NSCLC patients, we performed small RNA sequencing with illumina HiSeq 2000 platform (n=10; 4 NSCLC patients and 6 controls). The expression profile of miRNAs in each subject was analyzed using miRNAkey software and fold change was performed to identify differentially expressed miRNAs in NSCLC as compared to controls. We validated the expression of few differentially expressed miRNAs in the serum of 75 NSCLC patients and 40 controls using miScript qRT-PCR assay. The expression of miRNAs was correlated with overall survival (OS), progression-free survival (PFS), response to therapy and various clinico-pathological parameters.

      Result

      The mean age of NSCLC patients and controls was 56.2 years and 55.3 years, respectively (p = 0.3242). Majority of the NSCLC patient and controls were male. 67% of NSCLC patients and 53% of controls were smokers (p = 0.099). Global miRNA profiling revealed 16 differentially expressed miRNAs (cut-off: fold change > 2.0, or p < 0.05, or both) in the serum of NSCLC patients as compared to controls. Our qRT-PCR data revealed significant down-regulation of miR-15a-5p, miR-320a, miR-25-3p, miR-192-5p, let-7d-5p, let-7e-5p, miR-148a-3p and miR-92a-3p in the serum of NSCLC patients as compared to controls. None of the miRNAs were correlated with survival outcome and therapeutic response. The expression of miR-320a, miR-25-3p and miR-148a-3p significantly correlated with stage, while miR-375 expression significantly correlated with lymph node involvement and pleural effusion.

      Conclusion

      The expression of majority of miRNAs was down-regulated in the serum of NSCLC patients as compared to controls. Some of the miRNAs, such as miR-375 and miR-320a, are less studied for their involvement in the pathogenesis of NSCLC. Hence, future mechanistic studies are warranted to elucidate their role in disease biology and as candidate biomarkers for diagnosis and prognosis of NSCLC.

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      EP1.03-21 - Circulating Tumor Cells Isolation Is Not a Useful Prognostic Tool for Non-Small Cell Lung Cancer Patients Candidates to Surgical Treatment (ID 1271)

      08:00 - 18:00  |  Presenting Author(s): Lucia Milla Collado  |  Author(s): Carlos Alfredo Fraile Olivero, Carlos Cerdan Santacruz, Teresa Valverde Higueras, Isabel Cal Vazquez, José Ramón Jarabo Sarceda, Elena Fernández Martín, Jose Luis Gonzalez Larriba, Florentino Hernando-Trancho

      • Abstract
      • Slides

      Background

      It is well known that prognostic stratification according to TNM classification of non-small cell lung cancer (NSCLC) patients is somehow imprecise as there exist notable differences among patients endorsed in the same staging. Because of this it is mandatory to find complementary tools to reach a more accurate classification in order to the best selection of treatments for every patient. The presence of circulating tumor cells (CTC) in periferic blood samples has showed worse prognosis in other primary tumors. The aim of this study is analyzing the impact of CTC on disease free survival (DFS) and overall survival (OS).

      Method

      Periferic blood samples from 28 patients diagnosed with NSCLC in early stages candidates for surgical treatment were obtained. Study period was from June 2011 to October 2013. Blood samples were obtained at least at three different moments: before surgery (S1), one year after the operation (S2) and the last one 2 years after the operation (S3). Blood samples were analyzed by CellSearch method.

      Probability of survival was calculated following the Kaplan-Meier method; differences in survival were examined by the Long-Rank test.

      Result

      Median OS was 34 months and DFS was 11 months. There was no statistically significant differences among patients with or without CTC in S1, S2 and/or S3. When CTC were present, no relationship was observed between the variations in the number of CTCs among the different blood samples and the OS and DFS.

      Conclusion

      In our study, the presence of CTCs in any of the blood samples obtained during the follow-up showed no relationship with OS and DFS. The same results were observed in relation to variations of CTCs' count.

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      EP1.03-22 - Prognostic Value of Serum Inflammation Biomarkers in Early Stage Lung Adenocarcinoma (Now Available) (ID 1753)

      08:00 - 18:00  |  Presenting Author(s): Yanwei Zhang  |  Author(s): Minjuan Hu, Baohui Han

      • Abstract
      • Slides

      Background

      Non-small cell lung cancer is the main cause of cancer-related death worldwide, with a low 5-year survival rate even in early-stage. And adenocarcinoma accounts for the majority of all Non-small cell lung cancer cases. Biomarkers to identify prognosis of early stage lung cancer are needed. Increasing evidences indicate a relationship between inflammation and lung carcinogenesis. One of our previous studies found inflammation biomarkers, BLC and MDC, are significantly related with the risk of early stage lung cancer. The present study was performed to evaluated the value of inflammation biomarker in predicting the prognosis of early stage lung adenocarcinoma.

      Method

      Ten inflammation biomarkers were tested by Luminex bead-based assay in 157 patients with resected early-stage lung adenocarcinoma (IA-IIB) from whom serum samples were collected pre-surgery.

      Result

      A total of 152 early stage lung adenocarcinoma patients were analyzed in this study. The mean age (SD) of was 59.9 (9.4) years. 58.6% of them were females, and never smokers accounted for 84.0%. By TNM stage, 109 (71.7%) patients were at stage I and 43 (28.3%) at stage II. The median follow-up time was 60.6 months. Patients with higher MIG levels were at a 70% reduced risk of recurrence compared with patients with lower MIG levels (HR=0.3, 95% CI: 0.1–0.7, p=0.0035). As for BLC, patients with higher levels had the risk of recurrence decreased by 50% (HR=0.5, 95% CI: 0.3–0.9, p=0.031) compared with patients with lower levels. After the Bonferroni correction, only MIG was significantly associated with the recurrence risk of early stage lung adenocarcinoma. For overall survival (OS), patients with higher MIG levels were still have a reduced dead risk compared with the lower group (p=0.0065).

      Conclusion

      Our results demonstrate for the first time that pretreatment MIG level was identified as a protective factor for the prognosis of early stage lung adenocarcinoma.

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      EP1.03-23 - Update of the Analysis of the Status of Lymphocyte Infiltration in Patients with NSCLC (Now Available) (ID 1858)

      08:00 - 18:00  |  Presenting Author(s): Eduardo Richardet  |  Author(s): Patricia Hernandez, Martin Paradelo, Luciana Paola Acosta, Matias Molina, Aldo Riso, Gimena Ferreira, Martin Richardet

      • Abstract
      • Slides

      Background

      Current evidence highlights the potential role of tumor-infiltrating lymphocytes (TILS) as a prognostic factor in many types of tumors; in non-small cell lung cancer (NSCLC), this relationship is not well determined. TILs are being studied with different methods such as immunohistochemistry and optical microscopy. The primary endpoint is to identify TILS in patients with NSCLC, classified as present or absent, and its relation to progression free survival (PFS).

      Method

      Retrospective and analytical case study of Instituto Oncológico de Córdoba. 187 patients with stage IIIB and IV NSCLC were analyzed. TILS are descriptively classified as present or absent. Survival curves were calculated using the Kaplan-Meier method.

      Result

      63% of patients had adenocarcinoma and 37% squamous cell carcinoma. 72% were men. 82% were smokers. 65% of patients with squamous histology and % 58 with adenocarcinoma, showed TILS. Patients with adenocarcinoma with TILS present had higher PFS 13.3 months, compared to patients with absent, 8.8 months. These differences were statistically significant (PFS: p=0.004). The patients with squamous cell carcinoma with TILS had 10.8 months PFS. Those who had infiltrated absent had a PFS of 5.6 months. These differences were also statistically significant (PFS: 0.001).

      Conclusion

      Our study shows that patients whose pathological samples presented inflammatory infiltrate had higher PFS. The presence of TILS could be used as an important prognostic factor in this patient population.

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      EP1.03-24 - Clinicopathologic Characteristics and Survival Outcome in Chinese Patients with Non-Small Cell Lung Cancer and HGF Mutations (ID 137)

      08:00 - 18:00  |  Presenting Author(s): Chunwei Xu  |  Author(s): Wenxian Wang, Quxia Zhang, Wu Zhuang, Youcai Zhu, Yunjian Huang, Gang Chen, Meiyu Fang, Tangfeng Lv, Yong Song

      • Abstract

      Background

      Hepatocyte growth factor (HGF) is the ligand for the tyrosine kinase receptor MET (Mesenchymal Epithelial Transition Factor also known as Hepatocyte Growth Factor Receptor, HGFR). HGF and its receptor, MET, play critical roles in cell proliferation, angiogenesis and invasion in a wide variety of cancers, especially non-small cell lung caner (NSCLC). The aim of this study is to investigate mutations and prognosis of NSCLC harboring HGF mutations.

      Method

      A total of 526 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of HGF mutations and other genes were detected by next generation sequencing.

      Result

      HGF gene mutation rate was 4.56% (24/526) in non-small cell lung cancer, including E437K (1 patient) , L677I (1 patient), S386L (1 patient), R242Q (1 patient), H717N (1 patient), G520R (1 patient), R234H (1 patient), A713G (1 patient), P703S (1 patient), D264N (1 patient), N127K (1 patient), G506E (1 patient), C84* (1 patient), R647Q (1 patient), G133V (1 patient), D257N (1 patient), S386L (1 patient), S166R (1 patient), P27H (1 patient), C612* (1 patient), W528L (1 patient), G133V (1 patient), G694Wfs*31 (1 patient), and T143S plus G146A (1 patient), and median overall survival (OS) for these patients was 20.0 months. Among them, all patients were HGF gene with co-occurring mutations. Briefly, patients with (n=4) or without (n=20) co-occurring EGFR mutations had a median OS of not up to now and 20.0 months respectively (P=0.18); patients with (n=19) or without (n=5) co-occurring TP53 mutations had a median OS of 20.0 months and 21.0 months respectively (P=0.96); patients with (n=4) or without (n=21) co-occurring BRAF mutations had a median OS of not up to now and 20.0 months respectively (P=0.46); patients with (n=5) or without (n=19) co-occurring ERBB4 mutations had a median OS of 20.0 months and 19.6 months respectively (P=0.83).

      Conclusion

      EGFR, TP53, BRAF and ERBB4 gene accompanied may have less correlation with HGF mutation in NSCLC patients. Results of ongoing studies will provide a platform for further research to offer individualized therapy with the purpose of improving outcomes.

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      EP1.03-25 - Impact of Preoperative Complete Blood Cell Count-Derived Inflammation Biomarkers in Early-Staged Non-Small Cell Lung Cancer Patients (Now Available) (ID 705)

      08:00 - 18:00  |  Presenting Author(s): Fumihiro Shoji  |  Author(s): Yuka Kozuma, Gouji Toyokawa, Koji Yamazaki, Sadanori Takeo

      • Abstract
      • Slides

      Background

      Although stage IA non–small-cell lung cancer (NSCLC) has an optimistic survival rate, up to 10% of these patients relapse after surgery and die. Inflammation plays a critical role in the development and progression of various cancers by promoting cancer cell proliferation and survival, angiogenesis and tumor metastases. Inflammatory cells in the tumor microenvironment significantly affect tumor development, and markers of systemic inflammation may indicate tumor status. In recent years, complete blood cell count (CBC)-derived inflammation biomarkers such as systemic immune-inflammation index (SII), neutrophils lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR) and monocyte lymphocyte ratio (MLR), are used as prognostic factors in various malignancies. These markers are based on two or three parameters selected among neutrophils, lymphocytes, platelets and monocytes. SII has been investigated as a prognostic factor in several malignancies. NLR, PLR and MLR have been used as markers as systemic inflammation and are associated with poor outcomes in sloid tumors. Concerning non-small cell lung cancer, these parameters have been also reported as poor indicators, but few have specifically studied stage IA disease. We retrospectively analyzed clinicopathological features of patients with stage IA NSCLC to identify recurrence predictors and to investigate effects of preoperative CBC-derived inflammation biomarkers.

      Method

      We selected 311 consecutive patients with stage IA NSCLC treated from April 2006 to December 2012 for this study, and tested their preoperative SII, NLR, PLR and MLR in uni- and multivariate Cox proportional analyses of recurrence free survival (RFS).

      Result

      Preoperative high MLR level was significantly associated with sex, smoking status, postoperative recurrence (P<0.0001, =0.0307 and =0.0146) and preoperative high SII level was only correlated with postoperative recurrence (P= 0.0458), although both NLR and PLR were not found any related factors. Intratumoral vascular invasion (P= 0.0412), intratumoral lymphatic invasion (P= 0.0097) and preoperative MLR level (P= 0.0269) were identified as independent predictors of shorter RFS. Relative risk for preoperative high MLR level patients was 2.259 compared with patients with low MLR level (95% CI: 1.094–5.000). 5-year RFS rate in preoperative high MLR group was significantly lower than that in low MLR group (82.21% vs. 92.05%, p=0.0062).

      2019wclc fig.jpg

      Conclusion

      Preoperative MLR level is a simple and novel predictor of recurrence in patients with stage IA NSCLC.

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      EP1.03-26 - Analysis of Gene Expression Profiling of Lung Adenocarcinoma Brain Metastasis (Now Available) (ID 775)

      08:00 - 18:00  |  Presenting Author(s): Eun Su Park  |  Author(s): Nara Yoon, Taeeun Kim, Sun-Yong Jun, Ji Eun Kwon

      • Abstract
      • Slides

      Background

      The molecular biology of lung adenocarcinoma (ADC) brain metastasis is poorly understood. We aimed to explore genes that are implicated in the process of brain metastasis of primary lung adenocarcinoma.

      Method

      Twelve primary lung ADC with brain metastasis (ADCBM), six non-metastatic lung ADC (NMADC) and six lung ADC with metastasis except in the brain (ADCEB) were selected. Samples from all primary lung ADC were obtained after surgical resections performed at Incheon St. Mary’s hospital. All tumors were analyzed with the NanoString nCounter system for gene expression using the nCounter PanCancer Progression panel composed of 740 genes. Expression data were analyzed using the NanoString nSolver software ver 4.0 and nCouter Advanced Analysis ver 2.0.115.

      Result

      Eleven out of the 740 genes were differentially expressed between the ADCBM and ADC without brain metastasis including NMADC and ADCEB. The genes that were downregulated in the ADCBM included RGCC, ACHE, TPSB2, and FHL1. Expression levels of EPHB3, AGRN, ISLR, TNFRSF12A, TPM2, PTRF and BGN were upregulated in the ADCBM compared to ADC without brain metastasis including NMADC and ADCEB. The ADCBM was compared with NMADC and ADCEB, respectively. Four genes were differentially expressed between the ADCBM and NMADC. 23 genes were differentially expressed between the ADCBM and ADCEB. The differentially expressed genes (DEGs) in NMADC vs. ADCEB were not identified the same DEGs in ADCBM vs. NMADC and ADCEB. As a result, the EPHB3, AGRN and TNFRSF12A that were upregulated and the RGCC that was downregulated in ADCBM was common identified.

      Conclusion

      Conclusion: Although our findings are not conclusive, we have identified differentially expressed genes that might mediate the brain metastasis process. A prospective validation is needed to confirm candidate genes associated with ADCBM.

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      EP1.03-27 - The Anti-Migration and Anti-Invation Mechanisms of Capilliposide C from Lysimachia Capillipes on Lung Cancer (Now Available) (ID 1678)

      08:00 - 18:00  |  Presenting Author(s): Yasi Xu  |  Author(s): Shirong Zhang, Shenglin Ma

      • Abstract
      • Slides

      Background

      Approximately 50% of lung cancer patients had distant metastases when initial diagnosed. Lysimachia capillipes is one of traditional medicine in China. It is proved to be safety in clinical use. Several studies have showed the antitumor effects of Capilliposide from Lysimachia capillipes (LC) in vitro. Our preliminary data showed LC could inhibit the migration and invasion of lung cancer. This study aims to explore the detailed mechanisms of LC as well as its extracts on lung cancer.

      Method

      Four non-small cell lines were selected. The invasive response of lung cancer cells was determined by Wound Healing assay. Proteins and the phosphorylation of proteins were evaluated by iTRAQ-based proteomics. The phosphorylation chip was used to evaluate the phosphorylation effect. PC-9 xenografts were used to evaluate the antitumor of LC-C in vivo. Immunohistochemistry (IHC) was used to evaluate the antitumor mechanisms in vivo.

      Result

      The migration capa city of lung cancer cells was significantly reduced after treatment of LC-C. Proteomics showed there were 364 differentially expressed proteins and 456 differentially expressed phosphorylated proteins in both LC-C treated PC-9 and H1975 cells. Differentially expressed proteins were enriched in EGF receptor signaling pathway, Wnt signaling pathway, Cadherin signaling pathway, Notch signaling pathway, TGF-beta signaling pathway, and p38 MAPK pathway by bioinformatic analysis. Phosphorylation chip showed LC reduced the phosphorylation of AKT, WNK1 and PRAS40, but not EGFR. Western blot showed the phosphorylation of mTOR, AKT and PRAS40 were significantly inhibited after LC-C treatment; besides, the inhibitory effects of AKT and mTOR were dose-dependent. While the total proteins of AKT and mTOR were not changed. Western blot showed the phosphorylation of Smad2 and Smad3 were significantly inhibited after LC-C treatment. Western blot showed E-Cadherin was up-regulated and N-Cadherin was down-regulated after LC-C treatment; while other EMT related proteins including ZO-1, Snail and Vimentin were not changed. Nor did cell adhesion related protein Claudin-1. PC-9 xenograft model showed the tumor growth inhibitory rates were 114.4% in 7 days after LC-C administration. IHC showed the phosphorylation of AKT was down-regulation after LC-C administration, Ki-67 was also down-regulation, while cleaved caspase-3 was not changed.

      Conclusion

      The study showed LC-C inhibit the growth and the capacity of invasion and migration of lung cancer cells. The detailed mechanisms might crosstalk with several critical pathway such as AKT pathway, TGF-β pathway and EMT.

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      EP1.03-28 - Frequency and Molecular Characteristics of BRCA1 Mutations in Non-Small Cell Lung Cancer from East Asian Patients (ID 145)

      08:00 - 18:00  |  Presenting Author(s): Chunwei Xu  |  Author(s): Yixiong Huang, Wenxian Wang, Quxia Zhang, Wu Zhuang, Youcai Zhu, Yunjian Huang, Gang Chen, Meiyu Fang, Tangfeng Lv, Yong Song

      • Abstract

      Background

      Previously identified as a breast and ovarian cancer susceptibility gene, BRCA1 has gained major scientific interest as a potential prognostic and/or predictive marker for various tumors, including non-small-cell lung cancer (NSCLC), the leading cause of cancer related mortality worldwide. The aim of this study is to investigate mutations and prognosis of NSCLC harboring BRCA1 mutations.

      Method

      A total of 730 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of BRCA1 mutations and other genes were detected by next generation sequencing.

      Result

      BRCA1 gene mutation rate was 2.60% (19/730) in non-small cell lung cancer, including Y856H (3 patients), M1689T (2 patients), N909I (2 patients), G275D (2 patients), N473S (2 patients), S1217C (1 patient), M1628T (1 patient), E649* (1 patient), R1443* (1 patient), V191I (1 patient), I783V (1 patient), M669T (1 patient), and R71K (1 patient), and median overall survival (OS) for these patients was 14.0 months. Among them, all patients were BRCA1 gene with co-occurring mutations. Briefly, patients with (n=3) or without (n=16) co-occurring EGFR mutations had a median OS of 20.0 months and 13.0 months respectively (P=0.56); patients with (n=4) or without (n=15) co-occurring TP53 mutations had a median OS of 20.0 months and 19.5 months respectively (P=0.82); patients with (n=4) or without (n=15) co-occurring PIK3CA mutations had a median OS of not up to now and 13.5 months respectively (P=0.36); patients with (n=5) or without (n=14) co-occurring CDKN2A mutations had a median OS of not up to now months and 13.5 months respectively (P=0.28).

      Conclusion

      Our data reveal BRCA1 mutations represent a distinct subset of NSCLC. NGS might be useful for evaluation of BRCA1 unclassified variants. Our results show that BRCA1 mutations delineate an aggressive subtype of lung cancer for which a targeted treatment through PARP inhibition might offer new opportunities.

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      EP1.03-29 - The Evaluation of Non-Canonical WNT/β-Catenin Ligands Expression Status in Non-Small Cell Lung Cancer (Now Available) (ID 2528)

      08:00 - 18:00  |  Presenting Author(s): Mirosław Kozłowski  |  Author(s): Paweł Golec, Joanna Pancewicz, Radosław Charkiewicz, Anetta Sulewska

      • Abstract
      • Slides

      Background

      The family of secreted glycoproteins forming the WNT/β-catenin signaling pathway is shown to play a significant role in many types of carcinomas including NSCLC. Therefore, the aim of the study was to evaluate the WNT pathway status in NSCLC.

      Method

      The study was performed on 80 pairs of cancerous and non-cancerous tissue samples and 5 NSCLC cell lines (A549, H1299, H1395, Calu-3, H520 and non-cancerous control line HBEpC). Selected WNT genes expression analysis was assessed with qPCR with TaqMan Gene Expression Assays. The relative expression of chosen genes was estimated with ΔΔCt method. Statistical analyses were performed with the use of: Shapiro-Wilk test, T-test Wilcoxon matched pairs singed-rank test and Mann-Whitney U test.

      Result

      In the cell lines deregulation of most selected genes was detected. Fold-change analysis of obtained results has shown a down-regulation of WNT4, -5A, -7A and -11 expression in comparison to control. However, in H520 and A549 cell lines up-regulation of WNT-5A and WNT -11 was found.

      Analysis of patient’s tissue shows statistically significant (p < 0.05) inhibition of non-canonical WNT pathway ligands WNT-4, WNT-5A, WNT-7A and WNT-11 in cancerous tissue in comparison to non-cancerous tissue. In adenocarcinoma statistically significant dysregulation of WNT5A (p = 0.0094), -7A (p < 0.0001), and -11 (p < 0.0001) was identify. In squamous cell carcinoma statistically significant dysregulation of WNT4 (p , 0.0001), -7A (p < 0.0001) and -11 (p < 0.0001) was found. Moreover, in large cell carcinoma statistically significant dysregulation of WNT-4 (p = 0.0068), -5A (p = 0.0210), -7A (p = 0.0156) and -11 (p = 0.0117) was discovered. Furthermore, a statistically significant difference of WNT-7A expression between stage IA and IIA tumors (p = 0.0203) has been found.

      Conclusion

      Dysregulation of non-canonical WNT/β-catenin signaling pathway ligands expression profile in NSCLC tissue samples suggests that it play an important role in NSCLC. Further studies, are necessary to proof the mechanisms of WNT/β-catenin pathway in NSCLC.

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      EP1.03-30 - FAM83A and FAM83B as Prognostic Biomarkers and Potential New Therapeutic Targets in NSCLC (Now Available) (ID 587)

      08:00 - 18:00  |  Presenting Author(s): Sarah Richtmann  |  Author(s): Dennis Wilkens, Arne Warth, Felix Lasitschka, Hauke Winter, Petros Christopoulos, Felix Herth, Thomas Muley, Michael Meister, Marc Andre Schneider

      • Abstract
      • Slides

      Background

      Although targeted therapy improved survival rates in the last decade, non-small cell lung cancer (NSCLC) is still the most common cause of cancer related death. As most precision medicines lead to resistance, the challenge of identifying new targets for further effective therapies still remains. The FAMily with sequence similarity 83 (FAM83) members have recently been described as novel oncogenes in numerous human cancer specimens and shown to be involved in EGFR signaling. However, their function in cancer cells is largely unknown and especially their role in lung cancer remains unclear.

      Method

      Here, we investigated the expression and function of FAM83A and B in NSCLC. First, gene expression of the two FAM83 members was analyzed in a set of 362 NSCLC patients using qPCR. We further investigated relations in expression and their prognostic value using correlation and multivariate COX regression analyses. Functional assays in NSCLC cell lines were performed to analyze their involvement in proliferation, anchorage-independent growth, migration and the epidermal growth factor receptor (EGFR) pathway.

      Result

      We observed a highly increased gene expression level of FAM83A (ø = 68-fold) and FAM83B (ø = 20-fold) which resulted in poor survival prognosis (p < 0.0001 and p = 0.002). Correlation analysis showed poor relation between FAM83A and B in the two sub-histologies adenocarcinoma (ADC) and squamous cell carcinoma (SQCC) but confirmed correlation between FAM83A and B and EGFR expression levels in patients and cell lines. Their expression was further influenced by EGFR pathway signaling and mutation status. Both genes affected cell proliferation and FAM83A depletion resulted in reduced migration and AIG.

      Conclusion

      The results support the hypothesis that FAM83A and B have different specific functions in the histological subtypes of NSCLC and might be new therapeutic targets.

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      EP1.03-31 - Cell Migration and Epithelial Mesenchymal Transition in Lung Cancer - Different Roads and Common Themes (Now Available) (ID 930)

      08:00 - 18:00  |  Presenting Author(s): Karin Schelch  |  Author(s): Lisa Wimmer, Jelena Brankovic, Michael Grusch

      • Abstract
      • Slides

      Background

      Cell migration is an indispensable function for many cells in multicellular organisms. When deregulated, however, especially in conjunction with the ability to degrade extracellular matrix and invade surrounding tissues, it is a hallmark of malignancy and forms the basis for cancer metastasis. This is often linked to epithelial mesenchymal transition (EMT) which is widely recognized in cancer cell biology to be intricately connected to metastasis, drug resistance and stemness. Multiple extracellular stimuli that induce EMT and cell migration in diverse cellular contexts have been described, nevertheless, a lot still needs to be learned about pathway-specific mechanisms. We have chosen the Ras-mutated A549 lung adenocarcinoma cell line for investigating how the two growth factors EGF and TGFb, which each play fundamental roles in tumor development but activate clearly distinct signaling cascades both stimulate EMT and migration individually and when acting in cooperation.

      Method

      A549 cells were treated with EGF, TGFb or a combination of both in serum-free conditions. Also, inhibitors of downstream pathways were used at sub-lethal concentrations. Changes in cell morphology were determined using ImageJ from microscopy images. Cell migration was assessed by live cell videomicroscopy followed by singe cell tracking. The invasive capacity was determined by a 3D sprouting assay. Expression changes were identified by qPCR and immunoblots.

      Result

      Treatment with TGFb and EGF resulted in cell scattering and distinct changes in cell morphology, which were different for each growth factor. While cells treated with TGFb showed classic EMT-like, elongated morphology, cells exposed to EGF rounded up. Combining both factors resulted in a mixed population. EGF-induced changes could be prevented by Akt but not MAPK inhibitors. Importantly, each growth factor induced a significant increase in cell migration compared to untreated cells and the combination of both factors stimulated migration even further. Interestingly, the increase in migration occurred earlier with EGF than with TGFb, and this was in concordance with increased pERK levels. However, only TGFb was able to induce significantly increased sprouting.

      Conclusion

      Our data describes two independent signaling pathways which both are able to induce cell scattering and cell migration, albeit along different roads. Especially in cancer cells, a better understanding of signaling pathway-dependency of EMT and migration and potential cross talks could lead to more effective antimetastatic therapies.

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      EP1.03-32 - Prevalence of EGFR and ALK Mutations in Non Small Cell Lung Cancer in Viet Nam National Cancer Hospital (Now Available) (ID 979)

      08:00 - 18:00  |  Presenting Author(s): Voc Tai Dang

      • Abstract
      • Slides

      Background

      A significant percentage of non small cell lung cancer (NSCLC) have driver mutations. Epidermal growth factor receptor (EGFR) mutations and anaplastic large-cell lymphoma kinase (ALK) rearrangements are now routine biomarkers that have been incorporated into the practice of managing NSCLC. To date, there has been no assessment of the prevalence of these mutations in NSCLC in Viet Nam National Cancer Hospital. The prospective study of formalin fixed paraffin embedded (FFPE) tissues from patients diagnosed with NSCLC was performed to assess the prevalence of EGFR and ALK mutations in NSCLC in Viet Nam National Cancer Hospital.

      Method

      Patients with NSCLC in Viet Nam National Cancer Hospital were prospectively enrolled. FFPE tissue samples were tested for EGFR mutation by PCR and for EML4-ALK translocation by fluorescence in situ hybridization (FISH)

      Result

      A total of 103 patients were enrolled, 78 (76.7%) males and 25 females (23.3%), with a mean age of 57.7 years. Adenocarcinoma and Squamous cell carcinoma rate were 89.3% and 10.7%, respectively. EGFR testing of 103 patients (100%) demonstrated the wild type in 76 (73.8%) and mutated forms in 27 (26.2%). Some 74.0% of EGFR positive patients were non-smokers and 44.4% were females. Regarding the EML4-ALK translocation, testing in 103 cases (100%) gave positive results in only 11 (10.7%). Among 11 patients with EML4-ALK translocation, 6 patients (54.5 %) were females and 6 patients (54.5 %) were smokers. Moreover, only two squamous cell carcinoma patients had positive EGFR mutation and only one patient had concurrent EGFR mutation and ALK rearrangement

      Conclusion

      In this sudy investigating the prevalence of EGFR and ALK mutations in non small cell lung cancer in Vietnam National Cancer Hospital, 26.2% had EGFR mutation and 10.7% had ALK translocation mutations, as compared to 35% and 6.1%, respectively, in Asian

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      EP1.03-33 - CD26/DPP4 as a Novel Prognostic Marker for Lung Adenocarcinoma (Now Available) (ID 1734)

      08:00 - 18:00  |  Presenting Author(s): Jae-Hwi Jang  |  Author(s): Martina Haberecker, Alessandra Curioni, Florian Janker, Alex Soltermann, Ignacio Gil-Bazo, Ilseon Hwang, Kunyoung Kwon, Walter Weder, Wolfgang Jungraithmayr

      • Abstract
      • Slides

      Background

      CD26/dipeptidyl peptidase 4 (DPP4) is a transmembrane exopeptidase expressed on various malignancies in conjunction with activity of epithelial-mesenchymal transition (EMT). We found previously that the activity of CD26/DPP4 in human lung adenocarcinoma is four times higher than in normal lung tissue and the inhibition of CD26/DPP4 decreased the growth of lung tumors in experimental models. These data prompted us to analyze the expression of CD26/DPP4 and EMT markers in samples from non-small cell lung cancer patients to unravel a function of CD26/DPP4 as a prognostic marker and potential therapeutic target for lung cancer.

      Method

      We employed multi-organ tissue micro array (TMA) of non-small cell lung cancer patient samples from two institutions, University Hospital Zurich and Dongsan Medical Center. To identify CD26/DPP4 and EMT markers (Ecadherin, Vimentin, beta-Catenin, Elastin, Periostin, and Versican), immunohistochemistry (IHC) on TMA was performed. Three pathologists scored the intensity IHC from zero to six in a blinded manner. The cohort consisted of 1126 patients (adenocarcinoma: 593; squamous carcinoma: 443; others (large cell carcinoma, adeno-squamous carcinoma): 90). The overall survival rate of patients was considered as a measure of prognosis. To identify a correlation between CD26/DPP4 and EMT related protein expression in lung cancer the Pearson correlation coefficient test was applied.

      Result

      CD26/DPP4 IHC scores revealed that adenocarcinoma expresses significantly higher amount of the protein compared to normal lung or squamous carcinoma or others (p=0.035, p<0.0001, p<0.0001 respectively). In adenocarcinoma, patients with high CD26/DPP4 score (4-6) showed the worst overall survival compared to patients scoring low (1-3) or zero. The correlation analysis of CD26/DPP4 with EMT markers in adenocarcinoma showed that the epithelial marker Ecadherin was negatively correlated (p=0.001), while mesenchymal proteins Vimentin, beta-Catenin, Elastin were positively correlated with CD26/DPP4 (p=0.03, 0.01, and 0.001 respectively). Periostin and Versican showed no correlation with CD26/DPP4 expression.

      Conclusion

      The expression of CD26/DPP4 was significantly higher in adenocarcinoma among non-small cell lung cancers and associated with worse survival of patients. Furthermore, the expression of CD26/DPP4 was significantly correlated with the EMT status. We therefore deem CD26/DPP4 to be a novel prognostic marker for lung adenocarcinoma. In consideration with CD26/DPP4 expression of these cancer samples, inhibition of CD26/DPP4 can potentially improve lung cancer patients’ survival.

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      EP1.03-34 - Single Center Epidemiological Prevalence Study of Molecular Mutation in Bangladeshi Patients with Advanced Stage Non-Small Cell Lung Cancer (ID 1366)

      08:00 - 18:00  |  Presenting Author(s): Qamruzzaman Chowdhury  |  Author(s): Ferdous Ara Begum, Md Arifur Rahman, Farhia Chowdhury, S.M. Rayan Kabir, Zaheed Husain

      • Abstract
      • Slides

      Background

      In a private tertiary hospital of Bangladesh about 2953 patients have been diagnosed as primary cancer patient of which 17% (510) patients were primary lung cancer patients, 77% of which were in advanced (stage III and IV). The study was performed to investigate the molecular mutations and prevalence of EGRF, T-790M, ROS-1, and ALK mutations in Bangladeshi patients with advanced stage non-small cell lung cancer (NSCLC), as per available local molecular lab facilities.

      Method

      This study was retrospective and single center, conducted in 35 patients representing the 77% advanced stage lung cancer patients aged 20 years or above with NSCLC in the outpatient department The Bangladesh Specialized Hospital Ltd. (BSHL) within the timeframe of March 2016 – March 2019 recommended for molecular mutation study. Data were collected from the electronic prescription from hospital imformation system. EGFR, T-790M, ROS-1, and ALK frequency were calculated. The tests were done by tissue sample or Liquid biopsy when tissue sample was unavailable. The tests were carried out by Real Time PCR. The frequency of molecular mutation diagnosis was compared between the number of patients advised for molecular mutation study and number of patients who performed the investigation.

      Result

      Of 35 patients 63% (22) were male and 37% (13) were female, median age 61 (range 45-86) and 65% (23) test carried out with Liquid Biopsy. 25.7% (9) patients were found to be EGFR positive, and 74.3% (26) were EGFR negative; also, out of 16 patients recommended for T790M study only 6.3% (1) was positive. ROS positive was found in 40% (14), and 48.6% (17) were negative. ALK screening showed to be positive in 37.1% (13) and negative in 45.7% (16). Among the 392 patients, only 9% performed the study, due to low availability of moleculer diagnosis which was started in Bangladesh since the early July 2017.

      Conclusion

      The frequency of molecular testing may not reflect the international studies due to methods applied for the testing and also with the gender frequency as high predominance of male patients. With this limited data we have seen that the prevalence of ROS-1 (40%) mutation was higher than ALK (37.1%) and EGFR (25.7 %). Due to financial constrain and limited access to tests only 9% patients performed the study, though, molecular tests are recommended most oftenly. Due to time being a limiting factor for the sample size further studies can be performed on a larger scale.

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      EP1.03-35 - Prevalence, Clinicopathologic Characteristics, and Molecular Associations of IGF1R Mutations in East Asian Patients with NSCLC (ID 155)

      08:00 - 18:00  |  Presenting Author(s): Chunwei Xu  |  Author(s): Xudong Zhao, Wenxian Wang, Quxia Zhang, Wu Zhuang, Youcai Zhu, Yunjian Huang, Gang Chen, Meiyu Fang, Tangfeng Lv, Yong Song

      • Abstract

      Background

      IGF1R is a ubiquitous receptor tyrosine kinase that plays critical roles in cell proliferation, growth and survival. Clinical studies have demonstrated upregulation of IGF1R mediated signaling in a number of malignancies including colon, breast, and lung cancers. The aim of this study is to investigate mutations and prognosis of non-small cell lung cancer (NSCLC) harboring IGF1R mutations.

      Method

      A total of 812 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of IGF1R mutations and other genes were detected by next generation sequencing.

      Result

      IGF1R gene mutation rate was 1.60% (13/812) in non-small cell lung cancer, including N977I (2 patients), S751T (1 patient), E1043D (1 patient), G171W (1 patient), E563K (1 patient), R275C (1 patient), F921[2>1] (1 patient), E712K (1 patient), R222W (1 patient), D1024A (1 patient), A760T (1 patient), and K533N (1 patient), and median overall survival (OS) for these patients was 9.0 months. Among them, all patients were IGF1R gene with co-occurring mutations. Briefly, patients with (n=3) or without (n=10) co-occurring EGFR mutations had a median OS of 6.0 months and 11.0 months respectively (P=0.10); patients with (n=12) or without (n=1) co-occurring TP53 mutations had a median OS of 18.0 months and 8.0 months respectively (P=0.68); patients with (n=4) or without (n=9) co-occurring KRAS mutations had a median OS of 14.5 months and 7.0 months respectively (P=0.76); patients with (n=5) or without (n=8) co-occurring NF1 mutations had a median OS of not up to now and 6.5 months respectively (P=0.24).

      Conclusion

      EGFR, TP53, KRAS, NF1 gene accompanied may have less correlation with IGF1R mutation in NSCLC patients. We report different mutations than those previously reported, which emphasizes the importance of personalized medicine that could be empowered by the use of bioinformatics tools in the diagnostic process and therapeutic approaches.

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    EP1.04 - Immuno-oncology (ID 194)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Immuno-oncology
    • Presentations: 47
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.04-01 - Association of PD-L1 Expression with Lung Adenocarcinoma Containing Solid or Micropapillary Components (Now Available) (ID 1549)

      08:00 - 18:00  |  Presenting Author(s): Yoshiteru Kidokoro  |  Author(s): Atsuyuki Nakanishi, Shinji Matsui, Yasuaki Kubouchi, Yuzo Takagi, Tomohiro Haruki, Yuji Taniguchi, Yoshihisa Umekita, Hiroshige Nakamura

      • Abstract
      • Slides

      Background

      The assessment of programmed cell death ligand 1 (PD-L1) expression by immunohistochemistry (IHC) is important to treat patients in lung adenocarcinoma (LUAD). However, little is known about the relationship between PD-L1 expression and high-grade components, such as solid components (SCs) and/or micropapillary components (MPCs), which show worse prognosis. Here, the aim of this study is to evaluate the association of the PD-L1 expression with LUAD containing high-grade components.

      Method

      The expression of PD-L1 protein in 39 surgically resected LUAD was evaluated by IHC analysis using the clone 22C3. PD-L1 tumor proportion score (TPS) were divided to three groups: TPS at least ≥50% was high expression, ≥1% was intermediate expression, and <1% was negative expression. We compared retrospectively the three groups and the percentage of high-grade components.

      Result

      PD-L1 high expression was seen in eight patients (20.5%), intermediate expression in 22 patients (56.4%), and negative expression in 9 patients (23.1%). Thirty five cases with at least ≥1% SCs and/or MPCs were identified. The mean of the percentage of high-grade components was 60% in high expression group, 22% in intermediate expression group, and 10% in negative expression group. The statistical significance was shown comparing the PD-L1 high expression with the intermediate expression group (p<0.013), and comparing the high expression and the negative expression group (p<0.002).

      Conclusion

      LUAD with many high-grade components showed the PD-L1 high expression. Therefore, PD-L1 IHC should be performed on sections including a high percentage of SCs and/or MPCs in evaluating its expression in surgical resected specimen.

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      • Abstract
      • Slides

      Background

      Pembrolizumab, an anti-PD–1 antibody, is an immuno-checkpoint inhibitor (ICI) approved for advanced disease in frontline setting if PDL1 is ≥ 50%, in second line if PDL1 is >1%. ICIs are associated with immune-related adverse events (irAE), including pneumonitis or interstitial lung disease (ICI–ILD): the mechanisms that lead to irAE are not entirely known. Clinical trials found an incidence of ICI–ILD of 3 to 5% but in recent studies it is greater, with fatal cases described. Reports about real incidence, risk factors, features of pneumonitis are still few. We designed a prospective observational study in this setting of patients in order to predict pulmonary toxicity by clinical -radiological and respiratory functional variables.

      Method

      PRELUTOX is a prospective observational study. Our purpose is to enroll at least 50 patients in 2 years. Inclusion criteria: locally advanced or metastatic NSCLC whit PD-L1 expression ≥ 50%, with no EGFR or ALK-ROS1 mutations. Exclusion criteria: previous chemotherapy or thoracic radiotherapy; active infections or systemic autoimmune disease; interstitial lung diseases; prior pneumonitis requiring systemic steroids; immunosuppressive or corticosteroid treatment; renal or hepatic failure. Aims of our study: incidence of ICI – ILD; features of all patients including pulmonary function and comorbidities, especially the respiratory ones; features of patients who develop pneumonitis with greater attention to the HRCT pattern. Patients perform therapy and radiological exams according to routine clinical practice; pulmonary function tests (PFTs) at the beginning of Pembrolizumab and every three months

      Result

      This is an interim analysis. 33 patients have been recruited from May 2018 to March 2019. Patients characteristics are summarized in table 1.

      table 1.gif

      ILD occurred in one patient with thoracic massive involvement (incidence 3%) with an HRCT pattern of organizing pneumonia. He presented progressive worsening of the obstructive ventilatory defect and drastic reduction of diffusing capacity, associated with severe hypoxemia

      Conclusion

      In literature incidence of ICI-ILD seems to be higher for NSCLC compared with other cancers: this may be related to the underlying lung status (exposure to tobacco, COPD and the thoracic tumor burden). PFTs have been described in several studies for their capacity to predict lung toxicity. In our preliminary data, during Pembrolizumab therapy, if toxicity does not occur, airways obstruction parameters and lung volumes seem to remain constant and related to the respiratory comorbidity (COPD). The same appears for diffusing capacity. Finally we suppose that the thoracic tumor burden could be related to the risk of lung toxicity but the study is still ongoing.

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      EP1.04-03 - Immune Cell Filtration as a Biomarker for the Diagnosis and Prognosis of Lung Adenocarcinoma (Now Available) (ID 2243)

      08:00 - 18:00  |  Presenting Author(s): Yang Wo  |  Author(s): Tong Lu, Yuanyong Wang, Wenjie Jiao

      • Abstract
      • Slides

      Background

      Since tumor-infiltrating immune cells provides meaningfully information of prognosis in lung adenocarcinoma, we aimed to construct a novel prognostic immune model on the basis of a systematic assessment of the immune landscape calculated from cancer transcriptomes of lung adenocarcinoma patients.

      Method

      We used an advanced algorithm, which named “Cell type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT)”, to estimate the 22 immune cell types from public datasets. The selection operator model and least absolute shrinkage and random forest method were then applied to develop immune scores for tumor diagnosis and prognosis.

      Result

      355 lung adenocarcinoma patients and 204 normal controls were obtained to develop a diagnostic model and the diagnostic immune risk score (dIRS) suggested high sensitivity and specificity in both the training sets (AUC= 0.93, P<0.01) and validation sets (AUC=0.89). A prognostic immune score (pIRS) was also established and served as an independent prognostic factor for overall-free survival, which showed better prognostic value than TNM stage. Additionally, by integrating the pIRS with clinical information in a complete nomogram, the result suggested higher accuracy of recurrence risk prediction with well-calibrated curves.

      Conclusion

      In summary, we studied the potential application of immune cells in cancer diagnosis, prognosis and treatment. The proposed diagnostic and prognostic model (dIRS and pIRS) might provide integrative and meaningful signatures for precision medicine and personal management of lung adenocarcinoma patients.

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      EP1.04-04 - Pembrolizumab-Induced Fatal Encephalopathy (Now Available) (ID 2274)

      08:00 - 18:00  |  Presenting Author(s): Cláudia Freitas  |  Author(s): Gabriela Fernandes

      • Abstract
      • Slides

      Background

      Pembrolizumab is a monoclonal antibody against programmed cell death 1 (PD-1) receptor approved for PD-L1 positive metastatic non-small cell lung cancer (NSCLC). Neurologic adverse events associated with anti-PD-1 antibodies are rare but might be fatal.

      Method

      We report a case of fatal encephalopathy in a patient with metastatic NSCLC treated with pembrolizumab.

      Result

      A 65-year-old former smoker woman with advanced lung adenocarcinoma with a KRASmutation and an intermediate expression of PD-L1 (20-30%) previously treated with combination of carboplatin and pemetrexed started pembrolizumab (200 mg, every three weeks) after disease progression. After the second infusion of pembrolizumab, she presented with seizures and decreased level of consciousness. Concerning neurological examination, the patient was vigil, carried out only simple commands with absence of speech. Additionally, her muscular tonus was increased. Blood tests were unremarkable. Electroencephalogram was consistent with diffuse encephalopathy and also showed frequent epileptiform activity. Cerebral computed tomography and magnetic resonance revealed central nervous system (CNS) multifocal demyelination. Cerebrospinal fluid was acellular with glucose and protein within normal range. Also, microbiologic examination and polymerase chain reaction (PCR) assay for cytomegalovirus, herpes simplex 1 and 2 and John Cunningham (JC) virus were negative. Anti-onconeural antibodies were absent. Systemic corticosteroid therapy (dexamethasone 4 mg, every six hours) was initiated, with no improvement. Best supportive care was decided by a multidisciplinary team and patient died one month after admission.

      Conclusion

      After excluding other causes for encephalopathy as paraneoplastic syndrome, CNS infection and metastasis, temporal association with pembrolizumab administration made us suspect of an adverse event of this drug. A case of pembrolizumab-induced encephalopathy was reported in advanced NSCLC, after two doses administration and the patient recovered after high dose corticosteroids. However, another case of nivolumab-induced encephalopathy in advanced renal cell carcinoma was fatal, even with drug discontinuation and high dose corticosteroid therapy. Although anti-PD-1 rarely cause encephalopathy, our case highlights not only its occurrence but also shows that it may be rapidly progressive and irreversible. As this entity probably represents an autoimmune process due to PD-1 block, its course is impossible to predict.

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      EP1.04-05 - Outcomes of Immunotherapy in Elderly Patients. Retrospective Study of Clinical Characteristics in a Single-Center and a 4-Year Experience (ID 2961)

      08:00 - 18:00  |  Presenting Author(s): Ana Laura Ortega Granados  |  Author(s): David Fernández Garay, Nuria Cárdenas Quesada, Juan Francisco Marín Pozo, Leticica Díaz Beltrán, Capilla De La Torre Cabrera, María Ruiz Sanjuan, Mónica Fernández Navarro, Miguel Ángel Moreno Jiménez, Pedro Sánchez Rovira

      • Abstract

      Background

      Median age of patients with lung cancer is 71 years old. We have study outcomes of NSCLC patients with more than 75 years that have receive immunotherapy since 2014

      Method

      We have performed a retrospective observational study, reviewing all patients with lung cancer treated in Medical Oncology in our institution (tertiary center in Spain) in a 4-year period (2015 to 2019), and followed until April 2019. The inclusion criteria are: 1) Age of 75 years or older at the time of diagnosis of the lung cancer, and 2) Receiving any anti PD-1 or anti PD-L1 therapy in advance disease. We included 16 patients.

      Result

      Most patients were male, 79.2%, and average age is 77 years (75-84). They represent a 14.7% of all patients with advanced NSCLC that received any anti PD-1 or anti PD-L1 therapy in our institution (19 patients from a total of 128 patients, in a 4-year period). Squamous cell carcinomas represent a 57% of total, and adenocarcinoma a 39%. None of this patient harbour an oncogenic driver mutation. 51% of patients were diagnosed in stages II-III, and 49% in stage IV; but only 15% patients had a curative-intent therapy at the diagnosis. We study also the pattern of treatment in patients under active cancer therapy. Median survival time is 11.6 months (p-value: 0.001). Longer survival was seen in ECOG 0-1 patients (15.8 months) than in ECOG 2 patients (7 months)

      Most patients received immunotherapy in second line (16 patients, 2 in first line and 1 in third line). The drugs used were nivolumab (9 patients, 56.2%), followed by atezolizumab (7 patients, 37.5%) and pembrolizumab (3 patients, 6.2%). Median number of cycles received was 4 cycles (1-21). In terms of PD-1 status in biopsy, 5 patients were unknown, 8 patients were PD-1 negative and 6 patients were PD-1 positive (2 of them more than 50%). Most common adverse events related to immunotherapy were hypothyroidism (4 cases, 1 grade 1 and 3 grade 2), pneumonitis (3 cases, 2 grade 1 and 1 grade 2) and diarrhea (2 cases, grade 1). There were also dermatitis, adrenal insufficiency and xerostomia (1 case each).

      Conclusion

      Although our cohort is small, we can suggest that immunotherapy is slightly underused in this cohort of patients, because patients of 75 years and older are a 21% of all our patients, and only a 14% of patients received an anti PD-1/PD-L1 drug. Survival rates seems very similar that communicated in younger patients, and they are clearly lower in ECOG 2 patients.

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      EP1.04-06 - Analysis of the Relationship Between Ratio N / L and Survival in Patients Treated with Immunotherapy in Lung Cancer (ID 2605)

      08:00 - 18:00  |  Presenting Author(s): Noemi De Dios Alvarez  |  Author(s): Sara Agraso Busto, DIEGO Pereiro, ANA Alonso Herrero, MARTIN Lazaro, Gerardo Huidobro, JOAQUIN Casal

      • Abstract

      Background

      The neutrophil-lymphocyte (N / L) ratio is a marker of general immune response in different stress situations, having shown a relationship between the quotient and the evolution of patients treated with immunotherapy (IT), emphasizing the importance of inflammation in these patients.

      Method

      In order to evaluate this relationship in a context of usual clinical practice, a retrospective review of patients with pulmonary neoplasia who received IT treatment in the first line or successive, between November 2015 and December 2018, excluding those who received treatment within of ±±clinical trial. Data were collected from the clinical history of each patient, with special attention to baseline neutrophil and lymphocyte numbers, objective response to therapy by criteria iRECIST 1.1 after 3 months of treatment and overall survival (OS) defined from the beginning of treatment until death by progression of the disease.

      Result

      92 patients (29 women and 63 men) were analyzed with a mean age of 64 ±8 years.

      15 (16,3%) patients received immunotherapy as first line treatment, 65.2% (60 patients) received it as 2nd line and 18,4% (17 patients) as 3rd or succesive lines. The average number of cycles received was 14 (1-52).

      Two stretches of baseline N / L ratios ≤5 (low) and > 5 (high) were defined. Low ratio N / L (≤5) was identified in 62p (67.4%) of the patients treated with IT and high ratio N/L (> 5) in 30p (32,6%).

      Of the 62 patients with a low ratio: 41 patients (66.1%) had some type of response or stabilization of their disease, 13 patients (21%) had progression and 8 patients (12.8%) received less than three months of treatment, 6 patients for PS deterioration and the other 2 patients continue with the treatment and are pending reevaluation.

      Among the 30 patients patients with high N / L quotient: 7 patients (23.3%) presented response or stabilization of the disease, 23 patients (76,7%) presented progression or treatment was interrupted due to deterioration of the ECOG.

      The average survival in the group with a low N / L ratio (≤5) was 213 weeks compared to the group with a high N / L ratio (> 5) 144 weeks (p <0.05).

      Conclusion

      The N / L ratio has been identified in some studies as an adverse prognostic factor in patients treated with IT. Our data from the usual clinical practice support this theory. If these findings are confirmed in future studies, it could be used as a response biomarker for better patient selection.

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      EP1.04-07 - Influence of Radiotherapy in Second-Line Treatment with Immunotherapy in Patients with Non-Small Cell Lung Cancer (Now Available) (ID 197)

      08:00 - 18:00  |  Presenting Author(s): Eider Azkona  |  Author(s): Sergio Carrera, Itxiar Rubio, Juan Manuel Mañe, Inazio Lacambra, Aintzane Sancho, Eneko Novo, Guillermo López-Vivanco

      • Abstract
      • Slides

      Background

      Background: The aim of the present study is to analyze the influence of previous radiotherapy (RT) in the efficacy and toxicity in patients (pts) with non small cell lung cáncer (NSCLC) treated with inmunotherapy in second line.

      Method

      Methods: This is a retrospective study conduted between January 2017 and December 2018 at Hospital Universitario Cruces (Bizkaia) on pts treated with inmunotherapy (nivolumab or pembrolizumab) in second line. The primary end point was to analyze if the RT influence in the progression free survival (PFS) of inmunotherapy or in the toxicity. Secondary end points were overall survival (OS) and if any variable influences the difference between both cohorts in the PFS.

      Result

      Results: Forty eight pts were evaluated, and 22 (45.83%) had received RT previously. The baseline characteristics were as follows: median age 62 years (range 40-82); 62.5% males; 91.66% had an ECOG performance status (PS) 0-1; 37.5% had stage IV at diagnosis; only 3 of the 22 pts had received less tan 60 grays (Gys). There were no differences in the PFS, 14.49 months (m) in the cohort without RT and 18.19 m in those who have received it (p = 0.196) (image). The incidence of any grade of toxicity was similar, 26.92% and 22.72% in pts without and with RT respectively (p =0.112). 3 pts in the first group stopped inmonotherapy because of toxicity versus 2 pts in the cohort of RT. The OS was significantly longer in the cohort of RT, 36.49 vs. 20.54m, p = 0.034. It was calculated whether the time interval from the end of RT and the initiation of immunotherapy influences on the PFS; neither the cutoff point of 6 months (p = 0.788) nor the cutoff of 4 (p = 0.454) influenced the PFS. As in the second group more patients were diagnosed in EIII, the possible influence of the stage on the PFS was valued, and no significant differences were seen. Neither the previous QT scheme, sex, state of PD-L1 nor the baseline respiratory pathology influenced the PFS or the incidence of toxicity.diapositiva1.jpg

      Conclusion

      Conclusions: Our study suggests that having received prior RT does not influence the efficacy or toxicity of immunotherapy in the second line of treatment in NSCLC. A larger cohort and more follow-up time is needed to be able to draw conclusions.

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      EP1.04-08 - Is Pseudoprogression Really Uncommon After Immunotherapy in Lung Cancer? (Now Available) (ID 1118)

      08:00 - 18:00  |  Presenting Author(s): Jeong Eun Lee  |  Author(s): Da Hyun Kang, Chaeuk Chung

      • Abstract
      • Slides

      Background

      Immune checkpoint inhibitors (ICIs) are more effective and less toxic than cytotoxic chemotherapy, which has led to change in the paradigm of lung cancer treatment. However, unlike classical chemotherapy, pseudoprogression has been reported in which the size of a lesion is temporarily increased or a new lesion occurs due to the effect of treatment, not the actual progress of disease. Pseudoprogression was histologically confirmed by necrosis or inflammatory cell infiltration, which is thought to be due to immune-related responses. To date, the incidence of pseudoprogression has been reported to be 4-6% in lung cancer patients. The aim of this study was to evaluate the incidence and prognosis of pseudoprogression in lung cancer patients treated with ICIs.

      Method

      We retrospectively analyzed 74 patients who received ICIs at Chungnam National University Hospital from January 2017 to October 2018. Chest x-ray was examined 1 week after the first treatment to identify changes in initial lesions after immunotherapy. The response was evaluated in accordance with RECIST 1.1 and evaluated in chest x-ray as well as computed tomography (CT). Pseudoprogression was defined as the case in which the response was confirmed after continued treatment when the disease progression was showed on chest x-ray or CT.

      Result

      Five patients (6.8%) had partial response (PR) on the chest x-ray at 1 week after treatment, and PR of the first response evaluation CT was observed in 15 patients (20.3%). All 5 patients who had PR in the first week x-ray showed response in CT. On the other hand, 36 patients (48.6%) had increased tumor lesions at the first week after treatment. Of these, 24 patients were progression disease (PD), 6 patients were PR, and 6 patients were stable disease (SD) on CT at 2 months after treatment. Pseudoprogression was observed in 15 of 74 patients, with a frequency of 20.3%, which was higher than previously reported. Twelve patients (80%) had progression of lesion on chest x-ray at 1 week after treatment, and showed decreased lesion size on response evaluation CT. Of the 12 patients with early pseudoprogression, 4 patients were unable to proceed with further treatment due to progression-related symptoms and systemic deterioration.

      wclc_20190405.png

      Conclusion

      Unlike previous studies, pseudoprogression after immunotherapy is more frequent in lung cancer patients, especially during the early stage of treatment. Pseudoprogression at the beginning of treatment is relatively common to cause symptoms, so it is important to monitor early in the treatment.

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      EP1.04-09 - A Cross-Sectional Study of Clinical Trials on Radiotherapy Combined with Immunotherapy for Lung Cancer (ID 1292)

      08:00 - 18:00  |  Presenting Author(s): Meng Yuan  |  Author(s): Zhouguang Hui, Yu Men, Jingjing Kang, Xin Sun, Maoyuan Zhao, Yongxing Bao

      • Abstract

      Background

      For patients with lung cancer, remarkable advances have been made in Immune-Oncology (IO) therapy, especially immune checkpoint inhibitors (ICI). However, multi-modality treatment is needed to improve the efficacy or enlarge the beneficial populations of IO treatment. This study is to comprehensively summarize and analyze the clinical trials focusing on radiotherapy (RT) combined with IO therapy, explore the trend of research, as well as provide a view of the latest landscape of combination strategies.

      Method

      Trials registered on the electronic database(https://clinicaltrials.gov)between Jan.2009 and Jan.2019 were searched using “Radiotherapy AND Immunotherapy | Recruiting, Not yet recruiting, Active, not recruiting, Completed, Enrolling by invitation Studies | Interventional Studies | Lung Cancer”. SPSS 20.0 was used to analyze the data.

      Result

      Totally 69 clinical trials of RT and IO combination therapy for lung cancer were recorded, including 54 active and 15 completed. Geographically, most of the trials were carried out in the USA (n=47, 68.1%), followed by the European countries (n=18, 26.1%). From timeline, the past 2 years has seen a soaring number of 40 clinical trials accounting for 58.0% of the total. The combination therapy trials were more often in non-small cell lung cancer (NSCLC) (n=52, 75.4%) than small cell lung cancer (SCLC) (n=10, 14.5%), with the remaining 7 trials unspecified. As for combination strategies, trials of tumor vaccine combined with RT were the most frequent before 2016. But at present, ICI has exceeded tumor vaccine in the combination with RT and makes up the absolute most (n=62, 89.9%). On the whole, most of the combination therapy trials are in phase I/II (n=64, 92.8%). Although most trials are set for advanced or metastatic cancers (n=43, 62.3%), there are a few exploring the safety and effectiveness of combination therapy for early stage cancers or as adjuvant therapy (n=9, 13.0%). One trial was set as neo-adjuvant therapy. As for RT details, 22 trials were SBRT combined with IO therapy. Two trials were exploring the optimal sequence of RT and IO therapy. And one trial is to compare high versus low dose RT in the combination with ICI in NSCLC.

      Conclusion

      From the trials of RT and IO combination therapy for lung cancer, those of ICI combined with RT are increasing rapidly, although most are in phase I/II. Further studies are needed to explore the more detailed rational combination strategies, such as the sequencing, fractionation and dose of RT, and the optimal IO agent.

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      EP1.04-10 - Nivolumab in Non-Small Cell Lung Cancer (NSCLC): A Real-Life Study (ID 2012)

      08:00 - 18:00  |  Presenting Author(s): Daniel Oliveira Reis  |  Author(s): Aurora Mendes, Nuno China, Margarida Dias, Daniel Coutinho, Eloísa Silva, Sérgio Campainha, Telma Costa, Sara Conde, Ana Barroso

      • Abstract
      • Slides

      Background

      Immunotherapy is an option in locally advanced or metastatic lung cancer (LC), depending on the PD-L1 value. Nivolumab, an anti-PD1 immunological checkpoint inhibitor, can be used in LC in subsequent lines, regardless of the PD-L1 value. The aim of this study was to analyze patients with LC treated with nivolumab in the Multidisciplinary Thoracic Tumor Unit (MTTU) of our hospital.

      Method

      Retrospective analysis of patients treated in the MTTU of our hospital who with nivolumab in subsequent lines between Dec-2015 and Dec-2018.

      Result

      49 patients were enrolled in this study with a mean age at the start of immunotherapy of 62.1 ± 9.1 years. 38 patients (77.6%) were male. Regarding the histological type, 30 (61.2%) were adenocarcinomas, 16 (32.7%) squamous cell carcinomas and 3 (6.1%) corresponded to other histological types. Regarding the expression of PD-L1, 30 patients (61.2%) had no expression, 13 (26.5%) had PD-L1 ≥1%, and in 6 patients (12.2%) this parameter was unknown. 27 patients (55.1%) were treated with 1 prior therapeutic line, 12 patients (24.5%) with 2 and 10 patients (20.3%) with > 2 previous therapeutic lines. With immunotherapy, 7 (14.3%) had partial response, 22 (44.9%) stable disease and 12 (24.5%) progressive disease. 28 patients (57.1%) have died so far.

      The median PFS was 5 months (95% CI 1.4-8.6) and the median overall survival (OS) was 10 months (95% CI 7.6-12.4). There were no significant differences between patients with or without PD-L1 expression.

      Conclusion

      The OS of our patients treated with nivolumab was slightly lower than some literature which perhaps is related to the fact that this is a real-life study, patients had a high number of previous therapeutic lines and there were different histologic types of LC.

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