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Y. Zhang
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JCES01 - Joint IASLC - Chinese Society for Clinical Oncology - Chinese Alliance Against Lung Cancer Session (ID 413)
- Event: WCLC 2016
- Type: Joint Chinese / English Session
- Track:
- Presentations: 6
- Moderators:F.R. Hirsch, C. Bai
- Coordinates: 12/04/2016, 08:00 - 11:45, Stolz 1
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JCES01.09 - A Comparison of ddPCR and ARMS for Detecting EGFR T790M Status from Advanced NSCLC Patients with Acquired EGFR-TKI Resistance (ID 7053)
10:10 - 10:20 | Author(s): Y. Zhang
- Abstract
- Presentation
Background:
To assess the ability of droplet digital PCR and ARMS technology to detect epidermal growth factor receptor (EGFR) T790M mutations from circulating tumor DNA (ctDNA) in advanced non-small cell lung cancer (NSCLC) patients with acquired EGFR-TKI resistance. A sensitive and convenient method for detecting T790M mutation would be desirable to direct patient sequential treatment strategy.
Methods:
To assess the ability of droplet digital PCR and ARMS technology to detect epidermal growth factor receptor (EGFR) T790M mutations from circulating tumor DNA (ctDNA) in advanced non-small cell lung cancer (NSCLC) patients with acquired EGFR-TKI resistance. A sensitive and convenient method for detecting T790M mutation would be desirable to direct patient sequential treatment strategy.To assess the ability of droplet digital PCR and ARMS technology to detect epidermal growth factor receptor (EGFR) T790M mutations from circulating tumor DNA (ctDNA) in advanced non-small cell lung cancer (NSCLC) patients with acquired EGFR-TKI resistance. A sensitive and convenient method for detecting T790M mutation would be desirable to direct patient sequential treatment strategy.
Results:
A total of 108 patients were enrolled in this study. 108 patient plasma samples were detected by ddPCR and 75 were detected by ARMS. And 16 patients experienced re-biopsy were detected T790M status by ARMS method. 43.7% (47/108) had acquired T790M mutation by ddPCR. In 75 patient plasma samples, comparing ddPCR with ARMS, the rates of T790M mutation were 46.7% (35/75) and 25.3% (19/75) by ddPCR and ARMS, respectively. Of all, 16 patients both had tumor and plasma samples, the T790M mutation rates were 56.3% (9/16) by ARMS in tissue and 50.5% (8/16) by ddPCR in plasma ctDNA. Among them, there were two ctDNA T790M mutations by ddPCR but T790M gene negative in tumor tissue by ARMS method. For all patients, the median PFS and OS were 12.3 months and 32.8 months, respectively. The patients with T790M-positive tumors had a longer time to disease progression after treatment with EGFR-TKIs (median, 13.1 months vs 10.8 months; P=0.010) and overall survival (median, 35.3 months vs 30.3 months; P=0.214) compared with those with T790M-negative patients.
Conclusion:
Our study demonstrates dPCR assay provide feasibility and sensitive method in detecting EGFR T790M status in plasma samples from NSCLC patients with acquired EGFR-TKI resistance.And T790M-positive patients have better clinical outcomes to EGFR-TKIs than patients with T790M negative.
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JCES01.11 - Altered Expression of Programmed Death-Ligand 1 after Neo-Adjuvant Chemotherapy in Patients with Lung Squamous Cell Carcinoma (ID 7055)
10:30 - 10:40 | Author(s): Y. Zhang
- Abstract
- Presentation
Background:
Programmed death-ligand 1 (PD-L1) is known to be over-expressed in non-small cell lung cancer (NSCLC). However, the impact of chemotherapy on the altered status of PD-L1 expression has not been examined for NSCLC. The present study was intended to examine the impact of neoadjuvant chemotherapy on PD-L1 expression and its prognostic significance in lung squamous cell carcinoma (SCC).
Methods:
Matched tumor samples were obtained from SCC patients prior to and after neoadjuvant chemotherapy. The expression of PD-L1 was evaluated by immunohistochemistry. Survival analysis was performed by the Kaplan-Meier method.
Results:
A total of 76 eligible SCC patients were recruited. There were 51 males and 25 females with a median age of 60 (39-72) years. The smoking status was former (n=46) and never (n=34). Prior to neoadjuvant chemotherapy, PD-L1 expression was identified in 52.6% (40/76) of SCC patients while 61.8% (47/76) were positive for PD-L1 expression after neoadjuvant chemotherapy . Nine patients switched from negative to positive while another two patients’ samples showed the reverse of the above result. Multivariate analysis demonstrated that postoperative expression of PD-L1 was an independent prognostic factor for overall survival (HR=0.50, P=0.003), but not for PD-L1 expression prior to neoadjuvant chemotherapy.
Conclusion:
Neoadjuvant chemotherapy may up-regulate the expression of PD-L1. As compared with the status of PD-L1 expression prior to chemotherapy, the postoperative expression of PD-L1 is a better prognostic factor for overall survival in SCC.
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JCES01.14 - Mutational Profiling of Non-Small-Cell Lung Cancer Patients Resistant to First-Generation EGFR Tyrosine Kinase Inhibitors Using next Generation Sequencing (ID 7056)
11:10 - 11:10 | Author(s): Y. Zhang
- Abstract
Background:
Patients with advanced non-small-cell lung cancer (NSCLC) harboring sensitive epithelial growth factor receptor (EGFR) mutations invariably develop acquired resistance to EGFR tyrosine kinase inhibitors (TKIs). Although previous research have identified several mechanisms of resistance, the systematic evaluation using next generation sequencing (NGS) to establish the genomic mutation profiles at the time of acquired resistance has not been conducted.
Methods:
In our single center, we performed NGS of a pre-defined set of 416 cancer-related genes in a cohort of 97 patients with NSCLC harboring TKI-sensitive EGFR mutations at the time of acquired resistance to first-generation EGFR-TKIs between January 2015 to December 2015.
Results:
In 97 samples we found total 345 gene alterations (mean 3.6 mutations per patient, range 1-10). Fifty-six patients (57.7%) still exhibit EGFR-sensitive mutations as pretreatment, 93 patients (95.9%) exhibit at least one mutation except for previous existed EGFR-sensitive mutations. In all the 97 patients, most frequently mutated genes were TP53 (59.8%), T790M (28.9%), TET2 (11.3%), EGFR amplification (10.3%), PIK3CA (8.2%), BIM (8.2%), KRAS (7.2%), APC (7.2%), RB1 (7.2%), HER2 (6.2%), DNMT3A (6.2%) and MET (5.2%).
Conclusion:
NGS in this study uncovered many new genetic alterations potentially associated with EGFR TKI resistance and provided information for the further study of drug resistance and corresponding relevant tactics against the challenge of disease progression.
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JCES01.19 - Clinicopathologic Characteristics, Genetic Variability and Therapeutic Options of RET Rearrangement Patients in Lung Adenocarcinoma (ID 7061)
11:10 - 11:10 | Author(s): Y. Zhang
- Abstract
Background:
RET fusion gene is identified as a novel oncogene in a subset of non-small cell lung cancer (NSCLC). However, few data are available about the prevalence, clinicopathologic characteristics, genetic variability and therapeutic options in RET-positive lung adenocarcinoma patients.
Methods:
For 615 patients with lung adenocarcinoma, RET status was detected by reverse transcription-polymerase chain reaction (RT-PCR). Next-generation sequencing (NGS) and FISH were performed in positive cases. Thymidylate synthetase (TS) mRNA level was assayed by RT-PCR. Overall survival (OS) was evaluated by Kaplan-Meier method and compared with log-rank test.
Results:
Twelve RET-positive patients were identified by RT-PCR. However, one patient failed the detection of RET arrangement by FISH and NGS. Totally, 11 patients (1.8%) confirmed with RET rearrangements by three methods , including six females and five males with a median age of 54 years. The presence of RET rearrangement was associated with lepidic predominant lung adenocarcinoma subtype in five of 11 patients. RET rearrangements comprised of nine KIF5B–RET and two CCDC6–RET fusions. Four patients had concurrent gene variability by NGS detection,including EGFR(n=1),MAP2K1 (n=1), CTNNB1 (n=1) and AKT1 (n=1) . No survival difference existed between RET-positive and negative patients (58.1 vs. 52.0 months, P=0.504) . The median progression-free survival of first-line pemetrexed/platinum regimen was 7.5 months for four recurrent cases,and longer than RET-negative patients(7.5 vs.5.0 months, P=0.026). . The level of TS mRNA was lower in RET-positive patients than that in those RET-negative counterparts (239±188×10[-4] vs. 394±457×10[-4],P=0.019) .
Conclusion:
The prevalence of RET fusion is approximately 1.8% in Chinese patients with lung adenocarcinoma. RET arrangement is characterized by lepidic predominance and a lower TS level. RET-rearranged patients may benefit more from pemetrexed-based regimen.
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JCES01.20 - Patients with ROS1 Rearrangement Positive Non-Small Cell Lung Cancer Benefit from Pemetrexed-Based Chemotherapy (ID 7062)
11:10 - 11:10 | Author(s): Y. Zhang
- Abstract
Background:
ROS1 gene-rearrangement in non-small cell lung cancer (NSCLC) patients has recently been identified as a driver gene and benefited from crizotinib treatment. However, no data is available for ROS1-positivity NSCLC about chemotherapeutic options and prognostic data. We investigated pemetrexed-based treatment efficacy in ROS1 translocation NSCLC patients and determined the expression of thymidylate synthetase (TS) to provide a rationale for the efficacy results.
Methods:
We determined the ROS1 status of 1750 patients with lung adenocarcinoma. Patients’ clinical and therapeutic profile were assessed. In positive cases, thymidylate synthetase (TS) mRNA level was performed by RT-PCR. For comparison, we evaluated the TS mRNA status and pemetrexed-based treatment efficacy from 170 NSCLC patients with anaplastic lymphoma kinase (ALK) translocation(n=46), EGFR mutation (n=50), KRAS mutation (n=32) and wild-type of EGFR/ALK/ROS1/KRAS (n = 42).
Results:
Thirty-four ROS1 translocation patients were identified at two institutions. Among the 34 patients, twelve with advanced stage or recurrence were treated with pemetrexed-based first-line chemotherapy. The median progression-free survivals of pemetrexed-based first-line chemotherapy in ROS1 translocation, ALK translocation, EGFR mutation, KRAS mutation and EGFR/ALK/ROS1/KRAS wild-type patients were 6.8, 6.7, 5.2, 4.2 and 4.5 months, respectively (P=0.003). The TS mRNA level was lower in patients with ROS1-positive than ROS1-negative patients (264±469×10[-4] vs. 469 ± 615×10[-4] , P=0.03), but similar with ALK-positive patients (264±469×10-4 vs. 317±524×10[-4], P=0.64).
Conclusion:
Patients diagnosed with ROS1 translocation lung adenocarcinoma may benefit from pemetrexed-based chemotherapy. TS mRNA level enables the selection of therapeutic options for ROS1translocation patients.
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JCES01.21 - Molecular Profiling and Survival of Primary Pulmonary Neuroendocrine Carcinoma with Completely Resection (ID 7063)
11:10 - 11:10 | Author(s): Y. Zhang
- Abstract
Background:
According to the 2015 World Health Organization classification of lung tumors, pulmonary Large cell neuroendocrine carcinoma (PLCNC) is grouped with the small cell lung cancer (SCLC) and carcinoid as pulmonary neuroendocrine carcinoma(PNC) for the common features of neuroendocrine characteristics . Molecular profiles and prognosis of primary pulmonary neuroendocrine carcinoma(PNC) are not well investigated currently. We conducted present study to evaluate genomic abnormality and survivals in patients with primary PNC.
Methods:
Tumor samples of PNC after completely resection from Zhejiang Cancer Hospital were collected from 2008 to 2015. Nine driver genes including six mutation (EGFR, KRAS, NRAS, PIK3CA, BRAF, HER2) and three fusions (ALK, ROS1, RET) were evaluated by RT-PCR. Survival analysis was evaluated using the Kaplan-Meier method.
Results:
Totally, 108 patients with pathologic confirmed PNC were enrolled. Samples included 52 PLCNC, 44 small cell lung cancer (SCLC) and 12 carcinoid. Twelve patients were found to harbor genomic aberrations (11.1%). The most frequent gene abnormality was PIK3CA (n=5,4.6%),followed with EGFR (n=3,2.8%), KRAS (n=2,n=1.9%), ALK (n=1,0.9%), RET (n=1,0.9%). No ROS1,BRAF,NRAS and HER2 mutations were observed. The frequencies of gene aberrations in PLCNC, SCLC and carcinoid were 15.4%,6.8% and 8.3%,respectively. Sixty-seven patients were with recurrence or metastasis after surgery, including 32 PLCNC, 33 of SCLC, and two of carcinoid (both were atypical carcinoid). Among the 32 patients with PLCNC,none received molecular targeted treatment,28 received first-line chemotherapy,including 18 of etoposide/platinum regimen and 10 of other platinum-based treatment. The progression free survival in patients with etoposide/platinum regimen was longer than patients with non-etoposide/platinum treatment (4.8 vs.3.4 months,P=0.019) . Survival difference was observed among the PLCNC,SCLC and carcinoid group (37.0 vs. 34.0 vs.not reached, P=0.035), but no difference existed between the PLCNC and SCLC group (P=0.606).
Conclusion:
Common genomic abnormality is rare in PNC patients and most frequently observed in PLCNC. Patients with carcinoid had a superior survival than PLCNC and SCLC.
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P1.02 - Poster Session with Presenters Present (ID 454)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Biology/Pathology
- Presentations: 6
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.02-012 - Frequencies of Actionable Mutations and Survival in Variants of Invasive Adenocarcinoma of the Lung (ID 4509)
14:30 - 14:30 | Author(s): Y. Zhang
- Abstract
Background:
2015 new WHO classification lists four rare variants of invasive adenocarcinoma of the lung (VIA): invasive mucinous adenocarcinoma, colloid adenocarcinoma, fetal adenocarcinoma and enteric adenocarcinoma. Very little information is known regarding the molecular alterations and prognostic values for rarity of VIA. The aim of present study was to investigate the common actionable mutations and survival in VIA.
Methods:
Patients who with pathologic confirmed as VIA with completely resected stage I-ⅢA were enrolled from 2010 to 2013. For comparison, we evaluated the gene status and survival from 380 non-VIA lung adenocarcinoma patients in 2012. RT-PCR was utilized for detecting the mutations of EGFR, KRAS, NRAS, PIK3CA, BRAF, HER2 and the fusion of ALK, ROS1 and RET. Survival curves were plotted with Kaplan-Meier method.
Results:
Thirty one patients were recruited from 1120 lung adenocarcinoma,including invasive mucinous adenocarcinoma (n=15), enteric adenocarcinoma(n=9), colloid adenocarcinoma (n=4) and fetal adenocarcinoma(n=3) . The overall frequency of gene abnormality in VIA was 48.4% (15/31). The genes abnormality was as follows: KRAS mutation (n=5), ALK rearrangement (n=4),PIK3CA (n=2), EGFR mutation (n=2), HER2 mutation (n=1) and ROS1 rearrangement (n=1). No mutations of NRAS, BRAF or RET were observed . The frequency of gene abnormality was lower in VIA than non-VIA patients (48.4% vs.74.7%,P=0.0015). No recurrence free survival difference existed in the VIA and non-VIA patients (38.0 vs.47.0 months,P=0.524) . A trend of worse overall survival in VIA than those with non-VIA patients was found(48.0vs.57.0 months, P=0.052).
Conclusion:
VIA is rare in lung adenocarcinoma with lower frequency of common gene abnormality. Invasive mucinous adenocarcinoma was the most frequent subtype and KRAS was a predominant actionable mutation in VIA patients. A trend of worse survival existed in VIA than non-VIA patients.
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P1.02-013 - Clinicopathological Characteristics and Survival of ALK, ROS1 and RET Arrangements in Non-Adenocarcinoma Non-Small Cell Lung Cancer Patients (ID 4510)
14:30 - 14:30 | Author(s): Y. Zhang
- Abstract
Background:
ALK, ROS1 and RET rearrangements represent three most frequency of fusion genes in non-small cell lung cancer (NSCLC). Rearrangements of the three genes are predominantly found in lung adenocarcinoma，while,rare in non-adenocarcinoma. The aim of this study was to investigate the frequency, clinicopathological characteristics and survival of ALK, ROS1 and RET arrangements in non-adenocarcinoma NSCLC patients.
Methods:
We screened ALK,ROS1 and RET arrangements in patients with completely resected non-adenocarcinoma NSCLC using reverse transcriptase polymerase chain reaction (PCR). All positive samples were confirmed with fluorescence in situ hybridization (FISH). Survival analysis was performed with Kaplan-Meier method and log-rank for comparison.
Results:
Totally, 385 patients, who underwent complete resection, including 245 with squamous cell carcinoma, 85 with adenosquamous carcinoma and 55 with large cell carcinoma were enrolled. Twelve patients were identified as harboring fusion genes,including seven with ALK, three with ROS1 and two with RET rearrangements. The frequencies of fusions in adenosquamous carcinoma, squamous cell carcinoma, and large cell carcinoma were 8.2%,1.6% and 1.8%, respectively. The median age of 12 patients was 49.5 years and three patients had smoking history. No survival difference existed between fusion genes positive and negative patients (36.7 vs.50.2 months,P=0.21).
Conclusion:
The frequencies of ALK, ROS1 and RET rearrangements are low in non-adenocarcinoma NSCLC patients, and the clinical characteristics are similar with those in lung adenocarcinoma. Fusions of the three genes are not prognostic marker for non-adnocarcinoma NSCLC patients.
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P1.02-014 - HER2 Mutations in Chinese Patients with Non-Small Cell Lung Cancer (ID 4514)
14:30 - 14:30 | Author(s): Y. Zhang
- Abstract
Background:
ERBB2 (HER2) is a driver gene identified in non-small cell lung cancer (NSCLC). The prevalence, clinicopathology, genetic variability and treatment of HER2-positive NSCLC in Chinese population are unclear.
Methods:
Eight hundred and fifty-nine patients with pathologically confirmed NSCLC were screened for HER2 mutations using Sanger sequencing. Next-generation sequencing (NGS) was performed in positive cases. HER2 amplification was detected with FISH. Overall survival (OS) was evaluated using Kaplan-Meier methods and compared with log-rank tests.
Results:
Twenty-one cases carrying HER2 mutations were identified with a prevalence of 2.4%. HER2 mutations were more frequently encountered in females, non-smokers and adenocarcinoma. NGS was performed in 19 out of 21 patients, The results showed 16 cases with additional genetic aberrations, most commonly associated with TP53 (n = 6), followed by EGFR (n = 3), NF1 (n = 3), KRAS (n = 2) and other mutations. One patient harbored HER2 amplification(figure 1). Four patients with stage IV received afatinib treatment, and three showed stable disease with a median progression-free survival of 4 months and one patient was diagnosed with progressive disease. No survival difference existed between HER2 positive and negative patients( (49.3 months vs.45.0 months, P = 0.150).
Conclusion:
HER2 mutations represent a distinct subset of NSCLC. NGS showed that HER2 mutations commonly co-existed with other driver genes. Afatinib treatment displayed moderate efficacy in patients with HER2 mutations.
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P1.02-015 - A Multicenter Study of EGFR and EML4-ALK Detection in Non-Squamous, Non‒Small-Cell Lung Cancer Patients with Malignant Pleural Effusion (ID 4518)
14:30 - 14:30 | Author(s): Y. Zhang
- Abstract
Background:
Currently, multicenter studies involving a large number of patients have not been not undertaken to detect the frequencies of EGFR mutations and ALK rearrangement in malignant pleural effusion (MPE) samples of patients with non-squamous, non‒small-cell lung cancer (NSCLC), we undertook a multicenter, observational study of Asian patients with untreated stage IV NSCLC.
Methods:
Eligible patients had untreated of EGFR and ALK inhibitor stage IV non-squamous NSCLC patients with MPE. The EGFR and ALK status of MPE and partially paired tumor tissue was determined with reverse transcription polymerase chain reaction (RT-PCR).
Results:
Among 210 patients with pleural effusion samples confirmed as malignant, 16 had EML4-ALK fusion gene rearrangements and 89 had EGFR mutations. No ALK/EGFR coaltered gene was found. Tumor tissue of 56 patients were collected. EGFR and ALK concordance rates between MPE samples and matched tumor tissue samples from 56 patients were 87.5% (49/56) and 96.1% (49/51), respectively. There was a tendency for a longer progression free survival in patients with EGFR accordance in comparison with those with EGFR discordance between tumor tissue and MPE samples (9.8 vs 6.2 months, respectively; p = 0.078). A same trend was found in patients with ALK accordance and discordance (10.0 vs 3.2 months, respectively; p = 0.004) .
Conclusion:
These results demonstrate that MPE can be substituted for tumor tissues for EGFR and ALK gene detection. Patients with gene mutations or arrangement discordance between tumor tissue and MPE samples showed a inferior efficacy of targeted therapy than those with accordance.
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P1.02-069 - Genomic Alterations and Survival in Young Patients under 40 Years with Completely Resected Non-Small Cell Lung Cancer (ID 4508)
14:30 - 14:30 | Author(s): Y. Zhang
- Abstract
Background:
Young patients diagnosed as non-small cell lung cancer (NSCLC) is rare. Little is known for its genomic alterations and survival. This study retrospectively evaluated the genomic alterations,treatment and prognosis with NSCLC in our institution between January 2009 and July 2014 .
Methods:
All patients were examined for EGFR, KRAS, NRAS, PIK3CA, BRAF, HER2 mutations and ALK, ROS1, RET fusion genes based on reverse transcription PCR. The Kaplan-Meier method was used to estimate survival and comparison using the log-rank test.
Results:
Totally, 54 were with age under 40 years old among 640 patients. Among the 640 patients, three hundred and fifty eight patients were with identified genomic alterations with frequency of 55.9 %. The frequencies of genomic alterations in younger and older were 68.5% and 54.8%,respectively (P=0.05). The frequencies difference between younger and older existed in fusions genes ( 22.2% vs.4.1%,P<0.001), but not mutations genes (46.3% vs.45.6%,P=0.92). There was a trend of shorter recurrence free survival in younger than older (35.2 vs.43.8 months,P=0.050), while no survival difference was found between younger and older (50.2 vs 51.4 months,P=0.112).
Conclusion:
We concluded that younger age of NSCLC is associated with a trend of increased of harboring targeted genes and mainly with difference of fusion genes . An inferior overall survival existed in younger than older.
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P1.02-070 - Gene Spectrum and Survival Analyses of Pathologic Subtypes in Resected Lung Squamous Cell Carcinoma (ID 4516)
14:30 - 14:30 | Author(s): Y. Zhang
- Abstract
Background:
Based upon the 2015 Lung Cancer Pathologic Classification, squamous cell carcinoma of lung (SQCC) has been classified as three types of keratinized, non-keratinized and basaloid squamous cell carcinoma (BSCC). The spectrum of common driver genes and clinical prognosis were examined for different subtypes in SQCC in present study.
Methods:
From 2009 to 2013, a total of 201 patients with completely resected stages I-ⅢA SQCC were recruited. Reverse transcription-polymerase chain reaction (RT-PCR) was utilized for detecting the mutations of EGFR, KRAS, NRAS, PIK3CA, BRAF, DDR2, HER2 and the fusion genes of ALK, ROS1 and RET. Survival curves were plotted with Kaplan-Meier method. Cox’s proportional hazard model was used for multivariate analysis.
Results:
The pathological types were BSCC (n=16), non-keratinizing (n=83) and keratinizing (n=102). The overall frequency of gene abnormality was 18.4%. The most common driver genes in a decreasing frequency were PIK3CA mutation (n=14), EGFR mutation (n=8), DDR2 mutation (n=8), KRAS mutation (n=3), HER2 mutation (n=2), ALK rearrangement (n=1) and ROS1 rearrangement (n=1). No mutations of NRAS, BRAF or RET were observed . The frequency of gene abnormality was greater in keratinized (19.6%) ,followed with non-keratinized (19.2%) and BSCC types (6.3%). Targeted therapy was offered for 35 patients, including 32 on EGFR-TKIs (EGFR mutation, n=5; EGFR wild-type, n=27), ALK-positive on crizotinib (n=1) and HER2 mutation on afatinib (n=1). The median progression-free survival (PFS) of EGFR-TKIs were 6.0 and 1.87 months in EGFR mutant and wild types respectively (P=0.004). And the PFS for those two with crizotinib and aftatinib treatment were 8.0 and 3.5 months respectively. . The SQCC patients of BSCC subtype had significantly worse overall survival than those with non-BSCC subtypes (29.0 vs.47.0 months, P<0.001).
Conclusion:
The subtypes of SQCC were associated with varying frequency of gene abnormality. BSCC had a lower frequency of common driver gene abnormality and worse survival.
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P1.04 - Poster Session with Presenters Present (ID 456)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Pulmonology
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.04-024 - Molecular Profiling and Survival of Primary Pulmonary Neuroendocrine Carcinoma with Completely Resection (ID 4517)
14:30 - 14:30 | Author(s): Y. Zhang
- Abstract
Background:
According to the 2015 World Health Organization classification of lung tumors, pulmonary Large cell neuroendocrine carcinoma (PLCNC) is grouped with the small cell lung cancer (SCLC) and carcinoid as pulmonary neuroendocrine carcinoma(PNC) for the common features of neuroendocrine characteristics . Molecular profiles and prognosis of primary pulmonary neuroendocrine carcinoma(PNC) are not well investigated currently. We conducted present study to evaluate genomic abnormality and survivals in patients with primary PNC.
Methods:
Tumor samples of PNC after completely resection from Zhejiang Cancer Hospital were collected from 2008 to 2015. Nine driver genes including six mutation (EGFR, KRAS, NRAS, PIK3CA, BRAF, HER2) and three fusions (ALK, ROS1, RET) were evaluated by RT-PCR. Survival analysis was evaluated using the Kaplan-Meier method.
Results:
Totally, 108 patients with pathologic confirmed PNC were enrolled. Samples included 52 PLCNC, 44 small cell lung cancer (SCLC) and 12 carcinoid. Twelve patients were found to harbor genomic aberrations (11.1%). The most frequent gene abnormality was PIK3CA (n=5,4.6%),followed with EGFR (n=3,2.8%), KRAS (n=2,n=1.9%), ALK (n=1,0.9%), RET (n=1,0.9%). No ROS1,BRAF,NRAS and HER2 mutations were observed. The frequencies of gene aberrations in PLCNC, SCLC and carcinoid were 15.4%,6.8% and 8.3%,respectively. Sixty-seven patients were with recurrence or metastasis after surgery, including 32 PLCNC, 33 of SCLC, and two of carcinoid (both were atypical carcinoid). Among the 32 patients with PLCNC,none received molecular targeted treatment,28 received first-line chemotherapy,including 18 of etoposide/platinum regimen and 10 of other platinum-based treatment. The progression free survival in patients with etoposide/platinum regimen was longer than patients with non-etoposide/platinum treatment (4.8 vs.3.4 months,P=0.019) . Survival difference was observed among the PLCNC,SCLC and carcinoid group (37.0 vs. 34.0 vs.not reached, P=0.035), but no difference existed between the PLCNC and SCLC group (P=0.606) .
Conclusion:
Common genomic abnormality is rare in PNC patients and most frequently observed in PLCNC. Patients with carcinoid had a superior survival than PLCNC and SCLC.
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P2.03b - Poster Session with Presenters Present (ID 465)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 2
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.03b-046 - Clinicopathologic Characteristics, Genetic Variability and Therapeutic Options of RET Rearrangement Patients in Lung Adenocarcinoma (ID 4507)
14:30 - 14:30 | Author(s): Y. Zhang
- Abstract
Background:
RET fusion gene is identified as a novel oncogene in a subset of non-small cell lung cancer (NSCLC). However, few data are available about the prevalence, clinicopathologic characteristics, genetic variability and therapeutic options in RET-positive lung adenocarcinoma patients.
Methods:
For 615 patients with lung adenocarcinoma, RET status was detected by reverse transcription-polymerase chain reaction (RT-PCR). Next-generation sequencing (NGS) and FISH were performed in positive cases. Thymidylate synthetase (TS) mRNA level was assayed by RT-PCR. Overall survival (OS) was evaluated by Kaplan-Meier method and compared with log-rank test.
Results:
Twelve RET-positive patients were identified by RT-PCR. However, one patient failed the detection of RET arrangement by FISH and NGS. Totally, 11 patients (1.8%) confirmed with RET rearrangements by three methods , including six females and five males with a median age of 54 years. The presence of RET rearrangement was associated with lepidic predominant lung adenocarcinoma subtype in five of 11 patients. RET rearrangements comprised of nine KIF5B–RET and two CCDC6–RET fusions. Four patients had concurrent gene variability by NGS detection,including EGFR(n=1),MAP2K1 (n=1), CTNNB1 (n=1) and AKT1 (n=1) . No survival difference existed between RET-positive and negative patients (58.1 vs. 52.0 months, P=0.504) . The median progression-free survival of first-line pemetrexed/platinum regimen was 7.5 months for four recurrent cases,and longer than RET-negative patients(7.5 vs.5.0 months, P=0.026). . The level of TS mRNA was lower in RET-positive patients than that in those RET-negative counterparts (239±188×10[-4] vs. 394±457×10[-4], P=0.019) .
Conclusion:
The prevalence of RET fusion is approximately 1.8% in Chinese patients with lung adenocarcinoma. RET arrangement is characterized by lepidic predominance and a lower TS level. RET-rearranged patients may benefit more from pemetrexed-based regimen.
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P2.03b-078 - MET Gene Amplification and Overexpression in Chinese NSCLC Patients without EGFR Mutations (ID 4501)
14:30 - 14:30 | Author(s): Y. Zhang
- Abstract
Background:
The prevalence and clinic pathologic characteristics of MET amplification and overexpression in Chinese patients with non-small cell lung cancer (NSCLC) remain unknown. In this multicenter study, we focus on revealing the frequency and clinic pathological characteristics of MET amplification and explore the predictive value of MET amplification and overexpression status to survival in Chinese NSCLC patients.
Methods:
MET amplification was detected by fluorescence in-situ hybridization (FISH) in 791 patients with EGFR wild-type samples. MET protein expression was detected by immunohistochemistry.
Results:
In total, 8 patients were identified as harboring MET amplification from 791 NSCLC patients with EGFR wild-type. Among these 8 patients, one was with histology of adeno-squamous carcinoma and 7 of adenocarcinoma. There was no statistically significant difference among age, gender, smoking status and histologic type between patients with and without MET amplification. MET amplification was more frequent in advanced stage and solid predominant subtype of adenocarcinoma. MET protein expression was performed in 395 patients and 138 were positive. Patients with MET protein expression positive had an inferior overall survival compared to those without MET protein expression (45.0 months vs 65.8 months; P=0.001) . Multivariate analysis revealed that MET expression was independent prognostic factor for poor overall survival（HR=1.497,P=0.017),while,the MET amplification shows weak relevance for overall survival (HR=1.974,P=0.251).
Conclusion:
MET amplification was rare in Chinese NSCLC without EGFR mutation, with a prevalence of about 1%. MET expression but not amplification could be an independent prognostic factor for shorter OS among those EGFR wild-type NSCLC patients .
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P2.04 - Poster Session with Presenters Present (ID 466)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Mesothelioma/Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.04-022 - Impact of Metastasis Site for Survival of Patients with Advanced Thymic Epithelial Tumors (ID 4512)
14:30 - 14:30 | Author(s): Y. Zhang
- Abstract
Background:
The aims of present study was to investigate the impact of metastasis site for the survival of patients with advanced thymic epithelial tumors（TET).
Methods:
A retrospective review was conducted to investigate the medical records of patients with advanced TET between 2005 and 2015 in Zhejiang Cancer Hospital. Clinicopathologic characteristics, treatment and prognosis information were collected. Survival curves were plotted using the Kaplan-Meier method and comparison with log-rank. Multivariate analysis was estimated using the Cox proportional hazard model.
Results:
Totally, 92 patients were recruited including 57 of males and 35 females with median age of 51 years old. Thirty-one patients were with thymoma and 61 with thymic carcinoma. Thirty-six patients were with stage IVa and 56 with IVb. The metastasis sites were as follows: plural/pericardial (n=35), lung (n=29), lymph nodes (n=18), bone (n=16), liver (n=13),brain (n=3) and other sites (n=8) . Among these, 20 were multi-sites metastasis . The median overall survival for all patients was 25.4 months (95%CI:21.7-29.1). The median overall survival was shorter in patients with than that without liver metastasis (15.9 vs.26.6 months,P=0.015). A same trend was found in patients with and without brain metastasis (14.5vs.25.6 months,P=0,013) . In multivariate analyses, the brain and liver metastasis were independent unfavorable prognostic factors ( P were 0.015 and 0.008,respectively) .
Conclusion:
Our results suggest of TET with different metastasis sites may have diverse prognosis. Liver and brain metastasis were unfavorable factors for survival of TET patients.
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P3.02a - Poster Session with Presenters Present (ID 470)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 2
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.02a-003 - ALK and ROS1 Rearrangements, Coexistence and Treatment in EGFR-Wild Type Lung Adenocarcinoma - A Multicentre Study of 732 Cases (ID 4499)
14:30 - 14:30 | Author(s): Y. Zhang
- Abstract
Background:
Anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1) rearrangements represent two of the most frequency fusion targets in lung adenocarcinoma. The aim of this study was to investigate the clinicopathological characteristics, coexistence and treatment of ALK and ROS1- rearrangement patients in lung adenocarcinoma without EGFR mutations.
Methods:
Patients who harbored EGFR wild-type gene were screened for ALK and ROS1 gene in four Hospitals in China. ALK and ROS1 rearrangements were detected using RT-PCR. Progression free survival curves were plotted using the Kaplane-Meier method.
Results:
Seven hundred and thirty-two patients enrolled in current study.Of the 732 patients, the median age was 59 years (range: 28–81). ALK and ROS1 rearrangements were detected in 89 (12.2%) and 32 (4.4%) patients,respectively. One patient was identified with ALK/ROS1 coexistence. Both of ALK and ROS1 positive were predominantly found in younger and non-smokers. More patients with ALK/ROS1 rearrangements were associated with TTF1 expression，napsin A expression and solid predominant adenocarcinoma subtype(Figure 1 ). Figure 1Figure 2
Conclusion:
ALK and ROS1 rearrangements frequency was enriched in EGFR wild-type patients and ALK/ROS1 coexistence was rare. The ALK and ROS1 arrangements were associated with age, smoking status, TTF1 expression, napsin A expression and solid predominant adnocarcinoma subtype.
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P3.02a-029 - Patients with ROS1 Rearrangement Positive Non-Small Cell Lung Cancer Benefit from Pemetrexed-Based Chemotherapy (ID 4515)
14:30 - 14:30 | Author(s): Y. Zhang
- Abstract
Background:
ROS1 gene-rearrangement in non-small cell lung cancer (NSCLC) patients has recently been identified as a driver gene and benefited from crizotinib treatment. However, no data is available for ROS1-positivity NSCLC about chemotherapeutic options and prognostic data. We investigated pemetrexed-based treatment efficacy in ROS1 translocation NSCLC patients and determined the expression of thymidylate synthetase (TS) to provide a rationale for the efficacy results.
Methods:
We determined the ROS1 status of 1750 patients with lung adenocarcinoma. Patients’ clinical and therapeutic profile were assessed. In positive cases, thymidylate synthetase (TS) mRNA level was performed by RT-PCR. For comparison, we evaluated the TS mRNA status and pemetrexed-based treatment efficacy from 170 NSCLC patients with anaplastic lymphoma kinase (ALK) translocation (n=46), EGFR mutation (n=50), KRAS mutation (n=32) and wild-type of EGFR/ALK/ROS1/KRAS (n = 42).
Results:
Thirty-four ROS1 translocation patients were identified at two institutions. Among the 34 patients, twelve with advanced stage or recurrence were treated with pemetrexed-based first-line chemotherapy. The median progression-free survivals of pemetrexed-based first-line chemotherapy in ROS1 translocation, ALK translocation, EGFR mutation, KRAS mutation and EGFR/ALK/ROS1/KRAS wild-type patients were 6.8, 6.7, 5.2, 4.2 and 4.5 months, respectively (P=0.003). The TS mRNA level was lower in patients with ROS1-positive than ROS1-negative patients (264±469×10[-4] vs. 469 ± 615×10[-4] , P=0.03), but similar with ALK-positive patients (264±469×10-4 vs. 317±524×10[-4], P=0.64).
Conclusion:
Patients diagnosed with ROS1 translocation lung adenocarcinoma may benefit from pemetrexed-based chemotherapy. TS mRNA level enables the selection of therapeutic options for ROS1 translocation patients.
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P3.02b - Poster Session with Presenters Present (ID 494)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.02b-105 - Mutational profiling of non-small-cell lung cancer patients resistant to first-generation EGFR tyrosine kinase inhibitors using next generation sequencing (ID 3801)
14:30 - 14:30 | Author(s): Y. Zhang
- Abstract
Background:
Patients with advanced non-small-cell lung cancer (NSCLC) harboring sensitive epithelial growth factor receptor (EGFR) mutations invariably develop acquired resistance to EGFR tyrosine kinase inhibitors (TKIs). Although previous research have identified several mechanisms of resistance, the systematic evaluation using next generation sequencing (NGS) to establish the genomic mutation profiles at the time of acquired resistance has not been conducted.
Methods:
In our single center, we performed NGS of a pre-defined set of 416 cancer-related genes in a cohort of 97 patients with NSCLC harboring TKI-sensitive EGFR mutations at the time of acquired resistance to first-generation EGFR-TKIs between January 2015 to December 2015.
Results:
In 97 samples we found total 345 gene alterations (mean 3.6 mutations per patient, range 1-10). Fifty-six patients (57.7%) still exhibit EGFR-sensitive mutations as pretreatment, 93 patients (95.9%) exhibit at least one mutation except for previous existed EGFR-sensitive mutations. In all the 97 patients, most frequently mutated genes were TP53 (59.8%), T790M (28.9%), TET2 (11.3%), EGFR amplification (10.3%), PIK3CA (8.2%), BIM (8.2%), KRAS (7.2%), APC (7.2%), RB1 (7.2%), HER2 (6.2%), DNMT3A (6.2%) and MET (5.2%).
Conclusion:
NGS in this study uncovered many new genetic alterations potentially associated with EGFR TKI resistance and provided information for the further study of drug resistance and corresponding relevant tactics against the challenge of disease progression.
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P3.02c - Poster Session with Presenters Present (ID 472)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 2
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.02c-023 - Mutation and Prognostic Analyses of PIK3CA in Patients with Completely Resected Lung Adenocarcinoma (ID 4505)
14:30 - 14:30 | Author(s): Y. Zhang
- Abstract
Background:
PIK3CA mutation represents a clinical subset of diverse carcinomas. We explored the status of PIK3CA mutation and evaluated its genetic variability, treatment and prognosis in patients with lung adenocarcinoma.
Methods:
A total of 810 patients with completely resected lung adenocarcinoma were recruited between 2008 and 2013. The status of PIK3CA mutation and other three genes, i.e. EGFR mutation, KRAS mutation & ALK fusion, was examined by reverse transcription-polymerase chain reaction (RT-PCR). Survival curves were plotted with the Kaplan-Meier method and log-rank for comparison. Cox proportional hazard model was performed for multivariate analysis.
Results:
Among the 810 patients, 23 cases of PIK3CA mutation were identified with a frequency of 2.8%. There were 14 males and 9 females with a median age of 61 years. Seventeen tumors revealed concurrent gene abnormalities of EGFR mutation (n=12), KRAS mutation (n=3) and ALK fusion (n=2). Seven patients with EGFR & PIK3CA mutations recurred and the dosing of EGFR-TKIs yielded a median progression free-survival of 6.0 months. Among 4 eviromous-treated patients, stable disease was obtained in three patients with a median PFS of 3.5 months. Patients with and without PIK3CA mutation had different overall survivals (32.2 vs. 49.6 months, P=0.003). Multivariate analysis revealed that PIK3CA mutation was an independent predictor of poor overall survival (HR=2.37, P=0.017).
Conclusion:
The frequency of PIK3CA mutation was around 2.8% in Chinese patients of lung adenocarcinoma. PIK3CA mutation was associated with reduced PFS of EGFR-TKIs treatment and shorter overall survival.
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P3.02c-082 - Altered Expression of Programmed Death-Ligand 1 after Neo-Adjuvant Chemotherapy in Patients with Lung Squamous Cell Carcinoma (ID 4503)
14:30 - 14:30 | Author(s): Y. Zhang
- Abstract
Background:
Programmed death-ligand 1 (PD-L1) is known to be over-expressed in non-small cell lung cancer (NSCLC). However, the impact of chemotherapy on the altered status of PD-L1 expression has not been examined for NSCLC. The present study was intended to examine the impact of neoadjuvant chemotherapy on PD-L1 expression and its prognostic significance in lung squamous cell carcinoma (SCC).
Methods:
Matched tumor samples were obtained from SCC patients prior to and after neoadjuvant chemotherapy. The expression of PD-L1 was evaluated by immunohistochemistry. Survival analysis was performed by the Kaplan-Meier method.
Results:
A total of 76 eligible SCC patients were recruited. There were 51 males and 25 females with a median age of 60 (39-72) years. The smoking status was former (n=46) and never (n=34). Prior to neoadjuvant chemotherapy, PD-L1 expression was identified in 52.6% (40/76) of SCC patients while 61.8% (47/76) were positive for PD-L1 expression after neoadjuvant chemotherapy . Nine patients switched from negative to positive while another two patients’ samples showed the reverse of the above result. Multivariate analysis demonstrated that postoperative expression of PD-L1 was an independent prognostic factor for overall survival (HR=0.50, P=0.003), but not for PD-L1 expression prior to neoadjuvant chemotherapy.
Conclusion:
Neoadjuvant chemotherapy may up-regulate the expression of PD-L1. As compared with the status of PD-L1 expression prior to chemotherapy, the postoperative expression of PD-L1 is a better prognostic factor for overall survival in SCC.
