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Gang Chen
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MA 07 - ALK, ROS and HER2 (ID 673)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:Robert C. Doebele, J.C. Ho
- Coordinates: 10/17/2017, 15:45 - 17:30, Room 316
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MA 07.13 - NGS Sequencing Based Liquid / Tissue Biopsy Identified Coexistence of HER2 Amplification and Mutation in Advanced NSCLC Patients (ID 9737)
17:05 - 17:10 | Author(s): Gang Chen
- Abstract
- Presentation
Background:
Human epidermal growth factor 2 (HER2, ERBB2) mutations / amplifications have been identified as oncogenic drivers in 2-5% of lung cancers. It has been reported that hybridization capture-based next-generation sequencing (NGS) could reliably detect HER2 amplification in qualified breast and gastroesophageal tumor tissue samples. However, there is little data in lung cancer, especially for advance NSCLC with only ctDNA samples available.
Method:
We reviewed 2000 consecutive samples from advanced NSCLC patients sequenced in our institute between 2015 and 2016. Tumor biopsy and/or ctDNA samples were analyzed using hybridization capture-based NGS ER-Seq method, which enables simultaneously assess single-nucleotide variants, insertions/deletions, rearrangements, and somatic copy-number alterations at least 59 genes (range 59 – 1021 genes).
Result:
We identified 54 samples from 48 patients with HER2-mutation or amplification in the cohort (54/2000=2.7%). The 54 samples included 14 tissue biopsy samples, 37 ctDNA samples, and 3 pleural effusion samples. Thirty-six samples carried HER2 mutations, and 23 samples carried HER2 amplification with 5 samples have concurrent HER2 mutation and amplification. A 9-base pair (bp) in-frame insertion in exon 20 (Y772_A775dup) was detected in 18 samples (18/36=50%). In addition, there were 5 other insertions in exon 20; eight single bp substitutions (S310F) in exon 8; three exon 17 V659E mutations (from the sample patient with 3 ctDNA samples submitted at different time); one exon 19 D769H mutation; and one exon 21 V842I mutation. Amplification were identified in 23 samples, with copy number range from 3.8 to 19.6 in tissue samples (n=7, medium 11.6); from 4.3 to 51.8 in ctDNA samples (n=16, medium 7.3); 3.2 and 6 in the 2 pleural effusion samples. Interestingly, the allele frequency (AF) of HER2 mutation was the maximal in 4 of the 5 patients with concurrent HER2 mutation and amplification. Two patients were EGFR-TKI resistant with EGFR L858R mutation remaining and HER2 mutation and amplification might be the major reason for the resistance.
Conclusion:
HER2 mutations might coexist with HER2 amplification in advanced NSCLC patients, and it could be detected simultaneously with hybridization capture-based NGS sequencing both in tissue and liquid biopsy samples. Further quantative analysis of HER2 amplification / mutation and anti-HER2 therapeutic effects are underway.
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P1.01 - Advanced NSCLC (ID 757)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 2
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.01-002 - TP53 Mutations Predict for Poor Survival in ALK Rearrangement Lung Adenocarcinoma Patients Treated with Crizotinib (ID 8241)
09:30 - 09:30 | Presenting Author(s): Gang Chen
- Abstract
Background:
Advanced non-small-cell lung cancer patients who harbor anaplastic lymphoma kinase (ALK) rearrangement are sensitive to an ALK inhibitor (Crizotinib), but not all ALK-positive patients benefit equally from crizotinib treatment. We analyze the impact of TP53 mutations on response to crizotinib in patients with ALK rearrangement non-small cell lung cancer (NSCLC).
Method:
66 ALK rearrangement NSCLC patients receiving crizotinib were analyzed. 21 cases were detected successfully by the next generation sequencing validation FFPE before crizotinib. TP53 mutations were evaluated in 8 patients in relation to disease control rate (DCR), objective response rate (ORR), progression-free survival (PFS) and overall survival (OS).
Result:
TP53 mutations were observed in 2 (25.00%), 1 (12.50%), 1 (12.50%) and 4 (50.00%) patients in exons 5, 6, 7 and 8, respectively. The majority of patients were male (75.00%, 6/8), less than 60 years old (62.50%, 5/8) and never smokers (75.00%, 6/8). ORR and DCR for crizotinib in the entire case series were 61.90% and 71.43%, respectively. Statistically significant difference was observed in terms of PFS and OS between TP53 gene wild group and mutation group patients (P=0.038, P=0.021, respectively).
Conclusion:
TP53 mutations reduce responsiveness to crizotinib and worsen prognosis in ALK rearrangement NSCLC patients.
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P1.01-003 - Patients Harboring a Novel PIK3CA Point Mutation after Acquired Resistance to Crizotinib in ROS1 Rearrangement Adenocarcinoma: A Case Report (ID 8245)
09:30 - 09:30 | Author(s): Gang Chen
- Abstract
Background:
The c-ros oncogene 1 receptor tyrosine kinase (ROS1) rearrangement has been identified in 1%-2% of non-small cell lung cancer (NSCLC) cases, these patients would benefit from the inhibitor of anaplastic lymphoma kinase (ALK), crizotinib. But the resistance to crizotinib inevitably developed in the patients with ROS1 rearrangement NSCLC and shown a response to crizotinib initially. The mechanism of acquired resistance to crizotinib for the patients with ROS1 rearrangement NSCLC is not identified completely now.
Method:
A 66-year-old female diagnosed with adenocarcinoma, who shown EGFR wild and ALK negative detected by Polymerase Chain Reaction(PCR). According to the detection of ROS1 rearrangement by the next generation sequencing (NGS) in blood after the patient received chemotherapy twice (pemetrexed and carboplatin), the addition of bevacizumab to chemotherapy 4 times (pemetrexed, carboplatin and bevacizumab) and maintenance therapy 3 times (pemetrexed and bevacizumab), crizotinib was used. Disease progressed explosively 6 months later, although the patient shown a response to crizotinib initially. Then NGS was carried out on blood again, a novel point mutation (p.L531P)of the PIK3CA gene was detected.
Result:
This case was the second report for bypass activation conferred crizotinib resistance to the patient with ROS1 rearrangement NSCLC. And it also was the first report that confirmed mTOR signaling pathways activation would lead to acquired resistance to crizotinib in the clinical. And everolimus, the mTOR signaling pathway inhibitor, was used. However, the disease of the patient was too serious, and she still died of circulatory failure. In conclusion, progression-free survival was 5.0 months and overall survival was 16.0 months.
Conclusion:
Bypass activation is one of potential resistance mechanisms to ROS1 rearrangement NSCLC conferred crizotinib and regimen for mTOR signaling pathway inhibitor may be one of the treatment options.
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P1.02 - Biology/Pathology (ID 614)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 10
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.02-043 - A Comparison of Consistency of Detecting BRAF Gene Mutations in Peripheral Blood and Tumor Tissue of Non-Small-Cell Lung Cancer Patients (ID 8248)
09:30 - 09:30 | Presenting Author(s): Gang Chen
- Abstract
Background:
BRAF, one of the three members of the RAF kinase family, belongs to the group of serine-threonine kinases and plays a vital role in mitogen-activated protein kinase (MAPK) pathways. Mutations of BRAF have been found in 0.5-3% of non-small-cell lung cancer (NSCLC). Among the different mutations occurring in the BRAF gene, BRAF V600E is the most common. A number of BRAF inhibitors, including sorafenib, vemurafenib and dabrafenib, are under clinical development. Thus, the detection of genetic driver mutation in lung cancer patients has become the most important tool in clinical practice. The aim is to detect the consistency of the BRAF gene mutation in peripheral blood and tumor tissue of patients with NSCLC and discuss the clinical application value of BRAF gene mutation in peripheral blood.
Method:
Real-time fluorescent quantitative polymerase chain reaction (RT-PCR) was used to detect the tissues in 257 patients of NSCLC and the peripheral blood samples in 318 patients of NSCLC, of which 185 cases of peripheral blood specimens could match the tissue samples, and detected the BRAF gene mutation in them by comparison of mutations consistency in blood and tissue samples, and analyzed the correlation between BRAF gene mutations and clinical characteristics of patients.
Result:
The BRAF gene mutation rate was 7.23% in peripheral blood of 23 patients with NSCLC, and was 5.45% in 14 cancer tissues, the mutation consistency was 80.00% in peripheral blood tumor tissue matched samples. The consistency was statistically significant (κ=0.710, P<0.001).
Conclusion:
The consistency of the BRAF gene mutation in peripheral blood and tissue is high. BRAF gene mutations of peripheral blood could be used for clinical diagnosis and treatment in cases when tissue specimen is hard to get.
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P1.02-044 - Relationship between RET Rearrangement and Thymidylate Synthase mRNA Expression in Non-Small Cell Lung Cancer Tissues (ID 8266)
09:30 - 09:30 | Presenting Author(s): Gang Chen
- Abstract
Background:
RET fusion gene is identified as a novel oncogene in a subset of non-small cell lung cancer (NSCLC). However, few datas are available about the prevalence and clinicopathologic characteristics in RET rearrangement lung adenocarcinoma patients. The aim of this study is to investigate mRNA expressions and relationship of RET rearrangement and thymidylate synthase (TYMS) genes in NSCLC tissues.
Method:
The positive rate of RET rearrangement and the mRNA expressions of of TYMS gene in NSCLC tissues of 642 patients were detected by using real-time fluorescent quantitative PCR method, and the relationship and its correlation between the expression and clinicopathological features were also analyzed.
Result:
The positive rate of RET rearrangement in NSCLC was 0.93% (6/642); High mRNA expression of TYMS gene was 63.55%(408/642). The expressions showed no relationship with gender, age, smoking, tumor size, lymph node metastasis and clinical stages (P>0.05). The mRNA expressions between RET rearrangement and TYMS genes showed positive correlation (P<0.05).
Conclusion:
Thymidylate synthase gene shows low expression level in NSCLC patients with positive RET fusion gene, which may benefit from pemetrexed of first-line chemotherapy drug.
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P1.02-045 - PIK3CA Mutations in Chinese Patients with Non-Small-Cell Lung Cancer (ID 8264)
09:30 - 09:30 | Author(s): Gang Chen
- Abstract
Background:
PIK3CA mutation represents a clinical subset of diverse carcinomas. We explored the status of PIK3CA mutation and evaluated its genetic variability and prognosis in patients with lung adenocarcinoma. The aim of this study is to investigate mutations and prognosis of non-small-cell lung cancer(NSCLC) harboring PIK3CA mutations.
Method:
A total of 517 patients with NSCLC were recruited between July 2012 and December 2014. The status of PIK3CA mutation and other genes were detected by reverse transcription polymerase chain reaction(RT-PCR) or next generation sequencing.
Result:
PIK3CA gene mutation was detected in 3.09% (16/517) NSCLC patients, including H1047R (4 patients), E545A (2 patients), E453K (2 patients), H1065Y (2 patients), E545K (1 patient), E39K (1 patient), E542K (1 patient), C420R (1 patient), K111E (1 patient) and E545K plus L781F (1 patient), and median overall survival (OS) for these patients was 23.0 months. Among them, 12 patients with co-occurring mutations had a median OS of 28.0 months, and median OS of the 4 patients without complex mutations was 21.0 months. No statistically significant difference was found between the two groups (P=0.06). Briefly, patients with (n=5) or without (n=11) co-occurring EGFR mutations had a median OS of 28.5 months and 21.0 months repectively (P=0.45); patients with (n=4) or without (n=12) co-occurring TP53 mutations had a median OS of 30.6 months and 21.0 months repectively (P=0.51).
Conclusion:
There is no significant difference of molecular features in PIK3CA gene mutations in NSCLC. Patients with complex mutations benefited more from therapy than those with single mutations.
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P1.02-046 - Mutational Subtypes and Prognosis of Non-Small-Cell Lung Cancer Harboring HER2 Mutations (ID 8267)
09:30 - 09:30 | Presenting Author(s): Gang Chen
- Abstract
Background:
HER2 is a driver gene identified in non-small-cell lung cancer(NSCLC). The prevalence, clinicopathology and genetic variability of HER2 mutation non-small cell lung cancer patients are unclear. The aim of this study is to investigate mutational subtypes and prognosis of NSCLC harboring HER2 mutations.
Method:
A total of 781 patients with NSCLC were recruited between July 2012 and December 2014. The status of HER2 mutation and other genes were detected by reverse transcription polymerase chain reaction (RT-PCR) or next generation sequencing.
Result:
HER2 gene mutation rate was 1.92%(15/781) in NSCLC, including S310F (2 patients), A775_G776insYVM (2 patients), S280F (2 patients), P780_Y781insGSP (1 patient), C630Y (1 patient), L755P (1 patient), T327S (1 patient), K907R (1 patient), R70W (1 patient), E117D (1 patient), L970V (1 patient), and C965S (1 patient). Mutation rate of female was much higher than male(3.76% vs 1.23%, P=0.022), and current-smoker was much higher than no-smoker(3.17% vs 0.74%, P=0.027), and median overall survival (OS) for these patients was 42.6 months. Among them, 12 patients with co-occurring mutations had a median OS of 42.6 months, and median OS of the 3 patients without cpmplex mutations was 40.3 months. No statistically significant difference was found between the two groups(P=0.43). Briefly, patients with (n=8) or without (n=7) co-occurring EGFR mutations had a median OS of 50.6 months and 42.6 months repectively (P=0.19); patients with (n=9) or without (n=6) co-occurring TP53 mutations had a median OS of 40.4 months and 46.7 months repectively (P=0.39); patients with (n=2) or without (n=13) co-occurring SMARCA4 mutations had a median OS of 50.6 months and 42.6 months repectively (P=0.33); patients with (n=2) or without (n=13) co-occurring MTOR mutations had a median OS of 44.3 months and 42.6 months repectively (P=0.71); patients with (n=2) or without (n=13) co-occurring SMARCA4 mutations had a median OS of 50.6 months and 42.6 months repectively (P=0.33); patients with (n=2) or without (n=13) co-occurring APC mutations had a median OS of 39.0 months and 42.6 months repectively (P=0.92).
Conclusion:
There are some significant difference of molecular features in HER2 gene mutations with non-smoking women in NSCLC, along with the state of HER2 gene mutations little influence on prognosis. Afatinib treatment may displayed moderate efficacy in patients with HER2 mutations.
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P1.02-047 - Mutational Features and Prognosis of Non-Small-Cell Lung Cancer Harboring RAS Mutations (ID 8268)
09:30 - 09:30 | Author(s): Gang Chen
- Abstract
Background:
In non-small cell lung cancer (NSCLC) RAS-mutant status is a negative prognostic and predictive factor. The prevalence, clinicopathology and genetic variability of RAS mutation NSCLC patients are unclear. The aim of this study is to investigate mutations and prognosis of NSCLC harboring RAS mutations.
Method:
We retrospectively reviewed clinical features from 41 patients with RAS gene mutation NSCLC, and the survival rate was calculated by Kaplan-Meier method and log-rank test was used to compare the survival rates.
Result:
KRAS gene mutation rate was 8.00% (38/475) in NSCLC, including G12C (9 patients), G12D (8 patients), G12V (7 patients), G12A (2 patients), G12S (2 patients), G13D (2 patients), Q61H (2 patients), G12L (1 patient), G12 (1 patient), G12K (1 patient), G12fs*3 plus G12V (1 patient), G13C plus V14I(1 patient) and K5N(1 patient). Mutation rate of current-smoker was much higher than no-smoker(15.76% and 4.41%, P<0.01), and median overall survival (OS) for these patients was 18.3 months; NRAS gene mutation rate was 0.29% (1/346), G12D, and OS for these patients was 14.2 months; HRAS gene mutation rate was 0.63% (2/315), including H27N and N85I, and median OS for both patients was 19.2 months. Among them, 18 cases of the 41 RAS mutation patients with co-occurring mutations had a median OS of 28.0 months, and median OS of the 23 patients without cpmplex mutations was 21.0 months. No statistically significant difference was found between the two groups(P=0.06). Briefly, patients of KRAS mutations with (n=4) or without (n=34) co-occurring EGFR mutations had a median OS of 40.0 months and 16.3 months repectively (P=0.07); patients with (n=3) or without (n=35) co-occurring TP53 mutations had a median OS of 36.4 months and 18.3 months repectively (P=0.22); patients with (n=3) or without (n=35) co-occurring STK11 mutations had a median OS of not reached so far and 16.3 months repectively (P=0.22); patients with (n=2) or without (n=36) co-occurring KEAP1 mutations had a median OS of 43.6 months and 16.3 months repectively (P=0.06).
Conclusion:
Mutation rate of KRAS gene in current-smoker NSCLC patients was higher than no-smoker, there is no other significant difference of molecular features in RAS gene mutations in NSCLC. Patients with complex mutations benefited more from therapy than those with single mutations. Immunotherapy may displayed moderate efficacy in patients with TP53 and RAS co-exist mutations.
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P1.02-049 - Detection of CDKN2A Gene Mutations in Patients with Non-Small Cell Lung Cancer Patients (ID 8312)
09:30 - 09:30 | Author(s): Gang Chen
- Abstract
Background:
CDKN2A is the tumor suppressor, which regulates cell cycle progression by inhibiting cyclinD-CDK4 and cyclinD-CDK6 complexes responsible for initiating the G1/S phase transition. CDKN2A gene disruption happens by different types of mutations, such as the loss of heterozygosity, homozygous deletion, or promoter silencing. There is some clinical evidence for the use of CDKN2A 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 CDKN2A mutations.
Method:
A total of 1046 patients with NSCLC were recruited between July 2012 and December 2014. The status of CDKN2A mutation and other genes were detected by next generation sequencing.
Result:
CDKN2A gene mutation was detected in 0.77% (8/1046) NSCLC patients, including p.M53I (1 patient), p.R58* (2 patients), p.R80* (2 patients), c.193+2T>C (1 patient), p.A127T (1 patient) and p.D74Y (1 patient), and median overall survival (OS) for these patients was 29.8 months. Among them, all patients were CDKN2A gene with co-occurring mutations. Briefly, patients with (n=4) or without (n=4) co-occurring EGFR mutations had a median OS of 23.4 months and 33.6 months repectively (P=0.32); patients with (n=6) or without (n=2) co-occurring TP53 mutations had a median OS of 23.4 months and 34.8 months repectively (P=0.27).
Conclusion:
EGFR and TP53 gene accompanied may have less correlation with CDKN2A mutation in NSCLC patients. CDK4/6 inhibitor palbociclib drugs may displayed moderated efficacy in patients with CDKN2A mutation.The findings of this study could facilitate the identification of therapeutic target candidates for precision medicine of NSCLC
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P1.02-056 - BRAF Non-V600E Mutations Recurrently Found in Non-Small Cell Lung Cancer in Chinese Patients (ID 8291)
09:30 - 09:30 | Author(s): Gang Chen
- Abstract
Background:
Approximately half of BRAF-mutated non-small cell lung cancer (NSCLC) harbor a BRAF non-V600E mutation. Because of the rarity of those mutations, associated clinical features and prognostic significance have not been thoroughly described so far.
Method:
A total of 2979 patients with non-small-cell lung cancer were recruited between July 2012 and December 2014. The status of BRAF mutation and other genes were detected by pyrophosphate sequencing or the next generation sequencing.
Result:
BRAF gene mutation rate was 0.91% (27/2979) in NSCLC, and median overall survival (OS) for these patients was 14.0 months. Among them, 17 BRAF non-V600E patients (A308T, A569T, V377D, R626K, P345T, Q530*, A320T, G652E, N581S, T167I, G466V, L597V, D594G, D594G, R389C, G469A, W531S, 62.96%) had a median OS of 11.9 months, and median OS of the 10 BRAF V600E patients (37.04%) was 24.3 months. Statistically significant difference was found between the two groups (P=0.03). Briefly, patients with (n=2)(non-V600E), (n=3)(V600E) or without (n=22) co-occurring EGFR mutations had a median OS of 25.6 months, 14.8 months and 14.8 months repectively (P=0.43); patients with (n=12)(non-V600E), (n=4)(V600E) or without (n=11) co-occurring TP53 mutations had a median OS of 11.9 months, 26.8 months and 13.9 months repectively (P=0.23); patients with (n=2)(non-V600E), (n=1)(V600E) or without (n=24) co-occurring ATM mutations had a median OS of 25.8 months, 16.0 months and 12.9 months repectively (P=0.71); patients with (n=3)(non-V600E), or without (n=24) co-occurring KRAS mutations had a median OS of 10.4 months and 15.3 months repectively (P=0.14); patients with (n=5)(non-V600E), or without (n=22) co-occurring DNMT3A mutations had a median OS of 13.4 months and 15.3 months repectively (P=0.22).
Conclusion:
This one of the largest series of patients with BRAF mutant NSCLC. Our clinical datas suggest that BRAF non-V600E mutations define specific subsets of patients with NSCLC, the value of BRAF non-V600E mutations are poor prognosis than V600E mutations. And it may benefit from combined targeted therapy with a RAF inhibitor and a MEK-inhibitor in treating BRAF non-V600E mutantion NSCLC.
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P1.02-057 - Analysis of C-MET Amplification Non-Small Cell Lung Cancer Cell Blocks from Pleural Effusion (ID 8282)
09:30 - 09:30 | Presenting Author(s): Gang Chen
- Abstract
Background:
The MET receptor tyrosine kinase and its ligand, hepatocyte growth factor, is identified as a treatment target in lung cancer. c-MET gene abnormality can be distributed to various mechanisms including: overexpression, kinase activation, exon mutation, and amplification. c-MET gene amplification has been described as one of the reasons responsible for acquired EGFR tyrosine kinase inhibitor resistance. The aim of this study is to investigate the clinical value of c-MET gene amplification non-small cell lung cancer (NSCLC) blocks cell from pleural effusion.
Method:
Two hundred and fifeen cases of c-MET gene amplification non-small cell lung cancer (NSCLC) blocks cell from pleural effusion, Four hundred and four cases of tissues were detected by reverse transcription polymerase chain reaction (RT-PCR) method. The consistency of c-MET amplification was examined in 74 cases of patients with tissues and cell blocks.
Result:
c-MET amplification was found in 31 of 215 cell blocks (positive detection rate of 14.42%). c-MET amplification was detected in 35 of 404 tissue blocks (positive detection rate of 8.66%). There were 68cases in the 74 (91.89%) cases had the same consistency as tissue block. c-MET amplification was detected in 9 of 74 (12.16%) cell blocks, and 13 of 74 (17.57%) tissue blocks.
Conclusion:
The rate of c-MET amplification in cell blocks of NSCLC is higher than in matched tissue blocks. The patients with malignant pleural effusion are likely to tend c-MET amplification.
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P1.02-058 - Molecular Characteristics and Outcome of Chinese Patients with Non-Small Cell Lung Cancer Harboring NFE2L2 Mutations (ID 8293)
09:30 - 09:30 | Presenting Author(s): Gang Chen
- Abstract
Background:
Recently, the nuclear factor (erythroid derived 2)-like 2 (NFE2L2) gene mutations are identified in non-small-cell lung cancer(NSCLC). While the genetic variability of NFE2L2 mutation NSCLC patients is unclear. The aim of this study is to investigate mutations and prognosis of NSCLC harboring NFE2L2 mutations.
Method:
A total of 375 patients with non-small-cell lung cancer were recruited between July 2012 and December 2014. The status of NFE2L2 mutation and other genes were detected by the next generation sequencing.
Result:
NFE2L2 gene mutation was detected in 2.40% (9/375) in NSCLC patients, including R34Q (2 patients), R34G (2 patient), D77Y (2 patients), D29N (1 patient), E79Q (1 patient) and D29H (1 patient), stage of IIIB-IV was much higher than IA-IIIA (9.76% vs 0.34%, P<0.001), and smoker was much higher than no-smoker (4.14% vs 0.97%, P<0.001). The median overall survival (OS) for these patients was 33.6 months. Among them, 7 patients with co-occurring mutations had a median OS of 37.4 months, and median OS of the 2 patient without complex mutations was 18.1 months. No statistically significant difference was found between the two groups (P=0.12). Briefly, patients with (n=4) or without (n=5) co-occurring EGFR mutations had a median OS of 33.6 months and 28.6 months repectively (P=0.76); patients with (n=4) or without (n=5) co-occurring TP53 mutations had a median OS of 33.6 months and 19.7 months repectively (P=0.88); patients with (n=2) or without (n=7) co-occurring DNMT3A mutations had a median OS of 37.4 months and 26.7 months repectively (P=0.72).
Conclusion:
There are some significant difference of clinical features in NFE2L2 gene mutations with smoking advance non-small-cell lung cancer. TP53 accompanied mutations might play a good prognosis in NFE2L2 gene mutation non-small cell lung cancer.
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P1.02-059 - Molecular Characteristics of SMARCA4 Mutations Detection in Chinese Non-Small Cell Lung Cancer Patients (ID 8309)
09:30 - 09:30 | Presenting Author(s): Gang Chen
- Abstract
Background:
The SMARCA4 gene encodes an ATP-dependent helicase BRG1 and it belongs to SWI/SNF (switching defective/sucrose nonfermenting) complex. According to previous researches, SMARCA4 is one of the most broadly mutated subunits, developing an understanding of the mechanisms by which mutation of SMARCA4 drives cancer. The aim of this study is to investigate mutations and prognosis of NSCLC harboring SMARCA4 mutations.
Method:
A total of 1190 patients with non-small-cell lung cancer were recruited between July 2012 and December 2014. The status of SMARCA4 mutation and other genes were detected by next generation sequencing.
Result:
SMARCA4 gene mutation was detected in 0.84% (10/1190) NSCLC patients, including R370P (1 patient), N519Kfs*15 (1 patient), Q464K (1 patient), Q1440* (2 patients), E959* (1 patient), I1400M (1 patient), E882K (1 patient), D656H (1 patient) and A379T plus A39T (1 patient), and median overall survival (OS) for these patients was 17.9 months. Among them, all patients were RB1 gene with co-occurring mutations. Briefly, patients with (n=5) or without (n=5) co-occurring EGFR mutations had a median OS of 22.1 months and 14.7 months repectively (P=0.79); patients with (n=6) or without (n=4) co-occurring TP53 mutations had a median OS of 26.2 months and 16.3 months repectively (P=0.43); patients with (n=2) or without (n=8) co-occurring HER2 mutations had a median OS of 28.9 months and 14.7 months repectively (P=0.28);patients with (n=2)or without (n=9) co-occurring STK11 mutations had a median OS of 14.2 months and 26.2 months repectively (P=0.04);patients with (n=2) or without (n=8) co-occurring DNMT3A mutations had a median OS of 16.3 months and 26.2 months repectively (P=0.34); patients with (n=2) or without (n=8) co-occurring TERT mutations had a median OS of 22.1 months and 14.7 months repectively (P=0.88).
Conclusion:
mTOR pathway may play a poor prognosis in SMARCA4 gene mutation non-small cell lung cancer. HDAC inhibitor treatment may displayed moderated efficacy in patients with SMARCA4 gene mutations. Further research on SMARCA4 gene mutation is required. Maybe a panel of biomarkers will be necessary in the future.
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P2.01 - Advanced NSCLC (ID 618)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:00 - 16:00, Exhibit Hall (Hall B + C)
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P2.01-017 - Study on the Effect of Apatinib Salvage Treatment of Advanced Non-Small Cell Lung Cancer (ID 8285)
09:00 - 09:00 | Author(s): Gang Chen
- Abstract
Background:
No definitive chemotherapeutic regimen has been established in patients with non-small-cell lung cancer (NSCLC) who failed second-or third-line treatment. The study of this aim is to investigate the effect of apatinib in advanced non-small cell lung cancer.
Method:
72 patients with advanced non-small cell lung cancer treated in our hospital from March 2014 to March 2016 were selected and given oral apatinib (750mg, qd) to tumor progression, death or toxicity intolerance so far. The objective response rate (ORR), disease control rate (DCR), progression free survival (PFS), and toxic side effects were observed and observed. Single factor analysis was used to compare the relationship between the clinical features and PFS.
Result:
The median PFS of the patients was 4.8 months (95%CI:4.7-5.0). The results of single factor analysis showed that there were no significant differences between different gender, age, PS score, histological type, drive gene mutation and metastasis foci, the number of metastasis, metastasis, treatment history, line number and duration of treatment in patients with PFS (P>0.05). The ORR of this group was 13.89%, DCR was 83.33%. According to the clinical data of 72 patients in the treatment of patients with the clinical efficacy of the waterfall plot, we can see that there are 54 cases of patients with lesions to reduce the diameter of tumor lesions as the effective treatment of the standard, there were 10 patients with of PR. There are various types of adverse events occurred in 60 patients, the incidence rate was 83.33%, including 22 cases (30.55%) for the aged III.
Conclusion:
Apatinib is a effective and safe treatment in advanced non-small cell lung cancer, and can be carried out more in-depth research and application in clinic.
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P2.02 - Biology/Pathology (ID 616)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 6
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.02-004 - Gene Mutational Feature in Lung Enteric Adenocarcinoma by the Next Generation Sequencing (ID 8243)
09:30 - 09:30 | Presenting Author(s): Gang Chen
- Abstract
Background:
Primary lung enteric adenocarcinoma is a rare type of invasive lung carcinoma. Its morphology and immunohistochemistry is close to colorectal carcinoma, but there is no associated primary colorectal carcinoma. The purpose of this study is to assess the gene mutational feature in lung enteric adenocarcinoma by the next generation sequencing.
Method:
From Feb. 2013 to Dec. 2016, 11 lung enteric adenocarcinoma patients (5 males and 6 females) received treatment from three medical centers: including Beijing, Zhejiang and Fujian. All the patients were diagnosed by pathology. Analysis was used by the next generation sequencing.
Result:
ALK/ROS1 primary point mutations were confirmed in 5 patients (71.42%, 5/7). MSH2/MSH6 point mutations were confirmed in 3 patient (42.86%, 3/7). There was no case with drive genes changed, such as EGFR mutation, ALK rearrangement, ROS1 rearrangement, RET rearrangement, MET amplification or 14 exon skipping mutation. The median overall survival (OS) of 11 lung enteric adenocarcinoma patients was 9.0 months, Subgroup analysis the median OS of ALK/ROS1 primary point mutation patients was 6.5 months, the median OS of MSH2/MSH6 primary point mutation patients was 26.0 months.
Conclusion:
ALK/ROS1 primary point mutations or MSH2/MSH6 point mutations are the most frequent feature of heterozygous mutation in our study. The MSH2/MSH6 subgroup of the median OS is longer. Further investigations will be required to validate our findings.
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P2.02-005 - 13 Cases of Molecular Features Analysis in Pulmonary Mucoepidermoid Carcinoma (ID 8278)
09:30 - 09:30 | Presenting Author(s): Gang Chen
- Abstract
Background:
The cases of pulmonary mucoepidermoid carcinoma (PMEC) are extremely rare. There is only limited data on treatment outcome for chemotherapy in PMEC, and less so for targeted therapy such as targeted therapy with icotinib. The aim of this study is to investigate the molecular characteristics of pulmonary mucoepidermoid carcinoma (PMEC).
Method:
From July 2013 to December 2016, 13 PMEC patients received treatment. All the patients were diagnosed by pathology. We retrospectively reviewed the clinical data and genetic state.
Result:
EGFR mutation rate was 15.38% (2/13), and 2 cases were both L861Q point mutations, the relationship between EGFR gene status and gender (P=1.000), age (P=1.000), smoking (P=0.848) and stage (P=1.000) were no significant, respectively; the positive rate of MAML2 fusion gene was 45.45%(5/11). the relationship between MAML2 fusion gene status and gender (P=0.521), age (P=0.521), smoking (P=1.000) and stage (P=0.924) were no significant, respectively.
Conclusion:
The most common form change of pulmonary mucoepidermoid carcinoma is EGFR gene L861Q point mutation, MALM2 fusion gene exist in the EGFR gene wild type patients. icotinib treatment may benefit from patients with EGFR L861Q point mutations and MALM2 fusion gene.
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P2.02-006 - NovoSV: Identify and Parse the Pattern of Chromosomal Structural Variation (ID 8283)
09:30 - 09:30 | Presenting Author(s): Gang Chen
- Abstract
Background:
With the development of High-throughput DNA sequencing technologies, several tools have been developed aim at searching structural variations. However, most of available structural variation predication tools can only identity the abnormal connections, a systematically parsing the pattern of structure variation to obtain the length and connection type of SVs is still tough work.
Method:
In this study, we present a tool, NovoSV, which can identify the abnormal connections precisely, and based on associated abnormal connections NovoSV will report the length and connection type of the structural variation.
Result:
NovoSV took a BWA mapped results as input and identified abnormal connections and pattern of chromosomal structure variations would be reported. For validation, NovoSV was applied to target sequencing data derived from 10 samples, NovoSV identified 8 abnormal connections, and 7 of these results could be validated by polymerase chain reaction (PCR). When applied to whole-genome sequencing data derived from 5 samples, NovoSV reported 46 SVs with their length and connection type. Of the 4 random selected identified results, 3 were validated by Sanger sequencing.
Conclusion:
NovoSV is an efficient tool for chromosomal variation detection, which can accurately identify abnormal connections and parse the pattern of chromosomal variations. NovoSV has been validated on GNU/Linux systems, and an open source PERL program is available.
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P2.02-007 - Molecular Spectrum of STK11 Gene Mutations in Patients with Non-Small-Cell Lung Cancer in Chinese Patients (ID 8289)
09:30 - 09:30 | Presenting Author(s): Gang Chen
- Abstract
Background:
STK11 is commonly mutated in non-small cell lung cancer (NSCLC). In light of recent experimental data showing that specific STK11 mutantion can acquire oncogenic activities due to the synthesis of a short STK11 isoform, The aim of this study is to investigate whether this new classification of STK11 mutants can help refine its role as a prognostic marker.
Method:
A total of 879 patients with NSCLC were recruited between July 2012 and December 2014. The status of STK11 mutation and other genes were detected by the next generation sequencing (NGS).
Result:
STK11 gene mutation rate was 0.91% (8/879) in NSCLC, including p.K269fs*18 (1 patient), p.K329stop (1 patient), c.464 plus 1G>T (1 patient), p.D194E (1 patient), p.D176V (1 patient), p.D53Tfs*11 (1 patient), p.D194A (1 patient) and p.Y118* (1 patient), and median overall survival (OS) for these patients was 22.2 months. Among them, all patients were STK11 gene with co-occurring mutations. Briefly, patients with (n=2) or without (n=6) co-occurring EGFR mutations had a median OS of 29.0 months and 22.2 months repectively (P=0.73); patients with (n=5) or without (n=3) co-occurring TP53 mutations had a median OS of 29.0 months and 22.2 months repectively (P=0.95); patients with (n=3) or without (n=5) co-occurring KRAS mutations had a median OS of not reached so far and 13.8 months repectively (P=0.02); patients with (n=2) or without (n=6) co-occurring SMARCA4 mutations had a median OS of 14.0 months and 37.0 months repectively (P=0.11); patients with (n=3) or without (n=5) co-occurring KEAP1 mutations had a median OS of not reached so far and 14.6 months repectively (P=0.20).
Conclusion:
STK11 mutations represent a distinct subset of NSCLC. NGS showed that STK11 mutations commonly co-existed with other driver genes. Our results show that STK11 mutations delineate an aggressive subtype of lung cancer for which a targeted treatment through STK11 inhibition might offer new opportunities.
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P2.02-020 - Molecular Characteristics of Patients with PTEN Mutations in Chinese Non-Small Cell Lung Cancer (ID 8292)
09:30 - 09:30 | Author(s): Gang Chen
- Abstract
Background:
Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a known tumor suppressor in non-small cell lung cancer (NSCLC). Because of the rarity of those mutations, associated clinical features and prognostic significance have not been thoroughly described so far. The aim of this study is to investigate mutations and prognosis of NSCLC harboring PTEN mutations.
Method:
A total of 402 patients with non-small-cell lung cancer were recruited between July 2012 and December 2014. The status of PTEN mutation and other genes were detected by the next generation sequencing.
Result:
PTEN gene mutation was detected in 1.99% (8/402) NSCLC patients, including A333fs*10 (2 patients), D252N (1 patient), P38S (1 patient), Q171E (1 patient), S59* (1 patient), S10R(1 patient) and Y225Ifs*18(1 patient), and median overall survival (OS) for these patients was 19.7 months. Among them, 7 patients with co-occurring mutations had a median OS of 23.3 months, and OS of the 1 patient without complex mutations was 14.6 months. No statistically significant difference was found between the two groups (P=0.35). Briefly, patients with (n=5) or without (n=3) co-occurring EGFR mutations had a median OS of 33.6 months and 16.0 months repectively (P=0.33); patients with (n=4) or without (n=4) co-occurring TP53 mutations had a median OS of 14.9 months and 33.5 months repectively (P=0.18); patients with (n=2) or without (n=6) co-occurring DNMT3A mutations had a median OS of 17.8 months and 24.8 months repectively (P=0.27).
Conclusion:
Our results demonstrated that decreased PTEN gene mutation correlated with poor overall survival in non-small-cell lung cancer patients. PTEN gene mutation may define a subset of patients with lung cancer appropriate for investigational therapeutic strategies.
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P2.02-021 - Prevalence of PTPRD Gene Mutations in Chinese Non-Small Cell Lung Cancer Patients (ID 8311)
09:30 - 09:30 | Author(s): Gang Chen
- Abstract
Background:
PTPRD, encoding protein tyrosine phosphatases receptor type D, is located at chromosome 9p23-24.1, a loci frequently lost in many types of tumors. Recently, PTPRD has been proposed to function as a tumor suppressor gene. The aim of this study is to investigate mutations and prognosis of non-small-cell lung cancer(NSCLC) harboring PTPRD mutations.
Method:
A total of 962 patients with NSCLC were recruited between July 2012 and December 2014. The status of PTPRD mutation and other genes were detected by next generation sequencing.
Result:
PTPRD gene mutation was detected in 0.64% (6/962) NSCLC patients, including V693F (1 patient), V330L (1 patient), T1103A (2 patients), D388Y (1 patient) and R1692G plus G1213V (1 patient), and median overall survival (OS) for these patients was 31.4 months. Among them, all patients were PTPRD gene with co-occurring mutations. Briefly, patients with (n=2) or without (n=4) co-occurring EGFR mutations had a median OS of 41.0 months and 20.6 months repectively (P=0.06); patients with (n=4) or without (n=2) co-occurring TP53 mutations had a median OS of 27.6 months and 26.0 months repectively (P=0.79).
Conclusion:
PTPRD gene mutation coexist with other gene mutation in NSCLC. EGFR and TP53 gene accompanied may have less correlation with PTPRD mutation in NSCLC patients. Results of ongoing studies will provide more insight into effective treatment strategies for patients with PTPRD mutations.
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P2.03 - Chemotherapy/Targeted Therapy (ID 704)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Chemotherapy/Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.03-057 - Effectiveness of Icotinib on Uncommon EGFR Exon 20 Insert Mutations: A763_Y 764insFQEA in Non-Small-Cell Lung Cancer (ID 8286)
09:30 - 09:30 | Author(s): Gang Chen
- Abstract
Background:
Clinical features of epidermal growth factor receptor (EGFR) mutations: L858R, deletions in exon 19, T790M, G719X, and L861Q in non-small-cell lung cancer (NSCLC) are well-known. The clinical significance of other uncommon EGFR mutations, such as A763_Y764insFQEA, is not well understood. This study is aimed to improve the understanding of A763_Y764insFQEA, and the clinical response to icotinib of NSCLC patients with such an uncommon mutation.
Method:
Six cases of EGFR exon 20 A763_Y764insFQEA mutation and twelve cases of EGFR exon 20 other insert mutation NSCLC patients were retrospectively analyzed until the progress of the disease or the emergence of the side effects and clinical efficacy was observed after months of followed-up.
Result:
Six cases with EGFR exon 20 A763_Y764insFQEA and twelve cases of EGFR exon 20 other insert mutation NSCLC patients mutation manifested the median PFS (9.0months vs 1.2months, P<0.001). Clinical efficacy of icotinib with advanced NSCLC harboring EGFR exon 20 mutations between A763_Y764insFQEA and other insert mutation (ORR:33.33%, DCR: 100% vs ORR: 0, DCR: 16.16%).
Conclusion:
EGFR exon 20 A763_Y764insFQEA mutation of clinical benefit from icotinib is remarkable, and it close to the common mutation of clinical benefit. It illustrates the value of in-depth molecular testing with NGS of EGFR wild type NSCLC patients.
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P3.01 - Advanced NSCLC (ID 621)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 2
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.01-008 - Association between Icotinib Efficacy and Circulating Tumor Cell Levels in Advanced Non-Small Cell Lung Cancer (ID 8253)
09:30 - 09:30 | Author(s): Gang Chen
- Abstract
Background:
Advanced non-small cell lung cancer(NSCLC) studies indicated a potential association between chemotherapy efficacy and circulating tumor cells (CTC) counts in peripheral blood. The icotinib efficacy and circulating tumor cells (CTC) counts in non-small cell lung cancer remain unknown. The aim is to investigate association between the icotinib efficacy and CTC counts in advanced NSCLC patients.
Method:
A total of 74 advanced NSCLC patients consented to provide 5ml of peripheral blood before systematic therapy, and divided into two groups (those with high CTC counts and those with low CTC counts) based on the patients′ median CTC counts. All the patients were treated with icotinib, and the icotinib efficacy and prognoses were compared.
Result:
The treatment efficacies were 46.88% (15/32) and 23.81% (10/42) for the low CTC group and the high CTC group, respectively. The median overall survival was 22.0 months (95%CI: 19.6-28.7 months) for the low CTC group and 18.3 months (95% CI: 15.3-25.4 months) for the high CTC group. The median progression-free survival was 11.6 months (95% CI: 8.7-15.6 months) and 7.2 months (95% CI: 3.4-8.7 months) for the low group and the high CTC group, respectively.
Conclusion:
The CTC counts can be used as a important biomarker for therapy monitoring the icotinib effect on patients with advanced NSCLC. Efficacy and prognosis of icotinib and CTC counts were considered important, and the CTC counts could be used to predict the efficacy of icotinib and prognosis of advanced NSCLC. The change in CTC count levels can be used as a biomarker for evaluating the prognosis of patients with advanced NSCLC.
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P3.01-009 - Clinical Efficacy of Icotinib in Patients with Advanced Non-Small Cell Lung Cancer Harboring EGFR Exon 18 E709X Mutations (ID 8288)
09:30 - 09:30 | Author(s): Gang Chen
- Abstract
Background:
EGFR exon 18 E709X mutation is only reported in small case numbers of non-small cell lung cancer (NSCLC) in the literature, and their influences on the effectiveness of icotinib have not been fully understood. The study of this aim is to investigate the efficacy of icotinib in patients with NSCLC that carrying EGFR exon 18 E709X mutation.
Method:
Three cases of EGFR exon 18 E709X mutations were retrospectively analyzed until the progress of the disease or the emergence of the side effects and clinical efficacy was observed after months of followed-up.
Result:
The median progression-free survival (PFS) of three cases with EGFR exon 18 E709X (E709_T710>D, E709A, E709K plus L858R) was 3.1 months, patients with complex mutations showed a better PFS than those with single mutations (7.2 months vs. 2.7 months, P=0.225). Clinical efficacy of icotinib with advanced NSCLC harboring EGFR exon 18 E709X mutation (ORR: 66.67%, DCR: 66.67%).
Conclusion:
Icotinib is effective in patients with exon 18 E709X mutations. Patients with complex mutations benefited more from icotinib than those with single mutations.
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P3.02 - Biology/Pathology (ID 620)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 10
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.02-018 - Patients Harboring ALK Rearrangement Adenocarcinoma after Acquired Resistance to Crizotinib and Transformation to SCLC: A Case Report (ID 8244)
09:30 - 09:30 | Author(s): Gang Chen
- Abstract
Background:
Anaplastic lymphoma kinase(ALK) rearrangement responds to ALK tyrosine kinase inhibitors (TKIs) in lung cancer. Many cases ultimately acquired resistance to crizotinib. Resistance mechanisms have been described including ALK dominant or ALK non-dominant. A mechanism of transformation to small-cell lung cancer is rare.
Method:
A 54-year-old male diagnosed with adenocarcinoma, who shown EGFR wild and ALK rearrangement detected by RT-PCR and treatment with crizotinib. A re-biopsy showed a small cell lung cancer after disease progression.
Result:
The next generation sequencing (NGS) was carried out and it detected TP53 gene mutation and ALK rearrangement, no loss of retinoblastoma gene (RB). Regimen for small-cell lung cancer (SCLC) may be one of the treatment options. However, the heterogeneous tumor may be at diagnosed and the course of disease.
Conclusion:
Oncologists should realize the possibility of transformation to SCLC after patients acquire resistance to ALK-TKI therapy. A re-biopsy should be performed to enable histological and detect molecular analysis. And finding transformation to SCLC is important for choosing appropriate therapy due to the potential efficacy of standard SCLC treatments or combination of next generation AKL-TKIs.
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P3.02-025 - 65 Cases of Molecular Profiling Anaysis in Surgical Resected Pulmonary Neuroendocrine Carcinoma (ID 8274)
09:30 - 09:30 | Presenting Author(s): Gang Chen
- Abstract
Background:
Due to a low frequency of pulmonary neuroendocrine carcinoma, little is known for its molecular aberrations and prognosis. The aim of this study is to investigate the characteristics of surgical resected pulmonary neuroendocrine carcinoma and to analyze the prognostic factors.
Method:
We retrospectively reviewed the clinical data and genetic status from 65 patients with pulmonary neuroendocrine carcinoma[small-cell cancer (SCLC), n=26; large cell neuroendocrine carcinoma (PLCNC), n=34; carcinoid, n=5], and the survival rate was calculated by Kaplan-Meiermethod and log-rank test was used to compare the survival rates. Univariate and multivariate factors for survival were analyzed by COX proportional hazards regression model.
Result:
There was no significant difference with clinical characteristics in 65 cases of pulmonary neuroendocrine carcinoma (P>0.05); The genetic change was given priority to with PIK3CA gene mutations, SCLC and PLCNC and carcinoid the median overall survival time (26.7 months vs 30.4 months vs did not reach) (P=0.039) and staging was differences statistically significant by the single factor analysis in SCLC (P<0.05).
Conclusion:
Pulmonary neuroendocrine carcinoma genetic change was rare, and it is given priority to with PIK3CA gene mutations, common genomic aberrations are rare for PNC. Molecular profiles vary widely among different subtypes of PNC. Carcinoid offers better survival than PLCNC and SCLC, whereas no survival difference existed between PLCNC and SCLC.
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P3.02-026 - The Study of ROS1 Rearrangement in Advanced Primary Non-Small Cell Lung Cancer and Associated Metastatic Lesions (ID 8281)
09:30 - 09:30 | Presenting Author(s): Gang Chen
- Abstract
Background:
ROS1 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 are available for ROS1 rearrangement NSCLC about relationship between primary and metastatic patients. The aim of this study is to examine the positive rate of ROS1 rearrangement in primary and metastatic NSCLC, and to investigate their relationships.
Method:
From January 2013 to May 2015, 384 cases of primary NSCLC consisting of 246 cases of matched metastatic tumors and 47 cases of normal lung specimens as the control group were collected in multicenter. The positive rate of ROS1 rearrangement among NSCLC population was figured out, thus the consistency of ROS1 rearrangement in advanced primary NSCLC and associated metastases and the relationship between ROS1 rearrangement and clinical data was analyzed.
Result:
The positive rate of ROS1 rearrangement on primary tumor was 2.60% (10/384). For those 246 paired cases, the positive rate on primary tumor was 2.85% (7/246), with that of metastases 1.63% (4/246). Among the 246 cases, there was one case whose metastases was positive, primary tumors negative and 4 case whose primary tumor were positive, metastases were negative. Positive rate of ROS1 rearrangement was higher in the primary lesions than metastases. It was of statistical significance between the two groups (χ[2]=52.341, P<0.001). The positive rate of primary tumors could be predicted by metastases (κ=0.536, P<0.001). The sensitivity was 42.86% (3/7) and the specificity was 99.58% (238/239).
Conclusion:
The metastases of NSCLC can predict ROS1 rearrangement of the primary lesions. It can be used as alternative means for metastases to detect ROS1 rearrangement which are not readily available.
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P3.02-027 - Lung Adenocarcinoma Patient with EGFR 19 Exon Insert Mutation: I740_K745insIPVAIK and Its Response to Icotinib: A Case Report (ID 8287)
09:30 - 09:30 | Presenting Author(s): Gang Chen
- Abstract
Background:
Screening for epidermal growth factor receptor (EGFR) mutation before choosing a therapeutic strategy for patients with advanced non-small-cell lung cancer (NSCLC) is universally accepted at present. One of the reasons that certain patients without activating EGFR mutation respond to EGFR-tyrosine kinase inhibitor (TKI) treatment is possibly due to false-negative EGFR mutation. However, none of the available methods can provide the entire information of EGFR mutation; while maintaining the best sensitivity and specificity. Uncommon mutations are often evasive due to the limitation of screening methods.
Method:
A 74-year-old smoking male diagnosed with adenocarcinoma, who detected EGFR gene by reverse transcription polymerase chain reaction (RT-PCR) and the next generation sequencing (NGS)
Result:
Histopathological observations with hematoxylin and eosin staining was shown adenocarcinoma, Immunohistochemical staining for the expression of TTF-1, NapsinA and CK7. The gene detected by RT-PCR that found EGFR wild type, but it found EGFR p.I740_K745insIPVAIK and BRCA2 p.C315S by NGS. Albeit rare, this specific type of EGFR mutation deserves more attention because it was related to a good response to EGFR-TKI therapy. The patient received icotinib therapy, and icotinib therapy showed a good response. We report here, to our knowledge, the first case received icotinib in mainland China of EGFR exon 19 insert.
Conclusion:
To reduce the frequency of false negatives, hence not to lose any opportunities for a potential icotinib treatment, NGS for EGFR mutation examination according to the specimen quality and quantity (tumor load and DNA yield) is proposed.
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P3.02-028 - 276 Cases of EGFR/ALK Gene Status and Predominant Histologic Subtype in Chinese Surgically Resected Lung Adenocarcinoma (ID 8271)
09:30 - 09:30 | Presenting Author(s): Gang Chen
- Abstract
Background:
A new lung adenocarcinoma classification proposed by WHO (2015) classification of tumors of the lung has recently been published. The aim of this study is to investigate the mutations of EGFR gene and ALK fusion gene in Chinese surgically resected lung adenocarcinomas.
Method:
Reverse transcription polymerase chain reaction (RT-PCR) was used to detect the tissues in 276 patients of surgically resected lung adenocarcinomas with paraffin tissue EGFR gene mutation and ALK fusion gene.
Result:
The total mutation rate in 276 patients of surgically resected lung adenocarcinomas was 54.71% (151/276). EGFR gene mutation rate were found in 19del (28.99%, 80/276), L858R (23.19%, 64/276), 20-ins (0.72%, 2/276), L861Q (0.72%, 2/276), G719X (1.09%, 3/276), S768I (0.36%, 1/276) and T790M (0.72%, 2/276) in surgically resected lung adenocarcinomas, including one case of G719X plus S768I, 19del plus T790M, L858R plus T790M, respectively. The total fusion positive rate in 207 patients of surgically resected lung adenocarcinomas was 5.80% (12/207). There were statistically significant (P<0.001, P<0.001, P=0.023, P<0.001 and P=0.030) in each subtype of lung adenocarcinoma of EGFR gene mutation, including lepidic predominant adenocarcinoma, acinar predominant adenocarcinoma, papillary predominant adenocarcinoma, solid predominant adenocarcinoma and invasive mucous adenocarcinoma, and there were not statistically significant(P>0.05) among other types. There were not statistically significant(P>0.05) among each types of lung adenocarcinoma of ALK fusion gene.
Conclusion:
Histologic subtyping was found to be associated with EGFR mutations. The EGFR mutation frequency of lepidic predominant, acinar predominant and papillary predominant subtypes was found to be more pronounced than that of other subtypes.
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P3.02-029 - 218 Cases of EGFR/ALK Gene Status Anaysis in Chinese Lung Squamous Cell Carcinoma (ID 8272)
09:30 - 09:30 | Presenting Author(s): Gang Chen
- Abstract
Background:
Due to the low frequency of EGFR mutation and ALK fusion gene in lung squamous cell carcinoma. Thus the efficacy of icotinib and crizotinib for these patients is not well known. The aim of this study is to investigate the mutations of EGFR gene and ALK fusion gene in lung squamous cell carcinoma.
Method:
The reverse transcription polymerase chain reaction (RT-PCR) method was used to detect the tissues in 218 patients of lung squamous cell carcinoma with paraffin tissue EGFR gene mutation and ALK fusion gene.
Result:
The total mutation rate in 218 patients of squamous cell carcinoma was 54.71% (151/276). EGFR gene mutation rate was 2.29% (5/218), which was both found in 19del and L858R, ALK fusion gene positive rate was 6.14% (7/114).
Conclusion:
There are a certain proportion of EGFR gene mutation and ALK fusion gene in lung squamous cell carcinoma, and the detection the EGFR gene mutation and ALK fusion gene can not be ignored in squamous cell carcinoma.
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P3.02-065 - Lung Adenocarcinoma Patient with EGFR Kinase Domain Duplication(KDD) and Its Response to Icotinib: A Case Report (ID 8277)
09:30 - 09:30 | Author(s): Gang Chen
- Abstract
Background:
EGFR exon 18-25 kinase domain duplication (EGFR-KDD) mutations has rencently emerged as a new EGFR gene molecular subtype in non-small cell lung cancer(NSCLC) is extremely rare. And the curative effect to icotinib is still unclear.
Method:
A 63-year-old female diagnosed with adenocarcinoma, who was shown to have gene detected by the next generation sequencing (NGS) and treatment with icotinib.
Result:
Histopathological observations with hematoxylin and eosin staining was shown adenocarcinoma, immunohistochemical staining for the expression of TTF-1, NapsinA and CK7. The gene detected by NGS that found EGFR-KDD, PIK3CG p.R839C and NTRK2 p.P50Lfs*14. Our case is the first report EGFR-KDD in Chinese populations. The patient was treated surgically and received icotinib therapy. And the surgery and icotinib therapy showed a good response.
Conclusion:
For patients with this subtype, further research and experience are needed to summarize them. This case illustrates the value of in-depth molecular testing with NGS of EGFR wild type non-small cell lung cancer patients.
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P3.02-068 - 95 Cases of EGFR/ALK Gene Status Anaysis in Lung Adenosquamous Carcinoma (ID 8273)
09:30 - 09:30 | Author(s): Gang Chen
- Abstract
Background:
Adenosquamous carcinoma is a rare subtype of lung cancer, it is mixed glandular and squamous cell carcinoma with a more aggressive behavior and poor prognosis than the other histologic subtypes. The aim of this study is to investigate the characteristics of lung adenosquamous carcinoma and to analyze the prognostic factors.
Method:
The reverse transcription polymerase chain reaction (RT-PCR) method was used to detect the tissues in 95 patients of lung adenosquamous carcinoma with paraffin tissue EGFR gene mutation and ALK fusion gene. And the survival rate was calculated by Kaplan-Meiermethod and log-rank test was used to compare the survival rates. Univariate and multivariate factors for survival were analyzed by COX proportional hazards regression model.
Result:
95 cases of lung adenosquamous carcinoma were males, more than 60 years old and smoking patients predominant; COX univariate analysis revealed that gender, age, smoking history, EGFR gene status, ALK fusion gene status, stage, subtype patterns and subtype type were prognostic factors for lung adenosquamous carcinoma. COX multivariate analysis found that stage, subtype patterns and subtype type were independent prognostic factors for lung adenosquamous carcinoma (P<0.05).
Conclusion:
Lung adenosquamous carcinoma mainly occurred in men patients over 60 years old with smoking. Stage, subtype patterns and subtype type are the crucial prognostic factors for lung adenosquamous carcinoma.
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P3.02-069 - 58 Cases of EGFR/ALK Gene Status Anaysis in Pulmonary Sarcomatoid Carcinoma (ID 8276)
09:30 - 09:30 | Author(s): Gang Chen
- Abstract
Background:
Sarcomatoid carcinomas are a rare type of cancer found in the lung and other organs. The aim of this study is to investigate the characteristics of pulmonary sarcomatoid carcinoma (PSC) and to analyze the prognostic factors.
Method:
Fifty-eight patients with pulmonary sarcomatoid carcinoma were retrospectively reviewed on the clinical data and genetic state, and the survival rate was calculated by Kaplan-Meier method and log-rank test was used to compare the survival rates. Univariate and multivariate factors for survival were analyzed by COX proportional hazards regression model.
Result:
Fifty-eight cases of pulmonary sarcomatoid carcinoma were men, less than 65 years old and smoking patients predominant; COX univariate analysis revealed that gender, age, smoking history, EGFR gene status, ALK fusion gene status, stage, histologic subtype were prognostic factors for pulmonary sarcomatoid carcinoma. COX multivariate analysis found that ALK fusion gene status, histologic subtype were independent prognostic factors for pulmonary sarcomatoid carcinoma (P<0.05).
Conclusion:
There is no specificity in the clinical characteristics of PSC and its successful diagnosis depends on pathological analysis. ALK fusion status and histologic subtype are the crucial prognostic factors for pulmonary sarcomatoid carcinoma.
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P3.02-080 - DNMT3A Defines a Unique Molecular Class of Chinese Non-Small Cell Lung Cancer Patients (ID 8313)
09:30 - 09:30 | Presenting Author(s): Gang Chen
- Abstract
Background:
DNMT3A mutation is detected in approximately 18%-23% newly diagnosed AML patients, while the mutation is less frequently detected in cancer. The aim of this study is to investigate mutations and prognosis of non-small-cell lung cancer (NSCLC) harboring DNMT3A mutations.
Method:
A total of 1367 patients with NSCLC were recruited between July 2012 and December 2014. The status of DNMT3A mutation and other genes were detected by next generation sequencing.
Result:
DMNT3A gene mutation was detected in 1.1% (15/1367) NSCLC patients, including p.V636M (1 patient), p.Y735C (1 patient), p.Y660F (1 patient), p.R183W (1 patient), p.Q653H (1 patient), p.A741P (1 patient), p.Q226* (1 patient), p.D340Y (1 patient), p.A398T (1 patient), p.A187T (1 patient), p.A910V (1 patient), p.R729W (1 patient), p.S770L (1 patient), c.1755+1G>T (1 patient) and G510D plus F545V plus R582Q (1 patient), and median overall survival (OS) for these patients was 19.7 months. Among them, all patients were DNMT3A gene with co-occurring mutations. Briefly, patients with (n=11) or without (n=4) co-occurring EGFR mutations had a median OS of 19.1 months and 22.9 months repectively (P=0.82);patients with (n=13) or without (n=2) co-occurring TP53 mutations had a median OS of 16.0 months and 29.8 months repectively (P=0.98); patients with (n=5) or without (n=10) co-occurring HER2 mutations had a median OS of 44.3 months and 14.6 months repectively (P<0.01); patients with (n=2) or without (n=13) co-occurring SMARCA4 mutations had a median OS of 32.3 months and 19.7 months repectively (P=0.43); patients with (n=2) or without (n=13) co-occurring BRCA1 mutations had a median OS of 29.6 months and 19.7 months repectively (P=0.93).
Conclusion:
EGFR, TP53, HER2, SMARCA4 and BRCA1 gene accompanied may have less correlation with DNMT3A mutation in NSCLC patients. Chemotherapy drugs may displayed moderated efficacy in patients with DMNT3A mutation. Analysis of DNMT3A mutations shows promise as a way to refine individual patients with NSCLC, and provides a platform for further research to offer individualized therapy with the purpose of improving outcomes.
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P3.03 - Chemotherapy/Targeted Therapy (ID 719)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Chemotherapy/Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.03-005 - Diagnosis and Treatment Analysis of Lung Enteric Adenocarcinoma: 6 Case Report and Review of the Literature (ID 8284)
09:30 - 09:30 | Author(s): Gang Chen
- Abstract
Background:
Primary lung enteric adenocarcinoma is a rare type of invasive lung carcinoma. This study mainly discusses the clinicopathological characteristics, diagnosis and treatment of primary lung enteric adenocarcinoma.
Method:
Retrospectively analysed clinical records of 6 cases admitted in hospital from Feb. 2013 to May 2016, and reviewed the literature of primary lung enteric adenocarcinoma.
Result:
Two patients were male and four patients were female with the age ranged from 25 to 78 years. Their symptoms consisted mainly of cough chest stuffy with 4 patients, neck mass with 1 case, dizziness nausea vomiting with 1 case; imagining scan showed mass of lung and or mediastinal, pathology form and the immunochemistry showed all positive for intestinal immune phenotypes and some positive for lung cancer immunophenotypic. But no tumor was found by gastrointestinal endoscopes; 1 case recurrence and metastasis after radical operation; 1 patient underdone palliative surgery, 1 patient with brain solitary metastasis onset received Cyber Knife and without system treatment, and 5 patients underwent chemotherapy. At the end of follow-up, 4 patients died, over survival time as long as 32 months.
Conclusion:
The primary lung enteric adenocarcinoma is easily confused with pulmonary metastases from colorectal cancer, confirmed diagnosis need to rule out intestinal lesion, the main early treatment is surgery, and systematic treatment programs need to be further studied.
