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Y. Chen
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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 | Author(s): Y. 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): Y. 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: 6
- 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 | Author(s): Y. 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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P1.02-046 - Mutational Subtypes and Prognosis of Non-Small-Cell Lung Cancer Harboring HER2 Mutations (ID 8267)
09:30 - 09:30 | Author(s): Y. 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): Y. 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): Y. 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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P1.02-058 - Molecular Characteristics and Outcome of Chinese Patients with Non-Small Cell Lung Cancer Harboring NFE2L2 Mutations (ID 8293)
09:30 - 09:30 | Author(s): Y. 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 | Author(s): Y. 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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P2.02 - Biology/Pathology (ID 616)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 5
- 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 | Author(s): Y. 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 | Author(s): Y. 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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P2.02-007 - Molecular Spectrum of STK11 Gene Mutations in Patients with Non-Small-Cell Lung Cancer in Chinese Patients (ID 8289)
09:30 - 09:30 | Author(s): Y. 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): Y. 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): Y. 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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P3.01 - Advanced NSCLC (ID 621)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.01-008 - Association between Icotinib Efficacy and Circulating Tumor Cell Levels in Advanced Non-Small Cell Lung Cancer (ID 8253)
09:30 - 09:30 | Author(s): Y. 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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P3.02 - Biology/Pathology (ID 620)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 9
- 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): Y. 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 | Author(s): Y. 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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P3.02-027 - 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 | Author(s): Y. 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 | Author(s): Y. 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 | Author(s): Y. 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): Y. 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): Y. 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): Y. 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 | Author(s): Y. 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.
