Virtual Library

Start Your Search

Yong Song



Author of

  • +

    MA 03 - Chemotherapy (ID 651)

    • Event: WCLC 2017
    • Type: Mini Oral
    • Track: Advanced NSCLC
    • Presentations: 1
    • +

      MA 03.03 - Nedaplatin plus Docetaxel versus Cisplatin plus Docetaxel as First-Line Chemotherapy for Advanced Squamous Cell Carcinoma of the Lung (ID 8154)

      11:00 - 12:30  |  Author(s): Yong Song

      • Abstract
      • Presentation
      • Slides

      Background:
      A previous phase III randomized trial improved overall survival of patients with advanced or relapsed squamous cell lung carcinoma, compared with cisplatin plus docetaxel. However, evaluation of nedaplatin plus docetaxel’s effect on progression free survival (PFS) and time to progression (TTP) was limited.

      Method:
      To compare the efficacy and safety of nedaplatin plus docetaxel and cisplatin plus docetaxel. In this randomized, open-label, multicenter trial, patients diagnosed with advanced or relapsed squamous cell carcinoma pathologically or cytologically were enrolled in China. All the patients have no previous oncology medication. Patients were randomly assigned (1:1) to 80 mg/m² nedaplatin and 75 mg/m² docetaxel intravenously, or 75 mg/m² cisplatin and 75 mg/m² docetaxel, every 3 weeks for four cycles. The primary end points was PFS. Secondary endpoints included TTP and best overall response. The efficacy endpoint were analyzed in the intention-to-treat set and in the per protocol set. (Clinical trial number: NCT02088515; Funding:Jiangsu Simcere Pharmaceutical Co., Ltd.)

      Result:
      From December 2013 to December 2015, 286 patients were randomly assigned. Two hundred and eighty patients were included in the modified intention-to-treat analysis (141 in the nedaplatin group and 139 in the cisplatin group). In the intention-to-treat analysis set, median PFS was 4.63 months (95% confidence interval (CI), 4.43-5.10) in the nedaplatin group and 4.23 months (95% CI, 3.37-4.53) in the cisplatin group. PFS did not differ significantly between two groups (log-rank test, p =0.056). In per protocol set, PFS was significantly longer in the nedaplatin group (median 4.63 months, 95% CI, 4.43-5.10) than in the cisplatin group (median 4.27 months, 95% CI, 3.37-4.53; hazard ratio 0.760, 95% CI 0.585-0.989; p=0.039, log-rank test). Best overall response and TTP were improved in nedaplatin group than in cisplatin group (p= 0.002, median 4.57(4.30-4.80) vs 3.67(3.13-4.43) p= 0.020, respectively) in the intention-to-treat analysis set. Grade III or IV adverse events was more frequent in the cisplatin group than in the nedaplatin group (46 of 141 patients in the nedaplatin group and 62 of 139 in the cisplatin group, p=0.039). Grade 3 or worse nausea (0 vs 7) and fatigue (1 vs 3) were more frequent in the cisplatin group than in the nedaplatin group.

      Conclusion:
      There was no significant difference of PFS between cisplatin group and nedaplatin group. However, more adverse events was observed in the cisplatin group than in the nedaplatin group. Nedaplatin plus docetaxel could be a new treatment option for advanced or relapsed squamous cell lung cancer.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    MA 11 - Emerging Diagnostic/Biomarkers in NSCLC (ID 668)

    • Event: WCLC 2017
    • Type: Mini Oral
    • Track: Advanced NSCLC
    • Presentations: 1
    • +

      MA 11.03 - Gefitinib as First-Line Treatment of Plasma CtDNA EGFR Mutation-Positive NSCLC Detected by DdPCR: BENEFIT Study (CTONG1405) (ID 9278)

      11:00 - 12:30  |  Author(s): Yong Song

      • Abstract
      • Presentation
      • Slides

      Background:
      EGFR mutations in plasma circulating free tumor-derived DNA (ctDNA) as a predictor of EGFR TKI efficacy in patients with NSCLC requires validation in prospective studies. The large, prospective Phase II, single-arm, multicenter BENEFIT study (CTONG1405; NCT02282267) validated the efficacy of first-line gefitinib in EGFR mutation-positive NSCLC detected in plasma ctDNA using droplet digital PCR (ddPCR).

      Method:
      Patients with stage IV lung adenocarcinoma and plasma ctDNA EGFR-sensitizing mutations (exon 19 del or exon 21 L858R; by ddPCR) received first-line gefitinib (250 mg once-daily) until progressive disease (PD). Blood samples were collected every 8 weeks for dynamic EGFR analysis until PD. Primary endpoint was ORR. Secondary endpoints included PFS, DCR (Week 8), and analysis of baseline ctDNA samples by next-generation sequencing (NGS).

      Result:
      From December 2014-January 2016, 426 patients from 15 Chinese centers were screened: 391 had matched tissue and blood samples; 188 had ctDNA EGFR mutation-positive NSCLC and received gefitinib; and 183 had ≥1 post-baseline tumor assessment and plasma samples every 8 weeks until PD. At data cutoff (January 31, 2017), 152 patients had progressed. ORR was 72.1% (95% CI 65.0%,78.5%); DCR (Week 8) was 92.3% (95% CI 87.5%,95.8%); and median PFS was 9.5 months (95% CI 9.07,11.04). PFS was significantly shorter in the subgroup with baseline ctDNA de novo T790M mutations (5.0%, n=9) versus the EGFR-sensitizing mutations subgroup (5.6 vs 9.6 months, HR=2.60; 95% CI 1.32,5.12, p=0.004). In patients with Week 8 on-treatment plasma samples (n=167), the subgroup who showed EGFR mutation clearance in ctDNA by ddPCR (88%, 147/167) had longer PFS compared with those who did not (11.0 vs 2.1 months, HR=7.28; 95% CI 4.35,12.18, p<0.0001). The median time to emergence of acquired T790M mutation in plasma was 7.6 months. The T790M-positive rate increased from Week 24 (15.7%) to Week 48 (32.6%), with a corresponding increase in PD rate (24.7% at Week 24, 56.9% at Week 48). Among 180 patients with baseline NGS data, 21 (11.7%) harbored aberrations in additional oncogenic drivers (MET, ERBB2, KRAS, BRAF, RET, or ROS1) and tumor suppressors (TP53, RB1, and PTEN). This subgroup had worse PFS versus those with EGFR-sensitizing mutations alone (3.9 vs 13.0 months, HR=2.83; 95% CI 1.65,4.87, p=0.00016).

      Conclusion:
      The BENEFIT study prospectively demonstrated that ctDNA-based EGFR mutation detection can be used to select patients for treatment with first-line gefitinib. Dynamic alterations in EGFR mutations could be used to predict efficacy and disease progression, ahead of radiological results.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    P1.01 - Advanced NSCLC (ID 757)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 4
    • +

      P1.01-002 - TP53 Mutations Predict for Poor Survival in ALK Rearrangement Lung Adenocarcinoma Patients Treated with Crizotinib (ID 8241)

      09:30 - 16:00  |  Author(s): Yong Song

      • Abstract
      • Slides

      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.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

    • +

      P1.01-006 - Effect of EML-Alk Fusion Variant and Fusion Abundance on the Efficacy of Crizotinib in Non-Small Cell Lung Cancer (ID 8552)

      09:30 - 16:00  |  Author(s): Yong Song

      • Abstract

      Background:
      EML4-ALK fusion gene is a molecular subtype of non-small cell lung cancer (NSCLC), which is carcinogenic both in vitro and in vivo. Most of the EML4-ALK-positive NSCLC patients have effectively sensitivity with an ALK tyrosine kinase inhibitor (TKI), such as crizotinib. However, the treatment outcomes and duration of response are heterogeneous. EML4-ALK has several variants. The effects of ALK fusion variants on the efficacy of crizotinib is still unclear, although many scientists are committed to this work. In addition, we also unknown the effects of ALK variants allele fraction (AF) on the efficacy of crizotinib.

      Method:
      Among 54 patients with advanced NSCLC were treated with crizotinib as the first-line or further-line ALK-TKI between 2013 and 2017, eventually, we identified 48 patients whose the tumor samples were detected by IHC(38), FISH(2), NGS(5),PCR(1) and ARMS(2). Through retrospective analysis, we assumed the efficacy of crizotinib on the basis of the PFS according to the ALK variants and its allele fraction.

      Result:
      Among the 29 ALK-positive patients, the most common ALK variants was variant 1 in 13 patients (44.9%), followed by variant 3 in 7 patients (24.1%), variants 2 in 2 patients (6.9%), other variants in 7 patients (24.1%). We divided all variants into two subgroups: V1/3 and V2/others. We found 35.4% of the samples test results between the next generation sequencing (NGS) and hospital immunohistochemical were not concordence. Further analysis found that patients who did not match that PFS were shorter (p=0.036). By the NGS, we observed from the figure that the variant 2/others group, the median PFS had a longer trend than V1/3 group, although not statistically significant(p>0.05. The level of AF was no correlated with PFS (P=0.346).

      Conclusion:
      The above results show that next-generation sequencing (NGS) can identify ALK variants and AF, therefore, NGS can be used as a supplement to a detection method. The type of EML4-ALK fusion variants may has a certain correlation with PFS in patients who oral crizotinib treatment. Since the sample size of this study is small, we have not yielded accurate results and found only these phenomena. We believe that in the near future, most NSCLC patients can be detected by NGS detection of gene mutations, especially EML4-ALK fusion gene, and according the different of the fusion gene variant type which can be estimated the efficacy of the ALK-TKIs, to provide the basis of individualized treatment options for NSCLC patients.

    • +

      P1.01-037 - Circulating Tumor DNA Clearance During Treatment Associates with Improved Progression-Free Survival (ID 9653)

      09:30 - 16:00  |  Author(s): Yong Song

      • Abstract

      Background:
      Therapeutic selection has been shown to lead to marked clonal evolution, thus revealing limitations in imaging scan as a monitoring method, which does not reflect biological processes at a molecular level. However, currently, response assessment of patients with non-small cell lung cancer (NSCLC) primarily relies on imaging scans, necessitating the development of methodologies for dynamic monitoring of treatment response. We evaluated ctDNA as a tumor clonal response biomarker.

      Method:
      We screened 831 advanced NSCLC patients with a mixture of prior treatment exposure by performing capture-based ultra-deep targeted sequencing on plasma samples using a panel consisting of 168 NSCLC-related genes. Eighty-six patients with driver mutations and a minimum of 2 evaluation points in addition to baseline were included for further analysis.

      Result:
      At baseline, 79.9% patients harbored at least one mutation from this panel; the remaining 20.1% had no mutation detected. Sixty-nine percent of patients (570/831) harbored driver mutation. Patients harboring 2 mutations or fewer at baseline had a median progression-free survival (PFS) of 7.4 months; in contrast, patients harboring more than 2 mutations had a median PFS of 3.8 months (P=6.6x10[-5 ]HR=0.34), suggesting a significant inverse correlation between number of mutations at baseline and PFS. Next, we evaluated the ability of ctDNA as a tumor clonal response biomarker in 86 patients with a minimum of 2 follow-ups. After a median follow-up of 314 days, 64 patients (74.4%) reached disease progression. During treatment, 46 patients, treated with either matched targeted therapy (MTT) or chemotherapy, had a minimum of one time of ctDNA clearance, occurring from 1.6 months to 7.5 months after the commencement of treatment, with a median PFS of 8.07 months, an overall response rate (ORR) of 41% and a disease control rate (DCR) of 93%. Median overall survival (OS) for this group has not reached. In contrast, 40 patients who had consistent detectable ctDNA throughout the course of treatment had a median PFS of 3.47months, a median OS of 425 days, an ORR of 20% and a DCR of 53%. Our data revealed that patients with a minimum of one time ctDNA clearance are associated with a better ORR (p=0.05), DCR (p=5.9x10[-5]), a longer PFS (p=5.4x10[-10 ]HR=0.21) and OS (p=2.3x10[-5 ]HR=0.21), regardless the type of treatment commenced and the time of evaluation.

      Conclusion:
      This real world study comprising a heterogeneous population reveals the predictive and prognostic value of ctDNA and warrants further investigations to explore its clearance as a surrogate endpoint of efficacy.

    • +

      P1.01-073 - Over-Expression of GGPPs Contributes to Tumor Metastasis and Correlates with Poor Prognosis of Lung Adenocarcinoma (ID 8473)

      09:30 - 16:00  |  Presenting Author(s): Yong Song

      • Abstract

      Background:
      This study aimed to evaluate the biological role of geranylgeranyl diphosphate synthase (GGPPS) in the progression of lung adenocarcinoma

      Method:
      GGPPS expression was detected in lung adenocarcinoma tissues by qRT-PCR, tissue microarray (TMA), and western blotting. The relationship between GGPPS expression and the clinicopathological characteristics and prognosis of lung adenocarcinoma patients was assessed. GGPPS was downregulated in SPCA-1, PC9, and A549 cells, using siRNA, and upregulated in A549 cells, using an adenoviral vector. The biological role of GGPPS in cell proliferation, apoptosis, migration, and invasion was determined by MTT and colony formation assays, flow cytometry, and transwell and wound-healing assays, respectively. In addition, the regulatory role of GGPPS on the expression of several EMT markers was determined

      Result:
      GGPPS expression was significantly increased in lung adenocarcinoma tissues compared to that in adjacent normal tissues. Over-expression of GGPPS correlated with patients with large tumors, high TNM stage, lymph node metastasis and poor prognosis. Knockdown of GGPPS inhibited migration and invasion of lung adenocarcinoma cells, but did not affect cell proliferation and apoptosis. Meanwhile, GGPPS inhibition significantly increased the expression of E-cadherin, and reduced the expression of N-cadherin and vimentin in lung adenocarcinoma cells

      Conclusion:
      Over-expression of GGPPS correlates with poor prognosis of lung adenocarcinoma, and contributes to metastasis through the regulation of EMT

  • +

    P1.02 - Biology/Pathology (ID 614)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Biology/Pathology
    • Presentations: 11
    • +

      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 - 16:00  |  Author(s): Yong Song

      • Abstract
      • Slides

      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.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

    • +

      P1.02-044 - Relationship between RET Rearrangement and Thymidylate Synthase mRNA Expression in Non-Small Cell Lung Cancer Tissues (ID 8266)

      09:30 - 16:00  |  Author(s): Yong Song

      • Abstract
      • Slides

      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.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

    • +

      P1.02-045 - PIK3CA Mutations in Chinese Patients with Non-Small-Cell Lung Cancer (ID 8264)

      09:30 - 16:00  |  Author(s): Yong Song

      • Abstract
      • Slides

      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.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

    • +

      P1.02-046 - Mutational Subtypes and Prognosis of Non-Small-Cell Lung Cancer Harboring HER2 Mutations (ID 8267)

      09:30 - 16:00  |  Author(s): Yong Song

      • Abstract
      • Slides

      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.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

    • +

      P1.02-047 - Mutational Features and Prognosis of Non-Small-Cell Lung Cancer Harboring RAS Mutations (ID 8268)

      09:30 - 16:00  |  Author(s): Yong Song

      • Abstract
      • Slides

      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.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

    • +

      P1.02-048 - Somatic Mutation Analysis of RB1 Gene in Chinese Non-Small Cell Lung Cancer Patients (ID 8310)

      09:30 - 16:00  |  Author(s): Yong Song

      • Abstract
      • Slides

      Background:
      RB1 (retinoblastoma 1) was reportedly one of the major determinative factors for sensitivity to taxanes in previous studies. The dephosphorylated RB1 protein confers the higher sensitivity to chemotherapy drug, but the RB1 mutation non-small-cell lung cancer (NSCLC) genetic variability and prognosis is unclear. The aim of this study is to investigate mutations and prognosis of NSCLC harboring RB1 mutations.

      Method:
      A total of 728 patients with NSCLC were recruited between July 2012 and December 2014. The status of RB1 mutation and other genes were detected by next generation sequencing.

      Result:
      RB1 gene mutation was detected in 0.96% (7/728) NSCLC patients, including p.G449E (1 patient), p.L542stop (1 patient), p.R552* (1 patient), p.Y6511fs*7 (1 patient), c.2663+2T>C (1 patient), p.P23del (1 patient) and F684fs*7 plus R418T (1 patient), and median overall survival (OS) for these patients was 32.7 months. Among them, all patients were RB1 gene with co-occurring mutations. Briefly, patients with (n=3) or without (n=4) co-occurring EGFR mutations had a median OS of 34.9 months and 30.4 months repectively (P=0.95); patients with (n=5) or without (n=2) co-occurring TP53 mutations had a median OS of 32.7 months and 31.7 months repectively (P=0.90).

      Conclusion:
      EGFR or TP53 gene accompanied may have less correlation with RB1 mutation in NSCLC patients. Chemotherapy drugs may displayed moderated efficacy in patients with RB1 mutation, especially, accompanied with TP53. These data have implications for both clinical trial design and therapeutic strategies.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

    • +

      P1.02-049 - Detection of CDKN2A Gene Mutations in Patients with Non-Small Cell Lung Cancer Patients (ID 8312)

      09:30 - 16:00  |  Author(s): Yong Song

      • Abstract
      • Slides

      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

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

    • +

      P1.02-056 - BRAF Non-V600E Mutations Recurrently Found in Non-Small Cell Lung Cancer in Chinese Patients (ID 8291)

      09:30 - 16:00  |  Author(s): Yong Song

      • Abstract
      • Slides

      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.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

    • +

      P1.02-057 - Analysis of C-MET Amplification Non-Small Cell Lung Cancer Cell Blocks from Pleural Effusion (ID 8282)

      09:30 - 16:00  |  Author(s): Yong Song

      • Abstract
      • Slides

      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.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

    • +

      P1.02-058 - Molecular Characteristics and Outcome of Chinese Patients with Non-Small Cell Lung Cancer Harboring NFE2L2 Mutations (ID 8293)

      09:30 - 16:00  |  Author(s): Yong Song

      • Abstract
      • Slides

      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.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

    • +

      P1.02-059 - Molecular Characteristics of SMARCA4 Mutations Detection in Chinese Non-Small Cell Lung Cancer Patients (ID 8309)

      09:30 - 16:00  |  Author(s): Yong Song

      • Abstract
      • Slides

      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.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    P2.01 - Advanced NSCLC (ID 618)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 2
    • +

      P2.01-017 - Study on the Effect of Apatinib Salvage Treatment of Advanced Non-Small Cell Lung Cancer (ID 8285)

      09:00 - 16:00  |  Author(s): Yong Song

      • Abstract
      • Slides

      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.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

    • +

      P2.01-019 - The Necessity of Contrast-enhanced CT before CT-Guided Percutaneous Transthoracic Needle Biopsy for Lung Lesions (ID 8392)

      09:00 - 16:00  |  Author(s): Yong Song

      • Abstract

      Background:
      To evaluate the effect of pre-biopsy contrast-enhanced CT scanning on hemorrhage complicating percutaneous transthoracic needle biopsy

      Method:
      This retrospective study was approved by the institutional review board. We reviewed 1282 biopsy procedures, Chi-square test and multivariate analysis. We conduct propensity score matching by using MatchIt package in R with nearest-neighbor 1-to-1, 2-to-1 and 3-to-1 matching ,respectively

      Result:
      The incidence of pulmonary hemorrhage was 20.2% (259/1282), including 247(19.2%) mild hemorrhage, 7 (0.5%) moderate hemorrhage, and 5 (0.4%) severe hemorrhage. Pre-biopsy CECT scan was significantly associated with pulmonary hemorrhage, and had a positive effect (p=0.008, OR=0.671, 95% CI: 0.499-0.902). When matching hemorrhage and non-hemorrhage cases in proportion of 1 to 1, 1 to 2, and 1 to 3, the correlation of CECT and hemorrhage showed significancy and CECT was indeed a protective factor (p=0.039, 0.028 and 0.013, respectively). Additionally, biopsy position (p=0.016,OR=2.734, 95% CI: 1.207-6.194 for supine, lateral as reference), lesion sizes (p=0.005, OR=0.990, 95% CI: 0.983-0.997), puncture depth (P=0.000, OR=1.017, 95% CI: 1.009-1.025), number of pleural passes (P<0.05, for twice, third, fourth, OR= 1.546, 1.673, 8.746, 95% CI: 1.065-2.244, 1.082-2.588, 2.891-26.456, respectively ) were also related with hemorrhage.

      Conclusion:
      Pre-biopsy contrast-enhanced CT scan is a protective factor for hemorrhage. To reduce the incidence of hemorrhage to the greatest extent. We strongly suggest the patients scheduled to perform percutaneous transthoracic needle biopsy do pre-biopsy contrast-enhanced CT scan routinely.

  • +

    P2.02 - Biology/Pathology (ID 616)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Biology/Pathology
    • Presentations: 4
    • +

      P2.02-005 - 13 Cases of Molecular Features Analysis in Pulmonary Mucoepidermoid Carcinoma (ID 8278)

      09:30 - 16:00  |  Author(s): Yong Song

      • Abstract
      • Slides

      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.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

    • +

      P2.02-007 - Molecular Spectrum of STK11 Gene Mutations in Patients with Non-Small-Cell Lung Cancer in Chinese Patients (ID 8289)

      09:30 - 16:00  |  Author(s): Yong Song

      • Abstract
      • Slides

      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.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

    • +

      P2.02-020 - Molecular Characteristics of Patients with PTEN Mutations in Chinese Non-Small Cell Lung Cancer (ID 8292)

      09:30 - 16:00  |  Author(s): Yong Song

      • Abstract
      • Slides

      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.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

    • +

      P2.02-021 - Prevalence of PTPRD Gene Mutations in Chinese Non-Small Cell Lung Cancer Patients (ID 8311)

      09:30 - 16:00  |  Author(s): Yong Song

      • Abstract
      • Slides

      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.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    P2.03 - Chemotherapy/Targeted Therapy (ID 704)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Chemotherapy/Targeted Therapy
    • Presentations: 1
    • +

      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 - 16:00  |  Author(s): Yong Song

      • Abstract
      • Slides

      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.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    P3.01 - Advanced NSCLC (ID 621)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
    • +

      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 - 16:00  |  Author(s): Yong Song

      • Abstract
      • Slides

      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.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    P3.02 - Biology/Pathology (ID 620)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Biology/Pathology
    • Presentations: 9
    • +

      P3.02-025 - 65 Cases of Molecular Profiling Anaysis in Surgical Resected Pulmonary Neuroendocrine Carcinoma (ID 8274)

      09:30 - 16:00  |  Author(s): Yong Song

      • Abstract
      • Slides

      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.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

    • +

      P3.02-026 - The Study of ROS1 Rearrangement in Advanced Primary Non-Small Cell Lung Cancer and Associated Metastatic Lesions (ID 8281)

      09:30 - 16:00  |  Author(s): Yong Song

      • Abstract
      • Slides

      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.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

    • +

      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 - 16:00  |  Author(s): Yong Song

      • Abstract
      • Slides

      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.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

    • +

      P3.02-028 - 276 Cases of EGFR/ALK Gene Status and Predominant Histologic Subtype in Chinese Surgically Resected Lung Adenocarcinoma (ID 8271)

      09:30 - 16:00  |  Author(s): Yong Song

      • Abstract
      • Slides

      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.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

    • +

      P3.02-029 - 218 Cases of EGFR/ALK Gene Status Anaysis in Chinese Lung Squamous Cell Carcinoma (ID 8272)

      09:30 - 16:00  |  Author(s): Yong Song

      • Abstract
      • Slides

      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.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

    • +

      P3.02-065 - Lung Adenocarcinoma Patient with EGFR Kinase Domain Duplication(KDD) and Its Response to Icotinib: A Case Report (ID 8277)

      09:30 - 16:00  |  Author(s): Yong Song

      • Abstract
      • Slides

      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.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

    • +

      P3.02-068 - 95 Cases of EGFR/ALK Gene Status Anaysis in Lung Adenosquamous Carcinoma (ID 8273)

      09:30 - 16:00  |  Author(s): Yong Song

      • Abstract
      • Slides

      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.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

    • +

      P3.02-069 - 58 Cases of EGFR/ALK Gene Status Anaysis in Pulmonary Sarcomatoid Carcinoma (ID 8276)

      09:30 - 16:00  |  Author(s): Yong Song

      • Abstract
      • Slides

      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.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

    • +

      P3.02-080 - DNMT3A Defines a Unique Molecular Class of Chinese Non-Small Cell Lung Cancer Patients (ID 8313)

      09:30 - 16:00  |  Author(s): Yong Song

      • Abstract
      • Slides

      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.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    P3.07 - Immunology and Immunotherapy (ID 723)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Immunology and Immunotherapy
    • Presentations: 1
    • +

      P3.07-004 - GSDMD Is Required for Effector CD8+ T Cell Responses to Lung Cancer Cell (ID 8461)

      09:30 - 16:00  |  Author(s): Yong Song

      • Abstract

      Background:
      Cytotoxic T lymphocytes (CTLs) play a critical role in protection against intracellular pathogens and tumor. To induce target cell death, CTL mainly use two major contact-dependent cytotoxic pathways that are dependent on Fas ligand (FasL) and lytic granules. CTLs eliminate malignantly transformed cells principally by releasing the contents of cytotoxic granules into the immune synapse formed with their target cell. The granule serine proteases, known as granzymes (Gzms), induce apoptosis after they are delivered into the target cell cytoplasm by the pore-forming granule protein perforin. Therefore, we hypothesized that other pore-forming protein, especially those can form pores from within mammalian cells, may be implicated in the target cell killing process of CTL. Since GSDMD is a recently discovered pore-forming protein whose N-terminal domain can insert the inner leaflet of the cell membrane and form extensive pores, we speculate that GSDMD may participate in the CTL attack. GSDMD is a recently discovered pyroptosis executioner in monocyte, whose N-terminal domain can insert the inner leaflet of the cell membrane and form extensive pores. Although the role of GSDMD in the pyroptosis has been clear, the function of GSDMD in other biological system remains elusive. In the present study, we investigated the role of GSDMD during CTL responses to NSCLC cancer cells.

      Method:
      3LL and H1299 cells were cultured in RPMI-1640 (HyClone, USA) supplemented with 10% fetal bovine serum, Ovalbumin-expressing 3LL cells (3LL-OVA) were generated by transfection with a lentiviral plasmids harbouring cytosolic chicken ovalbumin. C57BL/6 mice and TCR-transgenic OT-1 mice. Mouse CD8[+] T cell isolation and stimulation, Human CD8[+] T cell isolation and stimulation, Real-time PCR analysis, Western blot analysis, Immunofluorescence cell staining, Immunohistochemistry, Lentiviral vectors transduction, In vitro cytotoxicity assays, Bioinformatics analysis,

      Result:
      We showed that GSDMD expression was consistently correlated with CD8[+] T cell markers in TCGA cohorts. The expression of GSDMD protein could be detected in the tumor infiltrating lymphocyte. GSDMD cleavage increased both in the OT-1 CTLs and the human activated CD8[+] T cells. Moreover, Colocalization of GSDMD with granzymeB was observed in proximity of immune synapse. GSDMD deficiency reduced the cytolytic capacity of human CD8[+] T cells.

      Conclusion:
      These results identified a previously unknown role of GSDMD in CTL and demonstrated that GSDMD is required for an optimal CTL response to lung cancer cell.