Virtual Library

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    Best abstracts selected from submissions 1 (ID 1)

    • Event: ACLC 2018
    • Type: Oral Session
    • Track:
    • Presentations: 2
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      OA01 - LKB1 Pathway Variant TSC2 rs30259 Predicts the Prognosis in Early Stage Non-Small Cell Lung Cancer (ID 60)

      10:55 - 11:30  |  Author(s): S.K. Do, Y. Lee, J.E. Choi, S.Y. Lee, E. Lee, J.Y. Park

      • Abstract

      Background:
      This study was conducted to investigate the associations between polymorphisms of genes involved in LKB1 pathway and the prognosis of patients with non-small cell lung cancer (NSCLC) after surgical resection.


      Method:
      Twenty-three single nucleotide polymorphisms (SNPs) in LKB1 pathway were investigated in a total of 782 patients with NSCLC who underwent curative surgery. The association of the SNPs with overall survival (OS) and disease free survival (DFS) were analyzed.


      Results:
      Among the 23 SNPs investigated, TSC2 rs30259G>A was significantly associated with survival outcomes in multivariate analyses. The TSC2 rs30259G>A was associated with significantly worse OS and DFS (adjusted hazard ratio [aHR] = 1.88, 95% confidence interval [CI] = 1.21-2.91, P = 0.005; aHR = 1.65, 95% CI = 1.15-2.38, P = 0.01, under codominant model, respectively). When stratified by tumor histology, the SNP (rs30259) was significantly associated with survival outcomes only in squamous cell carcinoma, but not in adenocarcinoma. List of analyzed SNPs and the association with survival outcomes. Pa for Overall survival Pa for Disease-free survival SNP ID Gene Base change MAF Dominant Recessive Codominant Dominant Recessive Codominant rs30259 TSC2 G>A 0.04 0.01 0.15 0.005 0.03 8 x 10-6 0.01 rs1130214 Akt1 G>T 0.13 0.90 0.65 0.94 0.23 0.65 0.35 rs2494750 Akt1 A>G 0.38 0.33 0.88 0.61 0.33 0.56 0.36 rs17036508 MTOR T>C 0.12 0.36 0.97 0.20 0.72 0.71 0.82 rs1135172 MTOR C>T 0.16 0.48 0.98 0.60 0.22 0.51 0.29 rs1034528 MTOR G>C 0.19 0.81 0.35 0.75 0.40 0.99 0.41 rs1057079 MTOR A>G 0.18 0.90 0.34 0.79 0.19 0.97 0.29 rs3765904 MTOR T>C 0.01 0.32 . 0.46 0.33 . 0.46 rs11121691 MTOR C>T 0.07 0.97 0.98 0.86 0.87 0.98 0.73 rs7711806 PRKAA1 T>C 0.24 0.50 0.99 0.57 0.24 0.85 0.30 rs1342382 PRKAA2 A>T 0.25 0.93 0.17 0.73 0.32 0.20 0.68 rs11581010 PRKAA2 A>G 0.11 0.88 0.98 0.72 0.66 0.96 0.54 rs857148 PRKAA2 G>T 0.42 0.94 0.99 0.85 0.81 0.96 0.82 rs9803799 PRKAA2 T>G 0.16 0.54 0.23 0.98 0.43 0.71 0.63 rs4912411 PRKAA2 C>A 0.38 0.39 0.25 0.25 0.47 0.06 0.18 rs3738568 PRKAA2 T>C 0.36 0.31 0.50 0.35 0.26 0.28 0.21 rs739441 TSC1 A>G 0.26 0.12 0.31 0.16 0.56 0.45 0.48 rs1050700 TSC1 A>G 0.25 0.14 0.77 0.14 0.62 0.84 0.70 rs2809244 TSC1 C>A 0.39 0.47 0.49 0.31 0.62 0.99 0.66 rs4962225 TSC1 A>C 0.12 0.76 0.24 0.45 0.66 0.56 0.54 rs2074969 TSC2 G>C 0.22 0.92 0.09 0.60 0.96 0.17 0.59 rs3806317 PRKAA2 C>T 0.12 0.71 0.51 0.37 0.50 0.48 0.32 rs701848 PTEN C>T 0.47 0.55 0.89 0.63 0.51 0.77 0.68 MAF, minor allele frequency a P-values calculated using multivariate Cox proportional hazard models, adjusted for age, gender, smoking status, tumor histology, pathologic stage, and adjuvant therapy.


      Conclusion:
      This study suggests that genetic variation in LKB1 pathway may be useful for the prediction of prognosis in patients with early stage NSCLC after curative surgery.

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      OA02 - Targeted Next-Generation Sequencing Reveals Relapse-Associated Genomic Alterations in Early Stage Non-Small Cell Lung Cancer (ID 98)

      10:55 - 11:30  |  Author(s): W. Cho, K. Tan, V. Ma, J. Li, R. Ngan, W. Cheuk, T. Yip, Y. Yang, S. Chen

      • Abstract

      Background:
      Although early stage non-small cell lung cancer (NSCLC) patients have better prognosis than advanced stage patients, there is a relatively high rate of recurrence and individual variations. The identification of genomic alterations related to recurrence may help better stratify high-risk individuals and guide treatment strategies. This study aimed to identify the molecular biomarkers of recurrence in early stage NSCLC.


      Method:
      Paired primary tumor and normal lung tissue samples were collected for targeted next-generation sequencing analysis. A targeted panel targets exons for 440 genes was used to assess the mutational and copy number status of selected genes in three clinically relevant groups of stage I/II NSCLC patients: 1) Early relapse; 2) Late relapse; and 3) No relapse.


      Results:
      Of the 42 tumors evaluable for genomic alterations, TP53 and EGFR were the most frequent alterations with population frequency 52.4% and 50.0%, respectively. Fusion genes were detected in four patients, which had lower mutational burden and relatively better genomic stability. EGFR mutation and fusion gene were mutually exclusive in this study. CDKN2A, FAS, SUFU and SMARCA4 genomic alterations were only observed in the relapsed patients. Tumor mutational burden and copy number alteration (CNA) index didn

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    Best abstracts selected from submissions 4 (ID 4)

    • Event: ACLC 2018
    • Type: Oral Session
    • Track:
    • Presentations: 2
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      OA07 - Clinical Characterization Of ERBB2 Exon 20 Insertions and Heterogeneity of Outcomes to Afatinib in Chinese Lung Cancers (ID 188)

      10:50 - 11:30  |  Author(s): Z. Liu, Y. Hu, L. Wu, J. Cao, Z. Yang, C. Zhou, L. Cao, H. Wu, H. Shen, M. Jin, Y. Zhang, J. Xiang, K. Ma, B. Li, T. Zhang, X. Mao

      • Abstract
      • Slides

      Background:
      Human epidermal growth factor 2 (HER2, ERBB2) gene alterations have been identified as oncogenic drivers in 2-5% of lung cancers. ERBB2 In-frame insertions in exon 20 (20ins) lead to constitutive activation of receptor and downstream pathways. However, response heterogeneity of different exon 20 insertions to ERBB2 inhibitor afatinib exists. In vitro and structural modeling results suggested that Glycine778 may facilitate inhibitor binding to ERBB2. In this study, our aim was to improve our understanding of clinical characteristics in ERBB2-mutated Chinese lung cancer and investigate the clinical outcomes of specific ERBB2 exon 20 insertions in response to afatinib.


      Method:
      We reviewed 7520 lung cancer patients whose tissue or plasma biopsies were sequenced in a CLIA-certified sequencing laboratory between 2015 to 2018. Clinical records of 19 patients (18 adenocarcinomas and 1 squamous cell carcinoma) with several different ERBB2 20ins after afatinib treatment were collected for clinical outcomes evaluation.


      Results:
      ERBB2 20ins were identified in 2.27% (171/7,520) in this Chinese lung cancer cohort. It occurred with a high proportion in females with adenocarcinoma histology. 11.7% (20/171) ERBB2 20ins-positive patients harbored concomitant ERBB2 amplification. Y772_A775dup (119/171, 69.6%) was the most frequently occurred 20ins subtype, followed by G778_P780dup (18/171, 10.5%). For the 19 patients treated with afatinib, they had a median PFS of 4.5 months and median OS of 11.5 months. The overall response rate in this cohort was 15.8% (3/19) and disease control rate was 68.4% (13/19). Next, we interrogated the clinical outcomes of specific 20ins subtype responding to afatinib. We found that patients harboring G778_P780dup (G778) achieved longer median PFS (10 vs 3.3 months, p=0.32) and median OS (19.7 vs 7 months, p=0.16) than non-G778 patients, consisting with in vitro results. Although statistical significance was not achieved due to limited number of G778_P780dup patients, this result warranted further investigation into this phenomenon. Moreover, to the best of our knowledge, we identified the first case of a lung squamous cell carcinoma patient harboring ERBB2 20ins from this cohort. He displayed favorable response to afatinib and achieved partial response with significant tumor shrinkage.


      Conclusion:
      We interrogated the characteristics of ERBB2 exon 20 insertions in a large cohort from single ethnicity. It demonstrated the response heterogeneity to afatinib among different ERBB2 exon 20 insertion subtypes. It highlighted the importance to correlate drug efficacy with specific ERBB2 exon 20 insertion variants in clinical application.

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      OA08 - Efficacy and Safety of Sintilimab Combined with 1st Line Chemotherapy in Advanced Squamous Cell Non-small Cell Lung Cancer (ID 99)

      10:50 - 11:30  |  Author(s): K. Ying, N. Xu, H. Jiang, Y. Liu, H. Zhou, S. Wang

      • Abstract
      • Slides

      Background:
      Sintilimab, a novel full-humanized IgG4 anti-PD-1 monoclonal antibody, showed its potent anti-tumor efficacy in preclinical models. Hence, we evaluated the efficacy and safety of sintilimab in combination with gemcitabine and cisplatin in treatment na

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    Plenary Session - Immunotherapy for lung cancer (ID 1005)

    • Event: ACLC 2018
    • Type: Oral Session
    • Track:
    • Presentations: 3
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      Development of immunotherapy in China (ID 2013)

      16:20 - 17:00  |  Author(s): Q Zhou

      • Abstract
      • Slides

      Abstract not provided

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      PDL1 expression versus TMB: Which should we use? (ID 2012)

      16:20 - 17:00  |  Author(s): G Lin

      • Abstract
      • Slides

      Abstract not provided

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      Walking through the maze of first line immunotherapy for advanced NSCLC (ID 2011)

      16:20 - 17:00  |  Author(s): F Hirsch

      • Abstract
      • Slides

      Abstract not provided

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    Plenary Session - Past, Present and Future of Targeted Therapy in NSCLC (ID 1001)

    • Event: ACLC 2018
    • Type: Oral Session
    • Track:
    • Presentations: 3
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      Clinical application of ctDNA in management of oncogenic driven lung cancer (ID 2003)

      16:20 - 17:00  |  Author(s): S Lu

      • Abstract
      • Slides

      Abstract not provided

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      Optimal sequence of EGFR TKI (ID 2001)

      16:20 - 17:00  |  Author(s): T Mok

      • Abstract
      • Slides

      Abstract not provided

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      Optimal sequence of ALK TKI (ID 2002)

      16:20 - 17:00  |  Author(s): I Ou

      • Abstract
      • Slides

      Abstract not provided

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