Virtual Library

Start Your Search

X. Ai



Author of

  • +

    Optimizing targeted therapy in lung cancer (ID 56)

    • Event: ELCC 2018
    • Type: Poster Discussion session
    • Track:
    • Presentations: 1
    • +

      52PD - EGFR clonality and tumor mutation burden (TMB) analysis based on circulating tumor DNA (ctDNA) sequencing in advanced non-small cell lung cancer (NSCLC) (ID 351)

      16:45 - 17:45  |  Presenting Author(s): X. Ai

      • Abstract

      Background:
      TKI has significantly improved survival time of NSCLC pts with sensitive mutation. However, pts present different outcome while receiving TKI treatment. We conduct a prospective multicenter clinical trial to determine whether clonality of sensitive mutation is related to the efficacy of TKI. We also evaluate the consistency of TMB between tissue and blood in this cohort.

      Methods:
      Paired tumor and plasma samples at diagnosis were obtained from systemic treatment naïve pts with advanced NSCLC. DNA was sequenced by target-capture deep sequencing of 1021 previously annotated genes related to solid tumors. Clonal EGFR mutation was defined if EGFR mutation was in the cluster with the highest mean variated allele frequency with PyClone, and otherwise subclonal EGFR mutation. TMB of tissue (tTMB) and blood (bTMB) analysis interrogated single nucleotide variants, small insertion and deletion, with VAF ≥3% and ≥0.5%, respectively. TMB-high pts were identified with ≥9 mut/MB (upper quartile of data from geneplus).

      Results:
      During February to November 2017, 80 advanced NSCLC pts were enrolled from 9 centers. A total of 371 somatic variations were detected in tissues. Mutations occurred most frequently in TP53 (52%), EGFR (47%), ALK (13%), KRAS (11%). In matched plasma, 258 (70%) tumor-derived mutations were detected by pan-caner panel sequencing. A total of 41 EGFR mutations were detected in 37 pts, most of which occurred in tyrosine kinase domain (Ex19del, 42%; L858R, 37%). Most EGFR mutation were clonal in tissue and plasma, with a consistence of 85% in paired samples. In addition, bTMB was significantly correlated to tTMB (Pearson r = 0.75, p-value = 2.3e-12), with a consistence of 90%. Interestingly, high TMB was observed in a small fraction of patients (6%) with driver mutations, such as mutations in EGFR, ALK fusion, ERBB2 and PIK3CA.

      Conclusions:
      Deep sequencing with the pan-cancer panel can effectively detect mutations and evaluate TMB in both tissue and blood with high consistence. EGFR mutations can be clonal or subclonal in both tissue and blood. Prospective multicenter study is ongoing to determine the EGFR clonality as a predictive factor for the TKI efficacy in NSCLC (TRACELib-NSCLC).

      Clinical trial identification:
      NCT03059641

      Legal entity responsible for the study:
      Shanghai Chest Hospital

      Funding:
      Geneplus-Beijing Institute

      Disclosure:
      All authors have declared no conflicts of interest.

  • +

    Poster Display session (Friday) (ID 65)

    • Event: ELCC 2018
    • Type: Poster Display session
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 4/13/2018, 12:30 - 13:00, Hall 1
    • +

      160P - Real world study of lung squamous cell carcinoma patients with EGFR mutation treated with EGFR-TKI (ID 527)

      12:30 - 13:00  |  Author(s): X. Ai

      • Abstract
      • Slides

      Background:
      EGFR tyrosine kinase inhibitors (TKIs) have greatly improved the outcomes of EGFR mutation-positive adenocarcinomas of the lung; however, the role of genetic testing and efficacy of EGFR-TKI in lung squamous cell carcinoma (SCC) remains controversial.

      Methods:
      A total of 265 patients with advanced SCC who underwent genetic testing at our institute from 2016 to 2017 were included for analysis. Mutation profiling was performed with targeted capture based next-generation sequencing, which enables simultaneously assess single-nucleotide variants, insertions/deletions, rearrangements, and somatic copy-number alterations across 59 genes. Response assessment was done using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1. Kaplan–Meier method was used for calculating time to progression (TTP).

      Results:
      EGFR mutation was detected in 28 out of 265 patients with SCC (10.6%). Of the patients, 12 was with EGFR exon 21 L858R mutation, 10 was exon 19 E746_A750del mutation and 2 was exon 21 L861Q mutation. In addition, 8 was exon 20 mutations with 2 T790M mutation, 2 S768I mutation and 1 P772_H773insR, S768_D770dup, V774M, N771dup mutation resprectively. For the 2 patients with de novo T790M mutation, one has concurrent L858R mutation and the other EGFR N771dup. Furthermore, 10 out of the 27 patients received TKIs during their treatment. Five patients were treated with chemotherapy as first line, and five were EGFR-TKI as the first line. The median TTP on EGFR TKI was 10.5 months. There was no significant difference of TTP between the two groups treated with EGFR-TKI as first line or not (16 months vs 7 months, p = 0.19).

      Conclusions:
      EGFR mutations are present in over 10% SCC patients. These patients predict a better outcome if given TKI, but it may be inferior to the outcomes of EGFR-positive adenocarcinomas treated with TKI.

      Clinical trial identification:


      Legal entity responsible for the study:
      N/A

      Funding:
      Has not received any funding

      Disclosure:
      All authors have declared no conflicts of interest.

      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.