Author of

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  P2.01 - Advanced NSCLC (Not CME Accredited Session) (ID 950)

  • Event: WCLC 2018
  • Type: Poster Viewing in the Exhibit Hall
  • Track:
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall

  • 26870

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    P2.01-68 - Capture-Based Sequencing Depicts Evolution Characteristics of Pulmonary Sarcomatoid Carcinoma (ID 13215)

    16:45 - 18:00  |  Author(s): Likun Chen
    • Abstract
    • Slides

    Background
    

    Pulmonary sarcomatoid carcinoma (PSC) is a very rare subset of highly aggressive and poorly differentiated non-small cell lung cancer. Mutation profiling of PSC was reported previously. However, the intratumor heterogeneity and evolution characteristics of PSC remains unknown.

    a9ded1e5ce5d75814730bb4caaf49419 Method
    

    This study enrolled 39 patients (pts) with PSC. A median follow-up time was 7 months (ranged from 3 to 33 months). Each tumor sample was divided to cancer tissue and sarcoma tissue by microdissection. Matched distant normal tissues were also collected for removing germline background. Capture-based sequencing was performed using a panel covering 1021 genes related to solid tumors. Somatic mutations were used to analyze intratumor heterogeneity and evolution characteristics. Tumor mutation burden (TMB) analysis interrogated single nucleotide variants, small insertion and deletion, with VAF ≥3 %. TMB-high pts were identified with ≥9 mut/MB (upper quartile of data from geneplus).

    4c3880bb027f159e801041b1021e88e8 Result
    

    Capture-based sequencing had been done on 90 tissues, including cancer tissues, sarcoma tissues and matched distant normal tissues from 30 pts. Nine patients were excluded due to insufficient DNA samples. A median effective depth of coverage of 1299 × was obtained in tissue samples. A total number of 608 mutations were detected, including driver mutations in TP53 (73%, 44/60), MET (22%, 12/60), EGFR (20%, 12/60), KRAS (20%, 12/60), and NF1 (17%, 10/60). Interestingly, mutations in MET and KRAS were demonstrated to be mutually exclusive in cancer and sarcoma tissues. Shared mutations between cancer and sarcoma tissues were 43%. The median of TMB of sarcoma and cancer samples were both 8.6 mutations/Mb. High TMB were identified in 40% (12/30 pts) of sarcoma samples and 43% (13/30 pts) of cancer samples, respectively. TMB of sarcoma tissues was significantly correlated to that of cancer tissues (Pearson r= 0.92, p-value<0.01), with a consistence of 90 % Furthermore, the fraction of brunch mutations in cancer tissues was related to the worse OS of PSC (Log-rank, HR=3.2, 95% CI=1.1-9.4, p=0.04).

    8eea62084ca7e541d918e823422bd82e Conclusion
    

    Sarcoma tissues shared mutations with cancer tissues. Mutations and TMB analysis could help to guide treatment decisions of PSC in both tyrosine kinase and immune checkpoint inhibitors. Evolution characteristics could serve as potential prognostic factors in PSC.

    6f8b794f3246b0c1e1780bb4d4d5dc53

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