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Yu Zhang



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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
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      P2.01-116 - The Potential of Assessing Blood Tumor Mutation Burden (bTMB) Using a Large Panel  (ID 13224)

      16:45 - 18:00  |  Author(s): Yu Zhang

      • Abstract
      • Slides

      Background

      TMB, measuring the number of non-synonymous mutation per megabase of DNA, has shown to associate with response to checkpoint inhibitors in a number of cancers, including lung cancer. Whole exome sequencing (WES), the gold standard for evaluating TMB, is less cost-effective. Multiple studies have shown large panels can yield comparable results in tissue samples. However, the feasibility of assessing bTMB using a large panel has not been extensively evaluated. In this study, we evaluated TMB of 30 treatment-naïve advanced NSCLC patients by performing WES on tissue samples as well as targeted sequencing on matched tissue and plasma samples.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      WES was performed on tissue samples with an average sequencing depth of 300x. Targeted sequencing was performed on matched tissue and plasma using a panel consisting of 520 cancer-related genes, spanning 1.6Mb of human genome. An average sequencing depth of 1,000X and 10,000x were achieved for tissue and plasma samples, respectively. TMB was calculated as the ratio of mutation count to the size of coding region of the panel (1.26Mb), excluding copy number variations, fusions, large genomic rearrangements and mutations occurring on the kinase domain of EGFR and ALK.

      4c3880bb027f159e801041b1021e88e8 Result

      In tissue samples, TMB derived from WES and our panel is comparable with a R2 value of 0.87, and a correlation value of 0.86. cfDNA from 8 patients had no mutation detected using the 520 panel potentially due to low fraction of ctDNA present in the circulation. TMB derived from cfDNA of the remaining 22 patients showed a good correlation with TMB derived from tissue using either our panel (R2=0.94, correlation =0.93) or WES (R2= 0.85, correlation=0.87), demonstrating the feasibility of assessing TMB from cfDNA using a large panel. Next, using TMB calculated from WES as gold standard, we attempted to derive a cutoff to stratify TMB high patients from TMB low patients. Our data revealed 15 mutations per mb as an optimal cutoff using the 520 panel, achieving an AUC of 97.6% for tissue samples and 97.2% for plasma samples.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Our study demonstrated the feasibility of evaluating TMB from cfDNA using a large panel, opening the avenue of TMB estimation using liquid biopsy. Further validations in prospective clinical trials are needed to solidify its predictive value in response to immunotherapy.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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