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J. Gong



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    JCES01 - Joint IASLC - Chinese Society for Clinical Oncology - Chinese Alliance Against Lung Cancer Session (ID 413)

    • Event: WCLC 2016
    • Type: Joint Chinese / English Session
    • Track:
    • Presentations: 1
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      JCES01.10 - Serial Quantitative Assessment of Plasma Circulating Tumor DNA by Digital NGS in Patients with Lung Cancer (ID 7054)

      08:00 - 11:45  |  Author(s): J. Gong

      • Abstract
      • Presentation
      • Slides

      Background:
      Next generation sequencing (NGS) has been increasingly used in oncology practice but proven practically difficult when serial tumor specimens are needed. The objectives of this study were to determine feasibility and explore clinical utility of serial NGS analyses of circulating tumor DNA (ctDNA) in patients (pts) with advanced solid tumors undergoing treatment.

      Methods:
      ctDNA digital NGS was performed by a CLIA-certified lab (70-gene panel with mutant allele fraction (MAF) quantification). ctDNA results were retrospectively analyzed and decreases/increases/stability of molecular tumor load (MTL) defined here as MAFs of truncal driver mutations were correlated with clinical and radiographic response to treatment (response, progression, or stable disease, respectively).

      Results:
      From Jan 2015 to July 2016, 38 consecutive pts with advanced lung tumors (84% LUAD, 5% LUSC, 5% SCLC, 5% NOS) receiving treatment (Table) had serial ctDNA analyses (median 2, range 2-7). ctDNA alterations were detected at least once in 37 (97.4%) pts. Changes in MTL correlated with or predicted all (95% CI, 82.0-99.8%) radiological and/or clinical responses except for the patient with no genomic alteration detected. MTL results clarified response status when radiographic responses were difficult to assess in 9 (28%) of pts with either complex pleural disease (n=6), pneumonitis during PD-1 inhibitor therapy (2). Two MTL change patterns were observed: 1) clonal changes while receiving targeted therapy, including EGFR (12), ALK (3), MET (2), ERBB2 (2); 2) global changes to PD-1 inhibitors, chemotherapy or radiation. Representative tumor response maps will be presented. Table. Summary of tumor types and cancer treatment.

      Cancer Type Targeted Therapy Immunotherapy Chemotherapy Radiation TOTAL
      LUAD 14 8 7 3 32
      LUSC 1 1 0 0 2
      SCLC 0 0 2 0 2
      NOS 1 0 1 0 2
      All 16 9 10 3 38


      Conclusion:
      Serial liquid biopsies and ctDNA digital NGS are feasible and clinically useful in monitoring MTL and genomic alterations during cancer treatment, especially in situations when radiographic responses are equivocal. Prospective evaluation of impact on clinical decision making is warranted.

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    P2.01 - Poster Session with Presenters Present (ID 461)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Biology/Pathology
    • Presentations: 1
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      P2.01-009 - Serial Quantitative Assessment of Plasma Circulating Tumor DNA by Digital NGS in Patients with Lung Cancer (ID 6267)

      14:30 - 15:45  |  Author(s): J. Gong

      • Abstract

      Background:
      Next generation sequencing (NGS) has been increasingly used in oncology practice but proven practically difficult when serial tumor specimens are needed. The objectives of this study were to determine feasibility and explore clinical utility of serial NGS analyses of circulating tumor DNA (ctDNA) in patients (pts) with advanced solid tumors undergoing treatment.

      Methods:
      ctDNA digital NGS was performed by a CLIA-certified lab (70-gene panel with mutant allele fraction (MAF) quantification). ctDNA results were retrospectively analyzed and decreases/increases/stability of molecular tumor load (MTL) defined here as MAFs of truncal driver mutations were correlated with clinical and radiographic response to treatment (response, progression, or stable disease, respectively).

      Results:
      From Jan 2015 to July 2016, 38 consecutive pts with advanced lung tumors (84% LUAD, 5% LUSC, 5% SCLC, 5% NOS) receiving treatment (Table) had serial ctDNA analyses (median 2, range 2-7). ctDNA alterations were detected at least once in 37 (97.4%) pts. Changes in MTL correlated with or predicted all (95% CI, 82.0-99.8%) radiological and/or clinical responses except for the patient with no genomic alteration detected. MTL results clarified response status when radiographic responses were difficult to assess in 9 (28%) of pts with either complex pleural disease (n=6), pneumonitis during PD-1 inhibitor therapy (2). Two MTL change patterns were observed: 1) clonal changes while receiving targeted therapy, including EGFR (12), ALK (3), MET (2), ERBB2 (2); 2) global changes to PD-1 inhibitors, chemotherapy or radiation. Representative tumor response maps will be presented. Table. Summary of tumor types and cancer treatment.

      Cancer Type Targeted Therapy Immunotherapy Chemotherapy Radiation TOTAL
      LUAD 14 8 7 3 32
      LUSC 1 1 0 0 2
      SCLC 0 0 2 0 2
      NOS 1 0 1 0 2
      All 16 9 10 3 38


      Conclusion:
      Serial liquid biopsies and ctDNA digital NGS are feasible and clinically useful in monitoring MTL and genomic alterations during cancer treatment, especially in situations when radiographic responses are equivocal. Prospective evaluation of impact on clinical decision making is warranted.