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Jeong-Sun Seo



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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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      P2.01-106 - A Comparative Analysis of Genomic Alterations by Tumor Tissue and Circulating Tumor DNA in Advanced Non-Small Cell Lung Cancer (ID 13524)

      16:45 - 18:00  |  Author(s): Jeong-Sun Seo

      • Abstract
      • Slides

      Background

      Genomic profiling of lung cancers using circulating tumor DNA (ctDNA) in the blood of patients is rapidly becoming established as a useful source of information to aid clinical decision-making. We evaluated the concordance of genomic alterations by ctDNA and tumor tissue DNA in Advanced Non-Small Cell Lung Cancer (NSCLC).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Tumor tissue DNA from formalin-fixed, paraffin-embedded (FFPE) samples and ctDNA from plasma samples were obtained at the time of diagnosis or at the time of progressive disease after receiving targeted therapy in 41 patients with stage IIIB or IV NSCLC in this prospective study (NCT03235765). Hybrid-capture based genomic profiling (Axen Cancer Panel, Macrogen) was performed to sequence 170 genes in both samples. Concordance is defined as the number of genomic alteration present in both samples divided by the number of genomic alteration in FFPE. Tumor mutation burden (TMB) was also measured.

      4c3880bb027f159e801041b1021e88e8 Result

      Most patients were adenocarcinoma (n=34, 82.9%). The total number of genomic alteration identified in FFPE and ctDNA were 751 and 561, respectively. Median concordance was 50% (8.0% – 100%). Among the clinical factors including smoking history, tumor size, PD-L1 status, EGFR mutation, TMB of tumor DNA, and concentration of ctDNA, concordance was negatively correlated with TMB of tumor DNA (Spearman's r= -0.504, P=0.001). When we divide low TMB (TMB-L) and high TMB (TMB-H) by the cut-off of 15/MB (median value), average concordance was 38.7% in TMB-H (N=20) and 59.7% in TMB-L (N=21) (Mann-Whitney, P=0.007). TMB by FFPE was significantly associated with the number of genomic alterations in FFPE (P<0.0001), but was not with the number of genomic alterations in ctDNA (P=0.128) or PD-L1 status (P=0.574).

      figure1 concordance in tmb-l and tmb-h.png

      8eea62084ca7e541d918e823422bd82e Conclusion

      This study suggests that ctDNA genomic profiling may replace tissue-based genomic profiling in NSCLC patients with low TMB. However, both tissue and blood-based genomic profiling may be necessary for NSCLC patients with high TMB.

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