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Lianpeng Chang



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    P2.03 - Biology (Not CME Accredited Session) (ID 952)

    • 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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      P2.03-26 - A Prospective Cohort Study of TMB and Determinants of ctDNA Detection by Comprehensive Genomic Profiling in Stage I Lung Adenocarcinomas (ID 12683)

      16:45 - 18:00  |  Author(s): Lianpeng Chang

      • Abstract
      • Slides

      Background

      Plasma tumor mutational burden (TMB) is a predictor of immune checkpoint inhibitors treatment in advanced lung cancer patients. A preliminary study has shown the feasibility of PD-1 treatment in resectable lung cancer. However, few studies investigated TMB and plasma circulating tumor DNA detection in stage I lung adenocarcinomas.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We prospectively enrolled 67 consecutive patients with pulmonary nodule who intended to undergo curative lung resection (NCT03320044). Comprehensive genomic profiling were used to identify somatic variants in both tissue and matched blood samples. Tissue clonal mutations were defined if mutations were in the cluster with the highest mean variated allele frequency with PyClone.

      4c3880bb027f159e801041b1021e88e8 Result

      Mean effective depth of coverage of 1045x and 27410x were obtained in tissue and plasma samples, respectively. Resected stage I lung adenocarcinoma patients were included (4 IA1, 20 IA2, 9 IA3, 12 IB)(Fig.1). An increasing tissue TMB was detected in Stage IA1, Stage IA2, Stage IA3 ( 1.5mut/Mb, 3mut/Mb, 4mut/Mb, p<0.05). Mixed invasive subtype appeared the highest TMB, followed by invasive adenocarcinoma and minimally invasive adenocarcinoma (4mut/Mb, 3mut/Mb, 1mut/Mb, p<0.05). A significant rise of TMB was identified in pure ground-glass nodule, subsolid nodule and solid nodule (1.5mut/Mb, 2 mut/Mb, 4 mut/Mb, p<0.05). 30.3 % (10/33) patients were demonstrated to be ctDNA-positive with a mean ctDNA abundance of 0.0415% (ranged from 0.012 to 0.119%). A series of factors such as gender, pleural invasion and solid tumor size affected ctDNA detection. 50% patients detected clonal alterations in plasma. Unlike tissue, blood TMB showed no relation with clinical-pathological characteristics.

      fig.1.jpg

      8eea62084ca7e541d918e823422bd82e Conclusion

      We evaluated the feasibility of TMB and determinants of ctDNA detection in stage I lung adenocarcinomas. TMB was related to the invasiveness of tumor, while no such correlation were found in ctDNA. Improving the sensitivity of ctDNA detection, such as incorporated methylation or cancer-related antibodies detection, may be necessary in early stage patients.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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