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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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      P2.01-110 - Unique Genomic Profile Revealed by Malignant Pleural Effusion (ID 13590)

      16:45 - 18:00  |  Author(s): Wei Du

      • Abstract
      • Slides

      Background

      The accumulation of malignant pleural effusion (MPE), often occurring in advanced lung cancer patients, is the result of pleural space invasion by malignant cells, which disrupt the drainage of pleural fluid. Numerous studies have confirmed the clinical utility of MPE for mutation detection from single gene perspective, often focusing on classic driver genes. Very few studies have interrogated MPE as a media for liquid biopsy using targeted sequencing. In this study we investigated the potential of using MPE as a media for liquid biopsy using targeted sequencing.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Matched plasma and MPE samples were obtained from 154 patients with advanced NSCLC. Among them, 17 patients had matched primary tissue sample and MPE precipitates. Ultra-deep targeted sequencing using a panel consisting of 168 lung cancer-related genes, spanning 160 kb of human genome was performed with an average sequencing depth of 10,000x for MPE and 1,000x for tissue samples.

      4c3880bb027f159e801041b1021e88e8 Result

      Using tissue sample as a reference, detection rates of driver mutations in MPE cfDNA (supernatant), MPE precipitates and plasma are 100%, 70.6% and 82.3%, respectively. The median maximum allelic fractions (MAF) for MPE cfDNA, precipitates and plasma are 12.9%, 14.8% and 3.6%, respectively. MPE and tissue have comparable median MAF, which is significantly higher than plasma (p=0.01), demonstrating the superiority of MPE cfDNA in mutation detection. Next, we compared and contrast genomic profiles derived from MPE cfDNA and plasma cfNDA. Collectively, in 154 patients, we identified 939 variants from MPE and 865 variant from plasma; among them, 770 variants were shared by the two media; 169 variants were MPE specific and 95 variants were plasma specific. EGFR and TP53 are the two most frequently occurring mutations in both MPE cfDNA and plasma cfDNA. MPE cfDNA of 56 patients had CNVs detected; in contrast, only 27 patients had CNVs detected from plasma sample, resulting in a significantly higher detection rate in MPE cfDNA (p<0.01). Collectively, we identified 201 CNVs; among them, 164 were shared by both media; 33 are MPE specific and the remaining 4 are plasma specific.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Collectively, our study demonstrates superiority of MPE cfDNA as an alternative media for liquid biopsy. In addition to higher detection rate and MAF, MPE cfDNA also revealed a unique genomic profile, especially in capturing CNV.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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