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      Analysis of Circulating Tumor DNA and Clinical Correlates in Patients with Esophageal, Gastroesophageal Junction and Gastric Adenocarcinoma

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          Abstract

          Purpose:

          Esophageal, gastro-esophageal junction and gastric adenocarcinoma (herein gastroesophageal adenocarcinomas) are associated with poor prognosis and limited systemic treatment options. To further understand the genomic landscape of gastroesophageal cancers and its clinical correlations, circulating tumor DNA (ctDNA) from patients’ plasma was evaluated using next-generation sequencing (NGS).

          Methods:

          We analyzed genomic alterations of 55 patients (mostly advanced disease; nine, surgically resectable) with gastroesophageal adenocarcinomas using clinical-grade NGS performed on plasma-derived ctDNA (54-73 gene panel). The test detects single nucleotide variants, as well as copy number amplifications, fusions and indels in selected genes.

          Results:

          Seventy-six percent of patients (42/55) had ≥1 genomic alteration (including variants of unknown significance [VUSs]) and 69.1% (38/55) had ≥1 characterized alteration (excluding VUSs). The median number of alterations per patient was 2 (range, 0–15). TP53 (50.9%, 28/55), PIK3CA (16.4%, 9/55), ERBB2 (14.5%, 8/55) and KRAS (14.5%, 8/55) genes were most frequently affected characterized alterations. Thirty-one patients also had tissue NGS. Concordance between tissue and ctDNA ranged from 61.3% ( TP53 alterations) to 87.1% ( KRAS alterations). ERBB2 alterations were significantly associated with poor overall survival (HR: 14.06, 95% CI: 2.44 – 81.03, P=0.003 multivariate analysis). Among patients with ≥1 alteration, no two patients had identical molecular portfolios. All patients with ≥1 characterized alteration had theoretically targetable alterations by an FDA-approved agent (on- or off-label). Illustrative case treated with cognate agent is presented.

          Conclusions:

          Evaluation of ctDNA by NGS among gastroesophageal adenocarcinoma patients is feasible. Patients harbored heterogeneous patterns of genomics, with most having alterations that are potentially pharmacologically tractable.

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          Author and article information

          Journal
          9502500
          8794
          Clin Cancer Res
          Clin. Cancer Res.
          Clinical cancer research : an official journal of the American Association for Cancer Research
          1078-0432
          14 February 2019
          22 October 2018
          15 December 2018
          15 December 2019
          : 24
          : 24
          : 6248-6256
          Affiliations
          [1 ]Center for Personalized Cancer Therapy and Division of Hematology and Oncology, Department of Medicine, UC San Diego Moores Cancer Center, La Jolla, CA, USA
          [2 ]Division of Surgical Oncology, Department of Surgery, UC San Diego Moores Cancer Center, La Jolla, CA, USA
          Author notes
          Corresponding author’s contact information: Shumei Kato, M.D., Center for Personalized Cancer Therapy and Division of Hematology and Oncology, Department of Medicine, UC San Diego Moores Cancer Center, 3855 Health Sciences Drive, La Jolla, CA 92093, smkato@ 123456ucsd.edu , Phone: 858-822-2372, FAX: 858-822-6186
          [*]

          Contributed equally

          [¶]

          Contributed equally

          Article
          PMC6384095 PMC6384095 6384095 nihpa1510413
          10.1158/1078-0432.CCR-18-1128
          6384095
          30348637
          a5e7ab2a-c8f9-4680-a56c-120195a7a447
          History
          Categories
          Article

          esophageal cancer,Circulating tumor DNA,next-generation sequencing,liquid biopsy,gastric cancer,gastro-esophageal cancer

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