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Circulating Tumor DNA Sequencing Analysis of Gastroesophageal Adenocarcinoma.


ABSTRACT: Purpose: Gastroesophageal adenocarcinoma (GEA) has a poor prognosis and few therapeutic options. Utilizing a 73-gene plasma-based next-generation sequencing (NGS) cell-free circulating tumor DNA (ctDNA-NGS) test, we sought to evaluate the role of ctDNA-NGS in guiding clinical decision-making in GEA.

Experimental design: We evaluated a large cohort (n = 2,140 tests; 1,630 patients) of ctDNA-NGS results (including 369 clinically annotated patients). Patients were assessed for genomic alteration (GA) distribution and correlation with clinicopathologic characteristics and outcomes.

Results: Treatment history, tumor site, and disease burden dictated tumor-DNA shedding and consequent ctDNA-NGS maximum somatic variant allele frequency. Patients with locally advanced disease having detectable ctDNA postoperatively experienced inferior median disease-free survival (P = 0.03). The genomic landscape was similar but not identical to tissue-NGS, reflecting temporospatial molecular heterogeneity, with some targetable GAs identified at higher frequency via ctDNA-NGS compared with previous primary tumor-NGS cohorts. Patients with known microsatellite instability-high (MSI-High) tumors were robustly detected with ctDNA-NGS. Predictive biomarker assessment was optimized by incorporating tissue-NGS and ctDNA-NGS assessment in a complementary manner. HER2 inhibition demonstrated a profound survival benefit in HER2-amplified patients by ctDNA-NGS and/or tissue-NGS (median overall survival, 26.3 vs. 7.4 months; P = 0.002), as did EGFR inhibition in EGFR-amplified patients (median overall survival, 21.1 vs. 14.4 months; P = 0.01).

Conclusions: ctDNA-NGS characterized GEA molecular heterogeneity and rendered important prognostic and predictive information, complementary to tissue-NGS.See related commentary by Frankell and Smyth, p. 6893.

SUBMITTER: Maron SB 

PROVIDER: S-EPMC6891164 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Circulating Tumor DNA Sequencing Analysis of Gastroesophageal Adenocarcinoma.

Maron Steven B SB   Chase Leah M LM   Lomnicki Samantha S   Kochanny Sara S   Moore Kelly L KL   Joshi Smita S SS   Landron Stacie S   Johnson Julie J   Kiedrowski Lesli A LA   Nagy Rebecca J RJ   Lanman Richard B RB   Kim Seung Tae ST   Lee Jeeyun J   Catenacci Daniel V T DVT  

Clinical cancer research : an official journal of the American Association for Cancer Research 20190819 23


<h4>Purpose</h4>Gastroesophageal adenocarcinoma (GEA) has a poor prognosis and few therapeutic options. Utilizing a 73-gene plasma-based next-generation sequencing (NGS) cell-free circulating tumor DNA (ctDNA-NGS) test, we sought to evaluate the role of ctDNA-NGS in guiding clinical decision-making in GEA.<h4>Experimental design</h4>We evaluated a large cohort (<i>n</i> = 2,140 tests; 1,630 patients) of ctDNA-NGS results (including 369 clinically annotated patients). Patients were assessed for g  ...[more]

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