Faculty Collaboration Database

Analysis of Circulating Tumor DNA and Clinical Correlates in Patients with Esophageal, Gastroesophageal Junction, and Gastric Adenocarcinoma. Clin Cancer Res 2018 Dec 15;24(24):6248-6256

Date

10/24/2018

Pubmed ID

30348637

Pubmed Central ID

PMC6384095

DOI

10.1158/1078-0432.CCR-18-1128

Scopus ID

2-s2.0-85058443864 (requires institutional sign-in at Scopus site)   81 Citations

Abstract

PURPOSE: Esophageal, gastroesophageal 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).

EXPERIMENTAL DESIGN: We analyzed genomic alterations of 55 patients (mostly advanced disease; 9, 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 (VUS)] 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% confidence interval, 2.44-81.03; P = 0.003 multivariate analysis). Among patients with ≥1 alteration, no 2 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 patients with gastroesophageal adenocarcinoma is feasible. Patients harbored heterogeneous patterns of genomics, with most having alterations that are potentially pharmacologically tractable.

Author List

Kato S, Okamura R, Baumgartner JM, Patel H, Leichman L, Kelly K, Sicklick JK, Fanta PT, Lippman SM, Kurzrock R

Author

Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adenocarcinoma
Adult
Aged
Aged, 80 and over
Biomarkers, Tumor
Circulating Tumor DNA
Esophageal Neoplasms
Esophagogastric Junction
Female
Gene Expression Profiling
Genetic Testing
High-Throughput Nucleotide Sequencing
Humans
Kaplan-Meier Estimate
Male
Middle Aged
Neoplasm Grading
Neoplasm Staging
Prognosis
Stomach Neoplasms
Treatment Outcome
Young Adult