Dataset Information

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

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.

SUBMITTER: Kato S

PROVIDER: S-EPMC6384095 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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

Kato Shumei S Okamura Ryosuke R Baumgartner Joel M JM Patel Hitendra H Leichman Lawrence L Kelly Kaitlyn K Sicklick Jason K JK Fanta Paul T PT Lippman Scott M SM Kurzrock Razelle R

Clinical cancer research : an official journal of the American Association for Cancer Research 20181022 24

<h4>Purpose</h4>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).<h4>Experimental design</h4>We analyzed genomic alterations of 55 patients (mostly advanced d ...[more]

PMID: 30348637

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Project description:ObjectiveTo explore the clinical utility of circulating tumor DNA (ctDNA) in esophageal adenocarcinoma (EAC) by developing a cost-effective and rapid technique utilising targeted amplicon sequencing.Summary of background dataEmerging evidence suggests that levels of ctDNA in the blood can be used to monitor treatment response and in the detection of disease recurrence in various cancer types. Current staging modalities for EAC such as computerised tomography of the chest/abdomen/pelvis (CT) and positron emission tomography (PET) do not reliably detect occult micro-metastatic disease, the presence of which signifies a poor prognosis. After curative-intent treatment, some patients are still at high risk of recurrent disease, and there is no widely accepted optimal surveillance tool for patients with EAC.MethodsSixty-two patients with EAC were investigated for the presence of ctDNA using a tumor-informed approach. We designed a custom targeted amplicon sequencing panel of target specific primers covering mutational foci in 9 of the most commonly mutated genes in EAC. Serial blood samples were taken before and after neoadjuvant treatment (NAT), and during surveillance.ResultsSomatic mutations were detected in pre-treatment biopsy samples of 55 out of 62 (89%) EAC patients. Mutations in TP53 (80%) were the most common. Out of these 55 patients, 20 (36%) had detectable ctDNA at baseline. The majority (90%) of patients with detectable ctDNA had either locally advanced tumors, nodal involvement or metastatic disease. In patients with locally advanced tumors, disease free survival (DFS) was more accurately stratified using pre-treatment ctDNA status [HR 4.34 (95% CI 0.93-20.21); P = 0.05] compared to nodal status on PET-CT. In an exploratory subgroup analysis, patients who are node negative but ctDNA positive have inferior DFS [HR 11.71 (95% CI 1.16-118.80) P = 0.04]. In blood samples taken before and following NAT, clearance of ctDNA after NAT was associated with a favourable response to treatment. Furthermore, patients who are ctDNA positive during post-treatment surveillance are at high risk of relapse.ConclusionsOur study shows that ctDNA has potential to provide additional prognostication over conventional staging investigation such as CT and PET. It may also have clinical utility in the assessment of response to NAT and as a biomarker for the surveillance of recurrent disease.

Dataset Information

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

Publications

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

Similar Datasets

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