Center for Personalized Cancer Therapy and Division of Hematology and Oncology, Department of Medicine, UC San Diego Moores Cancer Center, La Jolla, California.
Division of Surgical Oncology, Department of Surgery, UC San Diego Moores Cancer Center, La Jolla, California.
Clin Cancer Res. 2018 Dec 15;24(24):6248-6256. doi: 10.1158/1078-0432.CCR-18-1128. Epub 2018 Oct 22.
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).
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.
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). (50.9%, 28/55), (16.4%, 9/55), (14.5%, 8/55), and (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% ( alterations) to 87.1% ( alterations). alterations were significantly associated with poor overall survival (HR, 14.06; 95% confidence interval, 2.44-81.03; = 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.
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.
食管、胃食管交界处和胃腺癌（以下简称胃食管腺癌）预后不良，且系统治疗选择有限。为了进一步了解胃食管癌的基因组图谱及其临床相关性，我们使用下一代测序（NGS）评估了患者血浆中的循环肿瘤 DNA（ctDNA）。
我们使用临床级 NGS 分析了 55 名（主要为晚期疾病；9 名可手术切除）胃食管腺癌患者的基因组改变，该 NGS 是基于血浆衍生的 ctDNA 进行的（54-73 个基因panel）。该检测可检测到选定基因中的单核苷酸变异，以及拷贝数扩增、融合和插入缺失。
76%的患者（42/55）存在≥1 种基因组改变[包括意义不明的变异（VUS）]，69.1%（38/55）存在≥1 种特征改变（不包括 VUS）。每位患者的平均改变数为 2（范围 0-15）。最常发生特征改变的基因依次为 （50.9%，28/55）、 （16.4%，9/55）、 （14.5%，8/55）和 （14.5%，8/55）。31 名患者还进行了组织 NGS。组织和 ctDNA 之间的一致性范围为 61.3%（改变）至 87.1%（改变）。 改变与总生存期不良显著相关（HR，14.06；95%置信区间，2.44-81.03；=0.003 多变量分析）。在存在≥1 种改变的患者中，没有 2 例患者具有相同的分子谱。所有具有≥1 种特征改变的患者均具有理论上可通过 FDA 批准的药物（上市或非上市）靶向的改变。给出了一个用同源药物治疗的典型病例。
在胃食管腺癌患者中，通过 NGS 评估 ctDNA 是可行的。患者存在异质性的基因组学模式，大多数具有潜在可药物治疗的改变。
