Concordance of ctDNA and tissue genomic profiling in advanced biliary tract cancer

作者：Sohyun Hwang, Seonjeong Woo, Beodeul Kang, Haeyoun Kang, Jung Sun Kim, Sung Hwan Lee, Chang‐Il Kwon, Dong Soo Kyung, Hwang‐Phill Kim, Gwangil Kim, Chan Kim, Hong Jae Chon · 发表于：Journal of Hepatology · 年份：2024 · DOI：10.1016/j.jhep.2024.10.020 · 被引用次数：55 · 研究领域：Cholangiocarcinoma and Gallbladder Cancer Studies、Cancer Genomics and Diagnostics、Pancreatic and Hepatic Oncology Research

Background & Aims Recent advances in molecular profiling have enabled the identification of potential therapeutic targets for biliary tract cancer (BTC). However, in patients with BTC, molecular profiling is hindered by challenges in obtaining adequate tissue samples. Circulating tumor DNA (ctDNA) may offer an alternative to tissue-based analysis. Herein, we aimed to assess the concordance between ctDNA and tissue genomic profiling in a large cohort of Asian patients with advanced BTC, and to evaluate the feasibility of liquid biopsy in BTC treatment. Methods This study included patients with systemic treatment-naive advanced BTC, treated at CHA Bundang Medical Center between January 2019 and December 2022. We enrolled patients with available baseline tissue-based next-generation sequencing, and sufficient plasma samples for ctDNA analysis (AlphaLiquid®100 from IMBdx). Results Among 102 enrolled patients, 49.0% had intrahepatic cholangiocarcinoma, 26.5% extrahepatic cholangiocarcinoma, and 24.5% gallbladder cancer. The concordance between intra-patient ctDNA and tumor tissue mutations revealed a sensitivity of 84.8%, and positive predictive value of 79.4%. ctDNA revealed targetable alterations in 34.3% of patients – including FGFR2 fusions, IDH1 mutations, microsatellite instability-high, ERBB2 amplifications, PIK3CA mutations, BRCA1/2 mutations, and MET amplifications. Notably, a novel FGFR2-TNS1 fusion was identified in ctDNA, which was not targeted in the tissue NGS panel....