한빛사논문
Sohyun Hwang 1†, Seonjeong Woo 2†, Beodeul Kang 3†, Haeyoun Kang 1, Jung Sun Kim 3, Sung Hwan Lee 4, Chang Il Kwon 5, Dong Soo Kyung 6, Hwang-Phill Kim 6, Gwangil Kim 1*, Chan Kim 3*, Hong Jae Chon 3*
1Department of Pathology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Republic of Korea
2Department of Biomedical Science, CHA University, Seongnam, Republic of Korea
3Department of Medical Oncology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Republic of Korea
4Department of Surgery, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Republic of Korea
5Department of Gastroenterology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Republic of Korea
6IMBdx, Inc., Seoul, Republic of Korea
†Co-first authors
*Corresponding authors : Gwangil Kim, Chan Kim, Hong Jae Chon
Abstract
Background & Aims
Recent advances in molecular profiling enable 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. Here 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 (NGS), 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 fusion, IDH1 mutation, microsatellite instability (MSI)-high, ERBB2 amplification, PIK3CA mutations, BRCA1/2 mutations, and MET amplification. Notably, a novel FGFR2-TNS1 fusion was identified in ctDNA, which was not targeted in the tissue NGS panel. A high maximum somatic variant allele frequency in ctDNA was associated with poor prognosis after gemcitabine/cisplatin-based chemotherapy, in terms of both overall survival (p = 6.9 × 10−6) and progression-free survival (p = 3.8 × 10−7).
Conclusions
Among patients with advanced BTC, ctDNA-based genotyping showed acceptable concordance with tissue genomic profiling. Liquid biopsy using ctDNA could be a valuable complement to tissue-based genomic analysis in BTC.
Impact and implications
Our study is the first large-scale investigation of the clinical utility of liquid biopsy, focusing on ctDNA, as an alternative to conventional tumor tissue analysis, among Asian patients with advanced BTC. The results demonstrated acceptable concordance between analysis of ctDNA versus tissue for identifying therapeutic targets and potentially actionable genetic alterations. This indicates that ctDNA analysis can provide critical insights regarding advanced BTC treatment, particularly in cases where it is challenging to obtain or analyze tumor tissue.
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