111P The concordance between circulating tumor DNA and tissue genomic profiling in patients with advanced biliary tract cancer

Recent advances in molecular profiling have revealed potential therapeutic targets for biliary tract cancer (BTC). However, difficulties in obtaining an adequate sample could hamper molecular evaluations in patients with BTC. Circulating tumor DNA (ctDNA) can thus help address any challenges associated with the limited use of tissue-based analysis in BTC. In this study, we aimed to evaluate the concordance between ctDNA and tissue genomic profiling in patients with advanced BTC and evaluate the feasibility of liquid biopsy in the treatment of patients with BTC. Patients who underwent tissue-based next-generation sequencing (NGS) before systemic chemotherapy for advanced BTC at CHA Bundang Medical Center from January 2019 to December 2022 and for whom sufficient plasma samples were available for ctDNA analysis (AlphaLiquid®100 from IMB Dx) were included. Clinically important (tier 1 or 2) variants detected in tissues with a variant allele frequency (VAF) of >0.05 were considered as true positive for concordance. Of one hundred two patients, 49.0%, 26.5%, and 24.5% had intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gall bladder cancer, respectively. The concordance between intra-patient ctDNA and tumor tissue for mutations indicated 84.8% sensitivity and 79.4% positive predictive value. In ctDNA, targetable alterations were detected in 34.3% of patients, such as IDH1 mutation (7.8%), FGFR2 fusion (2.0%), microsatellite instability (MSI)-high (2.0%), ERBB2 amplification (4.9%), PIK3CA hotspot mutations (6.9%), BRCA1/2 mutations (9.8%), and MET amplification (2.9%). Among the two FGFR2 fusions, one FGFR2-TNS1 fusion was novel, because it was not targeted in tissue NGS panel. Lastly, patients with high ctDNA VAF showed poor prognosis in gemcitabine-cisplatin based chemotherapy in both overall survival and progression-free survival (p = 6.9 x 10-6 and p = 9.8 x 10-10), respectively. ctDNA-based genotyping demonstrated acceptable concordance with tissue genomic profiling in patients with advanced BTC. Thus, liquid biopsy using ctDNA could complement the limitation of tissue-based genomic analysis in BTC.