{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T23:00:26Z","timestamp":1783033226762,"version":"3.54.6"},"reference-count":30,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"9","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Precis Oncol"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:sec>\n            <jats:title>PURPOSE<\/jats:title>\n            <jats:p>An estimated 25% of patients with biliary tract cancer (BTC) do not undergo genotyping, representing a missed opportunity for therapeutic targeting.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS<\/jats:title>\n            <jats:p>Cell-free DNA (cfDNA) and matched tumor sample from patients with BTC were analyzed using targeted next-generation sequencing (NGS) assay and compared. We sought to define the molecular profile of cancer-derived cfDNA, frequency of OncoKB level 1\/2 alterations, plasma:tumor genotype concordance, the prognostic impact of cfDNA, and clonal evolution after targeted therapy progression.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS<\/jats:title>\n            <jats:p>\n              cfDNA-based genotyping was performed on 297 blood samples from 170 patients with BTC. The most frequently altered genes were\n              <jats:italic toggle=\"yes\">TP53<\/jats:italic>\n              (29%),\n              <jats:italic toggle=\"yes\">FGFR2<\/jats:italic>\n              (16%),\n              <jats:italic toggle=\"yes\">ARID1A<\/jats:italic>\n              (13%),\n              <jats:italic toggle=\"yes\">CDKN2A<\/jats:italic>\n              (11%), and\n              <jats:italic toggle=\"yes\">KRAS<\/jats:italic>\n              (11%); 25% of patients had OncoKB level 1\/2 alterations and 36.2% of potentially actionable alterations were detected in plasma alone. The cfDNA:tissue concordance accuracy was high (96%\n              <jats:italic toggle=\"yes\">IDH1<\/jats:italic>\n              , 98%\n              <jats:italic toggle=\"yes\">BRAF<\/jats:italic>\n              , 92%\n              <jats:italic toggle=\"yes\">KRAS<\/jats:italic>\n              mutations, 99%\n              <jats:italic toggle=\"yes\">ERBB2<\/jats:italic>\n              amplifications, and 96%\n              <jats:italic toggle=\"yes\">FGFR2<\/jats:italic>\n              fusions). Detectable tumor-derived cfDNA after resection did not predict recurrence. In treatment-na\u00efve metastatic BTC, high variant allele fraction was associated with worse progression-free survival and overall survival.\n              <jats:italic toggle=\"yes\">RAS<\/jats:italic>\n              alterations not detected in samples before treatment were identified at progression in 24% of patients who received BRAF-, FGFR-, or HER2-directed therapy, identifying\n              <jats:italic toggle=\"yes\">RAS<\/jats:italic>\n              alterations as a convergent mechanism of targeted therapy resistance.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSION<\/jats:title>\n            <jats:p>Molecular profiling of cfDNA from patients with BTC identified OncoKB level 1\/2 gene alterations and putative genomic resistance mechanisms to targeted therapy. Concordance analysis suggests that cfDNA-based NGS is complementary to that of tissue-based sequencing in the identification of potentially actionable alterations.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1200\/po-25-00355","type":"journal-article","created":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T19:59:28Z","timestamp":1758052768000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":5,"title":["Clinical Utility and Prognostic Implications of Circulating Cell-Free DNA in Biliary Tract Cancer"],"prefix":"10.1200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0969-3259","authenticated-orcid":true,"given":"Darren","family":"Cowzer","sequence":"first","affiliation":[{"name":"Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"},{"name":"Weill Medical College of Cornell University, New York, 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