{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T23:32:20Z","timestamp":1788046340898,"version":"build-2784847793"},"reference-count":37,"publisher":"American Medical Association (AMA)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n The prognosis of advanced pancreaticobiliary tumors is poor. Next-generation sequencing (NGS) of tissue samples is utilized to identify actionable alterations, but there are occasional limitations due to inadequate tissue acquisition. Circulating tumor DNA (ctDNA) is an alternative method, but its correlation with tissue-based NGS remains unexplored.<\/jats:p>\n <\/jats:sec>\n \n Objectives<\/jats:title>\n To assess the mutation concordance (mCR) rates between ctDNA and tissue testing for patients with pancreatic ductal adenocarcinoma (PDAC) and cholangiocarcinoma (CC) and to evaluate how ctDNA performs as a treatment response biomarker.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This retrospective cohort study was conducted among patients with PDAC and CC treated at academic institutions from January 2014 to January 2025. Patients underwent ctDNA testing using 1 platform and tissue NGS testing using 2 platforms.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n mCR, which measures the shared gene alterations observed by both ctDNA and tissue-based NGS testing, was calculated using the Spearman correlation for PDAC and CC. The performance of ctDNA as a treatment response biomarker was assessed by comparing serial ctDNA data with restaging scans and cancer antigen 19-9 levels in patients with PDAC.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Our cohort included 790 patients: 570 with advanced PDAC (265 [46.5%] female; median [IQR] age, 64 [33-84] years) and 220 with advanced CC (95 [43.2%] female; median [IQR] age, 66 [42-88] years). Overall, 461 patients with PDAC (80.9%) and 192 patients with CC (87.2%) underwent ctDNA testing, while 239 patients with PDAC (41.9%) and 70 patients with CC (31.8%) had tissue NGS testing. Among patients with PDAC, 85 of 130 patients (65.4%) showed shared specific gene alterations between ctDNA and tissue testing; there was a significant mCR, with a Spearman correlation of 0.47 (95% CI, 0.28-0.62;\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001). For patients with CC, 32 of 48 (66.7%) had shared alterations between ctDNA and tissue testing; there was a significant mCR, with a Spearman correlation of 0.56 (95% CI, 0.35-0.70;\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001). A subgroup analysis of patients with PDAC who underwent serial ctDNA testing suggested that new\n TP53<\/jats:italic>\n subclones and increased ctDNA variant allele frequency levels of\n TP53<\/jats:italic>\n and\n KRAS<\/jats:italic>\n were associated with higher odds of progressive disease (eg, increased\n TP53<\/jats:italic>\n frequency: odds ratio, 7.28; 95% CI, 2.15-24.66;\n P<\/jats:italic>\n \u2009=\u2009.001).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n In this cohort study of patients with pancreaticobiliary tumors, there was a significant mCR between ctDNA and tissue NGS testing. Additionally, results suggest that ctDNA might detect resistant clones and enable assessment of treatment response.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2025.31373","type":"journal-article","created":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T15:30:36Z","timestamp":1757691036000},"page":"e2531373","source":"Crossref","is-referenced-by-count":8,"title":["Circulating Tumor DNA and Tissue Testing for Pancreatobiliary Tumors"],"prefix":"10.1001","volume":"8","author":[{"given":"Himil","family":"Mahadevia","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Missouri\u2013Kansas City"},{"name":"Division of Hematology-Oncology, Department of Medicine, Mayo Clinic Florida, Jacksonville"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umair","family":"Majeed","sequence":"additional","affiliation":[{"name":"Division of Hematology-Oncology, Department of Medicine, Mayo Clinic Florida, 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