Bespoke ctDNA testing for diagnosis, surveillance, and treatment monitoring in hepatopancreatobiliary malignancies

Hepatopancreatobiliary (HPB) malignancies – including hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), pancreatic ductal adenocarcinoma (PDAC), and gallbladder cancer – are aggressive malignancies with limited treatment options and poor prognosis. The emergence of bespoke circulating tumor DNA (ctDNA) testing may offer new opportunities for improving clinical management. A retrospective study at the Mayo Clinic (Phoenix, AZ) analyzed the use of a personalized ctDNA in 54 patients with HPB malignancies (22 PDAC, 11 HCC, 21 CCA). ctDNA was assessed longitudinally for surveillance, treatment monitoring, or diagnostic clarification. ctDNA was evaluable in 37 of 54 patients (68.5%), with ctDNA positivity in 22 of 37 patients (59.5%). Success rates by tumor type were 72.7% in PDAC, 90.9% in HCC, and 52.4% in CCA. ctDNA concordance with imaging was observed in 72.6% of assessments and with tumor markers in 41%. Clinical applications included disease surveillance (38.9%), treatment monitoring (44.4%), and diagnostic clarification (29.6%). In patients with recurrence, ctDNA detected disease before imaging in several cases, with a median lead time of 28 days (range 1-7 months). The authors conclude that personalized ctDNA testing demonstrated meaningful utility across HPB malignancies.