According to a multicenter analysis published in Clinical Cancer Research and reported by Biotech Spain, circulating tumor DNA (ctDNA) next-generation sequencing has been validated as a clinically reliable alternative to tissue biopsy for molecular profiling in advanced biliary tract cancers — a rare, heterogeneous tumor group where anatomical access routinely limits patient eligibility for targeted therapy.
Concordance and cohort architecture
The study, coordinated by Spain's CIBERONC cancer research network in collaboration with Guardant Health and led by investigators at the Hospital del Mar Research Institute (HMRIB), drew on molecular data from 10,937 patients — described by the research team as the largest international cohort analyzed to date in this indication. A validation subset of 126 patients with metastatic or inoperable cholangiocarcinoma, sourced from nine Spanish centers, provided paired tissue and plasma samples for head-to-head comparison. Liquid biopsy detected the most clinically relevant molecular alterations with 83% concordance relative to tissue sequencing, and produced actionable results in 90% of patients versus 50% for tissue-based analysis — a stratification gap that materially determines who enters the precision-medicine pathway.
Clinical and laboratory implications
Roughly four in ten biliary tract cancer patients harbor molecular alterations eligible for existing targeted agents, yet routine tissue acquisition from bile ducts or hepatic parenchyma frequently fails on specimen quantity or quality. Dr. Laura Visa, consultant in Medical Oncology at Hospital del Mar and a researcher within HMRIB's Gastroesophageal Carcinogenesis Research Group, indicated that the data support liquid biopsy as a highly useful alternative when tumor tissue is insufficient — enabling identification of actionable alterations and facilitating access to targeted treatments. Dr. Clara Montagut, head of Medical Oncology at the same institution and deputy director of HMRIB, attributed the findings' clinical validity to the cohort's scale and the Guardant Health collaboration.
Parallel signal from ESMO MAP
Separately at the ESMO Molecular Analysis for Precision Oncology (MAP) Conference in London, VolitionRx presented data on its CTCF Capture-Seq platform — a direct chromatin immunoprecipitation sequencing approach isolating CTCF-protected plasma ctDNA from nucleosome-bound background cell-free DNA. According to the company, the assay identified 49 of 49 cancers in an initial cohort comprising 23 stage I/II cases alongside 21 healthy controls, 13 of 14 later-stage cancers in a blinded second cohort with 10 healthy controls, and a 95% detection rate in stage I/II disease across an additional 81-subject cohort of 59 colorectal and lung cancer patients. Andrew Retter, medical consultant at Volition, characterized the proof-of-concept and blinded validation results as clinically encouraging, while chief scientific officer Jake Micallef positioned the methodology as a potential backbone for multi-cancer early detection and minimal residual disease monitoring. The company indicated it is fast-tracking assay development through expanded clinical studies incorporating competing medical conditions and additional oncology key-opinion-leader collaboration.