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Updated: Aug 6, 2026
Detection and Monitoring of Tumor Associated Circulating DNA in Patient Biofluids
Published on: June 8, 2019
A prospective national precision medicine trial evaluating the feasibility of blood-based molecular profiling in
Alicia-Marie Conway1,2,3, Matthew Robinson4, Matthew Concannon3
1Division of Cancer Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK.
Background:
Cancer of Unknown Primary (CUP) is an aggressive malignancy with poor patient outcomes. For most patients, the primary site remains elusive, limiting therapeutic options to non-specific chemotherapy. The CUP-COMP study (NCT04750109) assessed the feasibility of integrating molecular profiling with a National Molecular Tumour Board (MTB) into the treatment pathway of patients with CUP.
Methods:
Patients with histologically confirmed CUP were recruited from seven UK sites. Blood- and/or tissue-based molecular profiling was performed with results interpreted via an MTB identifying potentially actionable alterations (PAA). Retrospective tissue and blood alteration analysis assessed concordance and utility.
Results:
113/117 patients recruited between June 2021 and February 2023 completed 12 months of follow-up. Of 115 patients with successful molecular profiling, blood-based profiling was more successful (93%) than tissue-based (61%). The MTB identified PAAs in 63% (73/115), with 26% (31/117) treated using a precision medicine (PM) approach. Primary tumours were subsequently confirmed/suspected in 41 patients. Median overall survival (OS) was 9.5 months. Detecting a PAA in blood was impacted by tumour fraction (33% of patients had a tumour fraction <1%).
Discussion:
CUP-COMP demonstrates liquid biopsies are highly feasible in CUP. While tissue profiling remains preferable, blood-based profiling offers a timely viable alternative to tissue, especially in selected patients.
