Deep sequencing of circulating tumour DNA as a biomarker of clinical outcome to transarterial chemoembolisation in hepatocellular carcinoma

Abstract Survival following transarterial chemoembolisation (TACE) for hepatocellular cancer (HCC) is variable. We explored targeted sequencing of circulating tumour DNA (ctDNA) as a prognostic biomarker. Plasma samples (n = 97) were collected at baseline and following TACE. Targeted, ultra-deep sequencing was conducted on 18 somatic mutations related to the molecular pathogenesis of HCC. Median progression-free survival and overall survival were 11.6 months (95% CI: 5.83–21.2) and 34 months (95% CI: 22.35–45.60), respectively. CTNNB1 and ARID1A were the most frequently mutated genes, present in 25% of baseline circulating samples, followed by SF3B1 (20%) and TERT (18%). The presence of mutations in CTNNB1, TP53 ARID1A, and KEAP1 predicted for poor OS on univariable analysis. Findings suggest that ctDNA profiling of known genetic drivers of HCC may serve as a valuable prognostic biomarker prior to TACE and may assist with the stratification of patients following further evaluation in larger studies.