Circulating tumor DNA (ctDNA) is a promising non-invasive biomarker in
cancer. The inventors aim to assess the dynamic evolution of ctDNA in patients with
hepatocellular carcinoma (HCC). For that, they analyzed 772 plasmas from 173 patients with HCC collected at the time of diagnosis or treatment (n=502), 24h after locoregional treatment (n=154), and during follow-up (n=116). All samples were analyzed for
cell free DNA (cfDNA) concentration, and for mutations in
TERT promoter, CTNNB1, TP53, PIK3CA and NFE2L2 by sequencing and droplet-based digital PCR. Results were compared to 232 corresponding tumor samples. In active HCC, the inventors identified 27-5% of mutations in
TERT promoter, 21 -3% in TP53, 13- 1% in CTNNB1, 0-4% in PIK3CA and 0-2% in NFE2L2, most of the times similar to those identified in the corresponding tumor. In 103 patients treated by
percutaneous ablation, the presence and number of mutations in the ctDNA before treatment were associated with higher
risk of death (p=0 001 ) and recurrence (p<0 001). In patients treated by
atezolizumab /
bevacizumab, persistence of
mutation in ctDNA was associated with radiological progression (63-6% versus 36-4% for disappearance, p=0 019). Thus,
circulating tumor DNA offers dynamic information reflecting
tumor biology and represents a non-invasive tool useful to guide HCC clinical management.