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
10 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%
15 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
20 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