In solid cancers, some more aggressive tumor cells actively detach from the primary lesion and then travel through the circulating compartment to reach distant organs and form micro-metastases. Detecting CTCs in the blood is also relevant for assessing tumor progression, prognosis and therapeutic follow-up. The non-invasive, highly sensitive for CTCs analysis is called liquid biopsy. Over the past few years, a multi-analyses approach (CTCs, circulating tumor DNA, extracellular vesicles, miRNA...) of liquid biopsy has been developed.~Hepatocellular carcinoma (HCC) is the predominant pathological type of primary liver cancer. It represents the sixth most common incidence worldwide and the third most common cause of cancer mortality.~Since 2021, the gold standard treatment for patients with advanced and/or unresectable HCC is the combination of atezolizumab (anti-PD-L1) and bevacizumab (VEGF inhibitor) in cases where chemoembolization is not indicated (patients with lymph node invasion and/or distant lesions or patients with portal flow abnormality). Indeed, this therapy offers a significant benefit in overall survival (19.2 vs 13.4 months, HR 0.66, p<0.0009) as well as in progression-free survival (6.9 vs 4.3 months, HR 0.65, p=0.0001). However, to date, there is no predictive biomarker for the efficacy of immune checkpoint inhibitors (ICI)~The purpose of this research project is to identify a predictive biomarker in patients with advanced HCC (stage B and C) using a combinatorial approach of the liquid biopsy (CTC, CTC expressing PD-L1, immune cell profiling).
The goal of this prospective clinical trial is to identify a predictive biomarker in patients with advanced HCC (stage B and C) using a combinatorial approach of the liquid biopsy.~The main questions it aims to answer are:~Is multi-omic liquid biopsy approach able to identify a strong predictive biomarker of immunotherapy efficiency?~Is there a correlation between tissue biopsy (PD-L1 tissue level of expression) and liquid biopsy (detection of CTC expressing PD-L1) in HCC patients?~Participants blood will be collected at several time points.