MVI-targeted carbon-ion radiotherapy combined with immunotherapy for advanced hepatocellular carcinoma: Phase Ib DEPARTURE trial

Hepatocellular carcinoma (HCC) with macrovascular invasion carries a poor prognosis, necessitating novel therapeutic strategies. This phase Ib trial evaluated the safety and preliminary efficacy of combining carbon-ion radiotherapy with immune checkpoint inhibitors in patients with advanced HCC. RNA-seq was conducted to investigate changes in the tumor microenvironment, aiming to identify molecular signatures predictive of response or resistance to the combination therapy. The reduction group showed enrichment of pathways related to inflammation, complement activation, which are often associated with immune activity. In contrast, the progression group exhibited enrichment of pathways linked to mesenchymal characteristics and angiogenesis, processes that may correlate with reduced therapy efficacy.