Efficacy and Safety of Hypofractionated Radiation Therapy Combined With Immunotherapy for Hepatocellular Carcinoma With Vp4 Portal Vein Tumor Thrombosis

Background Hepatocellular carcinoma (HCC) with Vp4 portal vein tumor thrombosis (PVTT) has an extremely poor prognosis, and evidence for effective systemic therapy is limited. Preclinical studies suggest that hypofractionated radiation therapy (HFRT) may enhance immune checkpoint inhibitor (ICI) efficacy through immunogenic cell death and modulation of the tumor microenvironment. Methods We conducted a retrospective feasibility study of HFRT combined with ICIs for unresectable HCC. Patients receiving atezolizumab plus bevacizumab (Atz/Bev) or durvalumab plus tremelimumab (Dur/Tre) as first‐line therapy between October 2020 and March 2025 were analyzed. Since July 2022, those with Vp4 PVTT received HFRT (5 Gy × 5) targeting PVTT with ICIs. Outcomes were compared among Vp4 patients with HFRT, Vp4 patients without HFRT, and patients without Vp4 invasion (non‐Vp4). Results Eight Vp4 patients received HFRT plus ICIs (Atz/Bev, n = 5; Dur/Tre, n = 3). The best responses of the main intrahepatic lesions by RECIST 1.1 were complete response (CR) in 1 (12.5%), partial response (PR) in 6 (75%), and stable disease in 1 (12.5%), yielding a high objective response rate (ORR) of 87.5%. By mRECIST, CR was achieved in 3 patients (37.5%). Overall survival in Vp4 patients with HFRT was comparable to non‐Vp4 patients and significantly better than Vp4 patients without HFRT. No gastrointestinal bleeding or perforation occurred, and ALBI scores were preserved at 12 weeks. Conclusions HFRT combined with ICIs is feasible, well tolerated, and may improve outcomes in HCC with Vp4 PVTT. Prospective studies are warranted to confirm efficacy and determine optimal treatment protocols.