Evaluation of the Safety and Therapeutic Effect of Multidisciplinary Treatment strategy involving RT after HAIC followed by immunotherapy for Advanced Hepatocellular Carcinoma with Major Vascular Invasion: A Prospective Registry Study (Preprint)

BACKGROUND Systemic therapy, including immune checkpoint inhibitors (ICIs), has improved survival in advanced hepatocellular carcinoma (HCC); however, its efficacy remains limited in patients with macroscopic vascular invasion (MVI), a subgroup with an extremely poor prognosis. Although combining immunotherapy with local treatments such as hepatic arterial infusion chemotherapy (HAIC) and radiation therapy (RT) is considered a promising approach, robust supportive evidence from routine clinical practice is lacking. OBJECTIVE This study aims to evaluate the safety and therapeutic effectiveness of a multidisciplinary treatment strategy involving RT after HAIC, followed by immunotherapy, in patients with MVI-positive HCC, using real-world clinical data from Japan. METHODS This is a prospective, multicenter registry study conducted at three hospitals in Hiroshima Prefecture, Japan. Eligible patients will have unresectable MVI-positive HCC confirmed by dynamic computed tomography. The treatment protocol follows a standardized sequence: one session of HAIC (cisplatin), RT targeting the MVI site (25 Gy in 5 fractions), and subsequent systemic immunotherapy. The primary endpoint is safety, which will be evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Secondary endpoints include progression-free survival (PFS) at 12 and 24 weeks, tumor response, overall PFS, and overall survival (OS), Objective response rate (ORR) at 12 and 24 weeks, assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST). Data will be collected prospectively and analyzed according to the intention-to-treat principle. RESULTS Patient enrollment begun in March 2025, with data collection and analysis ongoing as participants are followed. CONCLUSIONS This prospective registry study will generate real-world evidence on the safety and effectiveness of a multidisciplinary strategy combining HAIC, RT, and immunotherapy in patients with MVI-positive HCC. Given that all components are covered under Japan’s national health insurance, this approach could be readily implemented in clinical practice and may inform future treatment guidelines for MVI-positive HCC.