Efficacy and Safety of Intensity‐Modulated Radiotherapy Combined With Regorafenib With or Without Immune Checkpoint Inhibitors as Second‐Line Treatment for Advanced Hepatocellular Carcinoma: A Real‐World Cohort Study From a Single Center

PURPOSE: This study aimed to assess the efficacy and safety of intensity-modulated radiotherapy (IMRT) combined with regorafenib with or without immune checkpoint inhibitors (ICIs) as a second- or later-line treatment for advanced hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Patients diagnosed with advanced HCC who had received RT combined with concurrent or sequential regorafenib treatment or regorafenib plus ICIs after failures of at least one line of systemic treatment in a single center from April 2018 to August 2022 were retrospectively reviewed. Progression-free survival (PFS) was the primary endpoint, while overall survival (OS), objective response rate (ORR), disease control rate (DCR), and toxicity were the secondary endpoints. RESULTS: Fifty patients were included, with 44 (88.0%) in BCLC stage C, 37 (74.0%) having portal vein tumor thrombosis (PVTT), and 12 (24.0%) with extrahepatic metastasis. Thirty-eight patients received conventional fractionated RT (56.4Gy/22-28f), while 12 received hyperfractionated RT (50Gy/5-10f). Twenty-six were treated concurrently with regorafenib and 24 sequentially. ICIs were applied in 34 patients. For the entire cohort, when measured from the start of RT initiation, the median PFS and OS were 10.9 months and not reached. The corresponding 2-year PFS and OS rates were 25.3% and 53.5%, respectively. When assessed from regorafenib initiation, the median PFS and OS were 5.9 months and not reached, with 2-year PFS and OS rates of 22.8% and 54.9%, respectively. For tumors in the RT field, the ORR was 74.0% (RECIST) and 92.0% (mRECIST). The most common grade 3 toxicities were hand-foot syndrome (16.0%), thrombocytopenia (8.0%), dermatitis (8.0%), and transaminase elevation (6.0%). CONCLUSION: IMRT concurrently or sequentially combined with regorafenib with or without ICIs is an effective, well-tolerated, and promising regimen as second-line or further-line treatment in patients with advanced HCC.