Real-World Outcomes of Combined Carbon-Ion Radiotherapy and Systemic Immunotherapy for Hepatocellular Carcinoma (Atezolizumab Plus Bevacizumab or Durvalumab Plus Tremelimumab): A Single-Center Retrospective Study.

Background: Carbon-ion radiotherapy (CIRT) is an effective local treatment for hepatocellular carcinoma (HCC); however, evidence on systemic immunotherapy after CIRT and the role of CIRT following immunotherapy remains limited. This study aimed to assess clinical outcomes and sequencing of CIRT and systemic immunotherapy in real-world practice. Methods: We retrospectively analyzed 41 patients with HCC who received CIRT and systemic immunotherapy (atezolizumab plus bevacizumab or durvalumab plus tremelimumab). Patients were categorized into three groups: (i) systemic immunotherapy for recurrent HCC after CIRT (n = 20), (ii) curative-intent CIRT after systemic immunotherapy (n = 10), and (iii) CIRT for residual or insufficiently responding lesions (≤3 lesions) after systemic immunotherapy (n = 11). Results: In group (i), 14 of 20 patients achieved complete or partial responses. These responders had low tumor burden (within the up-to-7 criteria) and preserved liver function (modified albumin-bilirubin grade 1/2a) at treatment initiation and demonstrated significantly longer progression-free and overall survival than those with stable or progressive disease. In group (ii), 4 of 10 patients achieved a clinical complete response and became drug-free; notably, all had solitary intrahepatic tumors at immunotherapy initiation. In group (iii), the rate of transition to clinical complete response was low, and disease control remained limited. Conclusions: Systemic immunotherapy demonstrated high effectiveness in recurrent HCC following CIRT, particularly in patients with low tumor burden and preserved liver function. Moreover, curative-intent CIRT after immunotherapy may benefit patients with solitary intrahepatic tumors but appears limited in those with insufficient response to immunotherapy, including residual oligolesions.