Feasibility Study of Combined Systemic Therapy and Carbon‐Ion Radiotherapy for Hepatocellular Carcinoma Patients

ABSTRACT Background Recent advances in systemic therapy, including tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs), have improved outcomes for hepatocellular carcinoma (HCC) and enabled downstaging strategies that allow subsequent local treatments. Carbon‐ion radiotherapy (CIRT) can provide excellent tumor control with minimal impairment of liver function. However, the feasibility and safety of combining systemic therapy with CIRT have not been well evaluated. Methods We retrospectively reviewed 21 patients with HCC who received CIRT integrated with systemic therapy at a single institution. Systemic therapy consisted of TKIs or ICIs and was administered either before or after CIRT, reflecting real‐world clinical practice. The primary endpoint was feasibility and safety, assessed by the incidence of adverse events (AEs) graded by CTCAE v5.0 and changes in albumin–bilirubin (ALBI) and Child–Pugh scores. Secondary endpoints included overall survival (OS), progression‐free survival (PFS), and local control (LC). Results No grade ≥ 4 AEs were observed during peri‐radiotherapeutic integration of systemic therapy and CIRT. The most frequent AEs were grade 1 fatigue, radiation pneumonitis, and hepatobiliary disorders. Neither ALBI nor Child–Pugh scores showed clinically meaningful deterioration after CIRT, indicating preserved liver function. The 1‐year OS, PFS, and LC rates were 59.0%, 28.6%, and 70.6%, respectively. Despite large tumor burdens (median GTV 93.2 cm 3 ) and variable baseline liver function, treatment was generally well tolerated. Conclusions Integration of CIRT with systemic therapy was feasible and demonstrated an acceptable safety profile without worsening liver function. This multimodal approach may represent a treatment option for selected patients with HCC, particularly in downstaging or locally advanced settings. Prospective studies are needed to validate these findings.