Clinical outcomes of carbon-ion radiotherapy for residual or recurrent hepatocellular carcinoma after transarterial chemoembolization

Background: Transarterial chemoembolization (TACE) or embolization (TAE) for hepatocellular carcinoma (HCC) is often followed by an incomplete response or local recurrence, necessitating effective salvage therapies. Carbon-ion radiotherapy (CIRT) offers potential radiobiological advantages for treating TACE-refractory tumors. This study aimed to evaluate the efficacy and safety of CIRT for residual or recurrent HCC after TACE/TAE. Patients and methods: We retrospectively analyzed 99 patients (106 lesions) treated with CIRT between 2010 and 2021. Eligible patients had residual or recurrent HCC after 52.8-60.0 Gy [relative biological effectiveness (RBE)] in 4 fractions, or 60.0 Gy (RBE) in 12 fractions for tumors near critical structures. Efficacy endpoints were local control (LC), overall survival (OS), and progression-free survival (PFS). Toxicities were graded using the Common Terminology Criteria for Adverse Events version 4.0, and liver function was monitored using Child-Pugh and albumin-bilirubin (ALBI) scores. Results: At a median follow-up of 38 months, the 3-year OS, PFS, and LC rates were 70.3%, 34.8%, and 90.7%, respectively. On multivariate analysis, larger tumor size (≥3.5 cm) and poorer baseline liver function (modified ALBI grade ≥2b) were significant predictors of worse OS. The treatment was well tolerated; severe (grade ≥3) late toxicities were rare, including two cases of encephalopathy. There was no statistically significant deterioration in Child-Pugh or ALBI scores following treatment. Conclusions: CIRT is a safe and effective salvage therapy for TACE-refractory HCC, offering excellent LC, favorable survival outcomes, and preserved liver function.