Radiation-induced hepatic toxicity from radiotherapy plus immune checkpoint inhibitors with targeted therapy in HCC patients: a propensity score-matched study

PURPOSE: This aim of the study was to compare the outcomes of radiation-induced hepatic toxicity (RIHT) of hepatocellular carcinoma (HCC) patients treated with radiotherapy (RT) combined with immune checkpoint inhibitors (ICIs) and targeted therapy with those of RT alone or RT combined with ICIs. METHODS: A total of 146 patients with HCC who received RT between January 2017, and May 2023 were enrolled in the study; 50 and 96 patients received a combination of RT with ICIs plus targeted therapy (triple therapy), and RT alone or RT plus ICIs (RT/RT+ICIs), respectively. Propensity-score matched (PSM) analyses were performed to compare the hepatotoxicity, dosimetric, and clinical parameters between the groups. Non-classical radiation-induced liver disease (ncRILD) was evaluated using univariate and multivariate analyses. RESULTS: After matching, 50 patients were included per group. The ncRILD rates were 16.0% in the triple therapy group and 18.0% in the RT/RT+ICIs group, respectively (p = 0.790). Increased Child-Pugh (CP) scores ≥ 2 were observed in 16.0% each of the triple therapy and RT/RT+ICIs groups (p = 1.000). Increased CP scores ≥ 1 were observed in 38.0% and 40.0% of the triple therapy and RT/RT+ICIs groups, respectively (p = 0.838). The groups did not differ significantly in all hepatotoxicity metrics after PSM (p > 0.05). Normal liver volume (Vliver) was an independent predictor of ncRILD in the matched cohort. CONCLUSIONS: RT in combination with ICIs and targeted therapy is a seemingly safe treatment modality and achieves comparable RIHT with RT/RT+ICIs in HCC patients. Higher Vliver values indicate lower risks of developing ncRILD.