Hepatobiliary Toxicity Following Ablative Radiation for Centrally Located Hepatocellular Carcinoma

Objectives: Centrally located hepatocellular carcinoma (CL-HCC) poses a therapeutic challenge due to proximity to the central hepatobiliary tract (cHBT) and concern for radiation-related toxicity. We evaluated hepatobiliary toxicity, liver function changes, and oncologic outcomes following ablative external beam radiotherapy (EBRT) for CL-HCC across multiple modalities. Methods: We retrospectively reviewed 103 patients treated with ablative EBRT for HCC from 2014 to 2024. Tumors were classified as central if the planning target volume overlapped a 1-cm expansion around the portal vein. Modalities included stereotactic body radiotherapy (SBRT), intensity-modulated radiation therapy (IMRT), and proton therapy. The primary endpoint was Grade ≥3 CTCAE hepatobiliary toxicity. Secondary endpoints included change in albumin-bilirubin (ALBI) score at 6 months, local control (LC), and overall survival (OS). Dose-volume parameters were converted to EQD 2 for comparison. Results: Forty-eight patients (47%) had CL-HCC. Among central tumors, treatment included SBRT (29%), proton therapy (58%), and IMRT (13%), with a median EQD 2 of 82 Gy. No EBRT-attributable biliary strictures were observed; 1 patient developed possible treatment-related portal vein thrombosis. The cumulative incidence of Grades 1 to 2 ALBI worsening at 6 months was 52% in CL-HCC (57% SBRT, 46% proton, 50% IMRT) versus 44% in peripheral tumors. LC exceeded 90% in both groups without differences in local progression-free survival. Median OS was 28 months for central versus 42 months for peripheral tumors (HR=1.62, P =0.07). Conclusions: Ablative EBRT for CL-HCC achieved excellent local control with low rates of clinically significant hepatobiliary toxicity, supporting its use in this high-risk population.