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 EQD2 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 EQD2 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.