Hepatotoxicity of external radiotherapy for hepatocellular carcinoma in the setting of prior yttrium-90 radioembolization

Objectives: To evaluate the hepatotoxicity and clinical outcomes following external beam radiation therapy (EBRT) in patients with hepatocellular carcinoma (HCC) previously treated with Yttrium-90 radioembolization (Y-90), a setting in which cumulative liver radiation exposure raises concern for increased toxicity risk.

Methods: We performed a retrospective review of 94 HCC patients treated with EBRT from 2016 to 2024, including 15 treated with Y-90. Hepatotoxicity was assessed using Albumin-Bilirubin (ALBI) score changes at 3 and 6 months post-EBRT. Secondary outcomes included CTCAE toxicity, local control, and survival. Treatment details, prior locoregional therapies, and dosimetric parameters were collected. Fisher exact tests and Kaplan-Meier analyses were used for statistical comparisons.

Results: Baseline demographics and liver function were similar between groups. Over half the Y-90 cohort (53%) received fractionated proton therapy. At 6 months, grade 1 and 2 ALBI deterioration occurred in 2 (13%) and 4 patients (27%) with prior Y-90, compared with 17 (22%) and 21 patients (27%) without prior Y-90 (P=0.77). Grade ≥2 CTCAE toxicity occurred in 2 patients (13%) with prior Y-90 and in 5 patients (6%) without. Local control was 92% with no local failures in patients treated after Y-90. Median OS was 39 months without prior Y-90 and 34 months with prior Y-90 (P=0.89).

Conclusions: EBRT following Y-90 was not associated with increased hepatotoxicity or inferior oncologic outcomes compared with EBRT alone. When delivered with individualized planning, including fractionation, EBRT represents a safe and effective salvage modality for patients with residual or recurrent HCC after Y-90.