External Beam Radiation Therapy and Immunotherapy in the Management of Hepatobiliary Malignancies: A Meta-analysis of...

To evaluate, in a meta-analysis, the efficacy of external beam radiation therapy (EBRT) with immunotherapy (IO) in hepatobiliary malignancies, including hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), and identify factors associated with improved treatment response.

Observational studies or clinical trials reporting objective response rates (ORRs) and disease control rates (DCRs) for patients with advanced or unresectable HCC or CCA treated with EBRT plus at least one IO agent were included. PubMed, Web of Science, and Cochrane were searched through February 2025. Pooled ORR and DCR were calculated using random-effects models with inverse variance weighting and double-arcsine transformation. Subgroup analyses were performed by study design (retrospective studies vs clinical trials), radiation target (primary vs primary + metastasis), radiation dose (high vs low biologically effective dose [BED]), and IO regimen. Meta-regression was performed to study the associated between BED and response rates.

Twenty-two HCC studies (971 patients) and 3 CCA studies (136 patients) met inclusion criteria. Pooled ORR was 58% (95% CI, 50%-65%) and DCR was 79% (95% CI, 71%-85%) for HCC, with no difference between study designs. Radiation target, and dose were not associated with improved response in subgroup analysis. However, meta-regression showed an improved ORR for higher BED (1.14% increase per Gy) on clinical trials (P = .021). No differences were found in response rates between anti-programmed cell death protein 1 and anti-programmed death-ligand 1 agents or combination therapy with or without vascular endothelial growth factor inhibitors. For CCA, pooled ORR was 32% and DCR 70%. Subgroup analysis was unable to be performed because of sample size limitations.

EBRT in combination with IO shows favorable response rates in advanced hepatobiliary malignancies, particularly in HCC. Higher BED appears to enhance tumor response; however, it requires further prospective studies with current standard of care systemic therapies.