Abstract
BACKGROUND: Hepatocellular carcinoma (HCC) prognosis remains poor in advanced stages. Stereotactic body radiation therapy (SBRT) combined with pharmacological agents (targeted therapies/immunotherapies) represents a promising multimodal strategy, but its efficacy and safety require comprehensive evaluation. METHODS: This meta-analysis included 9 studies (n = 20,812). The adverse event analysis covered the overall adverse event data from 7 studies (n = 583) and grade ≥ 3 adverse events from 4 studies (n = 303). The survival outcome analysis included 9 studies (n = 20,781) and the progression-free survival analysis included 4 studies (n = 424). Hazard ratios (HRs) and risk ratios (RRs) with 95% CIs were calculated via fixed/random effects models. RESULTS: Compared with pharmacological agents, SBRT combined with pharmacological agents significantly improved 1-year OS (RR = 1.55, 95% CI:1.40–1.72), 2-year OS (RR = 1.63, 95% CI:1.33–1.99), objective response rate (RR = 1.87, 95% CI:1.52–2.39) and reduced mortality risk (HR = 0.54, 95% CI:0.40–0.72), progression risk (HR = 0.49, 95% CI:0.38–0.63) without increasing overall adverse events (RR = 1.03, 95% CI:0.98–1.09) or grade ≥ 3 toxicities (RR = 1.12, 95% CI:0.92–1.36). CONCLUSION: SBRT combined with pharmacological agents significantly improves survival and tumor response in advanced HCC without increasing overall toxicity. This synergy supports the integration of SBRT into systemic therapy paradigms for HCC. TRIAL REGISTRATION: PROSPERO CRD420251040157. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-025-15061-4.