An updated systematic review and meta-analysis of modern radiotherapy techniques for hepatocellular carcinoma

Introduction: The practice of radiotherapy (RT) is worldwide transitioning from 3-dimensional conformal RT to modern RT techniques for hepatocellular carcinoma (HCC); however, evidence remains insufficient to determine whether these advanced RT techniques improve treatment outcomes. Therefore, we updated the treatment outcomes of modern RT techniques, including intensity-modulated radiotherapy (IMRT), stereotactic body radiotherapy (SBRT), and proton beam therapy (PBT), for patients with liver-confined HCC. Methods: A systematic review of IMRT, SBRT, and PBT was conducted individually following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to April 2025. Results: We included 23 IMRT studies comprising 1,479 patients, 22 PBT studies comprising 1,968 patients, and 35 SBRT studies comprising 3,208 patients. When the total doses were converted to the biologically equivalent doses (BED, Gy10), the median BED (mBED) values ranged 48–180 Gy10 (median, 86) for SBRT, 69–110 GyE10 (median, 101) for PBT, and 55–75 Gy10 (median, 67) for IMRT. The pooled 3-year local progression-free survival rates were 64% (95% confidence interval [CI], 45–81%) for IMRT, 89% (95% CI, 86–91%) for PBT, and 86% (95% CI, 82–90%) for SBRT, respectively (p = 0.0076). The pooled 3-year overall survival rates were 19% (95% CI, 11–29%) for IMRT, 55% (95% CI, 48–62%) for PBT, and 65% (95% CI, 57–72%) for SBRT, respectively (p <0.0001). In addition, the pooled survival rates differed significantly according to the mBED using three cutoff points of 65 Gy10, 80 Gy10, and 100 Gy10. Meta-regression analysis showed that liver function, median tumor size, and portal vein tumor thrombosis were association with survivals in varying degrees. The incidence of severe toxicities after modern RT techniques was low. Conclusions: Modern RT techniques provide remarkable treatment outcomes in patients with HCC. The efficacies of SBRT and PBT were similar and superior to those of IMRT. This difference should be interpreted with caution as controlling for clinical parameters affecting efficacy is not feasible. And a minimal ablative dose between 65 and 100 Gy10 is required to achieve optimal efficacy for HCC.