Benefit of perioperative radiotherapy for hepatocellular carcinoma: a quality-based systematic review and meta-analysis

Introduction: Although surgery is the standard curative modality for hepatocellular carcinoma, more than two-thirds experience intrahepatic recurrence. Since no standard perioperative treatment has been established, the authors performed a meta-analysis to evaluate the benefits of perioperative radiotherapy (RT). Methods: The PubMed, MEDLINE, EMBASE, and Cochrane Library were searched until May 2023. Randomized or propensity-matched studies evaluating at least five major clinical factors investigating benefit of perioperative RT, were included. The main effect measure were the pooled odds ratios (OR) regarding the benefit of perioperative RT using 2-year overall survival (OS) and 1-year disease-free survival (DFS) data. Results: Seven studies (five randomized and two propensity-matched studies) involving 815 patients were included. The pooled ORs for 1-year DFS and 2-year OS were 0.359 (95% CI: 0.246-0.523) and 0.371 (95% CI: 0.293-0.576), respectively, favoring perioperative RT, with very low heterogeneity. In the subgroup analyses, the benefits of OS and DFS were consistent between the two subgroups [portal vein thrombosis (PVT) and narrow resection margin (RM) groups]. In the PVT subgroup, the pooled OS rates at both 1-year and 2-year (75.6 vs. 36.9%, P<0.001; 25.6 vs. 9.9%, P=0.004) and DFS rates at both 1-year and 2-year (25.2 vs. 10.3%, P=0.194; 11.9 vs. 3.0%, P=0.022) were higher in the perioperative RT group. In the narrow RM subgroup, the surgery and RT groups showed higher pooled OS rates for both 1-year and 2-year (97.3 vs. 91.9%, P=0.042; 90.4 vs. 78.7%, P=0.051) and DFS (88.1 vs. 72.6%, P<0.001; 70.1 vs. 51.7%, P<0.001). Grade 5 toxicity was not reported, and three studies reported grade >= 3 or higher liver function test abnormalities, ranging from 4.8-19.2%. Conclusion: The present study supports the oncological benefits of perioperative RT, for cases with high-risk of recurrence. Oncologic outcomes between subgroups differed according to clinical indications.