Proton beam therapy versus interventional procedures for hepatocellular carcinoma: A systematic review and meta-analysis of comparative studies.

e16280 Background: Proton beam therapy (PBT) is increasingly used for hepatocellular carcinoma (HCC) due to its dosimetric advantages and potential for liver function preservation. However, its comparative effectiveness versus interventional modalities such as transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) remains incompletely defined. Methods: A systematic search of PubMed and Web of Science (October 14, 2025) identified comparative studies evaluating PBT versus interventional procedures for HCC. Eligible studies included randomized and comparative observational studies reporting clinical outcomes. Random-effects meta-analyses were performed for overall survival (OS) and local control (LC). Toxicity profiles were compared between treatment modalities. Risk of bias was assessed using ROB-1 and ROBINS-I. Results: Six studies (2 randomized, 4 retrospective) comprising 1,625 patients (315 PBT, 1,310 interventional) met inclusion criteria. Comparator modalities included TACE, RFA, or combined approaches. PBT dose ranged from 66 to 80.5 GyE delivered in 10–38 fractions. Meta-analysis of five studies demonstrated no significant difference in OS (pooled HR 1.45, 95% CI 0.82–2.56) with substantial heterogeneity (I² = 71%). In contrast, pooled analysis of four studies showed significantly superior LC with PBT (pooled HR 2.34, 95% CI 1.56–3.50, p < 0.0001) with negligible heterogeneity (I² = 0%). Progression-free survival (PFS) and recurrence-free survival (RFS), reported inconsistently, favored PBT in individual studies (PFS HR 3.62; RFS HR 1.39). Across studies, PBT preserved liver function with stable ALBI scores and markedly lower hepatic toxicity: grade ≥3 ALT/AST elevation 0% vs 10.3-18.2%, ascites 0% vs 21.2%, and hospitalization 24 vs 166 days. No grade ≥3 hepatic toxicity or treatment-related mortality occurred with PBT. Conclusions: While OS appears comparable between PBT and interventional procedures for HCC, PBT provides significantly improved LC and markedly less treated-related hepato-toxicity . These findings support PBT as a compelling non-invasive alternative to interventional therapies, particularly for patients in whom hepatic reserve is critical. Further prospective trials are warranted to clarify long-term survival benefits.