Proton beam therapy versus photon therapy for multiple malignancies: An umbrella systematic review and meta-analysis.

[BACKGROUND] Direct comparative evidence between proton beam therapy (PBT) and photon therapy for the treatment of malignant diseases is lacking.

[METHODS] Electronic databases were searched for meta-analyses of PBT vs. photon therapy for patients with malignancies from database inception up until March 13, 2025. The methodological quality of meta-analyses was assessed using AMSTAR 2. Where possible, the DerSimonian and Laird random-effects model was used to repeat each meta-analysis. For pooled evidence from two-arm studies, the certainty of the evidence was assessed using GRADE criteria.

[RESULTS] Seventeen meta-analyses covering 11 cancers were included. Compared to photon therapy, PBT was associated with improved prognosis in glioma, head and neck cancer (for certain loci), esophageal cancer, intrahepatic cholangiocarcinoma, extrahepatic biliary tract cancer, renal cell carcinoma, and colorectal cancer with pelvic recurrence. Use of PBT also correlated with reduced toxic effects in head and neck cancer, pediatric CNS tumors, esophageal cancer, early-stage NSCLC, and prostate cancer. Within the 65 outcomes from two-arm studies, GRADE assessment found that only two outcomes were supported by moderate certainty of evidence, while 63 were supported by low or very low certainty of evidence.

[CONCLUSIONS] Our findings indicate, that for several tumors, PBT is associated with improved survival outcomes and toxicities. In the absence of high-quality evidence, these findings need to be validated by more large-scale comparative studies and clinical trials.