Selenium supplementation for preventing cancer therapy-related toxicities: a systematic review and meta-analysis of clinical trials.

Background: Trials of selenium for cancer supportive care vary in treatment context, formulation, dose, toxicity domain, and outcome definition. We evaluated the efficacy and safety of selenium supplementation for preventing or reducing cancer therapy-related toxicities. Methods: PubMed, Web of Science Core Collection, and the Cochrane Library were searched through June 30, 2026. Comparative clinical trials conducted during cancer therapy compared selenium with placebo, no selenium, observation, or selenium-free standard care. Two reviewers independently completed study selection, data extraction, outcome evaluation, and risk-of-bias assessment, with third-reviewer adjudication when required. Severe oral mucositis during head-and-neck radiotherapy or chemoradiotherapy was the primary outcome; broader pools were exploratory. Fixed- or random-effects analyses were supplemented by restricted maximum-likelihood models with Hartung-Knapp confidence intervals. Conference-abstract and derived-odds-ratio analyses were restricted to supplementary sensitivity analyses. Certainty was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD420261448497). Results: Of 444 records, 333 unique records were screened. Forty-one of 49 sought reports were assessed in full text, and 31 reports representing 30 study groups were included; 17 groups contributed to the main analysis and 13 to supplementary evidence. Overall risk of bias was judged to be Some concerns for nine studies and High risk for eight. The four-study primary analysis (188 participants) was inconclusive (risk ratio [RR] 0.89, 95% confidence interval [CI] 0.50 to 1.56; Conclusion: Current evidence does not establish prevention of severe oral mucositis, but the consistent cross-domain direction and several domain-specific exploratory estimates suggest that selenium may attenuate selected treatment-related toxicities, particularly gastrointestinal and hematologic events, in appropriately selected settings. Because the majority of estimates are based on few, heterogeneous, and high-risk studies, these signals should inform targeted trials rather than routine universal supplementation. Systematic review registration: This systematic review was registered with PROSPERO. Unique Identifier: CRD420261448497.