Background: Radiodermatitis is commonly experienced by patients with breast cancer undergoing radiotherapy, affecting their quality of life and potentially leading to cancer treatment postponement. Recently, people who use natural substances to treat radiodermatitis have attracted more and more attention. However, there is no unanimous conclusion to follow. Objective: We conducted a meta-analysis of randomized controlled trials (RCTs) that compared hyaluronic acid with other topical agents in patients with breast cancer. Methods: PubMed, Cochrane Library, and Embase databases were searched for eligible articles. The primary outcome indicating symptom relief was a decreased radiodermatitis grade. The secondary outcome indicating symptom relief was preference and desquamation. The study is registered with PROSPERO (number: CRD42021237793). Results: Eight RCTs that together enrolled 500 patients were analyzed. Six studies assessed the radiodermatitis grade and found significant differences in three of eight subgroups. The subgroups comparing hyaluronic acid with phytosterol, omega-3, 6, 9, and vitamin E showed significantly lower risk ratios. In two subgroups, the effect of hyaluronic acid was not significantly different from that of grapevine extract and Avene thermal water. The remaining three studies reported that other topical agents exerted a nonsignificantly better effect than hyaluronic acid did. Physicians’ preference was better for the control group, while the patients’ preference for hyaluronic acid was better, and there was no statistical difference. In addition, our study showed that desquamation events were few in the hyaluronic group. Conclusions: Hyaluronic acid can show a better effect than other topical drugs and the lower incidence in desquamation events. Since hyaluronic acid has no obvious side effects, we recommend it as one of the alternative options. Further research is required to evaluate this effect comprehensively.
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