Effect of hyaluronic acid on radiotherapy-induced mucocutaneous side effects: a meta-analysis of randomized controlled trials

Purpose: Radiotherapy (RT)–induced mucocutaneous side effects remain a clinical challenge in cancer patients. Hyaluronic acid (HA), a key molecule in tissue regeneration, may relieve these side effects. The aim of the study is to investigate the effects of HA on RT-induced side effects in patients with cancer. Methods: A systematic review and meta-analysis of randomized controlled trials (RCTs) was carried out. PubMed, Embase, and Cochrane Library were searched for published studies. A meta-analysis was conducted to calculate the pooled effect size using a random-effect model. Results: Fifteen trials with 1131 patients were included. The HA group demonstrated a significant improvement in skin pain scores (mean difference [MD]: − 1.14, 95% confidence interval [CI]: − 2.21 to − 0.08) at week 4, and significantly decreased pain frequency (risk ratio [RR]: 0.47, 95% CI: 0.24 to 0.93) at 5 to 8 weeks when compared with the control group. The HA group also exhibited a significantly lower incidence of desquamation (RR: 0.27, 95% CI: 0.15 to 0.5) at 4 to 5 weeks and the most severe mucosal problems (RR: 0.14, 95% CI: 0.04 to 0.45) compared with the control group. Moreover, the HA group had a significantly lower incidence of bleeding (RR: 0.18, 95% CI: 0.05 to 0.65) than the control group at 4 months and 18 months. Conclusion: HA treatment may reduce RT-induced mucosal problems and pain. Moreover, HA is safe and has the potential for application in diverse forms and textures for pharmacotherapeutic use. Additional trials involving a higher number of patients are recommended.