Introduction: Radiation dermatitis (RD) is a side effect of radiation therapy (RT) which is experienced by over 90% of patients being treated for breast cancer. The current clinical trial was conducted to measure the preventative effects of a boron-based gel on several different clinical outcomes (dermatitis, erythema, dry desquamation, and moist desquamation) after 25 radiotherapy sessions. Methods: This research used a double-blind parallel-group design with a placebo control (n = 76) and randomized group (n = 181), with all participants being between 18 and 75 years old. Fifteen minutes before each radiotherapy, participants in the intervention group were given a gel containing 3% sodium pentaborate pentahydrate, while those in the placebo group received a gel with no chemical substance. Dermatitis, erythema, dry desquamation, and moist desquamation were compared between the 2 groups. Results: At baseline, there were no significant differences between the groups (p > 0.05), except for body mass index. After 14 days of treatment, dermatitis (98.7% vs. 9.9%; p < 0.001), erythema (96.1% vs. 12.2%; p < 0.001), dry desquamation (50% vs. 3.9%; p < 0.001), and moist desquamation (18.4% vs. 0.6%; p < 0.001) were much more common in the placebo group than the intervention group. To prevent dermatitis, erythema, dry desquamation, and moist desquamation in 1 patient, on average, 1.1 (95% confidence interval [CI]: 1.1–1.2), 1.2 (95% CI: 1.1–1.3), 2.2 (95% CI: 1.7–2.9), and 5.6 (95% CI: 3.8–11.0) patients need to be treated, respectively. Conclusion: The boron-based gel has a significant preventive effect on several categories of RD which might be used by clinicians in breast cancer.

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