Topical Glucocorticosteroids for Proactive Therapy of Acute Radiation-Induced Skin Injury in Head and Neck Cancer: A...

Background: Acute radiation-induced skin injury (aRISI) is one of the most frequent adverse effects of radiotherapy (RT) in patients with head and neck cancer (HNC) and may compromise treatment delivery and quality of life. Topical glucocorticosteroids (GCS) are commonly used in clinical practice for aRISI management; however, evidence supporting their proactive use remains inconsistent. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of proactive topical GCS therapy during RT for HNC. Methods: A systematic search of PubMed, Embase, and the Cochrane Library was conducted from database inception to July 2025 in accordance with PRISMA 2020 guidelines. Randomized controlled trials comparing topical GCS with placebo or standard skin care in adult patients undergoing curative RT or RChT for HNC were included. The primary outcomes were incidence of clinically significant aRISI (grade ≥ 2) and severe aRISI (grade ≥ 3), assessed using validated grading systems (RTOG or CTCAE). Random-effects meta-analyses were performed to calculate pooled risk ratios (RRs) with 95% confidence intervals (CIs). Risk of bias was assessed using the Cochrane RoB 2 tool. Results: Three randomized controlled trials comprising 459 patients were included. Proactive topical GCS did not significantly reduce the pooled incidence of grade ≥ 2 aRISI compared with placebo or standard skin care (RR 0.87, 95% CI 0.60-1.27). Similarly, no statistically significant reduction in grade ≥ 3 aRISI was observed in pooled analysis (RR 0.81, 95% CI 0.22-3.06). Qualitative synthesis of secondary outcomes reported in individual trials suggested potential benefits of topical GCS, including delayed onset or slower progression of aRISI, and, in one large double-blind study, a reduced risk of severe reactions. No increase in treatment-related adverse events was observed in any included trial. Conclusions: Proactive topical GCS do not significantly reduce the overall incidence of aRISI in pooled analysis. Individual studies showed trend towards delayed onset, slower progression, and reduced severe aRISI without compromising safety. These findings support the judicious use of topical GCS as part of proactive supportive care in HNC RT, while highlighting the need for larger, standardized trials to define optimal regimens and patient selection.