Abstract / Summary
Background Radiotherapy (RT) is a cornerstone of head and neck cancer (HNC) treatment, but radiation-induced xerostomia (RIX) remains a common complication affecting oral function and quality of life. This review evaluated evidence from 2020–2025 on preventive and therapeutic interventions for RIX. Materials and Methods A PRISMA 2020 systematic review searched PubMed, Scopus, and Web of Science for English-language studies published from 2020–2025 evaluating RIX interventions in adults with HNC. RCTs and systematic reviews/meta-analyses reporting salivary flow or validated xerostomia outcomes were included. Of 670 records identified, 220 duplicates were removed, 100 full texts were assessed, and 35 studies were included. Results Thirty-five studies were included. IMRT and IMPT consistently improved salivary-gland preservation compared with conventional RT but did not eliminate RIX. Pilocarpine, cevimeline, and amifostine remained the principal pharmacological interventions, although adverse effects may limit adherence in some patients. Photobiomodulation, electrical nerve stimulation, and acupuncture showed potential benefits as adjunctive therapies, although the strength and consistency of evidence varied. Submandibular gland transfer and regenerative approaches, including mesenchymal stem cell therapy, have demonstrated preliminary safety and potential efficacy, but the available evidence remains insufficient to support routine clinical recommendations. Discussion Evidence most strongly supports salivary gland-sparing radiotherapy, particularly IMRT and IMPT. Pharmacological and supportive therapies may provide additional symptomatic benefit, while evidence for non-pharmacological and regenerative interventions remains limited. Conclusion Current evidence supports an individualized, multimodal approach combining salivary gland-sparing radiotherapy, pharmacotherapy, and supportive interventions. Larger, well-designed trials with standardized outcomes are needed to establish the long-term effectiveness of emerging therapies.