Dose-volume Predictors of Post-Radiation Xerostomia in Head and Neck Cancer: A Systematic Review

Background and purpose Radiation-induced xerostomia remains a major toxicity after radiotherapy for head and neck cancer (HNC). Although QUANTEC-based parotid dose constraints are widely applied, increasing evidence suggests that additional salivary and oral structures may contribute to xerostomia risk. This systematic review aimed to summarize contemporary evidence on dose-volume predictors of post-radiotherapy xerostomia in HNC. Materials and methods This PRISMA-based systematic review was registered in PROSPERO (CRD42024519338). PubMed, Embase, Cochrane Library, and Web of Science were searched for studies published between January 2013 and August 2025. Studies evaluating dose-volume predictors of xerostomia in adult HNC patients treated with curative-intent radiotherapy were included. Results Fifty-one studies involving 10,789 patients were included. Most patients received intensity-modulated radiotherapy. Contralateral parotid gland mean dose (Dmean) was the most consistently validated predictor of xerostomia and was supported by moderate-certainty evidence. Multiple studies reported increased risk of moderate-to-severe xerostomia when contralateral parotid Dmean exceeded 24–26 Gy, whereas Dmean below 20 Gy was associated with better salivary preservation. Bilateral parotid Dmean around 26 Gy was also reported. However, support for specific numerical planning thresholds remained limited. Dosimetric parameters of the submandibular glands and oral cavity were also independently associated with xerostomia risk. Emerging evidence suggested potential roles of parotid substructures, including ducts and stem cell-rich regions. Conclusion Parotid gland mean dose remains the most robust predictor of post-radiotherapy xerostomia in HNC. Additional dosimetric information from the submandibular glands, oral cavity, and parotid substructures may further improve xerostomia risk stratification and support future NTCP modeling.