UC San Diego

Purpose Xerostomia remains a common toxicity following head and neck radiotherapy (RT) that significantly impacts patients' quality of life (QOL). Although intensity-modulated RT reduces the dose to the salivary glands, many patients still experience salivary gland toxicity. Methods and Materials This study examined the association between radiation-induced volume changes in the parotid and submandibular glands, mean dose to the salivary glands, and intra-gland dose distribution, as well as its relationship to QOL scores, over a median follow-up period of 47 months. Results Analysis of 329 patients using a linear mixed-effects model revealed distinct volume change patterns. The parotid glands initially underwent significant volume reduction but subsequently showed dose-dependent recovery, increasing in volume by an average rate of 2.4% per doubling of time. This recovery was negatively impacted by higher age and poor performance status. Conversely, the submandibular glands gradually reduced in volume over time by 5.3% per doubling of time without evidence of recovery, even at low doses. Voxel-wise analysis of the parotid glands indicated that dose constraints targeting the cranial-ventral-lateral portion were critical for accurately predicting volume recovery. No regional dose effects were found for the submandibular gland. Persistent associations were found between salivary gland volumes and chronic xerostomia symptoms, including dry mouth and sticky saliva. Conclusions Objective measurement of salivary gland volume can be used as an indicator of damage and recovery. The observed differential longitudinal patterns suggest that distinct dosing strategies and regenerative approaches may be necessary for the parotid and submandibular glands.