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Xerostomia is one of the most significant adverse events caused by radiotherapy and severely reduces patients' quality of life for a lengthy period in patients with head and neck cancer. Intensity-modulated radiation therapy (IMRT) reduces the incidence of xerostomia compared to conventional radiotherapy. However, most patients experience temporary severe xerostomia, which requires several years to recover, and limited reports indicate individual differences in the recovery time. The purpose of this study was to evaluate the salivary recovery time and rate after IMRT for head and neck cancer.

In this study, we evaluated 57 patients with head and neck cancer who received IMRT for curative intent and stimulated salivary flow measurement between Jan 2012 and Dec 2018 at our institution. Xerostomia was graded with the CTCAE v.4.0. The salivary recovery time was defined as when salivary flow recovered beyond the mean salivary recovery rate after radiotherapy. The salivary recovery rate was defined as "(the third quartile of salivary flow after radiotherapy) / (pre-treatment salivary flow)." Patients were divided into two groups for each explanatory variable; mean parotid glands dose, mean oral cavity dose, pre-treatment salivary flow, age, sex, and chemotherapy status. The salivary recovery time was compared using Cox proportional hazard model, and the cumulative salivary recovery rate was estimated using the Kaplan-Meier method. The salivary recovery rate was analyzed using the t-test and multiple regression analysis. To evaluate the relevance between the salivary recovery rate and the subjective symptoms, the difference in salivary recovery rate between each xerostomia grade was analyzed using a one-way analysis of variance. P values < 0.05 were considered statistically significant.

The median follow-up period of salivary flow was 48 months, and the median salivary recovery rate was 58.2%. The median salivary recovery time and the cumulative recovery rate at four years were 48 months and 52.9% in the high pre-treatment salivary flow group, whereas 18 months and 79.6% in the low pre-treatment salivary flow group (P = 0.026). The mean parotid glands and oral dose were insignificant in the salivary recovery time [Figure]. In the univariate analysis, the salivary recovery rate was significantly lower in patients with higher mean parotid glands dose, higher mean oral dose, and higher pre-treatment salivary flow. In multivariate analysis, only pre-treatment salivary flow remained a significant factor [Table]. Patients with a higher grade of xerostomia had a lower salivary recovery rate (P < 0.001).

Patients with higher pre-treatment salivary flow experienced slower and lower salivary recovery rates. Parotid glands and oral cavity mean doses were not significantly associated with salivary recovery time. Parotid glands and oral cavity doses should be reduced as much as possible, even for patients with high pre-treatment salivary flow.