Functional Parotid Sparing: Does Sparing the Parotid Ducts Yield Improvements in Patient Reported Xerostomia?

Abstract

Literature suggests that salivary gland stem cells, capable of regenerating salivary tissue, may preferentially reside in the large ducts of salivary glands. We conducted a prospective trial in patients receiving definitive chemoradiotherapy (CRT) for oropharyngeal cancer where we preferentially spared the major parotid ducts (localized via MRI sialography) during treatment planning. We hypothesized that (1) this technique would yield improvements in patient reported xerostomia (PRX) at 6- and 12-months post-CRT compared to a prospectively accrued cohort of similar patients, and (2) that parotid duct doses would be predictive for PRX.A total of 38 Patients were prospectively enrolled and underwent MRI sialography guided ductal sparing. 28/38 patients received de-escalated CRT (60Gy). PRX was classified as none/mild versus moderate to very severe. (1) PRX in the 28 de-escalated patients were compared using a fisher exact test to a cohort of 232 patients on the same clinical trials but who did not undergo ductal sparing. (2) Competing nested multivariate logistic models (+/- parotid duct doses) were assessed using dosimetric data from all 38 patients for their ability to predict PRX. Models included contralateral submandibular mean dose, mean parotid gland dose (both) +/- parotid duct mean dose (both). The two nested models were compared using a likelihood ratio test to determine if incorporating mean parotid duct doses significantly improved model fit.(1) Patients reporting moderate to very severe xerostomia was lower in patients with vs without parotid-ductal sparing at 6 months post-CRT (46% vs 67%, P = 0.03), and trended lower at 12 months post-CRT (32% vs 49%, P = 0.11). At 6 months post CRT, the mean parotid duct dose was the only covariate significantly associated with PRX (P = 0.047). At 12 months post CRT, no covariate was significantly associated with PRX but both mean contralateral submandibular dose and mean parotid duct dose approached significance (P = 0.06 and 0.07, respectively). (2) The models +/- parotid duct doses were compared and the addition of parotid ductal mean dose significantly improved model fit at 6- and 12-months post CRT (P = 0.030 and 0.047, respectively).The absolute rates of moderate to very severe patient reported xerostomia were approximately 20% lower for those undergoing MRI sialography guided parotid ductal sparing versus those without ductal sparing at 6- and 12-months post CRT. The significant improvement of model fit upon adding mean parotid ductal dose to the mean major salivary gland doses at 6 and 12 months suggests that the dose received by the parotid ducts relates to patient reported xerostomia severity even when considering traditional metrics such as mean parotid and contralateral submandibular dose.