A prospective study of salivary function sparing in patients with head-and-neck cancers receiving intensity-modulated or three-dimensional radiation therapy: Initial results

Objectives: In a prospective clinical study, we tested the hypothesis that sparing the parotid glands may result in significant objective and subjecti ve improvement of xerostomia in patients with head-and-neck cancers, The Fu nctional outcome 6 months after the completion of radiation therapy is pres ented. Methods and Materials: From February 1997 to February 1999, 41 patients wit h head-and-neck cancers were enrolled in a prospective salivary function st udy. inverse-planning intensity-modulated radiation therapy (IMRT) was used to treat 27 patients, and forward-planning three-dimensional radiation the rapy in 14, To avoid potential bias in data interpretation, only patients w hose submandibular glands received greater than 50 Cy were eligible. Attemp ts were made to spare the superficial lobe of the parotid glands to avoid u nderdosing tumor targets in the parapharyngeal space; however, the entire p arotid volume was used to compute dose-volume histograms (DVHs) for this an alysis. DVHs were computed for each gland separately, Parotid function was assessed objectively by measuring stimulated and unstimulated saliva flow b efore and 6 months after the completion of radiation therapy. Measurements were converted to how rate (mL/min) and normalized relative to that before treatment. The corresponding quality-of-life (QOL) outcome was assessed by five questions regarding the patient's oral discomfort and eating/speaking problems. Results: We observed a correlation between parotid mean dose and the fracti onal reduction of stimulated saliva output at 6 months after the completion of radiation therapy. We further examined whether the functional outcome c ould be modeled as a function of dose. Two models were found to describe th e dose-response data well. The first model assumed that each parotid gland is comprised of multiple independent parallel functional subunits (correspo nding to computed tomography voxels) and that each gland contributes equall y to overall flow, and that saliva output decreases exponentially as a quad ratic function of irradiation dose to each voxel. The second approach uses the equivalent uniform dose (EUD) metrics, which assumes loss of salivary f unction with increase in EUD for each parotid gland independently. The anal ysis suggested that the mean dose to each parotid gland is a reasonable ind icator for the functional outcome of each gland. The corresponding exponent ial coefficient was 0.0428/Gy (95% confidence interval: 0.01, 0.09), The QO L questions on eating/speaking function were significantly correlated with stimulated and unstimulated saliva flow at 6 months. In a multivariate anal ysis, a toxicity score derived from the model based on radiation dose to th e parotid gland was found to be the sole significant predictive factor for xerostomia, Neither radiation technique (IMRT vs. non-IMRT) nor chemotherap y (yes or no) independently influenced the functional outcome of the saliva ry glands. Conclusion: Sparing of the parotid glands translates into objective and sub jective improvement of both xerostomia and QOL scores in patients with head -and-neck cancers receiving radiation therapy. Modeling results suggest an exponential relationship between saliva flow reduction and mean parotid dos e for each gland. We found that the stimulated saliva how at 6 months after treatment is reduced exponentially, for each gland independently, at a rat e of approximately 4% per Gy of mean parotid dose. (C) 2001 Elsevier Scienc e Inc.