Radiotherapy dose-volume effects on salivary gland function

Abstract

Publications relating parotid dose-volume characteristics to radiotherapy-induced salivary toxicity were reviewed. Late salivary dysfunction has been correlated to the mean parotid gland dose, with recovery occurring with time. Severe xerostomia (defined as long-term salivary function of <25% of baseline) is usually avoided if at least one parotid gland is spared to a mean dose of less than approximately 20 Gy or if both glands are spared to less than approximately 25 Gy (mean dose). For complex, partial-volume RT patterns (e.g., intensity-modulated radiotherapy), each parotid mean dose should be kept as low as possible, consistent with the desired clinical target volume coverage. A lower parotid mean dose usually results in better function. Submandibular gland sparing also significantly decreases the risk of xerostomia. The currently available predictive models are imprecise, and additional study is required to identify more accurate models of xerostomia risk.

Fig. 1

Stimulated whole mouth salivary measurements vs. mean parotid gland dose. Summary of Washington University stimulated salivary results at 6 and 12 months of follow-up. Data showed that when either gland was spared (<20 Gy mean dose), ratio of post-radiotherapy (RT) to pre-RT flow is usually >0.25. Note, if either gland was highly spared (<10–15 Gy), resulting salivary function will usually be high, regardless of irradiation level of the other parotid gland (data originally presented in Blanco et al. [6], but redrawn here).

Fig. 2

Mean percentage of reduction in stimulated salivary flow rate vs. mean parotid gland dose for different follow-up durations (8, 10, 12, 14, 15, 16). Follow-up durations of 1, 6, and 12 months represent ranges of 1–1.5, 6–7, and 12 months, respectively. Linear fits of data from different follow-up intervals shown. Dose–response effect appears present at all times, with shift of data to right with time, suggesting functional repair or regeneration.

Fig. 3

Reported tissue dose required for 50% response for loss of stimulated saliva flow after radiotherapy (RT) (, , , –20) for single parotid gland. Endpoint considered in reports was salivary flow reduction to <25% (black symbols) or <50% (gray symbols) of pretreatment value. Tissue dose required for 50% response defined as dose at which 50% of patients developed complications. Error bars (if shown) indicate 95% confidence intervals; refer to original publications for exact meaning. 95% Confidence intervals for studies by Munter et al. (19, 20) were estimated from standard errors provided. Lines connect points from data sets with measurements taken at more than one interval after radiotherapy. Most studies used salivary gland scintigraphy. Some studies measured physical production (ipsilateral salivary flow or whole salivary flow; marked with “I” or “W”, respectively). Data from Buus et al. (2) (which did not include preradiotherapy assessments) derived by comparing different regions of parotid gland that had received different doses. Each label gives number of patients. Note, most imaging-derived endpoint data had greater values for tissue dose required for 50% response (TD50) than measured salivary data. CRT = conformal radiotherapy; IMRT = intensity-modulated radiotherapy.

Fig. 4

Population-based dose vs. local function response (salivary function at rest) from imaging study by Buus et al. (2). Local functional decline in metabolic clearance of parotid salivary glands vs. local dose, according to voxel-by-voxel estimated time-activity curves of intravenously injected C11-methionine. Data points from 12 patients shown, along with best-fit curve and 95% confidence intervals of curve fit. Individual gland curves reported by Buus et al. (2) deviated significantly from this population average curve (reproduced from Buus et al. [2], used with permission.) This population curve demonstrated functional decline in salivary function even at low doses.