The impact of dose on parotid salivary recovery in head and neck cancer patients treated with radiation therapy

Abstract

Purpose: A common side effect experienced by head and neck cancer patients after radiation therapy (RT) is impairment of the parotid glands' ability to produce saliva. Our purpose is to investigate the relationship between radiation dose and saliva changes in the 2 years after treatment.

Methods and materials: The study population includes 142 patients treated with conformal or intensity-modulated radiotherapy. Saliva flow rates from 266 parotid glands are measured before and 1, 3, 6, 12, 18, and 24 months after treatment. Measurements are collected separately from each gland under both stimulated and unstimulated conditions. Bayesian nonlinear hierarchical models were developed and fit to the data.

Results: Parotids receiving higher radiation produce less saliva. The largest reduction is at 1-3 months after RT followed by gradual recovery. When mean doses are lower (e.g., <25 Gy), the model-predicted average stimulated saliva recovers to pretreatment levels at 12 months and exceeds it at 18 and 24 months. For higher doses (e.g., >30 Gy), the stimulated saliva does not return to original levels after 2 years. Without stimulation, at 24 months, the predicted saliva is 86% of pretreatment levels for 25 Gy and <31% for >40 Gy. We do not find evidence to support that the overproduction of stimulated saliva at 18 and 24 months after low dose in 1 parotid gland is the result of low saliva production from the other parotid gland.

Conclusions: Saliva production is affected significantly by radiation, but with doses <25-30 Gy, recovery is substantial and returns to pretreatment levels 2 years after RT.

Figure 1

Stimulated saliva flow rates versus mean radiation dose at baseline and 1, 3, 6, 12, 18, 24 months after the completion of RT. The flow rates are plotted on a log(flow rates + 1) transformed scale for each gland. The solid line is the LOESS smoothing line describing the relationship between flow rates and mean doses.

Figure 2

Unstimulated saliva flow rates versus mean radiation dose at baseline and 1, 3, 6, 12, 18, 24 months after the completion of RT. The flow rates are plotted on a log(flow rates + 1) transformed scale for each gland. The solid line is the LOESS smoothing line describing the relationship between flow rates and mean doses.

Figure 3

Mean stimulated saliva counts predicted by the estimated model specified in equation (i) for baseline and 1, 3, 6, 12, 18, 24 months after RT.

Figure 4

Mean unstimulated saliva counts predicted by the estimated model specified in equation (i) for baseline and 1, 3, 6, 12, 18, 24 months after RT.

Figure 5

Distribution of saliva flow rates with and without stimulation at 18 months after radiation therapy when the mean radiation dose is 0, 20, 30, and 40Gy, respectively,