Dose, volume, and function relationships in parotid salivary glands following conformal and intensity-modulated irradiation of head and neck cancer

Purpose: To determine the relationships between the three-dimensional dose distributions in parotid glands and their saliva production, and to find th e doses and irradiated volumes that permit preservation of the salivary flo w following irradiation (RT). Methods and Materials: Eighty-eight patients with head and neck cancer irra diated with parotid-sparing conformal and multisegmental intensity modulati on techniques between March 1994 and August 1997 participated in the study. The mean dose and the partial volumes receiving specified doses were deter mined for each gland from dose-volume histograms (DVHs). Nonstimulated and stimulated saliva flow rates were selectively measured from each parotid gl and before RT and at 1, 3, 6, and 12 months after the completion of RT. The data were fit using a generalized linear model and the normal tissue compl ication probability (NTCP) model of Lyman-Kutcher.In the latter model, a "s evere complication" was defined as salivary flow rate reduced to less than or equal to 25% pre-RT flow at 12 months. Results: Saliva flow rates data were available for 152 parotid glands. Glan ds receiving a mean dose below or equal to a threshold (24 Gy for the unsti mulated and 26 Gy for the stimulated saliva) showed substantial preservatio n of the flow rates following RT and continued to improve over time (to med ian 76% and 114% of pre-RT for the unstimulated and stimulated flow rates, respectively, at 12 months). In contrast, most glands receiving a mean dose higher than the threshold produced little saliva with no recovery over tim e. The output was not found to decrease as mean dose increased, as long as the threshold dose was not reached. Similarly, partial volume thresholds we re found: 67%, 45%, and 24% gland volumes receiving more than 15 Gy, 30 Gy, and 45 Gy, respectively. The partial volume thresholds correlated highly w ith the mean dose and did not add significantly to a model predicting the s aliva flow rate from the mean dose and the time since RT. The NTCP model pa rameters were found to be TD,, (the tolerance dose for 50% complications ra te for whole organ irradiated uniformly) = 28.4 Gy, n (volume dependence pa rameter) = 1, and m (the slope of the dose/response relationship) = 0.18. C linical factors including age, gender, pre-RT surgery, chemotherapy, and ce rtain medical conditions were not found to be significantly associated with the salivary flow rates. Medications (diuretics, antidepressants, and narc otics) were found to adversely affect the unstimulated but not the stimulat ed flow rates. Conclusions: Dose/volume/function relationships in the parotid glands are c haracterized by dose and volume thresholds, steep dose/response relationshi ps when the thresholds are reached, and a maximal volume dependence paramet er in the NTCP model. A parotid gland mean dose of less than or equal to 26 Gy should be a planning goal if substantial sparing of the gland function is desired. (C) 1999 Elsevier Science Inc.