Submandibular function recovery after IMRT in head and neck cancer: A prospective dose modelling study.

Abstract

To estimate the dose response relationship for submandibular gland (SMG) recovery using salivary scintigraphy in patients diagnosed with head and neck cancer treated with curative image guided chemoradiation. Ninety newly diagnosed head and neck cancer patients (T1-3, N0-2c, M0) treated with intensity modulated radiotherapy on a prospective clinical trial were assessed for salivary toxicity at predefined intervals using dynamic salivary scintigraphy. The SMG function was measured using salivary excretion fraction (SEF) ratios at baseline and 6 monthly. Tolerance dose (TD) 50 for submandibular gland was estimated from dose response curves. The mean SEF ratio of 180 SMGs decreased at 6 months with a nadir at 12 months after treatment (SEF ratio 15%) and progressively recovered over time reaching 38% over 24 months. There was significant inverse correlation between SEF ratio and mean SMG dose at 6 months (r = -0.18, p = 0.04); 12-months (r = -0.36, p < 0.001); 18-months (r = -0.48, p < 0.001); 24-months (r = -0.42, p < 0.001); and more than 24-months (r = -0.56, p < 0.001). The estimated TD 50 values at 1 year and 2 year post treatment were 36 Gy and 44 Gy respectively with SEF ratio of ≤45% used to define severe xerostomia. For every 1 Gy reduction in mean dose below 54 Gy, there is 2-2.5% reduction in the probability of severe xerostomia. The submandibular gland function declines after radiotherapy with a nadir at 12 months and there is incomplete recovery over time with continued improvement over 24 months. The TD 50 at 1 year and 2 year was 36 Gy and 44 Gy with a 2-2.5% reduction in the probability of severe xerostomia for every 1 Gy reduction in mean dose.