Prospective longitudinal assessment of parotid gland function using dynamic quantitative pertechnate scintigraphy and estimation of dose-response relationship of parotid-sparing radiotherapy in head-neck cancers

Purpose: To estimate dose-response relationship using dynamic quantitative Tc-99m-pertechnate scintigraphy in head-neck cancer patients treated with parotid-sparing conformal radiotherapy. Methods: Dynamic quantitative pertechnate salivary scintigraphy was performed pre-treatment and subsequently periodically after definitive radiotherapy. Reduction in salivary function following radiotherapy was quantified by salivary excretion fraction (SEF) ratios. Dose-response curves were modeled using standardized methodology to calculate tolerance dose 50 (TD50) for parotid glands. Results: Salivary gland function was significantly affected by radiotherapy with maximal decrease in SEF ratios at 3-months, with moderate functional recovery over time. There was significant inverse correlation between SEF ratios and mean parotid doses at 3-months (r = -0.589, p < 0.001); 12-months (r = -0.554, p < 0.001); 24-months (r = -0.371, p = 0.002); and 36-months (r = -0.350, p = 0.005) respectively. Using a post-treatment SEF ratio <45% as the scintigraphic criteria to define severe salivary toxicity, the estimated TD50 value with its 95% confidence interval (95% CI) for the parotid gland was 35.1Gy (23.6-42.6Gy), 41.3Gy (34.6-48.8Gy), 55.9Gy (47.4-70.0Gy) and 64.3Gy (55.8-70.0Gy) at 3, 12, 24, and 36-months respectively. Conclusions: There is consistent decline in parotid function even after conformal radiotherapy with moderate recovery over time. Dynamic quantitative pertechnate scintigraphy is a simple, reproducible, and minimally invasive test of major salivary gland function.