Model Based Radiation Therapy: Submandibular Dose-Response NTCP-Curve Based on Objective Measurements

Abstract

Submandibular gland (SMG) normal tissue complication probability (NTCP) curves will be part of model-based indication for proton therapy in the Netherlands. Subjective measurements of xerostomia and sticky saliva reflect whole saliva, and are not suitable for the determination of the SMG NTCP curve. Therefore, we performed direct measurements of salivary flow, including the SMG flow. Based on a large database with a broad mean SMG dose distribution we obtained NTCP curves 6 weeks and 1 year after therapy. We utilized dose-response data of 200 head-and-neck patients, obtained from prospective salivary gland function studies. SMG flow was measured before, 6 weeks, and 1 year after therapy. Thirty patients were treated after unilateral neck dissection. Patients with N2c or N3 nodes were excluded. Tumors were localized in the oropharynx (69%), larynx (14%), nasopharynx (9%), oral cavity (4%), and hypopharynx (3%), 38% were N0, 32% T3-4. Treatment consisted of conventional RT, non-SMG sparing IMRT, SMG sparing IMRT, in 34, 84, and 82 patients, respectively. The mean dose to the ipsilateral submandibular gland was 62Gy, for the contralateral submandibular gland 47 Gy (range 0-72 Gy). Flow rates were converted to the baseline unilateral SMG flow rate, and compared with the contralateral SMG mean dose. Data were fitted to logistic regression (LR) and the Lyman-Kutcher-Burman (LKB) model, with a complication defined as a flow 6 weeks/ 1 year after therapy <25% of the flow before therapy [1]. There was a highly significant correlation between increasing mean SMG dose and decreasing absolute and relative SMG flow 6 weeks and 1 year after therapy. Mean contralateral SMG dose could be divided in five groups: ≤30 Gy (n=30), 30-40 Gy (28) 40-50 Gy (32), 50-60 Gy (57), > 60 Gy (53), the complication rate at 6 weeks was 22%, 50%, 73%, 76% and 86%, respectively; at 1 year 30%, 31%, 75%, 86% and 94%, respectively (P<.001). The D50 after 6 weeks was 31 Gy (95% CI 24-37), and 28 Gy (95% CI 21-34) after 1 year after analysis with the LKB model; 33 Gy (26-40) and 34 Gy (28-40), respectively, using the LR model. This NTCP-curve for submandibular gland function is based on the largest database of objective measurements in the literature. For planning purposes, usually a mean SMG-dose constraint of 40 Gy is chosen. We recommend a mean SMG dose of less than 30 Gy. [1] Dijkema et al. Int J Radiat Oncol Biol Phys. 2010:78;449-453.