Salivary Dysfunctions and Conséquences After RadioiodineTreatment for Thyroid Cancer: Protocol for a Self-Controlled Study(START Study)

Background: Following radioiodine (131I) therapy of differentiated thyroid cancer, salivary glands may become inflamed, leading to dysfunctions, then leading to decreases in patients’ nutrition and quality of life. The incidence of these dysfunctions after 131I-therapy is poorly known, and no clinical or genetic factors have been identified to date to define patients at risk, allowing the delivered activity to be adapted to the expected risk of salivary dysfunctions.Objective: this study aims to estimate the incidence of salivary dysfunctions after 131I-therapy, to characterize patients at risk of developing post-treatment dysfunctions using clinical, biomolecular and biochemical factors, and to validate a dosimetric method to calculate the dose received at the salivary gland level in order to analyze the dose response relationship between absorbed doses to salivary glands and salivary dysfunctions.Methods: This prospective cohort aims to include patients for whom a 131I-therapy is indicated within the treatment of their differentiated thyroid cancer in a Paris hospital (40 and 80 patients in a 1.1 GBq and a 3.7 GBq groups respectively). The follow-up is based on 3 scheduled visits: at inclusion (T0, immediately before 131I-therapy), 6 months (T6) and 18 months (T18) after treatment. For each visit, questionnaires on salivary dysfunctions (validated French tool), quality of life (HAD-scale, MOS-SF-36), and nutritional status are administered by a trained clinical research associate. At T0 and at T6, saliva samples and individual measurement of the salivary flow, without and with salivary glands stimulation, are performed. External thermoluminescent dosimeters are positioned on the skin opposite the salivary glands and at the sternal fork immediately before radioiodine administration and removed 5 days after treatment. From dosimeters, an estimation of the dose received at the salivary glands will be performed using physical and computational phantoms.Genetic and epigenetic analyses will be performed in order to look for potential biomarkers of predisposition to develop salivary dysfunctions after 131I-therapy.Results: 139 patients (71% women, mean age=47.4 (±14.3) years old) were included between September 2020 and April 2021 (45 and 94 patients in 1.1GBq and 3.7GBq groups respectively). The 6-months follow-up is still ongoing, and the 18-months follow-up will start in February 2022. Statistical analyses will study the links between salivary dysfunctions a