Baudin Clémence, Lussey-Lepoutre Charlotte, Bressand Alice, Buffet Camille, Menegaux Fabrice, Soret Marine, Broggio David, Bassinet Céline, Huet Christelle, Armengol Gemma, Leenhardt Laurence, Bernier Marie-Odile
Ionizing Radiation Epidemiology Laboratory, Institute for Radiological Protection and Nuclear Safety, Fontenay-aux-Roses, France.
Department of Nuclear Medicine, Sorbonne University, Pitié-Salpêtrière Hospital APHP, Paris, France.
JMIR Res Protoc. 2022 Jul 22;11(7):e35565. doi: 10.2196/35565.
Following radioiodine (I) therapy of differentiated thyroid cancer, the salivary glands may become inflamed, leading to dysfunctions and decreases in patients' nutritional status and quality of life. The incidence of these dysfunctions after I-therapy is poorly known, and no clinical or genetic factors have been identified to date to define at-risk patients, which would allow the delivered activity to be adapted to the expected risk of salivary dysfunctions.
The aims of this study are to estimate the incidence of salivary dysfunctions, and consequences on the quality of life and nutritional status for patients after I-therapy; to characterize at-risk patients of developing posttreatment dysfunctions using clinical, biomolecular, and biochemical factors; and to validate a dosimetric method to calculate the dose received at the salivary gland level for analyzing the dose-response relationship between absorbed doses to salivary glands and salivary dysfunctions.
This prospective study aims to include patients for whom I-therapy is indicated as part of the treatment for differentiated thyroid cancer in a Paris hospital (40 and 80 patients in the 1.1 GBq and 3.7 GBq groups, respectively). The follow-up is based on three scheduled visits: at inclusion (T0, immediately before I-therapy), and at 6 months (T6) and 18 months (T18) posttreatment. For each visit, questionnaires on salivary dysfunctions (validated French tool), quality of life (Hospital Anxiety and Depression scale, Medical Outcomes Study 36-Item Short Form Survey), and nutritional status (visual analog scale) are administered by a trained clinical research associate. At T0 and T6, saliva samples and individual measurements 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 I administration and removed after 5 days. From the doses recorded by the dosimeters, an estimation of the dose received at the salivary glands will be carried out using physical and computational phantoms. Genetic and epigenetic analyses will be performed to search for potential biomarkers of the predisposition to develop salivary dysfunctions after I-therapy.
A total of 139 patients (99 women, 71.2%; mean age 47.4, SD 14.3 years) were enrolled in the study between September 2020 and April 2021 (45 and 94 patients in the 1.1 GBq and 3.7G Bq groups, respectively). T6 follow-up is complete and T18 follow-up is currently underway. Statistical analyses will assess the links between salivary dysfunctions and absorbed doses to the salivary glands, accounting for associated factors. Moreover, impacts on the patients' quality of life will be analyzed.
To our knowledge, this study is the first to investigate the risk of salivary dysfunctions (using both objective and subjective indicators) in relation to organ (salivary glands) doses, based on individual dosimeter records and dose reconstructions. The results will allow the identification of patients at risk of salivary dysfunctions and will permit clinicians to propose a more adapted follow-up and/or countermeasures to adverse effects.
ClinicalTrials.gov NCT04876287; https://clinicaltrials.gov/ct2/show/NCT04876287.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/35565.
在分化型甲状腺癌接受放射性碘（I）治疗后，唾液腺可能会发生炎症，导致功能障碍，并使患者的营养状况和生活质量下降。I治疗后这些功能障碍的发生率鲜为人知，迄今为止尚未发现可用于确定高危患者的临床或遗传因素，而这将有助于使给予的活度适应唾液功能障碍的预期风险。
本研究的目的是评估I治疗后患者唾液功能障碍的发生率及其对生活质量和营养状况的影响；利用临床、生物分子和生化因素对发生治疗后功能障碍的高危患者进行特征描述；并验证一种剂量测定方法，以计算唾液腺水平所接受的剂量，从而分析唾液腺吸收剂量与唾液功能障碍之间的剂量-反应关系。
这项前瞻性研究旨在纳入巴黎一家医院中被指示接受I治疗作为分化型甲状腺癌治疗一部分的患者（1.1GBq组和3.7GBq组分别为40例和80例患者）。随访基于三次预定的访视：纳入时（T0，即I治疗前即刻）、治疗后6个月（T6）和18个月（T18）。每次访视时，由经过培训的临床研究助理发放关于唾液功能障碍（经过验证的法语工具）、生活质量（医院焦虑和抑郁量表、医学结局研究36项简短问卷）和营养状况（视觉模拟量表）的问卷。在T0和T6时，进行唾液样本采集以及在无唾液腺刺激和有唾液腺刺激情况下的唾液流量个体测量。在给予I之前，将外部热释光剂量计放置在唾液腺对面的皮肤上以及胸骨柄处，5天后取下。根据剂量计记录的剂量，将使用物理和计算体模对唾液腺所接受的剂量进行估算。将进行基因和表观遗传分析，以寻找I治疗后发生唾液功能障碍易感性的潜在生物标志物。
2020年9月至2021年4月期间，共有139例患者（99例女性，71.2%；平均年龄47.4岁，标准差14.3岁）纳入研究（1.1GBq组和3.7GBq组分别为45例和94例患者）。T6随访已完成，T18随访正在进行中。统计分析将评估唾液功能障碍与唾液腺吸收剂量之间的关联，并考虑相关因素。此外，还将分析对患者生活质量的影响。
据我们所知，本研究首次基于个体剂量计记录和剂量重建，研究了与器官（唾液腺）剂量相关的唾液功能障碍风险（使用客观和主观指标）。研究结果将有助于识别有唾液功能障碍风险的患者，并使临床医生能够提出更合适的随访方案和/或针对不良反应的应对措施。
ClinicalTrials.gov NCT04876287；https://clinicaltrials.gov/ct2/show/NCT04876287。
国际注册报告识别码（IRRID）：DERR1-10.2196/35565。
