Radioactive Iodide Therapy of Pediatric Graves' Disease

描述(由申请人提供)： 研究人员不知道有研究直接评估了131I辐射暴露和儿童GD治疗的潜在癌症风险。研究人员假设，131I是治疗GD儿童的有效方法，在年龄较大的儿童中使用时，不会与长期癌症风险相关，但可能与幼儿全身辐射水平过高有关。为了提供评估不同形式GD治疗的相对优点和风险所需的基本数据，需要更好地了解在这种情况下接受131I治疗的男孩和女孩的潜在辐射暴露和致癌风险。为了解决131I在儿科人群中的安全性和癌症风险的问题，考虑了几种方法，包括流行病学、辐射评估和癌症风险生物标记物研究。流行病学研究虽然有吸引力，但由于在确定大量接受131I治疗的儿童方面存在后勤问题，因此不可能进行，因为据估计，30多年前不到10岁时接受131I治疗的10 000多名受试者将需要进行充分的、统计上有效的研究。相比之下，辐射暴露研究和癌症风险生物标记物研究是实用的，并将产生大量数据。 将招募300名18岁以下被诊断为GD的患者。该样本的一半将接受131I治疗，另一半将由未接受放射治疗(例如，接受抗甲状腺药物(ATDS)或手术治疗)的受试者组成，年龄和性别与131I组受试者相当。在这项试验中，儿童不会随机接受治疗，但将按照医生规定的护理进行治疗。为了确保两组儿童的年龄和性别分布均等，我们按性别(男性与女性)和年龄(5-10岁、10-15岁、15-18岁)对入学人数进行分层。该提案的主要目的是(1)进行剂量测定，以评估接受131I治疗的GD儿童在接受131I治疗后的全身辐射暴露；以及(2)评估接受131I治疗与不接受131I治疗的GD(通过药物或手术治疗)对染色体易位的影响。第二个目标包括：(I)作为第一个主要目标的后续行动，将根据辐射暴露数据计算潜在的癌症风险；(Ii)在第二个主要目标的分析中，将计算接受131I治疗的儿童与未接受131I治疗的儿童的染色体易位，这与年龄和131I剂量有关。 这些研究将涉及与131I剂量学专家Patrick Zanzonico博士(纪念斯隆-凯特琳癌症中心)和韦恩州立大学辐射细胞遗传学影响专家James Tucker博士的合作。这些研究将涉及在耶鲁大学和贝勒大学接受GD治疗的儿童。这些研究是在耶鲁大学临床研究中心生物统计学支持单位的帮助下设计的，该中心将参与数据分析。 这些被认为是FDA的第二阶段研究，因为它们将收集更多关于有效性和安全性的信息，这对于评估产品的总体风险-收益比并为产品标签提供可接受的基础是必要的。

DESCRIPTION (provided by applicant): The investigators are unaware of studies that have directly evaluated 131I radiation exposure and potential cancer risks with GD therapy in children. The investigators hypothesize that 131I is an effective therapy for children with GD and will not be associated with long-term cancer risks when used in older children, but may be associated with excessive levels of whole body radiation in young children. To provide essential data needed to assess the relative merits and risks of different forms of GD therapy, a better understanding of potential radiation exposure and oncogenic risks in boys and girls treated with 131I for this condition is needed. To address issues of 131I safety and cancer risk in the pediatric population, several approaches were considered, including epidemiology, radiation assessment, and cancer-risk biomarker studies. Epidemiology studies, although attractive, are not possible due to logistical problems in being able to identify large numbers of children treated with 131I, as it is estimated that more than 10,000 subjects treated with 131I when less than 10 years of age, more than three decades ago, would be needed for a sufficient, statistically powered study. In comparison, studies of radiation exposure and cancer-risk biomarker studies are practical and will yield substantive data. A total of 300 patients diagnosed with GD younger than 18 years of age will be recruited. Half of this sample is to be treated with 131I and another half will consist of subjects not treated with radiation therapy (e.g., receiving antithyroid drugs (ATDs) or treated with surgery), and comparable in age and gender to the subjects in 131I group. In this trial, children will not be randomized to treatment, but will be treated per physician prescribed care. To ensure an equal distribution of age and gender between the two groups of children, we stratify enrollment by gender (male vs. female) and age (5-10 yrs, 10-15 yrs, 15-18 yrs). The proposal's primary aims are to (1) perform dosimetry to assess whole body radiation exposure following 131I therapy in children treated for GD; and (2) assess the effects of 131I treatment vs. no 131I treatment of GD (treated with medication or surgery) on chromosome translocations. The secondary aims include (i) As a follow-up to the first primary aim, the potential cancer risk will be calculated from the radiation exposure data; and (ii) within the analyses for the second primary aim, chromosomal translocation in children treated with 131I vs. not will be calculated, as related to age and dose of 131I. These studies will involve collaborative efforts with Dr. Patrick Zanzonico (Memorial Sloan-Kettering Cancer Center), who is an expert in 131I dosimetry and Dr. James Tucker (Wayne State University), who is an expert in cytogenetic effects of radiation. The studies will involve children treated for GD at Yale University and Baylor University. These studies have been designed with the help of the Yale Center for Clinical Investigation, Biostatistics Support Unit, which will be involved in data analysis. These are considered Phase 2 FDA studies as they will gather more information about effectiveness and safety that is necessary to evaluate the overall risk-benefit ratio of the product and to provide an acceptable basis for product labeling.