Radioactive Iodide Therapy of Pediatric Graves' Disease

描述（由申请人提供）： 研究人员不知道直接评估131 I辐射暴露和儿童GD治疗潜在癌症风险的研究。研究人员假设，131 I是治疗GD儿童的有效疗法，并且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，需要更好地了解接受131 I治疗的男孩和女孩的潜在辐射暴露和致癌风险。 为了解决131 I在儿科人群中的安全性和癌症风险问题，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志物研究。流行病学研究虽然有吸引力，但由于能够识别大量接受131 I治疗的儿童的后勤问题而不可能进行，因为据估计，30多年前，需要10，000多名10岁以下接受131 I治疗的受试者才能进行充分的统计学研究。 相比之下，辐射照射研究和癌症风险生物标志物研究是切实可行的，将产生大量数据。 将招募总计300例年龄小于18岁的诊断为GD的患者。该样本的一半将用131 I治疗，另一半将由未用放射疗法治疗的受试者组成（例如，接受抗甲状腺药物（ATDs）或手术治疗），年龄和性别与131 I组受试者相当。 在本试验中，儿童不会随机接受治疗，而是按照医生处方治疗。为了确保年龄和性别在两组儿童之间的平等分布，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GD治疗的儿童接受131 I治疗后的全身辐射暴露;以及（2）评估接受131 I治疗与不接受131 I治疗的GD（接受药物治疗或手术治疗）对染色体易位的影响。 次要目的包括（i）作为第一个主要目的的随访，将根据辐射暴露数据计算潜在癌症风险;以及（ii）在第二个主要目的的分析中，将计算接受131 I治疗与未接受131 I治疗的儿童的染色体易位，与年龄和131 I剂量相关。 这些研究将涉及与帕特里克Zanzonico博士（纪念斯隆-凯特琳癌症中心）和James Tucker博士（韦恩州立大学）的合作，前者是131 I剂量测定专家，后者是辐射细胞遗传学效应专家。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部门的帮助下设计的，该部门将参与数据分析。 这些研究被认为是FDA II期研究，因为它们将收集更多关于有效性和安全性的信息，这些信息对于评价产品的总体风险-受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.