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.
Graves' Disease (GD) accounts for more than 95% of cases of hyperthyroidismin the pediatric population and is an orphan disease. 131I is an effective treatment forGD in children and is widely used. These are Phase 2 studies aimed at examining131I safety in children by assessing radiation expose and genetic damage.
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