The National Wilms Tumor Study (NWTS) approach to treating stage III favorable-histology Wilms tumor (FHWT) is Regimen DD4A (vincristine, dactinomycin, and doxorubicin) and radiation therapy. Further risk stratification is required to improve outcomes and reduce late effects. We evaluated clinical and biologic variables for patients with stage III FHWT without combined loss of heterozygosity (LOH) at chromosomes 1p and 16q treated in the Children's Oncology Group protocol AREN0532. MethodsFrom October 2006 to August 2013, 588 prospectively treated, centrally reviewed patients with stage III FHWT were treated with Regimen DD4A and radiation therapy. Tumor LOH at 1p and 16q was determined by microsatellite analysis. Ineligible patients (n = 5) and those with combined LOH 1p/16q (n = 40) were excluded. ResultsA total of 535 patients with stage III disease were studied. Median follow-up was 5.2 years (range, 0.2 to 9.5). Four-year event-free survival (EFS) and overall survival estimates were 88% (95% CI, 85% to 91%) and 97% (95% CI, 95% to 99%), respectively. A total of 58 of 66 relapses occurred in the first 2 years, predominantly pulmonary (n = 36). Eighteen patients died, 14 secondary to disease. A better EFS was associated with negative lymph node status (P , .01) and absence of LOH 1p or 16q (P , .01), but not with gross residual disease or peritoneal implants. In contrast, the 4-year EFS was only 74% in patients with combined positive lymph node status and LOH 1p or 16q. A total of 123 patients (23%) had delayed nephrectomy. Submitted delayed nephrectomy histology showed anaplasia (n = 8; excluded from survival analysis); low risk/completely necrotic (n = 7; zero relapses), intermediate risk (n = 63; six relapses), and high-risk/blastemal type (n=7; five relapses). ConclusionMost patients with stage III FHWT had good EFS/overall survival with DD4A and radiation therapy. Combined lymph node and LOH status was highly predictive of EFS and should be considered as a potential prognostic marker for future trials.

These results indicate that the TSH reference range should be narrowed and support a value of approximately 4.0 as the upper-reference limit.

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Context Approximately 740000 Ci (2.73 ϫ 10 16 Bq) of iodine 131 (131 I) were released to the atmosphere from the Hanford Nuclear Site in Washington State from 1944 through 1957. The risk of thyroid disease resulting from prolonged environmental 131 I exposure is poorly understood. Objective The Hanford Thyroid Disease Study (HTDS) was conducted to determine if thyroid disease is increased among persons exposed as children to atmospheric releases of 131 I from Hanford. Design Retrospective cohort study. Exposure could have occurred from December 1944 through 1957. Follow-up occurred until the time of the HTDS examination (December 1992-September 1997). Participants' thyroid radiation doses from Hanford's 131 I releases were estimated from interview data regarding residence and dietary histories. Setting The cohort included a sample of all births from 1940 through 1946 to mothers with usual residence in 1 of 7 counties in eastern Washington State. Participants Of 5199 individuals identified, 4350 were located alive and 3440 were evaluable; ie, had sufficient data for dose estimation and received an HTDS evaluation for thyroid disease, including a thyroid ultrasound, physical examination, and fine needle biopsy if required to evaluate thyroid nodularity. Main Outcome Measures Thyroid cancer, benign thyroid nodules, total neoplasia, any thyroid nodules, autoimmune thyroiditis, and hypothyroidism. Results There was no evidence of a relationship between Hanford radiation dose and the cumulative incidence of any of the outcomes. These results remained unchanged after taking into account several factors that might confound the relationship between radiation dose and the outcomes of interest. Conclusion These results do not support the hypothesis that exposure during infancy and childhood to 131 I at the dose levels (median, 97 mGy; mean, 174 mGy) and exposure circumstances experienced by our study participants increases the risk of the forms of thyroid disease evaluated in this study.