This proposal is to study the long term health of children treated for Wilms tumor (WT), and to monitor their offspring for cancer and birth defects. The study is based in the unique and well described cohort of 9,236 patients enrolled during 1969-2002 on one of 5 clinical trials conducted by the National Wilms Tumor Study (NWTS). NWTS studies 3-5 developed treatment protocols that today are administered as "standard therapy" to the vast majority of patients. With this therapy, 90% of children with WT are cured. Survivors, however, are at risk for delayed complications of their disease or its treatment that may compromise their quality of life. Since the disease typically occurs in early childhood, many decades of follow-up are required to appreciate the consequences for adult survivors. Four life-threatening conditions are targeted: secondary malignant neoplasms;congestive heart failure;end stage renal disease (ESRD);and restrictive pulmonary disease. Most occurrences are validated by examination of medical records. Specific goals are to identify new subgroups of patients from NWTS-3-5 at high risk for each condition based on treatment, disease and host factors. Patients at high risk for ESRD, for example, may be considered for renal sparing surgery. Biological samples collected from patients on NWTS-5 will be used to test the hypothesis that mutations in the WT1 gene not only predispose to WT in childhood but also to ESRD in adolescence and adulthood. Systematically collected information on birth weights, congenital anomalies, nephrogenic rests, histologic type, and on radiation and chemotherapy doses will be used to construct risk functions for ESRD and to investigate whether treatment effects on congestive heart failure and secondary malignant neoplasms differ according to the biological subtype of Wilms tumor. The study will estimate rates of ovarian failure in female patients and rates of live birth and risks of pregnancy complications in partners of male patients. Heritability and recurrence risks of WT, together with the frequency of birth defects in the next generation, will be estimated through follow-up of a unique cohort of patient offspring.

Public Health Relevance

By elucidating the late complications of WT and its treatment, and by identifying susceptible subgroups, this study will enable future generations of childhood cancer patients and their physicians to select optimum treatments based on knowledge of long term risks as well as short term benefits. It will assist survivors to make informed decisions regarding the risks of pregnancy and the likelihood that their children will also develop Wilms tumor or birth defects.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
Project #
Application #
Study Section
Epidemiology of Cancer Study Section (EPIC)
Program Officer
Elena, Joanne W
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Fred Hutchinson Cancer Research Center
United States
Zip Code
Maschietto, Mariana; Williams, Richard D; Chagtai, Tasnim et al. (2014) TP53 mutational status is a potential marker for risk stratification in Wilms tumour with diffuse anaplasia. PLoS One 9:e109924
Lange, Jane M; Takashima, Janice R; Peterson, Susan M et al. (2014) Breast cancer in female survivors of Wilms tumor: a report from the national Wilms tumor late effects study. Cancer 120:3722-30
Green, Daniel M; Breslow, Norman E; D'Angio, Giulio J et al. (2014) Outcome of patients with Stage II/favorable histology Wilms tumor with and without local tumor spill: a report from the National Wilms Tumor Study Group. Pediatr Blood Cancer 61:134-9
Dome, Jeffrey S; Fernandez, Conrad V; Mullen, Elizabeth A et al. (2013) Children's Oncology Group's 2013 blueprint for research: renal tumors. Pediatr Blood Cancer 60:994-1000
Ehrlich, Peter F; Anderson, James R; Ritchey, Michael L et al. (2013) Clinicopathologic findings predictive of relapse in children with stage III favorable-histology Wilms tumor. J Clin Oncol 31:1196-201
Weiss, Aaron R; Lyden, Elizabeth R; Anderson, James R et al. (2013) Histologic and clinical characteristics can guide staging evaluations for children and adolescents with rhabdomyosarcoma: a report from the Children's Oncology Group Soft Tissue Sarcoma Committee. J Clin Oncol 31:3226-32
Malogolowkin, M; Spreafico, F; Dome, J S et al. (2013) Incidence and outcomes of patients with late recurrence of Wilms' tumor. Pediatr Blood Cancer 60:1612-5
Peng, Gang; Fan, Yu; Palculict, Timothy B et al. (2013) Rare variant detection using family-based sequencing analysis. Proc Natl Acad Sci U S A 110:3985-90
Gratias, Eric J; Jennings, Lawrence J; Anderson, James R et al. (2013) Gain of 1q is associated with inferior event-free and overall survival in patients with favorable histology Wilms tumor: a report from the Children's Oncology Group. Cancer 119:3887-94
Green, Daniel M; Lange, Jane M; Qu, Annie et al. (2013) Pulmonary disease after treatment for Wilms tumor: a report from the national wilms tumor long-term follow-up study. Pediatr Blood Cancer 60:1721-6

Showing the most recent 10 out of 42 publications