This is a revised proposal for the long term follow-up of survivors from the National Wilms' Tumor Study (NWTS) and their offspring so as to elucidate the genetic origins of Wilms' tumors, to estimate the risk of adverse pregnancy outcomes and congenital defects and to determine the rates of second tumors and heart disease in patients treated for cancer in childhood. The NWTS is a large collaborative trial organized in 1969 that currently registers an estimated 70% or more of the children diagnosed with Wilms' tumor in the United States. Patients are followed on the clinical trial for five years from diagnosis, by which time those who have survived may be considered cured of their initial disease. This proposal is to develop and implement efficient means of continued follow-up beyond five years so that the lessons to be learned from this invaluable cohort of children and young adults will not be lost to science, and to perfect these methods as a model for others engaged in similar studies. Late effects to be ascertained in this longitudinal study include second malignant tumors, benign tumors, serious heart disease, reproductive outcomes, and congenital defects and cancer, including familial Wilms' tumors, that may develop in offspring. The treatment interventions used in the NWTS are combinations of four chemotherapeutic agents with and without radiation therapy. This will permit the comparison of rates of occurrence of key events among randomized patient subgroups that differ with respect to the use and dosage of radiation therapy and the specific type of chemotherapy. Data on Wilms' tumors in family members and offspring will be collected so as to determine the population frequency, degree of dominance and penetrance of the putative """"""""Wilms' gene"""""""" and to assist others in the location of the gene or genes via linkage analysis. Data on late effects will be analyzed according to type and duration of therapy, years elapsed since initiation of treatment, age and host factors. Patients will be followed by means of an automated system that maintains annual contact with survivors and actively pursues those patients and families who become lost to follow-up. Information on health status and other key events will be obtained from periodic physical exams and medical histories, with questionnaires and reviews of medical records used to obtain details on reproductive outcomes and diagnoses of key medical conditions.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA054498-05
Application #
2095986
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Project Start
1991-08-15
Project End
1996-06-30
Budget Start
1995-07-01
Budget End
1996-06-30
Support Year
5
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
075524595
City
Seattle
State
WA
Country
United States
Zip Code
98109
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Venkatramani, Rajkumar; Chi, Yueh-Yun; Coppes, Max J et al. (2017) Outcome of patients with intracranial relapse enrolled on national Wilms Tumor Study Group clinical trials. Pediatr Blood Cancer 64:
Gratias, Eric J; Dome, Jeffrey S; Jennings, Lawrence J et al. (2016) Association of Chromosome 1q Gain With Inferior Survival in Favorable-Histology Wilms Tumor: A Report From the Children's Oncology Group. J Clin Oncol 34:3189-94
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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
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
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
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

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