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Grant Details

Grant Number: 2R01CA054498-21A1 Interpret this number
Primary Investigator: Breslow, Norman
Organization: Fred Hutchinson Can Res Ctr
Project Title: Late Effects of Treatment in Wilms Tumor Survivors and Offspring
Fiscal Year: 2012
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Abstract

DESCRIPTION (provided by applicant): 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.

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Publications

Children's Oncology Group's 2013 blueprint for research: renal tumors.
Authors: Dome JS, Fernandez CV, Mullen EA, Kalapurakal JA, Geller JI, Huff V, Gratias EJ, Dix DB, Ehrlich PF, Khanna G, Malogolowkin MH, Anderson JR, Naranjo A, Perlman EJ, COG Renal Tumors Committee
Source: Pediatr Blood Cancer, 2013 Jun;60(6), p. 994-1000.
EPub date: 2012 Dec 19.
PMID: 23255438
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Radiation therapy for favorable histology Wilms tumor: prevention of flank recurrence did not improve survival on National Wilms Tumor Studies 3 and 4.
Authors: Breslow NE, Beckwith JB, Haase GM, Kalapurakal JA, Ritchey ML, Shamberger RC, Thomas PR, D'Angio GJ, Green DM
Source: Int J Radiat Oncol Biol Phys, 2006 May 1;65(1), p. 203-9.
EPub date: 2006 Mar 20.
PMID: 16542795
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Renal failure in the Denys-Drash and Wilms' tumor-aniridia syndromes.
Authors: Breslow NE, Takashima JR, Ritchey ML, Strong LC, Green DM
Source: Cancer Res, 2000 Aug 1;60(15), p. 4030-2.
PMID: 10945603
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Factors affecting the risk of contralateral Wilms tumor development: a report from the National Wilms Tumor Study Group.
Authors: Coppes MJ, Arnold M, Beckwith JB, Ritchey ML, D'Angio GJ, Green DM, Breslow NE
Source: Cancer, 1999 Apr 1;85(7), p. 1616-25.
PMID: 10193955
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Familial Wilms' tumor: a descriptive study.
Authors: Breslow NE, Olson J, Moksness J, Beckwith JB, Grundy P
Source: Med Pediatr Oncol, 1996 Nov;27(5), p. 398-403.
PMID: 8827065
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Non-11p constitutional chromosome abnormalities in Wilms' tumor patients.
Authors: Olson JM, Hamilton A, Breslow NE
Source: Med Pediatr Oncol, 1995 May;24(5), p. 305-9.
PMID: 7700182
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Increased birth weights of National Wilms' Tumor Study patients suggest a growth factor excess.
Authors: Leisenring WM, Breslow NE, Evans IE, Beckwith JB, Coppes MJ, Grundy P
Source: Cancer Res, 1994 Sep 1;54(17), p. 4680-3.
PMID: 8062264
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Cancer in twins of Wilms tumor patients.
Authors: Olson JM, Breslow NE, Barce J
Source: Am J Med Genet, 1993 Aug 1;47(1), p. 91-4.
PMID: 8396323
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Wilms' tumour and parental age: a report from the National Wilms' Tumour Study.
Authors: Olson JM, Breslow NE, Beckwith JB
Source: Br J Cancer, 1993 Apr;67(4), p. 813-8.
PMID: 8385980
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Epidemiology of Wilms tumor.
Authors: Breslow N, Olshan A, Beckwith JB, Green DM
Source: Med Pediatr Oncol, 1993;21(3), p. 172-81.
PMID: 7680412
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