Grant Number:	5R01CA054498-20 Interpret this number
Primary Investigator:	Breslow, Norman
Organization:	Fred Hutchinson Cancer Research Center
Project Title:	Late Effects of Treatment in Wilms Tumor Survivors and Offspring
Fiscal Year:	2011

DESCRIPTION: This proposal is to study the long term health of 9,240 patients enrolled during 1969-2002 on Nationa Wilms Tumor Study (NWTS) clinical trials and to monitor their offspring for cancer and birth defects. Wit current therapy, 90% of children with Wilms tumor (WT) will be cured. Survivors, however, are at risk fo delayed complications of their disease or treatment that may compromise their quality of life. Therapy for W has changed over time but still includes surgery, multi-agent chemotherapy and (for some) radiation therapy The disease typically occurs in early childhood; thus many years of follow-up are required to appreciate it consequences for adult survivors. As the complex genetic and epigenetic events involved in the etiology an pathogenesis of WT are unraveled, we may also discover the mechanisms underlying its long-term sequela and thus help to develop appropriate preventive strategies. Our specific goals are to determine th incidence, spectrum and risk factors, including disease, treatment and host factors, for selected life threatening endpoints affecting WT survivors: a) congestive heart failure; b) respiratory failure; c) rena failure; d) second malignant neoplasms; and e) diabetes. We will determine the incidence and causes of lat mortality in WT patients and, where possible, compare mortality and chronic disease rates with nationa population rates. We will study birth rates in WT survivors, pregnancy outcomes and complications, an congenital malformations in their offspring. Heritability and recurrence risks will be estimated through study of familial disease and follow-up of offspring. We will exploit the unique NWTS resource, including.::- systematically collected information on birth weights, congenital anomalies, nephrog.enic rests, histologic type, radiation doses, therapeutic drugs and clinical outcomes, to better characterize, subgroups of patient that may differ with respect to the etiology and pathogenesis of their WT and their susceptibility to long ter complications. We will collaborate with molecular biologists by facilitating access to particularly informativ patients and by combining the laboratory, clinical, pathology and epidemiologic data for analysis. B elucidating the late complications of WT and its treatment, and by identifying susceptible subgroups, thi study will enable future generations of childhood cancer patients and their physicians to select optimu treatments based on knowledge of long term risks as well as short term benefits.




Children's Oncology Group's 2013 blueprint for research: renal tumors.
Authors: Dome J.S. , Fernandez C.V. , Mullen E.A. , Kalapurakal J.A. , Geller J.I. , Huff V. , Gratias E.J. , Dix D.B. , Ehrlich P.F. , Khanna G. , et al. .
Source: Pediatric Blood & Cancer, 2013 Jun; 60(6), p. 994-1000.
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 N.E. , Beckwith J.B. , Haase G.M. , Kalapurakal J.A. , Ritchey M.L. , Shamberger R.C. , Thomas P.R. , D'Angio G.J. , Green D.M. .
Source: International Journal Of Radiation Oncology, Biology, Physics, 2006-05-01 00:00:00.0; 65(1), p. 203-9.
EPub date: 2006-05-01 00:00:00.0.
PMID: 16542795
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Renal failure in the Denys-Drash and Wilms' tumor-aniridia syndromes.
Authors: Breslow N.E. , Takashima J.R. , Ritchey M.L. , Strong L.C. , Green D.M. .
Source: Cancer Research, 2000-08-01 00:00:00.0; 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 M.J. , Arnold M. , Beckwith J.B. , Ritchey M.L. , D'Angio G.J. , Green D.M. , Breslow N.E. .
Source: Cancer, 1999-04-01 00:00:00.0; 85(7), p. 1616-25.
PMID: 10193955
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Familial Wilms' tumor: a descriptive study.
Authors: Breslow N.E. , Olson J. , Moksness J. , Beckwith J.B. , Grundy P. .
Source: Medical And Pediatric Oncology, 1996 Nov; 27(5), p. 398-403.
PMID: 8827065
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Non-11p constitutional chromosome abnormalities in Wilms' tumor patients.
Authors: Olson J.M. , Hamilton A. , Breslow N.E. .
Source: Medical And Pediatric Oncology, 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 W.M. , Breslow N.E. , Evans I.E. , Beckwith J.B. , Coppes M.J. , Grundy P. .
Source: Cancer Research, 1994-09-01 00:00:00.0; 54(17), p. 4680-3.
PMID: 8062264
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Cancer in twins of Wilms tumor patients.
Authors: Olson J.M. , Breslow N.E. , Barce J. .
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Wilms' tumour and parental age: a report from the National Wilms' Tumour Study.
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Epidemiology of Wilms tumor.
Authors: Breslow N. , Olshan A. , Beckwith J.B. , Green D.M. .
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