Grant Number:	5R01CA079060-02 Interpret this number
Primary Investigator:	Lipshultz, Steven
Organization:	University Of Rochester
Project Title:	Cardiac Risk Factors in Pediatric Cancer Survivors
Fiscal Year:	1999

DESCRIPTION: (Applicant's Description) Although subclinical cardiac abnormalities are common and often progressive in long-term survivors of childhood cancer who have been treated with anthracycline chemotherapy or mediastinal irradiation, a comprehensive assessment of risk factor for premature symptomatic cardiovascular disease has never been performed. The relationship between emerging late effects of treatment (lipid abnormalities, obesity, and cardiomyopathy) warrants further study. In this application, the investigators will study and identify a comprehensive cardiac risk factor profile on all eligible long-term survivors of childhood cancer within the catchment area of upstate New York. The primary hypothesis is that these patients will have more risk factors for subsequent symptomatic cardiovascular disease than two control populations that will be studied. The first will be matched siblings of treated patients, and the second will be long-term survivors of childhood cancer who have not been treated with therapy known to be cardiotoxic. The investigators will be able to determine whether there are increased risk factors and whether these risk factors are related to prior oncologic therapy. The second hypothesis is that there are differences in the number of cardiac risk factors for three groups of long-term survivors: those treated with anthracyclines alone, those treated with radiation to the heart alone, and those treated with both. The applicants will specifically determine the presence of depressed left ventricular (LV) function, thin LV wall, elevated LV afterload, increased body fat, elevated blood pressure, abnormal endothelial function, and abnormal lipid profiles. These will be compared to the control populations. Other secondary risk factors will be determined. Longitudinal changes in study and control patients will be determined as well to chart the trajectory over time in risk factors in different populations. If the hypotheses are true, this should enable more rational recommendations for preventive cardiology in long-term survivors to be made and to standardize care and management for this population.




Impaired mitochondrial function is abrogated by dexrazoxane in doxorubicin-treated childhood acute lymphoblastic leukemia survivors.
Authors: Lipshultz S.E. , Anderson L.M. , Miller T.L. , Gerschenson M. , Stevenson K.E. , Neuberg D.S. , Franco V.I. , LiButti D.E. , Silverman L.B. , Vrooman L.M. , et al. .
Source: Cancer, 2016-03-15 00:00:00.0; 122(6), p. 946-53.
EPub date: 2016-03-15 00:00:00.0.
PMID: 26762648
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Impact of hemochromatosis gene mutations on cardiac status in doxorubicin-treated survivors of childhood high-risk leukemia.
Authors: Lipshultz S.E. , Lipsitz S.R. , Kutok J.L. , Miller T.L. , Colan S.D. , Neuberg D.S. , Stevenson K.E. , Fleming M.D. , Sallan S.E. , Franco V.I. , et al. .
Source: Cancer, 2013-10-01 00:00:00.0; 119(19), p. 3555-62.
EPub date: 2013-10-01 00:00:00.0.
PMID: 23861158
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Cranial irradiation as an additional risk factor for anthracycline cardiotoxicity in childhood cancer survivors: an analysis from the cardiac risk factors in childhood cancer survivors study.
Authors: Landy D.C. , Miller T.L. , Lipsitz S.R. , Lopez-Mitnik G. , Hinkle A.S. , Constine L.S. , Adams M.J. , Lipshultz S.E. .
Source: Pediatric Cardiology, 2013 Apr; 34(4), p. 826-34.
PMID: 23080542
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Exercise capacity in long-term survivors of pediatric cancer: an analysis from the Cardiac Risk Factors in Childhood Cancer Survivors Study.
Authors: Miller A.M. , Lopez-Mitnik G. , Somarriba G. , Lipsitz S.R. , Hinkle A.S. , Constine L.S. , Lipshultz S.E. , Miller T.L. .
Source: Pediatric Blood & Cancer, 2013 Apr; 60(4), p. 663-8.
PMID: 23255294
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Dietary quality, caloric intake, and adiposity of childhood cancer survivors and their siblings: an analysis from the cardiac risk factors in childhood cancer survivors study.
Authors: Landy D.C. , Lipsitz S.R. , Kurtz J.M. , Hinkle A.S. , Constine L.S. , Adams M.J. , Lipshultz S.E. , Miller T.L. .
Source: Nutrition And Cancer, 2013; 65(4), p. 547-55.
PMID: 23659446
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Cardiac failure 30 years after treatment containing anthracycline for childhood acute lymphoblastic leukemia.
Authors: Goldberg J.M. , Scully R.E. , Sallan S.E. , Lipshultz S.E. .
Source: Journal Of Pediatric Hematology/oncology, 2012 Jul; 34(5), p. 395-7.
PMID: 22584777
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Cardiotoxicity in childhood cancer survivors: strategies for prevention and management.
Authors: Harake D. , Franco V.I. , Henkel J.M. , Miller T.L. , Lipshultz S.E. .
Source: Future Cardiology, 2012 Jul; 8(4), p. 647-70.
PMID: 22871201
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Aggregating traditional cardiovascular disease risk factors to assess the cardiometabolic health of childhood cancer survivors: an analysis from the Cardiac Risk Factors in Childhood Cancer Survivors Study.
Authors: Landy D.C. , Miller T.L. , Lopez-Mitnik G. , Lipsitz S.R. , Hinkle A.S. , Constine L.S. , French C.A. , Rovitelli A.M. , Adams M.J. , Lipshultz S.E. .
Source: American Heart Journal, 2012 Feb; 163(2), p. 295-301.e2.
PMID: 22305850
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Characteristics and determinants of adiposity in pediatric cancer survivors.
Authors: Miller T.L. , Lipsitz S.R. , Lopez-Mitnik G. , Hinkle A.S. , Constine L.S. , Adams M.J. , French C. , Proukou C. , Rovitelli A. , Lipshultz S.E. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2010 Aug; 19(8), p. 2013-22.
PMID: 20647396
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An improved estimator for the hydration of fat-free mass from in vivo measurements subject to additive technical errors.
Authors: Kinnamon D.D. , Lipsitz S.R. , Ludwig D.A. , Lipshultz S.E. , Miller T.L. .
Source: Physiological Measurement, 2010 Apr; 31(4), p. 497-512.
PMID: 20181998
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Anthracycline associated cardiotoxicity in survivors of childhood cancer.
Authors: Lipshultz S.E. , Alvarez J.A. , Scully R.E. .
Source: Heart (british Cardiac Society), 2008 Apr; 94(4), p. 525-33.
PMID: 18347383
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Anthracycline-induced cardiotoxicity: course, pathophysiology, prevention and management.
Authors: Barry E. , Alvarez J.A. , Scully R.E. , Miller T.L. , Lipshultz S.E. .
Source: Expert Opinion On Pharmacotherapy, 2007 Jun; 8(8), p. 1039-58.
PMID: 17516870
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Long-term effects of treatments for childhood cancers.
Authors: Alvarez J.A. , Scully R.E. , Miller T.L. , Armstrong F.D. , Constine L.S. , Friedman D.L. , Lipshultz S.E. .
Source: Current Opinion In Pediatrics, 2007 Feb; 19(1), p. 23-31.
PMID: 17224658
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Anthracycline cardiotoxicity in long-term survivors of childhood cancer.
Authors: Scully R.E. , Lipshultz S.E. .
Source: Cardiovascular Toxicology, 2007; 7(2), p. 122-8.
PMID: 17652816
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Incidence, causes, and outcomes of dilated cardiomyopathy in children.
Authors: Towbin J.A. , Lowe A.M. , Colan S.D. , Sleeper L.A. , Orav E.J. , Clunie S. , Messere J. , Cox G.F. , Lurie P.R. , Hsu D. , et al. .
Source: Jama, 2006-10-18 00:00:00.0; 296(15), p. 1867-76.
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Factors associated with establishing a causal diagnosis for children with cardiomyopathy.
Authors: Cox G.F. , Sleeper L.A. , Lowe A.M. , Towbin J.A. , Colan S.D. , Orav E.J. , Lurie P.R. , Messere J.E. , Wilkinson J.D. , Lipshultz S.E. .
Source: Pediatrics, 2006 Oct; 118(4), p. 1519-31.
PMID: 17015543
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Frequency of clinically unsuspected myocardial injury at a children's hospital.
Authors: Lipshultz S.E. , Wong J.C. , Lipsitz S.R. , Simbre V.C. , Zareba K.M. , Galpechian V. , Rifai N. .
Source: American Heart Journal, 2006 Apr; 151(4), p. 916-22.
PMID: 16569563
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Impact of HIV and highly active antiretroviral therapy on leukocyte adhesion molecules, arterial inflammation, dyslipidemia, and atherosclerosis.
Authors: Fisher S.D. , Miller T.L. , Lipshultz S.E. .
Source: Atherosclerosis, 2006 Mar; 185(1), p. 1-11.
PMID: 16297390
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Establishing norms for echocardiographic measurements of cardiovascular structures and function in children.
Authors: Lipshultz S.E. , Miller T.L. .
Source: Journal Of Applied Physiology (bethesda, Md. : 1985), 2005 Aug; 99(2), p. 386-8.
PMID: 16020433
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Pathophysiology of anthracycline- and radiation-associated cardiomyopathies: implications for screening and prevention.
Authors: Adams M.J. , Lipshultz S.E. .
Source: Pediatric Blood & Cancer, 2005-06-15 00:00:00.0; 44(7), p. 600-6.
PMID: 15856486
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Cardiac changes associated with growth hormone therapy among children treated with anthracyclines.
Authors: Lipshultz S.E. , Vlach S.A. , Lipsitz S.R. , Sallan S.E. , Schwartz M.L. , Colan S.D. .
Source: Pediatrics, 2005 Jun; 115(6), p. 1613-22.
PMID: 15930224
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Chronic progressive cardiac dysfunction years after doxorubicin therapy for childhood acute lymphoblastic leukemia.
Authors: Lipshultz S.E. , Lipsitz S.R. , Sallan S.E. , Dalton V.M. , Mone S.M. , Gelber R.D. , Colan S.D. .
Source: Journal Of Clinical Oncology : Official Journal Of The American Society Of Clinical Oncology, 2005-04-20 00:00:00.0; 23(12), p. 2629-36.
PMID: 15837978
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Cardiotoxicity of cancer chemotherapy: implications for children.
Authors: Simbre V.C. , Duffy S.A. , Dadlani G.H. , Miller T.L. , Lipshultz S.E. .
Source: Paediatric Drugs, 2005; 7(3), p. 187-202.
PMID: 15977964
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Cardiovascular status in long-term survivors of Hodgkin's disease treated with chest radiotherapy.
Authors: Adams M.J. , Lipsitz S.R. , Colan S.D. , Tarbell N.J. , Treves S.T. , Diller L. , Greenbaum N. , Mauch P. , Lipshultz S.E. .
Source: Journal Of Clinical Oncology : Official Journal Of The American Society Of Clinical Oncology, 2004-08-01 00:00:00.0; 22(15), p. 3139-48.
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The effect of dexrazoxane on myocardial injury in doxorubicin-treated children with acute lymphoblastic leukemia.
Authors: Lipshultz S.E. , Rifai N. , Dalton V.M. , Levy D.E. , Silverman L.B. , Lipsitz S.R. , Colan S.D. , Asselin B.L. , Barr R.D. , Clavell L.A. , et al. .
Source: The New England Journal Of Medicine, 2004-07-08 00:00:00.0; 351(2), p. 145-53.
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Effects of environmental exposures on the cardiovascular system: prenatal period through adolescence.
Authors: Mone S.M. , Gillman M.W. , Miller T.L. , Herman E.H. , Lipshultz S.E. .
Source: Pediatrics, 2004 Apr; 113(4 Suppl), p. 1058-69.
PMID: 15060200
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A clinic-based, comprehensive care model for studying late effects in long-term survivors of pediatric illnesses.
Authors: Hinkle A.S. , Proukou C. , French C.A. , Kozlowski A.M. , Constine L.S. , Lipsitz S.R. , Miller T.L. , Lipshultz S.E. .
Source: Pediatrics, 2004 Apr; 113(4 Suppl), p. 1141-5.
PMID: 15060211
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Radiation-associated cardiovascular disease: manifestations and management.
Authors: Adams M.J. , Lipshultz S.E. , Schwartz C. , Fajardo L.F. , Coen V. , Constine L.S. .
Source: Seminars In Radiation Oncology, 2003 Jul; 13(3), p. 346-56.
PMID: 12903022
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The incidence of pediatric cardiomyopathy in two regions of the United States.
Authors: Lipshultz S.E. , Sleeper L.A. , Towbin J.A. , Lowe A.M. , Orav E.J. , Cox G.F. , Lurie P.R. , McCoy K.L. , McDonald M.A. , Messere J.E. , et al. .
Source: The New England Journal Of Medicine, 2003-04-24 00:00:00.0; 348(17), p. 1647-55.
PMID: 12711739
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Cardiovascular risk factors, monitoring, and therapy for HIV-infected patients.
Authors: Lipshultz S.E. , Fisher S.D. , Lai W.W. , Miller T.L. .
Source: Aids (london, England), 2003 Apr; 17 Suppl 1, p. S96-122.
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Cardiac management by pediatricians versus pediatric cardiologists in an inpatient academic center.
Authors: Benun J. , Fisher S.D. , Orav E.J. , Schwartz M.L. , Exil V. , Messere C. , Lipshultz S.E. .
Source: American Heart Journal, 2003 Mar; 145(3), p. 424-9.
PMID: 12660664
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Long-term enalapril therapy for left ventricular dysfunction in doxorubicin-treated survivors of childhood cancer.
Authors: Lipshultz S.E. , Lipsitz S.R. , Sallan S.E. , Simbre V.C. , Shaikh S.L. , Mone S.M. , Gelber R.D. , Colan S.D. .
Source: Journal Of Clinical Oncology : Official Journal Of The American Society Of Clinical Oncology, 2002-12-01 00:00:00.0; 20(23), p. 4517-22.
PMID: 12454107
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Cardiovascular monitoring and therapy for HIV-infected patients.
Authors: Lipshultz S.E. , Fisher S.D. , Lai W.W. , Miller T.L. .
Source: Annals Of The New York Academy Of Sciences, 2001 Nov; 946, p. 236-73.
PMID: 11762991
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Epidemiology of anthracycline cardiotoxicity in children and adults.
Authors: Grenier M.A. , Lipshultz S.E. .
Source: Seminars In Oncology, 1998 Aug; 25(4 Suppl 10), p. 72-85.
PMID: 9768828
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