) 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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA079060-05
Application #
6513184
Study Section
Special Emphasis Panel (ZCA1-RLB-X (M2))
Program Officer
Aziz, Noreen M
Project Start
1998-09-02
Project End
2004-12-31
Budget Start
2002-08-01
Budget End
2004-12-31
Support Year
5
Fiscal Year
2002
Total Cost
$337,486
Indirect Cost
Name
University of Rochester
Department
Pediatrics
Type
Schools of Dentistry
DUNS #
208469486
City
Rochester
State
NY
Country
United States
Zip Code
14627
Lipshultz, Steven E; Anderson, Lynn M; Miller, Tracie L et al. (2016) Impaired mitochondrial function is abrogated by dexrazoxane in doxorubicin-treated childhood acute lymphoblastic leukemia survivors. Cancer 122:946-53
Lipshultz, Steven E; Lipsitz, Stuart R; Kutok, Jeffery L et al. (2013) Impact of hemochromatosis gene mutations on cardiac status in doxorubicin-treated survivors of childhood high-risk leukemia. Cancer 119:3555-62
Landy, David C; Lipsitz, Stuart R; Kurtz, Joy M et al. (2013) 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. Nutr Cancer 65:547-55
Landy, David C; Miller, Tracie L; Lipsitz, Stuart R et al. (2013) 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. Pediatr Cardiol 34:826-34
Miller, Angela M; Lopez-Mitnik, Gabriela; Somarriba, Gabriel et al. (2013) Exercise capacity in long-term survivors of pediatric cancer: an analysis from the Cardiac Risk Factors in Childhood Cancer Survivors Study. Pediatr Blood Cancer 60:663-8
Landy, David C; Miller, Tracie L; Lopez-Mitnik, Gabriela et al. (2012) 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. Am Heart J 163:295-301.e2
Harake, Danielle; Franco, Vivian I; Henkel, Jacqueline M et al. (2012) Cardiotoxicity in childhood cancer survivors: strategies for prevention and management. Future Cardiol 8:647-70
Goldberg, John M; Scully, Rebecca E; Sallan, Stephen E et al. (2012) Cardiac failure 30 years after treatment containing anthracycline for childhood acute lymphoblastic leukemia. J Pediatr Hematol Oncol 34:395-7
Miller, Tracie L; Lipsitz, Stuart R; Lopez-Mitnik, Gabriela et al. (2010) Characteristics and determinants of adiposity in pediatric cancer survivors. Cancer Epidemiol Biomarkers Prev 19:2013-22
Kinnamon, Daniel D; Lipsitz, Stuart R; Ludwig, David A et al. (2010) An improved estimator for the hydration of fat-free mass from in vivo measurements subject to additive technical errors. Physiol Meas 31:497-512

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