) 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.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
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Special Emphasis Panel (ZCA1-RLB-X (M2))
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Aziz, Noreen M
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University of Rochester
Schools of Dentistry
United States
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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
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