Novel Markers of Anthracycline-induced Myocardial Damage

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DESCRIPTION (provided by applicant): Anthracyclines are key components of chemotherapy regimens in the treatment of early stage breast and pediatric cancers with curative intent. Despite various strategies for reducing the risk of anthracycline-related cardiac damage routinely employed in clinical practice, individuals who receive anthracyclines today will continue to be at risk for cardiac damage that possibly adds to the increasing incidence of cardiac disease in women related to normal aging, or cause cardiac problems in young adults after they received anthracyclines as children. The problem is that there are no effective means of detecting early anthracycline-related myocardial damage and predicting who is at subsequent risk for developing clinically significant cardiac problems. Echocardiography and radionuclide gated scans are standard tests for cardiac monitoring that are regarded as too insensitive to detect early myocardial damage; likewise the results of blood markers to detect early myocardial damage, such as troponins and natriuretic peptides, are conflicting and not routinely used in practice. The development of a novel approach to detect early myocardial damage is the goal of this trial. This prospective feasibility trial combines two relatively recent applications in cardiology: cardiac magnetic resonance (CMR) imaging, in which the myocardial tissue is directly visualized and endothelial progenitor cells (EPCs), which increase in response to cardiac injury. They are combined to determine if they serve as markers of early anthracycline- related myocardial damage. The trial specific aims are to prospectively quantitate changes in left ventricular ejection function (LVEF) and assess myocardial tissue damage by CMR and measure EPCs, troponins/BNP at pretreatment, after one cycle of anthracycline therapy, 4-6 weeks after completing anthracycline treatment in 30 breast cancer and 30 pediatric cancer patients receiving anthracyclines as part of Cooperative Group Clinical Trials. The second aim is to compare the effects of anthracyclines on LVEF, myocardial tissue damage and EPCs in the adult and pediatric heart. Having a reliable way to detect early anthracycline-related myocardial damage would represent a major advance in that it may facilitate defining who is at risk for subsequent anthracycline-related myocardial damage, facilitate intervention trials for those at risk, and ultimately reduce morbidity of late-onset cardiac damage in long-term survivors. PUBLIC HEALTH RELEVANCE: This prospective feasibility trial is designed to develop a novel test to detect anthracycline-related heart damage. Having a reliable and early method of detecting anthracycline-related heart damage represents a major advance in that it may facilitate defining which patients are at risk for subsequent anthracycline-related heart damage, facilitate intervention trials for those at risk, and ultimately reduce morbidity of late-onset heart problems in long-term cancer survivors.