Novel Markers of Anthracycline-induced Myocardial Damage

描述（由申请方提供）：蒽环类药物是治疗早期乳腺癌和儿童癌症的化疗方案的关键组成部分。尽管在临床实践中常规采用各种策略来降低蒽环类药物相关心脏损伤的风险，但今天接受蒽环类药物的个体仍将面临心脏损伤的风险，这可能增加与正常衰老相关的女性心脏病发病率的增加，或在年轻人中引起心脏问题。问题是没有有效的方法来检测早期蒽环类药物相关的心肌损伤，并预测谁是在随后的风险发展临床上显着的心脏问题。超声心动图和放射性核素门控扫描是心脏监测的标准测试，被认为对检测早期心肌损伤太不敏感;同样，检测早期心肌损伤的血液标志物（如肌钙蛋白和利钠肽）的结果相互矛盾，在实践中不常使用。本试验的目的是开发一种新的方法来检测早期心肌损伤。这项前瞻性可行性试验结合了心脏病学中两个相对较新的应用：心脏磁共振（CMR）成像，其中心肌组织直接可视化，内皮祖细胞（EPCs），其对心脏损伤的反应增加。将它们结合起来以确定它们是否作为早期蒽环类药物相关心肌损伤的标志物。该试验的具体目标是前瞻性定量左心室射血功能（LVEF）的变化，并通过CMR评估心肌组织损伤，并在治疗前、一个周期的蒽环类药物治疗后、完成蒽环类药物治疗后4-6周测量EPCs、肌钙蛋白/BNP。作为合作组临床试验的一部分，接受蒽环类药物治疗的30名乳腺癌和30名儿科癌症患者。第二个目的是比较蒽环类药物对成人和儿童心脏LVEF、心肌组织损伤和EPCs的影响。有一个可靠的方法来检测早期蒽环类药物相关的心肌损伤将是一个重大的进步，因为它可以帮助确定谁是在随后的蒽环类药物相关的心肌损伤的风险，促进对那些有风险的干预试验，并最终降低发病率迟发性心脏损伤的长期幸存者。 公共卫生相关性：这项前瞻性可行性试验旨在开发一种新的检测蒽环类药物相关心脏损害的试验。有一个可靠的和早期的方法检测蒽环类药物相关的心脏损害代表了一个重大的进步，因为它可能有助于确定哪些患者有随后的蒽环类药物相关的心脏损害的风险，促进对那些有风险的干预试验，并最终降低发病率迟发性心脏问题的长期癌症幸存者。

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.