Novel Markers of Anthracycline-induced Myocardial Damage

描述(由申请人提供)：在治疗早期乳腺癌和儿童癌症时，蒽环类药物是化疗方案的关键成分。尽管在临床实践中经常采用各种策略来降低与蒽环类药物相关的心脏损害的风险，但今天接受蒽环类药物治疗的人仍将面临心脏损害的风险，这可能会增加与正常年龄相关的女性心脏病的发病率，或者在儿童时期接受蒽环类药物治疗后导致年轻人的心脏问题。问题是，目前还没有有效的手段来检测与蒽环类药物相关的早期心肌损害，并预测谁随后有可能出现临床上重大的心脏问题。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，被认为过于不敏感，无法发现早期心肌损害；同样，用于检测早期心肌损害的血液标记物，如肌钙蛋白和钠尿肽，结果相互矛盾，在实践中不经常使用。开发一种新的方法来检测早期心肌损伤是这项试验的目标。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)成像和内皮祖细胞(EPC)，在CMR成像中，心肌组织直接可视化，内皮祖细胞(EPC)在心脏损伤后增加。将它们结合起来确定它们是否可以作为与蒽环类药物相关的早期心肌损伤的标志物。作为合作组临床试验的一部分，这项试验的特定目的是前瞻性地量化30名乳腺癌患者和30名接受蒽环类药物治疗的儿童癌症患者的左心室射血功能(LVEF)的变化，并通过CMR评估心肌组织损伤，并测定治疗前、一个周期后以及完成蒽环类药物治疗后4-6周的EPC、肌钙蛋白/BNP。第二个目的是比较蒽环类药物对成人和儿童心脏的LVEF、心肌组织损伤和内皮祖细胞的影响。拥有一种可靠的方法来检测早期与蒽环类药物相关的心肌损害将是一项重大的进步，因为它可能有助于确定谁是随后与蒽环类药物相关的心肌损害的危险因素，促进对那些有风险的人的干预试验，并最终降低长期存活者中迟发性心脏损害的发病率。 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方法来检测与蒽环类药物相关的心脏损害。拥有一种可靠和早期检测与蒽环类药物相关的心脏损伤的方法是一项重大进步，因为它可能有助于确定哪些患者存在随后与蒽环类药物相关的心脏损伤的风险，促进对有风险的患者进行干预试验，并最终降低长期癌症幸存者中迟发性心脏问题的发病率。

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.