Early Imaging Detection of CV Injury after Cancer

描述（由申请方提供）：导致心肌梗死（MI）、心源性死亡、卒中和充血性心力衰竭（CHF）的心血管（CV）损伤是基于蒽环类药物的化疗用于辅助治疗乳腺癌、白血病和淋巴瘤的主要障碍。对于需要这种治疗的儿童或成人，没有临床上可接受的替代方案。组装的学术-工业团队将开发和优化一个具有成本效益的，自动化的，可重复的硬件/软件平台，用于获取，分析和报告亚临床和临床CV损伤，识别这种损伤的机制并预测CV事件风险。这一重要信息可用于临床前治疗 其他高CV风险人群使用时，可降低CV不良事件发生率的方案。这项旨在验证这些技术的精心设计和有效性的关键临床研究将： “收集蒽环类药物暴露前以及暴露后3和24小时的人内纵向结果 暴露后3个月，以确定短期结果是否预测长期亚临床 预示着不良预后的疾病~ “确定这种新平台在10至80岁的儿童和成人中的疗效~ “导出人群（年龄、性别、种族和心脏风险因素匹配）预测指标 与6,000名没有已知冠状动脉的人相比， 多种族动脉粥样硬化研究（梅萨） “标准化自动化平台，使世界各地的医疗中心， 很少有MRI专业知识来可靠和可重复地执行研究。 该平台创新基于强大的NCI资助的初步数据，为以前未解决的临床问题提供了一个非常重要的成本效益解决方案，该解决方案可无创地定义早期CV风险，并实现靶向治疗干预，以大幅降低这些风险。减少癌症幸存者的CV事件将降低以下患者的总体发病率 提高癌症相关生存率。 公共卫生相关性：我们将翻译一个磁共振成像（MRI）的解决方案被忽视的主要问题，没有有效的临床能力来检测，治疗和监测继发于癌症化疗与蒽环类药物的早期亚临床心血管损伤的风险。组装的学术-工业合作伙伴团队将开发和优化MRI硬件和软件平台，以获取，分析和报告心脏和主动脉功能的多种测量，识别损伤机制，并预测成人和儿童个体的心血管事件风险，为全球已安装的临床MR扫描仪提供高时效性，低操作员依赖性，可重现性和成本效益升级。这种用于癌症研究的技术和方法解决方案（PAR-10-169）将建立一种创新的方法来检测早期心血管疾病的风险，从而及时制定新的临床前治疗指南，旨在减少潜在的心血管事件，从而提高癌症治疗患者的总生存率。

DESCRIPTION (provided by applicant): Cardiovascular (CV) injury leading to myocardial infarction (MI), cardiac death, stroke, and congestive heart failure (CHF) is a major impediment to the curative use of anthracycline-based chemotherapy for the treatment of adjuvant breast cancer, leukemia, and lymphoma. No clinically acceptable alternatives exist for children or adults that require this therapy. The assembled academic-industrial team will develop and optimize a cost-effective, automated, reproducible hardware/software platform that acquires, analyzes, and reports subclinical and clinical CV injury, identifies the mechanisms of this injury and forecasts CV event risks. This important information can be utilized for preclinical treatment protocols that, when administered to other high CV risk populations, reduce the rates of adverse CV events. This well-designed and powered pivotal clinical study to validate these technologies will: " Collect within person longitudinal results before anthracycline exposure and at 3 and 24 months after exposure to determine if short-term results predict long-term subclinical disease that portends an adverse prognosis~ " Determine the efficacy of this new platform in children and adults aged 10 to 80 years~ " Derive population (age, gender, race, and cardiac risk factor-matched) predictive metrics for the platform compared against 6,000 individuals without known coronary artery disease from the existing Multi-Ethnic Study of Atherosclerosis (MESA)~ " Standardize the automated platform to enable medical centers throughout the world with little MRI expertise to reliably and reproducibly perform the studies. This platform innovation is based on strong NCI funded preliminary data and provides a highly significant cost effective solution for a previously unsolved clinical problem that noninvasively defines early CV risk and enables targeted therapeutic interventions to dramatically reduce these risks. Reducing CV events in cancer survivors will reduce overall morbidity in patients with cancer and improve cancer-related survival. PUBLIC HEALTH RELEVANCE: We will translate a magnetic resonance imaging (MRI) solution to the neglected major problem of no effective clinical capacity to detect, treat, and monitor the risks of early subclinical cardiovascular injury secondary to cancer chemotherapy with anthracyclines. The assembled academic-industrial partner team will develop and optimize a MRI hardware and software platform to acquire, analyze, and report multiple measures of cardiac and aortic function, identify mechanisms of injury, and forecast cardiovascular event risks for individual adults and children in a highly time efficient, low operator dependent, reproducible, and cost effective upgrade for installed clinical MR scanners worldwide. This technical and methodologic solution for cancer investigations (PAR-10-169) will establish an innovative methodology to detect the risk for early cardiovascular disease, and thereby enable timely new preclinical therapy guidelines designed to reduce potential cardiovascular events and thus improve the overall survival in those treated for cancer.