Resonance Imaging Trial for Heart bioMarkers (RITHM) in AYA Cancer Survivors

描述(申请人提供)：儿童癌症的治疗是20世纪后半叶医学上取得的巨大成功之一，因为在美国，每640名年轻人中就有一人是儿童癌症的幸存者。随着人类寿命的增加，心血管疾病现在是儿童癌症幸存者非癌症死亡的主要原因。蒽环类药物化疗是这种心血管疾病发病率和死亡率的主要风险。缺乏心血管风险的功能性标记物限制了心脏保护和二级预防策略。心脏磁共振成像(CMR)提供了主动脉和心脏功能的精确测量，使其成为在较小人群中建立亚临床疾病替代标记物的理想选择。我们的项目是一项横断面和纵向设计的观察性临床试验，旨在评价CMR在检测蒽环类药物治疗后心脏损伤的亚临床标志物方面的应用。我们计划使用CMR来测量青少年/年轻成年癌症患者停止治疗后的主动脉僵硬和心肌壁应变，并与未接受癌症治疗的对照组进行比较。此外，我们还将评估CMR检测和跟踪接受蒽环类药物化疗的新诊断青少年患者的主动脉功能变化的能力。在两个儿童癌症项目中的试验将导致：新的蒽环类药物心脏亚临床毒性的CMR生物标记物~理解以前未探索过的病理生理学中主动脉僵硬和心肌应变的概念~以及建立一个年轻的暴露于蒽环类药物的队列，他们可以通过CMR进行后续的技术研究和有针对性的干预。CMR的这一快速试验将有助于开发所需的替代终点，以便及时、有针对性地进行药物或行为干预，以减轻癌症人群中心血管疾病的负担。

DESCRIPTION (provided by applicant): Treatment of childhood cancer has been one of the resounding successes of medicine in the last half of the 20th century, as 1 in 640 young adults in the US is a survivor of childhood cancer. With increased person-years of life impacted, cardiovascular (CV) disease is now the leading cause of non-cancer death in childhood cancer survivors. Anthracycline chemotherapy is a major risk for this CV morbidity and mortality. A lack of functional markers of CV risk has limited cardioprotection and secondary prevention strategies. Cardiac magnetic resonance imaging (CMR) provides precise measures of aortic and cardiac function, making it ideal for establishing surrogate markers of subclinical disease in smaller populations. Our project is an observational clinical trial with a cross-sectional and longitudinal design to evaluate the application of CMR in detecting subclinical markers of cardiac injury after anthracycline therapy. We plan to use CMR to measure aortic stiffness and myocardial wall strain in adolescent/young adult survivors of childhood cancer off therapy in comparison to a control group without cancer. In addition we will evaluate the ability of CMR to detect and follow changes in aortic function in newly diagnosed adolescent patients receiving anthracycline chemotherapy. The trial at two childhood cancer programs will lead to: novel CMR biomarkers of subclinical anthracycline cardiotoxicity~ an understanding of previously unexplored concepts of aortic stiffness and myocardial strain in the pathophysiology~ and the establishment of a young anthracycline exposed cohort who can be followed with CMR for future studies of the technology and targeted interventions. This Quick Trial of CMR will facilitat development of needed surrogate endpoints for timely, targeted pharmacologic or behavioral interventions to alleviate the burden of CV disease in this cancer population.