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

描述（由申请人提供）：儿童癌症的治疗是20世纪下半叶医学取得的巨大成功之一，因为美国每640名年轻人中就有1人是儿童癌症的幸存者。随着受影响的人年寿命的增加，心血管（CV）疾病现在是儿童癌症幸存者非癌症死亡的主要原因。蒽环类化疗是这种心血管发病率和死亡率的主要风险。缺乏心血管风险的功能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志物的理想选择。我们的项目是一项观察性临床试验，采用横断面和纵向设计，评估CMR在检测蒽环类药物治疗后心脏损伤亚临床标志物中的应用。我们计划使用CMR来测量青少年/年轻成年儿童癌症治疗后幸存者的主动脉僵硬度和心肌壁应变，并与无癌症的对照组进行比较。此外，我们将评估CMR检测和跟踪新诊断的接受蒽环类药物化疗的青少年患者主动脉功能变化的能力。在两个儿童癌症项目中进行的试验将导致：新的亚临床蒽环类药物心脏毒性的CMR生物标志物，对病理生理学中先前未探索的主动脉僵硬和心肌应变概念的理解，以及建立一个年轻的蒽环类药物暴露队列，他们可以接受CMR随访，用于未来的技术研究和靶向干预。CMR的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，以减轻这类癌症人群的心血管疾病负担。

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.