Longitudinal Cardiotoxicity in Adult Survivors Childhood Cancer

成年幸存者儿童癌症的纵向心脏毒性

• 批准号: 8777088
• 负责人: Gregory Armstrong
• 金额: $ 60.05万
• 依托单位: ST. JUDE CHILDREN'S RESEARCH HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-02-27 至 2015-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8777088
• 关键词: Activities of Daily Living; Address; Adult; Aftercare; Age; Age-Years; Aging; Anthracyclines; Cardiac; Cardiac Death; Cardiotoxicity; Cardiovascular system; Child; Childhood; Clinical; Cross-Sectional Studies; Data; Detection; Development; Diagnosis; Dose; Drug Formulations; EFRAC; Early Diagnosis; Echocardiography; Evaluation; Exercise; Failure; Foundations; Functional disorder; Funding; Future; Guidelines; Heart failure; Hospitalization; Institution; Intervention; Intervention Trial; Knowledge; Lead; Left; Life; Literature; Longitudinal Studies; Malignant Childhood Neoplasm; Malignant Neoplasms; Measures; Methods; Modality; Myocardial; Myocardial dysfunction; Natural History; Outcome; Outcomes Research; Population; Population Intervention; Prevalence; Prevention; Prevention approach; Publishing; Radiation therapy; Recommendation; Reporting; Resources; Risk; Saint Jude Children' s Research Hospital; Survivors; Testing; Time; Toxic effect; Validation; Ventricular; aging population; base; cardiovascular risk factor; chemotherapeutic agent; chemotherapy; childhood cancer survivor; clinical care; cohort; emerging adult; follow-up; improved; instrument; novel; prevent; screening; standard measure

DESCRIPTION (provided by applicant): There is a need for comprehensive, objective cardiac evaluation of aging adult survivors of childhood cancer to determine: 1) the prevalence and trajectory of cardiac dysfunction in adulthood, and 2) ideal screening instruments for early detection of late-onset cardiac dysfunction. Eighty percent of children diagnosed with a pediatric malignancy will become 5-year survivors of their cancer, and more than 50% of these survivors received treatment with the anthracycline class of chemotherapeutic agents and/or cardiac-directed radiation therapy (RT). There is a well established association between anthracycline and/or cardiac RT exposure and the development of late-onset cardiotoxicity (>1 year from exposure). However, most published literature reporting this outcome among childhood cancer survivors is limited to clinical cohorts followed for less than 15 years post treatment. As pediatric institutions have been unable to follow childhood cancer survivors into adulthood, the trajectory of cardiac function has not been adequately documented as survivors age. Furthermore, the current standard measure of cardiotoxicity (ejection fraction by echocardiogram) likely detects toxicity late in the natural history of the progression to left ventricular failure. Novel echocardiographic methods for early detection are needed. We propose a cross-sectional study that will compare a novel echocardiographic measure of regional myocardial dysfunction (strain), to traditional echocardiography (ejection fraction) for evaluation of cardiac toxicity in 810 adults treated with anthracycline chemotherapy and/or cardiac-directed RT for childhood cancer and 484 controls. We hypothesize that abnormal strain measures will be more strongly associated with reduced functional capacity (VO2 max) than the standard measure of ejection fraction. A sub-population (n=170) of adults with previous echocardiographic evaluation 10 years prior to this study will be assessed for longitudinal trajectory of cardiac function in adulthood. Longitudinal assessment of this population will provide evidence for the trajectory and rate of cardiac decline in early adulthood, thus providing additional evidence for screening recommendations in this population. Furthermore, this application will validate a novel modality (myocardial strain) for early detection of cardiac toxicity. To date, such a study has not been done because of numerous barriers encountered in long-term retention and assessment of a large cohort of adult survivors by a pediatric cancer institution. The unique resource of the St. Jude Lifetime Cohort, an institutionally funded cohort of >4,000 adult survivors with lifetime follow-up, allows for such a study. Results will provide a foundation for future research using early detection (strain) to target a population for intervention approaches that may prevent heart failure in anthracycline/RT-exposed childhood cancer survivors.

描述（由申请人提供）：需要对儿童癌症的成年成年幸存者进行全面，客观的心脏评估，以确定：1）成年期心脏功能障碍的患病率和轨迹，以及2）理想的筛查工具，用于早期发现晚期心脏功能障碍。被诊断出患有儿科恶性肿瘤的儿童中有80％将成为其癌症的5年幸存者，其中超过50％的幸存者接受了对邻苯二酚类化学治疗剂和/或心脏指导放射治疗（RT）的治疗。蒽环类和/或心脏RT暴露与晚期心脏毒性的发展之间存在良好的关联（暴露于1年> 1年）。但是，大多数发表的文献报道了儿童癌症幸存者中这种结果的限制，仅限于临床人群，在治疗后不到15年。由于小儿机构无法跟踪儿童癌症幸存者成年，因此心脏功能的轨迹尚未被充分记录为幸存者年龄。此外，当前的心脏毒性标准度量（超声心动图的射血分数）可能在左心室衰竭的自然史中检测到毒性。需要新的超声心动图方法，以提早检测。我们提出了一项横断面研究，该研究将比较一种新型的区域心肌功能障碍（菌株）的超声心动图测量，即传统的超声心动图（射血分数），以评估810名接受原毒素化疗和/或Cardiac-Diaciac-Diaciac-Diaciac-Diackiac consections the Childed Rt for Child of Child Hoodhood癌症和484.对照组的心脏毒性。我们假设异常应变度量与降低的功能能力（VO2 MAX）更密切相关，而不是射血分数的标准度量。在本研究前10年，将评估具有先前超声心动图评估的成年人的亚人群（n = 170），将评估成年后心脏功能的纵向轨迹。对该人群的纵向评估将为成年初期的心脏下降速度和心脏下降率提供证据，从而为该人群提供了筛查建议的其他证据。此外，该应用将验证一种新型的方式（心肌菌株），以早日检测心脏毒性。迄今为止，由于小儿癌症机构在长期保留和评估大量成人幸存者的长期保留和评估中遇到了许多障碍，因此还没有进行此类研究。圣裘德终生队列的独特资源是由机构资助的人群组成的> 4,000名成人幸存者，并进行了终生跟进，可以进行这项研究。结果将为未来研究的基础，使用早期检测（应变）针对人群采用干预方法，以防止蒽环类/RT暴露于儿童癌症幸存者的心力衰竭。