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: 8434145
• 负责人: Gregory Armstrong
• 金额: $ 56.42万
• 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 2016-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8434145
• 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; 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）：需要对儿童癌症的老年幸存者进行全面、客观的心脏评估，以确定：1) 成年期心功能不全的患病率和轨迹，以及 2) 用于早期发现晚期心功能不全的理想筛查工具。 - 出现心功能不全。 80% 被诊断患有儿科恶性肿瘤的儿童将成为癌症 5 年幸存者，其中超过 50% 的幸存者接受了蒽环类化疗药物和/或心脏定向放射治疗 (RT) 的治疗。蒽环类药物和/或心脏 RT 暴露与迟发性心脏毒性（暴露后 > 1 年）的发生之间存在明确的关联。然而，大多数报道儿童癌症幸存者这一结果的已发表文献仅限于治疗后随访不到 15 年的临床队列。由于儿科机构无法跟踪儿童癌症幸存者直至成年，因此心脏功能的轨迹尚未充分记录为幸存者的年龄。此外，目前心脏毒性的标准测量（超声心动图射血分数）可能在左心室衰竭进展的自然史后期检测到毒性。需要用于早期检测的新型超声心动图方法。我们提出了一项横断面研究，将对 810 名接受蒽环类化疗和/或儿童心脏定向放疗的成人进行心脏毒性评估，将局部心肌功能障碍（应变）的新型超声心动图测量方法与传统超声心动图（射血分数）进行比较癌症和对照484。我们假设，与射血分数的标准测量相比，异常应变测量与功能能力（最大摄氧量）降低的相关性更强。将评估在本研究 10 年前接受过超声心动图评估的成年人亚群 (n=170) 成年后心功能的纵向轨迹。对该人群的纵向评估将为成年早期心脏衰退的轨迹和速率提供证据，从而为该人群的筛查建议提供额外的证据。此外，该应用将验证一种用于早期检测心脏毒性的新方式（心肌应变）。迄今为止，由于儿科癌症机构在长期保留和评估大量成年幸存者方面遇到了许多障碍，因此尚未进行此类研究。圣裘德终生队列是一个由机构资助的队列，由超过 4,000 名成年幸存者组成并进行终生随访，其独特的资源允许进行此类研究。结果将为未来的研究奠定基础，利用早期检测（菌株）针对人群采取干预措施，以预防接受蒽环类药物/放疗的儿童癌症幸存者的心力衰竭。