Longitudinal Cardiotoxicity in Adult Survivors Childhood Cancer

描述（由申请人提供）：需要对老年儿童癌症幸存者进行全面、客观的心脏评估，以确定：1)成年期心功能障碍的患病率和发展轨迹；2)早期发现迟发性心功能障碍的理想筛查工具。80%被诊断患有儿童恶性肿瘤的儿童将成为癌症的5年幸存者，其中50%以上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的发生（暴露后1年）之间有明确的关联。然而，大多数报道儿童癌症幸存者中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到成年，心脏功能的轨迹随着幸存者年龄的增长没有充分的记录。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晚期检测到毒性。需要新的超声心动图方法进行早期检测。我们提出了一项横断面研究，将一种新的局部心肌功能障碍超声心动图测量（张力）与传统超声心动图（射血分数）进行比较，以评估810名接受蒽环类化疗和/或心脏定向RT治疗的儿童癌症成人和484名对照者的心脏毒性。我们假设，异常应变测量将更强烈地与降低功能容量（VO2 max）比标准测量的射血分数。在本研究前10年进行超声心动图评估的成人亚群（n=170）将被评估成人心功能的纵向轨迹。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，该应用将验证早期检测心脏毒性的新模式（心肌应变）。到目前为止，这样的研究还没有完成，因为在儿童癌症机构长期保留和评估大量成年幸存者队列时遇到了许多障碍。圣犹达终身队列的独特资源允许进行这样的研究，这是一个由机构资助的队列，有1000 000名成年幸存者进行终身随访。结果将为未来的研究提供基础，使用早期检测（菌株）来针对人群进行干预方法，以预防蒽环类药物/ rt暴露的儿童癌症幸存者的心力衰竭。

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.