The St. Jude Lifetime Cohort

 描述(由申请人提供)：由于儿童癌症治疗的许多副作用可能在幸存者达到成熟或老年之前不会在临床上显现，因此从儿童到成年的整个生命周期的持续跟踪是必不可少的。美国有超过42万名儿童癌症幸存者，迫切需要准确地描述与癌症相关的超晚期后遗症的发展和表现。2007年，圣裘德儿童研究医院启动了一个独特的临床(即医学评估)队列，主要目的是建立对儿科癌症老年成年幸存者健康相关和生活质量的终身评估。参加圣犹大终身队列(SJLIFE)的资格是从确诊之日起存活10年，并达到18岁。截至2014年1月，3026名幸存者(90%的接触者和80%的符合条件者)成功地完成了一项或多项评估(通常涉及3-4天的门诊访问)，提供了丰富的生物标本和结果数据存储库，用于更准确地描述不利的生物医学和心理社会结果的流行程度，确定与人口、遗传、治疗和心理/行为相关的负面健康结果预测因素，为正在进行的健康监测建议提供信息，并指导健康维护干预措施。SJLIFE队列已经产生了重要的发现，包括确定在儿童时期接受癌症治疗的成年人中与癌症治疗相关的器官功能障碍的更准确的患病率，调查创新的健康监测方法，以及确定新的和意想不到的晚期健康结果。然而，SJLIFE队列目前的样本量，其对成年参与者(即18岁以上)的限制，以及利用风险导向筛查的方法对重大新发现的可能性施加了限制。因此，为了提高SJLIFE队列及其推进我们对儿童时期癌症诊断及其相关治疗暴露如何影响长期健康的理解的能力，我们建议：(1)扩大SJLIFE队列的资格，以包括具有良好临床特征的五年幸存者队列，(2)在所有队列参与者中进行统一的医学评估，(3)开发和测试维持SJLIFE队列的创新方法，以及(4)为未来以干预为基础的创新研究建立资源。在赠款的五年期间，SJLIFE队列将扩大到包括大约9800名五年幸存者(即，可评估晚期死亡率)，其中7825人预计仍活着，并将同意积极参加SJLIFE(即，可用于对发病率和生活质量的纵向评估 结果)。SJLIFE队列的独特之处在于，它能够对与癌症及其治疗相关的发病率的风险和病理生理学提供新的见解，这对于设计当代治疗方案和公共卫生倡议，以方便幸存者获得预防和补救服务至关重要。

 DESCRIPTION (provided by applicant): Because many adverse effects of treatment for childhood cancer may not become clinically apparent until the survivor attains maturity or older ages, continued follow-up across the lifespan, from childhood through adulthood, is essential. With more than 420,000 childhood cancer survivors in the U.S., there is a critical need to accurately characterize the development and manifestation of very late cancer-related sequel. In 2007, St. Jude Children's Research Hospital initiated a unique clinical (i.e., medically evaluated) cohort with the primary aim of establishing lifelong evaluation of health-related and quality of life outcomes in aging adult survivors of pediatric cancer. Eligibility for participatio in the St. Jude Lifetime Cohort (SJLIFE) is survival > 10 years from diagnosis, and attained age of > 18 years. As of January, 2014, 3026 survivors (90 percent of those contacted and 80 percent of those eligible) have successfully completed one or more evaluations (typically involving a 3-4 day outpatient visit) providing a rich repository of biospecimens and outcomes data that has been used to more accurately characterize the prevalence of adverse biomedical and psychosocial outcomes, to identify demographic, genetic, treatment and psychosocial/behavioral-related predictors of negative health outcome, to inform ongoing health surveillance recommendations, and to guide health preserving interventions. The SJLIFE cohort has yielded important findings including determination of a more accurate prevalence of cancer treatment-related organ dysfunction among adults treated for cancer during childhood, investigation of innovative methods of health surveillance, and identification of novel and unexpected late health outcomes. However, the current sample size of the SJLIFE cohort, its restriction to adult participants (i.e., those 18+ years), and methods utilizing risk-directed screening imposes limits on the potential for significant new discovery. Thus, to enhance the SJLIFE cohort and its ability to advance our understanding about how the diagnosis of cancer during childhood and its associated therapeutic exposures impact long-term health, we propose to: (1) expand eligibility of the SJLIFE cohort to include a clinically well-characterized cohort o five- year survivors, (2) undertake uniform medical assessments in all cohort participants, (3) develop and test innovative methodologies to maintain the SJLIFE cohort, and (4) establish a resource for future innovative intervention-based research. Over the five-years of the grant, the SJLIFE cohort will be expanded to include approximately 9800 five-year survivors (i.e., evaluable for late mortality), of whom 7825 are projected to be alive and will agree to actively participate in SJLIFE (i.e., available for longitudinal assessment of morbidity and quality of life outcomes). The SJLIFE cohort will be unique in its ability to provide new insights into the risks and pathophysiology of morbidity associated with cancer and its therapy, which is critical to the design of contemporary treatment protocols and public health initiatives to facilitate survivor access to preventive and remedial services.