The St. Jude Lifetime Cohort

 描述（由申请人提供）：由于儿童癌症治疗的许多不良反应可能在幸存者达到成熟或更大年龄之前不会在临床上变得明显，因此从儿童期到成年期的整个生命周期的持续随访至关重要。美国有超过42万儿童癌症幸存者，迫切需要精确地表征非常晚期的癌症相关后遗症的发展和表现。2007年，圣裘德儿童研究医院发起了一项独特的临床（即，医学评价）队列，主要目的是建立对儿科癌症老年幸存者健康相关和生活质量结局的终身评价。参加圣裘德终身队列研究（SJLIFE）的资格是从诊断开始生存> 10年，并且达到> 18岁。截至2014年1月，3026名幸存者（90%的联系人和80%的合格人员）已成功完成一项或多项评估（通常涉及3-4天的门诊访视）提供了丰富的生物样本和结局数据库，用于更准确地描述不良生物医学和心理社会结局的患病率，以确定人口统计学，遗传学，治疗和心理社会/行为相关的负面健康结果的预测因素，为正在进行的健康监测建议提供信息，并指导健康保护干预措施。SJLIFE队列研究取得了重要的发现，包括确定儿童时期接受癌症治疗的成人中癌症治疗相关器官功能障碍的更准确患病率，调查健康监测的创新方法，以及识别新的和意外的晚期健康结局。然而，SJLIFE队列的当前样本量，其对成人参与者的限制（即，18岁以上的人），并且利用风险导向筛选的方法限制了重大新发现的潜力。因此，为了加强SJLIFE队列及其促进我们对儿童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队列的合格性，以包括临床特征良好的五年存活者队列，（2）对所有队列参与者进行统一的医学评估，（3）开发和测试创新的方法，以维持SJLIFE队列，（4）为未来的创新干预研究建立资源。在赠款的五年内，SJLIFE队列将扩大到包括大约9800名五年幸存者（即，晚期死亡率可评估），其中7825人预计存活并同意积极参与SJLIFE（即，可用于发病率和生活质量的纵向评估 成果）。SJLIFE队列将是独一无二的，它能够提供与癌症及其治疗相关的发病率的风险和病理生理学的新见解，这对于设计当代治疗方案和公共卫生举措以促进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.