The St. Jude Lifetime Cohort

摘要 因为儿童癌症治疗的许多副作用可能在临床上不明显， 幸存者达到成熟或年龄较大，从儿童期到老年， 成年，是必不可少的。随着美国儿童癌症幸存者人数接近50万， 是一个关键的需要，以准确地描述发展和表现非常晚的癌症相关的 后遗症2007年底，圣裘德儿童研究医院发起了一项独特的临床（即，医学上 评估）队列，主要目的是对健康相关和生活质量进行终身评估 儿科癌症的老年幸存者的结果。参与圣犹达终身队列研究的资格 （SJLIFE）最初定义为从诊断起生存>10年，并且达到>18岁的年龄。与 2015年7月，U 01队列基础设施补助金（U 01 CA 195547）的授予，队列的资格是 修改为包括>5年存活者。这一群体的参与率仍然很高，在7152人中占80.4%。 成功入组的联系幸存者，另有6.8%表示有兴趣 参与，但等待校园访问提供知情同意。截至2019年2月1日，总计 在SJLIFE上登记的是5753名幸存者和629名对照。自授予以来43个月的成就 U 01包括：新入组2657人，实施统一体检评估4096人 校内临床评估（反映了263，165项临床试验的表现），生物标本库， 94%的新参与者（43，240瓶），4422名幸存者的生殖系全基因组测序，22名活跃 利用队列研究，22项基于积极干预的试验，27项数据共享， 合作，并提交了78份手稿，其中69份已出版/正在印刷。在这次竞争激烈的续约中 我们建议在这些成功的基础上，通过各种活动来维持和加强SJLIFE 队列作为儿科癌症生存研究的独特和高产资源，并直接：（1） 通过建立创新的基于云的 数据共享平台，将SJLIFE队列的临床和基因组数据提供给全球 研究社区;（2）促进遗传贡献和病理生理学的调查， 儿童癌症幸存者中治疗相关的不良长期结局;（3）促进 建立经验证的风险预测工具组合，用于儿科临床管理 癌症患者从诊断到存活的时间。SJLIFE队列将继续保持独特性 在其能力，以提供新的见解的风险和病理生理学的发病率与癌症和 它的治疗，这是至关重要的当代治疗方案和公共卫生倡议的设计， 使幸存者能够获得预防和补救服务。

Abstract 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 the number of childhood cancer survivors in the U.S approaching 500,000, there is a critical need to accurately characterize the development and manifestation of very late cancer-related sequelae. In late 2007, St. Jude Children’s Research Hospital initiated a unique clinical (i.e., medically evaluated) cohort with the primary aim of undertaking lifelong evaluation of health-related and quality of life outcomes in aging adult survivors of pediatric cancer. Eligibility for participation in the St. Jude Lifetime Cohort (SJLIFE) was initially defined as survival >10 years from diagnosis, and attained age of >18 years. With the award of the U01 Cohort Infrastructure grant (U01 CA195547) in July 2015, eligibility for the cohort was modified to include >5 year survivors. Participation rates for the cohort remain high with 80.4% of the 7152 contacted survivors having been successfully enrolled and an additional 6.8% with expressed interest in participating but pending an on-campus visit to provide informed consent. As of February 1, 2019, total enrollment on SJLIFE is 5753 survivors and 629 controls. Accomplishments over the 43 months since award of the U01 include: 2657 new participants enrolled, implementation of uniform medical assessments with 4096 on-campus clinical evaluations (reflecting performance of 263,165 clinical tests), banking of biospecimens for 94% of new participants (43,240 vials), germline whole genome sequencing of 4422 survivors, 22 active investigator-initiated funded grants utilizing the cohort, 22 active intervention-based trials, 27 data sharing collaborations, and 78 manuscripts submitted with 69 published/in press. In this competitive renewal application we propose to build upon these successes through activities to maintain and enhance the SJLIFE cohort as a unique and highly productive resource for pediatric cancer survivorship research and to directly: (1) facilitate an accelerated rate of discovery in survivorship research by establishing an innovative cloud-based data sharing platform to make clinical and genomic data from the SJLIFE cohort available to the global research community; (2) facilitate the investigation of genetic contributions to and pathophysiology of treatment-associated adverse long-term outcomes among survivors of childhood cancer; and, (3) facilitate establishment of a portfolio of validated risk prediction tools for clinical use in the management of pediatric cancer patients from the time of diagnosis through survivorship. The SJLIFE cohort will continue to 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 enable survivor access to preventive and remedial services.