Long-term Treatment Related CNS Injury in Survivors of Childhood Cancer

儿童癌症幸存者长期治疗相关的中枢神经系统损伤

基本信息

批准号：
8065365
负责人：
Gregory Armstrong
金额：
$ 17.87万
依托单位：
ST. JUDE CHILDREN'S RESEARCH HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-07-01 至 2012-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8065365
关键词：
Acute Lymphocytic Leukemia Adult Aftercare Age Aging Alzheimer&apos s Disease Arterial Occlusive Diseases Brain Cephalic Child Childhood Childhood Acute Lymphocytic Leukemia Chronic Cognition Cognitive Cognitive deficits Cranial Irradiation Cross-Sectional Studies Data Dementia Development Diagnosis Diffusion Magnetic Resonance Imaging Dose Drug Formulations Evaluation Exposure to Functional Magnetic Resonance Imaging Future Gender Guidelines Hippocampus (Brain)Imaging Techniques Impaired cognition Injury Intervention Investigation Life Magnetic Resonance Imaging Malignant Childhood Neoplasm Malignant Neoplasms Medical Memory Memory Loss Memory impairment Nervous system structure Neuraxis Neurocognitive Neurocognitive Deficit Outcome Outcomes Research Parietal Parietal Lobe Pattern Population Prevalence Protocols documentation Quality of life Radiation Radiation therapy Recruitment Activity Reporting Research Risk Saint Jude Children&apos s Research Hospital Screening procedure Social Functioning Steno Stroke Structure Survivors Testing Time Vascular Diseases cancer therapy central nervous system injury chemotherapy childhood cancer survivor clinical care cognitive function cohort early childhood follow-up frontal lobe long term memory memory recall neuroimaging prevent public health relevance treatment duration white matter

项目摘要

DESCRIPTION (provided by applicant): Children who received cranial radiation for treatment of childhood cancer are at significant risk for long- term central nervous system (CNS) injury. Our preliminary data suggests long-term memory (delayed recall) is significantly impacted in these adult survivors similar to patterns seen in aging adults with Alzheimer's disease, raising concern that this population may be at risk for early dementia. Furthermore, it is established that cognitive deficits increase with time after exposure to CNS radiation, however, to date, most evaluations of this population have occurred in the first 10 years from exposure. It is unknown whether cognitive status (full scale IQ) worsens beyond this immediate post-treatment period. Ongoing cognitive decline into adulthood would increase risk for many other poor long-term outcomes. The underlying mechanisms of treatment-induced CNS injury and its relationship to long-term cognition are poorly understood. We propose a study to 1) determine the prevalence of long-term memory deficits among 535 adult survivors of childhood ALL treated with cranial radiotherapy and now 15-45 years (mean 30 years) from diagnosis and 2) identify change in cognitive function since the time of the last post-therapy examination (mean 6.9 year from diagnosis) among 145 adult survivors of childhood ALL treated with cranial radiotherapy and now 11-37 years (mean 26 years) from previous examination. In addition, we will use advanced, non-invasive, magnetic resonance imaging techniques to explore associations between long-term memory deficits and 1) alterations in CNS structure and function using advanced MRI volumetric analysis, diffusion tensor imaging and functional MRI and 2) cerbrovasculopathy (including stroke) of both large and small vessels in a randomly selected subset of 140 survivors providing sufficient statistical power to identify associations between structure, function and memory outcomes. The results of this study will guide future screening practices for both neurocognitive deficits and cerbrovasculopathy in adult survivors. If long-term memory deficits are confirmed in this study, future longitudinal investigation will be necessary to determine long-term risk for dementia as well as intervention strategies to prevent or delay dementia. Access to more than 4,000 adult survivors of childhood cancer treated at St. Jude Children's Research Hospital makes this study feasible. PUBLIC HEALTH RELEVANCE: Identifying long-term memory loss and evidence for worsening cognitive status will benefit survivors and those who treat survivors of childhood cancer. Results from this proposed cross-sectional study of radiation exposed adult survivors of childhood cancer will directly inform 1) future outcomes research, 2) formulation of clinical care guidelines, including screening practices 3) development and testing of intervention strategies.

描述（由申请人提供）：接受颅辐射治疗儿童癌症的儿童面临长期中枢神经系统（CNS）损伤的巨大风险。我们的初步数据表明，这些成年幸存者的长期记忆（延迟回忆）受到了与阿尔茨海默氏病衰老的成年人相似的模式的显着影响，这引起了人们的担忧，即该人群可能有早期痴呆症的风险。此外，已经确定，认知缺陷会随着CNS辐射暴露后的时间而增加，但是，迄今为止，该人群的大多数评估都发生在暴露的头10年中。尚不清楚认知状况（全尺度智商）是否在此后立即进行后期的后期恶化。持续的认知能力下降到成年，将增加许多其他差的长期结局的风险。对治疗引起的中枢神经系统损伤的潜在机制及其与长期认知的关系知之甚少。我们提出一项研究至1）确定535名儿童期长期记忆缺陷的普遍性，所有这些都接受了颅放疗治疗，现在有15 - 45年（平均30年）（平均30年）的诊断和2）确定认知功能的变化，自上次疗法时期及其均为145年的cran delectiation以来，均为145年的6年习惯（平均6.9年），现在是145年的成年人习惯，所有这些习惯的习惯都在诊断中，所有这些习惯都在诊断中，所有诊断的人都习惯了，所有习惯的习惯都在所有诊断中，所有诊断的人都在所有诊断中的习惯。几年）以前的考试。此外，我们将使用先进的，非侵入性的磁共振成像技术来探索长期记忆缺陷之间的关联和1）使用先进的MRI体积分析，扩散量张量成像和功能性MRI和2）CERBascasculopAsculopathy（包括较大的遗迹）中的CNS结构和功能的变化，并进行了2），该量均可及时选择了型号。结构，功能和内存结果之间的关联。这项研究的结果将指导成人幸存者中神经认知缺陷和CER骨骼病的未来筛查实践。如果在本研究中确认了长期记忆缺陷，则必须进行未来的纵向调查，以确定痴呆症的长期风险以及预防或延迟痴呆症的干预策略。在圣裘德儿童研究医院接受治疗的儿童癌症的4,000多名成年幸存者的机会使这项研究可行。公共卫生相关性：确定长期记忆力丧失和认知状况恶化的证据将使幸存者和治疗儿童癌症幸存者的人受益。这项提出的对辐射暴露于儿童癌症的成年成人幸存者的横断面研究的结果将直接告知1）未来结果研究，2）制定临床护理指南，包括筛查实践3）开发和测试干预策略。