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

• 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
• 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' 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' 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

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(申请人提供)：接受颅脑放射治疗儿童癌症的儿童有长期中枢神经系统(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)受到显著影响，类似于阿尔茨海默病老年患者的模式，这引发了人们对这一人群可能面临早期痴呆症风险的担忧。此外，已经证实，暴露于中枢神经系统辐射后，认知缺陷会随着时间的推移而增加，然而，到目前为止，对这一人群的大多数评估都发生在暴露后的前10年。目前尚不清楚认知状态(满分智商)是否会在治疗后立即恶化。持续到成年的认知衰退会增加许多其他不良长期结果的风险。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尚不清楚。我们建议进行一项研究：1)确定所有接受颅脑放疗的儿童成年幸存者中长期记忆缺陷的发生率，现在是15-45岁(平均30岁)；2)确定145名接受颅脑放疗的成年幸存者自最后一次治疗后检查(自确诊起平均6.9年)以来的认知功能变化。此外，我们将使用先进的非侵入性磁共振成像技术来探索长期记忆缺陷与1)使用先进的MRI体积分析、弥散张量成像和功能MRI的中枢神经系统结构和功能的变化以及2)随机选择的140名幸存者的大血管和小血管的脑血管病变(包括中风)之间的联系，提供足够的统计能力来确定结构、功能和记忆结果之间的联系。这项研究的结果将指导未来对成年幸存者的神经认知缺陷和脑血管病变的筛查实践。如果长期记忆缺陷在这项研究中得到证实，未来的纵向调查将有必要确定痴呆症的长期风险以及预防或延缓痴呆症的干预策略。接触到在圣犹大儿童研究医院接受治疗的4000多名成年儿童癌症幸存者，使这项研究具有可行性。 公共卫生相关性：确定长期记忆丧失和认知状况恶化的证据将使幸存者和那些治疗儿童癌症幸存者的人受益。这项拟议的儿童癌症成年幸存者辐射暴露横断面研究的结果将直接为1)未来结果研究、2)临床护理指南的制定，包括筛查实践3)干预策略的开发和测试提供信息。