Brain Integrity in Survivors of Childhood Cancer Treated with Thoracic Radiation

接受胸部放射治疗的儿童癌症幸存者的大脑完整性

• 批准号: 8639508
• 负责人: Kevin R Krull
• 金额: $ 68.82万
• 依托单位: ST. JUDE CHILDREN'S RESEARCH HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-04-01 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8639508
• 关键词: Address; Adult; Age; Attention; Blood Vessels; Brain; Brain Pathology; Brain imaging; Brain region; Cancer Survivor; Carbon Monoxide; Cardiac; Cardiopulmonary; Cardiovascular Diseases; Characteristics; Chest; Child; Communities; Congenital neurologic anomalies; Cranial Irradiation; Deposition; Development; Diagnosis; Diffuse; Dose; Early Intervention; Ethnic Origin; Future; Goals; Guidelines; Health; Heart; Hemosiderin; Hodgkin Disease; Impairment; Injury; Intervention; Lead; Left Ventricular Ejection Fraction; Leukoencephalopathy; Long-Term Survivors; Lung; Lung Capacity; Lung diseases; Magnetic Resonance Imaging; Malignant Neoplasms; Measures; Memory; Microvascular Dysfunction; Morbidity - disease rate; Neuraxis; Neurocognitive; Outcome; Oxygen; Oxygen Consumption; Pathology; Patients; Performance; Perfusion; Peripheral; Population; Prevalence; Prevention; Process; Pulse Pressure; Race; Radiation; Radiation therapy; Recording of previous events; Risk; Risk Reduction; Stroke; Structure; Survivors; Testing; Therapeutic; Thick; Time; White Matter Hyperintensity; cardiovascular risk factor; cerebrovascular; chemotherapy; childhood cancer survivor; cohort; comparison group; follow-up; high risk; indexing; novel; public health relevance; screening; sex; standard of care; white matter

DESCRIPTION (provided by applicant): Survivors of childhood cancer treated with thoracic radiation therapy (TRT) are at risk for cardiovascular and pulmonary morbidity, though risk is not recognized for Central Nervous System (CNS) pathology. In non- cancer populations, cardiopulmonary health is associated with CNS integrity. Adults with cardiovascular disease demonstrate neurocognitive problems, and small vessel disease reflected through multi-focal white matter hyper intensities (i.e., leukoencephalopathy) on brain magnetic resonance imaging (MRI). Pulmonary disease also increases risk of CNS abnormalities in non-cancer populations, including stroke, leukoencephalopathy, and neurocognitive impairment. We recently identified significant associations between thoracic radiation and brain pathology in 62 adult survivors of Hodgkin lymphoma (mean [range] age = 42.2 [34-55] years; time since diagnosis = 27.1 [18-40] years) who received no CNS chemotherapy and no cranial radiation. These survivors demonstrated high rates of neurocognitive impairment, and brain imaging revealed 53% had leukoencephalopathy and 37% had evidence of cerebrovascular injury consistent with small vessel disease. Thoracic radiation dose was associated with leukoencephalopathy and cortical thickness in numerous brain regions, and these pathologies were associated with neurocognitive impairment. These novel results lead us to propose a more comprehensive follow-up of an expanded cohort to examine the impact of specific treatment characteristics and potential pathophysiological processes involved in CNS outcomes, with the goal of developing an early intervention for CNS risk reduction. We propose to examine the prevalence and predictors of brain integrity in adult survivors of childhood cancer who are at risk for cardiac an pulmonary morbidity, but who have not received cranial radiation or CNS-directed chemotherapies. We will examine neurocognitive and brain imaging outcomes in reference to indices of cardiac, vascular, and pulmonary health. Results of this study have the potential to significantly impact current standard of care and long-term follow-up guidelines, as cancer survivors treated without direct CNS exposure are not presently recommended for screening of neurocognitive function or CNS morbidity. Findings will be used to develop and pilot specific interventions aimed at reducing risk for CNS morbidity, including overt cerebrovascular injury.

描述（由申请人提供）：接受胸部放射治疗（TRT）治疗的儿童癌症幸存者存在心血管和肺部发病的风险，但中枢神经系统（CNS）病理学的风险尚未得到认可。在非癌症人群中，心肺健康与中枢神经系统完整性相关。患有心血管疾病的成年人表现出神经认知问题，以及通过脑磁共振成像 (MRI) 上的多灶性白质高强度（即白质脑病）反映出来的小血管疾病。肺部疾病还会增加非癌症人群中枢神经系统异常的风险，包括中风、白质脑病和神经认知障碍。我们最近在 62 名未接受 CNS 化疗的成年霍奇金淋巴瘤幸存者（平均 [范围] 年龄 = 42.2 [34-55] 岁；诊断后时间 = 27.1 [18-40] 岁）中发现胸部放射与脑病理学之间存在显着关联并且没有颅脑辐射。这些幸存者表现出高比例的神经认知障碍，脑成像显示 53% 的人患有白质脑病，37% 的人有与小血管疾病一致的脑血管损伤证据。胸部辐射剂量与许多大脑区域的白质脑病和皮质厚度有关，而这些病变与神经认知障碍有关。这些新颖的结果促使我们提出对扩大的队列进行更全面的随访，以检查特定治疗特征和涉及中枢神经系统结果的潜在病理生理过程的影响，目标是制定降低中枢神经系统风险的早期干预措施。我们建议检查儿童癌症成年幸存者的大脑完整性的患病率和预测因素，这些幸存者有心脏病和肺部疾病的风险，但尚未接受过颅脑放射或中枢神经系统定向化疗。我们将根据心脏、血管和肺部健康指标检查神经认知和脑成像结果。这项研究的结果有可能对当前的护理标准和长期随访指南产生重大影响，因为目前不建议对未直接接触中枢神经系统的癌症幸存者进行神经认知功能或中枢神经系统发病率的筛查。研究结果将用于制定和试点具体干预措施，旨在降低中枢神经系统发病风险，包括明显的脑血管损伤。