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）：接受胸腔放射治疗（TRT）治疗的儿童癌症的幸存者有患心血管和肺部发病率的风险，尽管中枢神经系统（CNS）病理尚未确定风险。在非癌症种群中，心肺健康与中枢神经系统完整性有关。患有心血管疾病的成年人表现出神经认知问题，而小血管疾病通过多焦点白质超强度（即白血病）在脑磁共振成像（MRI）上反射出来。肺部疾病还增加了非癌症种群中枢神经系统异常的风险，包括中风，白细胞脑病和神经认知障碍。我们最近在62名霍奇金淋巴瘤的成年成人幸存者中确定了胸腔辐射与脑病理学之间的显着关联（平均[范围]年龄= 42.2 [34-55]年；诊断以来= 27.1 [18-40]年以来，他们没有接受CNS化学疗法和颅骨放射。这些幸存者表现出高度的神经认知障碍率，大脑成像显示53％的白血病患病和37％的人有脑血管损伤与小血管疾病一致的迹象。胸腔辐射剂量与众多大脑区域的白细胞膜病和皮质厚度有关，这些病理与神经认知障碍有关。这些新颖的结果使我们提出了对扩展的队列的更全面的随访，以研究中枢神经系统结果中涉及的特定治疗特征和潜在的病理生理过程的影响，目的是为减少中枢神经系统的风险降低提供早期干预。我们建议检查儿童癌症成年癌症的大脑完整性的患病率和预测因素，他们有肺部发病的风险，但尚未接受颅骨辐射或CNS指导的化学疗法。我们将参考心脏，血管和肺部健康指数检查神经认知和脑成像结果。这项研究的结果有可能显着影响当前的护理标准和长期随访指南，因为目前不建议未直接进行中枢神经系统暴露治疗的癌症幸存者筛查神经认知功能或中枢神经系统发病率。调查结果将用于开发和试点特定的干预措施，以降低CNS发病率的风险，包括明显的脑血管损伤。