An Exploratory Study of Biologic and Pathophysiologic Efects of Radiation Therap

这项微创研究旨在探索辐射对儿童中枢神经系统的各种生物效应，试图1)获得辐射损伤的病理生理学信息，2)探索神经心理缺陷与生物标记物和神经成像异常的联系，3)通过纵向综合神经心理评估与各种放射治疗技术的比较来记录神经行为功能的变化，4)描述接受放射治疗的儿童患者生活质量的变化，以及5)尝试识别辐射导致神经毒性风险增加的儿童。我们正在通过检测血管生成相关细胞因子、蛋白质和细胞，包括血和尿样中的血管生成相关细胞因子、蛋白质和细胞，包括血管生成因子、碱性成纤维细胞生长因子、凝血酶反应蛋白、肿瘤坏死因子-α、白介素12、白介素8、循环内皮细胞和基质金属蛋白酶来具体评估对血管生成的影响。我们正在通过成像评估血管生成和血管的变化，包括动态敏感性对比灌注和动态增强MRI扫描。神经毒性将通过测量与神经毒性相关的生物标记物来表征，并通过纵向综合评估记录神经行为功能的变化。此外，我们将描述生活质量(QOL)的变化，评估记忆的变化，定义与辐射相关的眼科研究的变化，并检测与辐射相关的听力测量变化。22岁以下因原发中枢神经系统肿瘤的放射治疗而转诊至NCI的患者符合条件。大约有21名患者已经登记，并由一个多学科的专家团队进行纵向跟踪，其中包括来自儿科肿瘤学、眼科、放射学、听力学和神经心理学的专家。

This minimally invasive study is designed to explore various biologic effects of radiation on the pediatric CNS in an attempt to 1) obtain information on the pathophysiology of radiation-induced damage, 2) explore the association of neuropsychological deficits with biologic markers and neuroimaging abnormalities, 3) document changes in neurobehavioral functioning through longitudinal comprehensive neuropsychological assessments with comparison of various radiation therapy techniques, 4) describe changes in quality of life in pediatric patients who have received radiation therapy, and 5) attempt to identify children at increased risk of radiation-induced neurotoxicity. We are specifically evaluating effects on angiogenesis by measurement of angiogenesis related cytokines, proteins and cells including VEGF, bFGF, thrombospondin, TNF-alpha, IL-12, IL-8, circulating endothelial cells (CECs) and matrix metalloproteinases in blood and urine specimens. We are evaluating the changes in angiogenesis and vascularity by imaging, including dynamic susceptibility contrast perfusion and dynamic enhanced MRI scans. Neurotoxicity will be characterized by measuring biomarkers associated with neurotoxicity and documentation of changes in neurobehavioral functioning through longitudinal comprehensive assessments. In addition, we will describe changes in quality of life (QOL), assess changes in memory, define changes in ophthalmologic studies associated with radiation and detect changes in audiometry associated with radiation. Patients under 22 yrs of age who are referred to NCI for radiation therapy of a primary CNS tumor are eligible. Approximately 21 patients have enrolled and are followed longitudinally by a multidisciplinary team of specialists, including those from pediatric oncology, ophthalmology, radiology, audiology and neuropsychology.