Exploratory Study of Biologic and Pathophysiologic Effects of Radiation Therapy

这项微创研究旨在探索辐射对儿童CNS的各种生物学效应，试图1）获得辐射诱导损伤的病理生理学信息，2）探索神经心理学缺陷与生物标志物和神经影像学异常的相关性，第三章通过纵向综合神经心理学评估记录神经行为功能的变化，并比较各种放射治疗技术，4）描述接受放射治疗的儿科患者生活质量的变化，5）试图识别辐射诱导神经毒性风险增加的儿童。我们通过测量血液和尿液标本中血管生成相关的细胞因子、蛋白质和细胞（包括VEGF、bFGF、血小板反应蛋白、TNF-α、IL-12、IL-8、循环内皮细胞（CEC）和基质金属蛋白酶），专门评价对血管生成的影响。我们正在通过成像评估血管生成和血管分布的变化，包括动态磁敏感对比灌注和动态增强MRI扫描。将通过测量与神经毒性相关的生物标志物并通过纵向综合评估记录神经行为功能的变化来表征神经毒性。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定的变化。年龄在22岁以下，转诊至NCI接受原发性CNS肿瘤放射治疗的患者符合资格。大约有55名患者入组，并由一个多学科专家小组纵向跟踪，包括儿科肿瘤学、眼科、放射学、听力学和神经心理学专家。

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 55 patients have enrolled and are followed longitudinally by a multidisciplinary team of specialists, including those from pediatric oncology, ophthalmology, radiology, audiology and neuropsychology.