Exploratory Study of Biologic and Pathophysiologic Effects of Radiation Therapy

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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.