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 37 patients have enrolled and are followed longitudinally by a multidisciplinary team of specialists, including those from pediatric oncology, ophthalmology, radiology, audiology and neuropsychology. A manuscript is In Press.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
Application #
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
National Cancer Institute Division of Basic Sciences
Zip Code
Warren, Katherine E (2014) Measuring the pons: a non-invasive biomarker for pediatric diffuse intrinsic pontine glioma. CNS Oncol 3:181-3
Steffen-Smith, Emilie A; Baker, Eva H; Venzon, David et al. (2014) Measurements of the pons as a biomarker of progression for pediatric DIPG. J Neurooncol 116:127-33
Warren, Katherine E; Poussaint, Tina Y; Vezina, Gilbert et al. (2013) Challenges with defining response to antitumor agents in pediatric neuro-oncology: a report from the response assessment in pediatric neuro-oncology (RAPNO) working group. Pediatr Blood Cancer 60:1397-401
Ko, Christine; Kaushal, Aradhana; Hammoud, Dima A et al. (2012) Role of early postradiation magnetic resonance imaging scans in children with diffuse intrinsic pontine glioma. Int J Radiat Oncol Biol Phys 83:1252-1256
Steffen-Smith, Emilie A; Venzon, David J; Bent, Robyn S et al. (2012) Single- and multivoxel proton spectroscopy in pediatric patients with diffuse intrinsic pontine glioma. Int J Radiat Oncol Biol Phys 84:774-9
Fitzhugh, Courtney D; Wise, Barbara; Baird, Kristin et al. (2009) Secondary supratentorial primitive neuroectodermal tumor following treatment of childhood osteosarcoma. Pediatr Blood Cancer 53:496-8