Side Effects of Radiation Therapy in Young Patients With CNS Tumors

OBJECTIVES:

Primary

- Assess changes in angiogenesis associated with radiotherapy of the CNS by measuring
angiogenic markers in blood and urine (e.g., vascular endothelial growth factor [VEGF],
basic fibroblast growth factor [bFGF], thrombospondin, tumor necrosis factor alpha
[TNF-alpha], interleukin [IL]-12, IL-8, and matrix metalloproteinases [MMPs]), and by
measuring brain imaging changes by magnetic resonance perfusion and dynamic
contrast-enhanced MRI (DEMRI) in pediatric patients with CNS tumors.

- Assess changes in blood-brain barrier permeability associated with radiotherapy of the
CNS by measuring S100-ß and transthyretin in blood of these patients.

- Measure biomarkers associated with neurotoxicity, including neurofibromatosis type 1
(NF-1), neuron-specific enolase (NSE), S100-ß, glial fibrillary acidic protein (GFAP),
and quinolinic acid in blood and cerebrospinal fluid of these patients.

- Assess changes in neurobehavioral functioning in these patients using longitudinal
comprehensive assessments that compare various radiotherapy techniques (i.e.,
intensity-modulated radiotherapy vs. focal radiotherapy).

- Assess changes in the quality of life (QOL) of these patients as measured by the Impact
of Pediatric Illness Scale and validate this QOL scale for children with chronic
illness.

- Assess changes in memory and executive functions of these patients as measured by the
Test of Executive Control and the Immediate Post-Concussion Assessment and Cognitive
Testing and validate these novel computerized tests for use in young children.

- Determine changes in ophthalmologic studies associated with radiotherapy in these
patients.

- Determine changes in audiometry associated with radiotherapy in these patients.

Secondary

- Assess changes in tumor and normal-appearing areas of the brain by proton nuclear
magnetic resonance spectroscopic imaging and by diffusion-tensor MRI in patients with
brain tumors or patients receiving cranial radiation.

- Assess radiotherapy-induced changes in endocrine function in patients with CNS tumors.

- Assess changes in serum proteome in these patients during and after radiotherapy.

- Correlate patterns of germline polymorphisms with frequency and severity of
neurotoxicity in these patients.

OUTLINE: This is a longitudinal study. Patients undergo the following assessments:

- Biomarker studies: Patients undergo blood, urine, and cerebrospinal fluid (if
available) collection for evaluation of post-radiotherapy changes using immunoenzyme
techniques, bioluminescence, and mass spectrometry. The following biomarkers are
evaluated: angiogenic biomarkers (e.g., vascular endothelial growth factor [VEGF],
basic fibroblast growth factor [bFGF], thrombospondin, tumor necrosis factor alpha
[TNF-alpha], interleukin [IL]-12, IL-8, and matrix metalloproteinases [MMPs]);
biomarkers of blood-brain barrier permeability (S100-ß and transthyretin);
neurotoxicity biomarkers (e.g., neurofibromatosis type 1 [NF-1], neuron-specific
enolase [NSE], S100ß, glial fibrillary acidic protein [GFAP], and quinolinic acid); and
serum proteome. Biomarkers are measured at baseline, after the first dose of
radiotherapy, within 2 weeks after completion of radiotherapy, at 3, 6, and 12 months,
and then annually thereafter.

- Genetic studies: Patients undergo blood collection for analysis of DNA for
polymorphisms associated with an increased susceptibility to the neurotoxic effects of
radiotherapy.

- Imaging: Some patients undergo radiographic imaging by standard and dynamic
contrast-enhanced MRI, proton nuclear magnetic resonance spectroscopy, MR perfusion,
and diffusion-tensor MRI (DT-MRI). Imaging studies are performed at baseline, at 1-2
and 6-8 weeks after completion of radiotherapy, at 6 and 12 months, and then annually
for 5 years.

- Neuropsychological assessment: Patients undergo neuropsychological assessments
comprising testing of executive function, attention, working memory, and processing
speed, as well as behavior. Neuropsychological assessments also include testing of
general intelligence, verbal comprehension and expression, perceptual reasoning, verbal
learning and memory, fine motor skills, academic achievement, and social-emotional
functioning. Neuropsychological assessments are performed at baseline, within 2 weeks
after completion of radiotherapy, and then at 6 and 12 months.

- Quality of life (QOL) assessment: Patients undergo QOL assessments at baseline, within
approximately 2 weeks after completion of radiotherapy, at 6 and 12 months, and then
annually thereafter.

- Ophthalmology examination: Patients undergo ophthalmologic testing comprising vision,
eye pressure, and fundus evaluation after dilation, Ishihara color plates, and 3-2
visual fields (if appropriate for age). Examinations are performed at baseline, at 6
months after completion of radiotherapy, and then annually thereafter.

- Audiometric testing: Patients undergo standard Clinical Center, age-appropriate
audiometric testing at baseline, within 2 weeks and at 6-8 weeks after completion of
radiotherapy, at 6 and 12 months, and then annually thereafter.

PROJECTED ACCRUAL: A total of 150 patients will be accrued for this study.