Bethesda, Maryland 20892

  • Radiation Toxicity

Purpose:

RATIONALE: Radiation therapy directed at the central nervous system may change the way blood vessels form in young patients. It may also change brain function, the ability to see and hear, and the patient's quality of life. A study that evaluates young patients for several years after undergoing CNS radiation therapy may help doctors predict a patient's response to treatment and help plan the best treatment. PURPOSE: This clinical trial is studying the side effects of radiation therapy in young patients with CNS tumors.


Study summary:

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.


Criteria:

DISEASE CHARACTERISTICS: - Diagnosis of any primary CNS tumor - Concurrently enrolled and undergoing radiotherapy on protocol NCI-03-C-0241 PATIENT CHARACTERISTICS: - Any Karnofsky performance status (for patients ≥ 16 years of age) OR Lansky performance status (for patients < 16 years of age) allowed - Able to undergo an MRI PRIOR CONCURRENT THERAPY: - No prior radiotherapy - Prior surgery allowed - Prior and concurrent chemotherapy allowed - Concurrent enrollment on another clinical trial using investigational agents allowed - Concurrent corticosteroids allowed


NCT ID:

NCT00401037


Primary Contact:

Principal Investigator
Katherine Warren, MD
NCI - Pediatric Oncology Branch


Backup Contact:

N/A


Location Contact:

Bethesda, Maryland 20892
United States

Clinical Trials Office - Warren Grant Magnusen Clinical Center
Phone: 888-NCI-1937

Site Status: Recruiting


Data Source: ClinicalTrials.gov

Date Processed: November 27, 2022

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