Exploratory Study of Effects of Radiation Therapy in Pediatric Patients With Central Nervous System Tumors

An Exploratory Study of Biologic and Pathophysiologic Effects of Radiation Therapy in Pediatric Patients With Central Nervous System Tumors

This study will analyze the effects of radiation given to children who have tumors of the central nervous system (CNS). Researchers want to learn more about changes in the quality of life that patients may experience as a result of radiation.

Patients ages 21 and younger who have a primary CNS tumor and who have not received radiation previously may be eligible for this study. They will have a medical history and physical examination. Collection of blood (about 2-1/2 tablespoons) and urine will be done, as well as a pregnancy test. Patients will complete neuropsychological tests, which provide information about their changes in functioning over time. An expert in psychology will give a number of tests, and the patient's parents or guardian will be asked to complete a questionnaire about the patient's behavior. Also, patients will be given a quality of life questionnaire to complete and vision and hearing tests. The radiation itself is prescribed by patients' doctors and is not part of this study.

Magnetic resonance imaging (MRI) will give researchers information about the tumor and brain, through several scanning sequences . MRI uses a strong magnetic field and radio waves to obtain images of body organs and tissues. Patients will lie on a table that slides into the enclosed tunnel of the scanner. They will need to lie still, and medication may be given to help them to do that. They may be in the scanner for up to 2 hours. As the scanner takes pictures, patients will hear knocking or beeping sounds, and they will wear earplugs to reduce the noise. A contrast agent will be administered, to allow images be seen more clearly. Blood and urine tests will be conducted after the first dose of radiation. MRI scans will be done 2 weeks after patients finish radiation therapy and again at 6 to 8 weeks, 6 months, 12 months, and yearly. Also at those follow-up periods, patients will undergo similar procedures as previously, including blood and urine tests and neuropsychological testing. Patients can remain in this study for 5 years.

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Study Overview

• Status: Completed
• Conditions: Ependymoma; Medulloblastoma; PNET; Diffuse Intrinsic Pontine Glioma; Germinoma

Detailed Description

Background:

This exploratory study will be performed in pediatric patients with CNS tumors who are undergoing radiation therapy to investigate pathophysiologic effects of radiation on the CNS. The study includes the analysis of blood, urine, and CSF (if available) to measure biological markers involved with angiogenesis, blood: brain barrier integrity, and neurotoxicity. It also entails comprehensive MR imaging techniques and neuropsychological testing in an effort to correlate changes with biomarker measurements.

Objectives:

1. To detect changes in angiogenesis related to radiation of the CNS by:

   • Measurement of VEGF, bFGF, thrombospondin, TNF-alpha, IL-12, IL-8, and MMP in blood and urine specimens.
   • MR perfusion and DEMRI.
2. To describe changes in blood:brain barrier permeability associated with radiation of the CNS.

3. To characterize neurotoxicity by:

   • Measuring biomarkers associated with neurotoxicity
   • Documenting changes in neurobehavioral functioning through longitudinal comprehensive assessments
   • Describing changes in quality of life (QOL)
   • Assessing changes in memory
   • Defining changes in ophthalmologic studies associated with radiation.
   • Detecting changes in audiometry associated with radiation.

Eligibility Criteria:

• Patients must have a primary CNS tumor for which radiation therapy is recommended.
• Patients must be less than or equal to 21 years of age.
• Prior/Concurrent: Patients will be eligible if they have not received prior radiation. Patients who have undergone surgery or received chemotherapy are eligible.
• Performance Status: Patients will be eligible regardless of performance score.

Design:

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.

• Study Type: Observational
• Enrollment (Actual): 76

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Institutes of Health Clinical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Pediatric patients 21 years of age or younger with CNS tumors for which radiation therapy is recommended@@@

Description

• INCLUSION CRITERIA:

Age: Patients must be less than or equal 21 years of age.

Tumor: Any primary CNS tumor.

Referred for radiation therapy at NCI.

Signed informed consent by patient, parent or legal guardian.

PERFORMANCE SCORE: any.

PRIOR/CONCURRENT THERAPY: Patients will be eligible if they have not received prior radiation.

Patients who have undergone prior surgery or who have received chemotherapeutic regimens are eligible.

EXCLUSION CRITERIA:

Patients who have received prior radiation.

Patients who are unable to have MRI performed for any reason.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
1; Pediatric Patients with Central Nervous System Tumors

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure changes in antiogenesis, blood brain barrier permability and neurotoxicity re to radiation of the CNS	Measurement of VEGF, bFGF, thrombospondin, TNF-a, IL-12, IL-8, and MMP in blood and urine specimens	before and up to 8 years after

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Describe changes in imaging, endocrine function after xrt to the brain	Measurement of S100-beta and transthyretin in blood	before and up to 8 years after
Monitor changes in serum proteome and germline polymorphisms	Assesed changed in memory, QOL, neurobehavioral functioning, ophthalmologic studies, and audiometry associated with radiation	before and up to 8 years after

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: John W Glod, M.D., National Cancer Institute (NCI)

Publications and helpful links

General Publications

• Garcia-Barros M, Paris F, Cordon-Cardo C, Lyden D, Rafii S, Haimovitz-Friedman A, Fuks Z, Kolesnick R. Tumor response to radiotherapy regulated by endothelial cell apoptosis. Science. 2003 May 16;300(5622):1155-9. doi: 10.1126/science.1082504.
• Wyllie AH, Kerr JF, Currie AR. Cell death: the significance of apoptosis. Int Rev Cytol. 1980;68:251-306. doi: 10.1016/s0074-7696(08)62312-8. No abstract available.
• Mulhern RK, Hancock J, Fairclough D, Kun L. Neuropsychological status of children treated for brain tumors: a critical review and integrative analysis. Med Pediatr Oncol. 1992;20(3):181-91. doi: 10.1002/mpo.2950200302.

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Actual): December 5, 2006

Study Registration Dates

• First Submitted: September 30, 2011
• First Submitted That Met QC Criteria: September 30, 2011
• First Posted (Estimated): October 3, 2011

Study Record Updates

• Last Update Posted (Estimated): April 19, 2024
• Last Update Submitted That Met QC Criteria: April 18, 2024
• Last Verified: February 7, 2024

More Information

Terms related to this study

• Keywords: Imaging; Children; Brain Tumor; Natural History; Angiogenesis; Neurotoxicity; Central Nervous System Tumor; CNS Tumor
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Brain Neoplasms; Neuroectodermal Tumors, Primitive; Brain Stem Neoplasms; Infratentorial Neoplasms; Nervous System Neoplasms; Central Nervous System Neoplasms; Ependymoma; Medulloblastoma; Diffuse Intrinsic Pontine Glioma; Germinoma
• Other Study ID Numbers: 060219; 06-C-0219

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: .All IPD recorded in the medical record will be shared with intramural investigators upon request.
• IPD Sharing Time Frame: Clinical data available during the study and indefinitely.@@@@@@Genomic data are available once genomic data are uploaded per protocol GDS plan for as long as the database is active.
• IPD Sharing Access Criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI. @@@@@@Genomic data are made available via dbGaP through requests to the data custodians.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No