Exploratory Study of Effects of Radiation Therapy in Pediatric Patients With Central Nervous System Tumors
Condition: Diffuse Intrinsic Pontine Glioma; PNET; Ependymoma; Germinoma; Medulloblastoma
MeSH terms: Ependymoma; Nervous System Neoplasms; Central Nervous System Neoplasms; Medulloblastoma; Diffuse Intrinsic Pontine Glioma; Germinoma
Study type: Observational

Summary: 
      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.

      ...
    

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.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Pediatric patients 21 years of age or younger with CNS tumors for which radiation therapy
        is recommended@@@
      
Keywords: Neurotoxicity; Brain Tumor; Children; Angiogenesis; Imaging; Natural History; Central Nervous System Tumor; CNS Tumor