Risk-Adapted Therapy for Young Children With Embryonal Brain Tumors, Choroid Plexus Carcinoma, High Grade Glioma or Ependymoma

RATIONALE: In this study a combination of anti-cancer drugs (chemotherapy) is used to treat brain tumors in young children. Using chemotherapy gives the brain more time to develop before radiation is given. The chemotherapy in this study includes the drug methotrexate. This drug was an important part of the two clinical trials which resulted in the best survival results for children less than 3 years of age with medulloblastoma. Most patients treated on this trial will also receive radiation which is carefully targeted to the area of the tumor. This type of radiation (focal conformal or proton beam radiotherapy) may result in fewer problems with thinking and learning than radiation to the whole brain and spinal cord. PURPOSE: This clinical trial is studying how well giving combination chemotherapy together with radiation therapy works in treating young patients with newly diagnosed central nervous system tumors.

All patients with medulloblastoma who were diagnosed prior to their 3rd birthday will contribute to both the biology and therapeutic primary objectives of this protocol. Furthermore patients who were ≥3 and \<5 years old at the time of diagnosis will also be included in the cohort for these primary objectives as long as they meet the eligibility criteria as outlined in Amendment 8.0 of this protocol. Patients in the 3-5 year old age cohort who enrolled on previous versions of this protocol and who do not meet the criteria as outlined in Amendment 8.0 of this protocol will be excluded from the outcome analyses of the biology and therapeutic primary objectives of the protocol. OBJECTIVES: Primary * To identify patterns of methylation profiling that are associated with progression-free survival among young pediatric patients with medulloblastoma treated with risk-adapted therapy. * To estimate the event-free survival distribution of young medulloblastoma patients treated with risk-adapted therapy. Secondary * To perform high-resolution genome-wide analyses of chromosomal abnormalities and gene expression patterns, and evaluate the relationship of these to other clinicopathological variables. * To evaluate specific tumor types for molecular abnormalities with suspected prognostic or therapeutic significance. * To evaluate the feasibility of collecting frozen and fixed tumor samples for analysis using high-resolution molecular biology tools. * To estimate the event-free and overall survival of patients treated with the proposed risk-adapted therapy regimen, and to descriptively compare these survival rates to historical controls. * To estimate the rates of local and distant disease progression in patients treated with focal radiotherapy (RT) to the post-operative tumor bed using a 5 mm clinical target volume margin. * To estimate the objective response rate (sustained for 8 weeks) to induction chemotherapy including high-dose intravenous methotrexate for patients with residual or metastatic disease. * To evaluate the feasibility and toxicity of administering low-dose intravenous vinblastine in conjunction with induction chemotherapy to patients with metastatic disease. * To evaluate the feasibility and toxicity of administering consolidation therapy including cyclophosphamide and pharmacokinetically targeted topotecan to patients with metastatic disease, and to estimate the sustained (for 8 weeks) objective response rate (complete response and partial response) to such therapy in patients with measurable residual disease after induction. * To evaluate the feasibility and toxicity of administering oral maintenance therapy in young children. * To use quantitative magnetic resonance (MR) measures (volumetric, diffusion, and perfusion) of young brain tumor patients receiving chemotherapy including high-dose intravenous methotrexate to assess impact of treatment on developing brain. * To investigate the feasibility of using PET as an in-vivo dosimetri Покажи пълното описание...

Histologically confirmed newly diagnosed CNS tumors of any of the following : * Medulloblastoma (all histologic subtypes, including medullomyoblastoma and melanotic medulloblastoma) * Supratentorial primitive neuroectodermal tumor (PNET) (including CNS neuroblastoma or ganglioneuroblastoma, medulloepithelioma, and ependymoblastoma) * Pineoblastoma * Atypical teratoid rhabdoid tumor (ATRT) * Choroid plexus carcinoma * High grade glioma (including anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic ganglioglioma, pleomorphic xanthoastrocytoma with anaplastic features, high-grade astroblastoma , anaplastic pilocytic astrocytoma, malignant glioneuronal tumor, glioblastoma multiforme), or gliosarcoma, * Ependymoma (including all ependymoma histological variants) * Age \< 3 years at time of diagnosis for all histological diagnosis. Medulloblastoma patients ≥ 3 and \< 5years old at diagnosis who have non-metastatic disease with no more than 1cm2 of residual tumor are also eligible. * Meets criteria for 1 of the following risk groups: * Low-risk group: * Histologically confirmed nodular desmoplastic medulloblastoma, including medulloblastoma with extensive nodularity * Focal areas of anaplasia or other atypical features suggesting more aggressive phenotype in a tumor otherwise considered nodular desmoplastic should be treated on the intermediate-risk group, with final risk stratification at the discretion of principal investigator and study pathologist * No evidence of CNS metastasis 7 to 28 days after surgery by MRI and cytologic examination of lumbar cerebrospinal fluid (CSF) * Ventricular CSF from a shunt or Ommaya reservoir may be used to rule out M1 disease when lumbar puncture is medically contraindicated * Intermediate-risk group assignment when there is no other evidence of metastasis and CSF sampling is not possible * Gross total resection, defined as residual tumor or imaging abnormality (not definitive for residual tumor) with a size of \< 1 cm2 confirmed on postoperative CT scan or MRI * Brain stem invasion by the tumor in the absence of imaging evidence of residual tumor (tumor size \< 1 cm2) and otherwise meets criteria for the low-risk group, the patient will be classified as low-risk * Desmoplastic medulloblastoma patients who are ≥3 -\<5 years of age will NOT be eligible for the low risk arm of the protocol. * Intermediate-risk group: * Histologically confirmed nodular desmoplastic medulloblastoma with less than gross total resection and no evidence of metastasis * Any eligible histologic diagnosis other than desmoplastic medulloblastoma with no evidence of CNS metastasis * Medulloblastoma patients who are ≥3 and \< 5 yrs of age irrespective of histology and with no evidence of CNS metastasis * High-risk group: * Any eligible histologic diagnosis with evidence of CNS metastasis * Patients with extraneural metastasis are eligible for treatment on the high-risk group PATIENT CHARACTERISTICS: * Lansky performance status ≥ 30 (except for posterior fossa syndrome) * WBC \> 2,000/mm3 * Platelets \> 50,000/mm3 (without support) * Hemoglobin \> 8 g/dL (with or without support) * ANC \> 500/mm3 * Serum creatinine \< 3 times upper limit of normal (ULN) * ALT \< 5 times ULN * Total bilirubin \< 3 times ULN PRIOR CONCURRENT THERAPY: * See Disease Characteristics * No more than 31 days since prior definitive surgery * No prior radiotherapy or chemotherapy other than corticosteroid therapy