• Time to recurrence, progression, or death due to cancer at 3 years [ Designated as safety issue: No ]
• Time to death at 3 years [ Designated as safety issue: No ]
• Local Posterior Fossa (LPF) Failure as determined by tumor recurrence or progression within the tumor bed at 3 years [ Designated as safety issue: No ]
• Non-local Posterior Fossa (NLPF) Failure as determined by recurrence outside CTVboost but within CTVPF at 3 years [ Designated as safety issue: No ]
• Non-Posterior Fossa (NPF) Failure as determine by recurrence within the neuroaxis but outside of CTVPF at 3 years [ Designated as safety issue: No ]
• Post-treatment neurocognitive function as measured by Neuropsychometric battery at 3 years [ Designated as safety issue: No ]
• Post-treatment hearing loss as measure by Audiogram or brainstem auditory evoked response (BAER) at 3 years [ Designated as safety issue: No ]
• Post-treatment endocrine function (e.g., growth, sexual maturation, and need for hormone replacement) by laboratory assesment, clinical history, and exam at 3 years [ Designated as safety issue: No ]
• Quality of Life as measured by Pediatric Quality of Life Inventory (PedsQL), Behavior Assessment System for Children (BASC), Behavior Rating Inventory of Executive Function (BRIEF), and Adaptive Behavior Assessment System (ABAS) at 3 years [ Designated as safety issue: No ]

• Time to recurrence, progression, or death due to cancer at 3 years
• Time to death at 3 years
• Local Posterior Fossa (LPF) Failure as determined by tumor recurrence or progression within the tumor bed at 3 years
• Non-local Posterior Fossa (NLPF) Failure as determined by recurrence outside CTVboost but within CTVPF at 3 years
• Non-Posterior Fossa (NPF) Failure as determine by recurrence within the neuroaxis but outside of CTVPF at 3 years
• Post-treatment neurocognitive function as measured by Neuropsychometric battery at 3 years
• Post-treatment hearing loss as measure by Audiogram or brainstem auditory evoked response (BAER) at 3 years
• Post-treatment endocrine function (e.g., growth, sexual maturation, and need for hormone replacement) by laboratory assesment, clinical history, and exam at 3 years
• Quality of Life as meastured by Pediatric Quality of Life Inventory (PedsQL), Behavior Assessment System for Children (BASC), Behavior Rating Inventory of Executive Function (BRIEF), and Adaptive Behavior Assessment System (ABAS) at 3 years

RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy, such as vincristine, cisplatin, lomustine, and cyclophosphamide, work in different ways to stop tumor cells from dividing so they stop growing or die. Giving radiation therapy with chemotherapy after surgery may kill any remaining tumor cells. It is not yet known whether standard-dose radiation therapy combined with chemotherapy after surgery is more effective than reduced-dose craniospinal (head and spine) radiation therapy plus either posterior fossa (back of the brain) boost or tumor bed (site of the tumor) boost radiation therapy combined with chemotherapy in treating medulloblastoma.

PURPOSE: This randomized phase III trial is studying standard-dose radiation therapy to see how well it works compared to reduced-dose craniospinal radiation therapy AND posterior fossa boost radiation therapy to see how well it works compared to tumor bed boost radiation therapy when given together with chemotherapy in treating young patients who have undergone surgery for newly diagnosed standard-risk medulloblastoma.

OBJECTIVES:

Primary

• Compare event-free and overall survival of pediatric patients (3 to 7 years of age) with newly diagnosed standard-risk medulloblastoma treated with standard-dose vs reduced-dose craniospinal radiotherapy and posterior fossa boost vs tumor bed boost radiotherapy in combination with chemotherapy comprising vincristine, cisplatin, lomustine, and cyclophosphamide.
• Compare event-free and overall survival of these patients (8 to 21 years of age) treated with standard-dose craniospinal radiotherapy and posterior fossa boost vs tumor bed boost radiotherapy in combination with this chemotherapy regimen.

Secondary

• Compare patterns of failure in patients treated with these regimens.
• Compare the cognitive, auditory, and endocrinologic effects of these regimens in these patients.
• Compare the audiologic and endocrinologic toxicity from these regimens in these patients.
• Develop an optimal gene expression medulloblastoma outcome predictor.
• Assess quality of life and functional status in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients will undergo radiotherapy on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 43-47 (weeks 0-6). Patients receive vincristine IV on days 8, 15, 22, 29, 36, and 43 (weeks 1-6) beginning 31 days after surgery.Patients 3 to 7 years of age are randomized to 1 of 2 chemoradiotherapy arms. Patients 8-21 years old are assigned to arm II.

• Chemoradiotherapy:Patients will undergo radiotherapy on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 43-47 (weeks 0-6). Patients receive vincristine IV on days 8, 15, 22, 29, 36, and 43 (weeks 1-6) beginning 31 days after surgery. Patients 3 to 7 years of age are randomized to 1 of 2 radiotherapy arms (arms I and II). Patients 8-21 years old are assigned to arm II.

  • Radiotherapy (first randomization):

    • Arm I: Patients undergo reduced-dose craniospinal radiotherapy with boost.
    • Arm II: Patients undergo standard-dose craniospinal radiotherapy with boost. All patients are then randomized to 1 of 2 chemoradiotherapy arms (arms III and IV).

  • Radiotherapy boost (second randomization):

    • Arm III: Patients will undergo radiotherapy boost to the entire posterior fossa.
    • Arm IV: Patients will undergo radiotherapy boost to the tumor bed only.

• Maintenance chemotherapy: Beginning 4 weeks after completion of chemoradiotherapy, patients receive 2 different regimens of maintenance chemotherapy for a total of 9 courses. Each course in regimen A is 6 weeks (42 days) in duration. Each course in regimen B is 4 weeks (28 days) in duration.

  • Regimen A (courses 1, 2, 4, 5, 7, and 8): Patients receive oral lomustine and cisplatin IV over 6 hours on day 1 and vincristine IV on days 1, 8, and 15 of weeks 11, 17, 27, 33, 43, and 49.
  • Regimen B (courses 3, 6, and 9): Patients receive cyclophosphamide IV over 1 hour on days 1 and 2 and vincristine IV on days 1 and 8 of weeks 23, 39, and 55. Treatment continues in the absence of disease progression or unacceptable toxicity.

Quality of life and neurocognitive function are assessed at 3-6 months after completion of radiotherapy and at 3-4 years after study entry.

Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

• Drug: cisplatin
• Drug: cyclophosphamide
• Drug: lomustine
• Drug: vincristine sulfate
• Radiation: radiation therapy

• Experimental: Patients undergo reduced-dose craniospinal radiotherapy with boost.
• Active Comparator: Patients undergo standard-dose craniospinal radiotherapy with boost.
• Active Comparator: Patients will undergo radiotherapy boost to the entire posterior fossa.
• Experimental: Patients will undergo radiotherapy boost to the tumor bed only.
• Experimental: Patients receive oral lomustine and cisplatin IV over 6 hours on day 1 and vincristine IV on days 1, 8, and 15 of weeks 11, 17, 27, 33, 43, and 49.
• Experimental: Patients receive cyclophosphamide IV over 1 hour on days 1 and 2 and vincristine IV on days 1 and 8 of weeks 23, 39, and 55.

DISEASE CHARACTERISTICS:

• Histologically confirmed medulloblastoma located in the posterior fossa

  • Standard-risk disease

• Minimal volume, non-disseminated disease, defined by the following:

  • Residual tumor ≤ 1.5 cm^2 confirmed by MRI with contrast imaging within 21 days after surgery

  • No metastatic disease in the head, spine, or cerebrospinal fluid (CSF) confirmed by both of the following:

    • Enhanced MRI of the spine within 5 days before surgery OR within 28 days after surgery
    • Negative cytological examination of CSF after surgery, but before study enrollment
• Brain stem involvement allowed

PATIENT CHARACTERISTICS:

Age

• 3 to 21 at diagnosis

Performance status

• Karnofsky 50-100% (> 16 years of age) OR
• Lansky 30-100% (≤ 16 years of age)

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count > 1,500/mm^3
• Platelet count > 100,000/mm^3 (transfusion independent)
• Hemoglobin > 10 g/dL (transfusions allowed)

Hepatic

• Bilirubin < 1.5 times upper limit of normal (ULN)
• AST or ALT < 1.5 times ULN

Renal

• Creatinine clearance OR radioisotope glomerular filtration rate ≥ 70 mL/min

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy

Endocrine therapy

• Prior corticosteroids allowed

Radiotherapy

• No prior radiotherapy

Surgery

• See Disease Characteristics