Low-Dose Radiation and Combination Chemotherapy Following Surgery in Children With Newly Diagnosed Medulloblastoma

RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells, but also damages normal cells in the developing brains of children. Combining low-dose radiation therapy in combination with chemotherapy should be effective in treating medulloblastoma while avoiding the long-term side effects of giving higher dose radiation to children with newly diagnosed average risk medulloblastoma.

OBJECTIVES:

* By giving reduced dose craniospinal radiation followed by nine cycles of maintenance chemotherapy comprised of alternating cycles of lomustine, cisplatin, and vincristine alternating with cyclophosphamide and etoposide, we will reduce the late effects of higher dose radiation in children while maintaining the therapeutic efficacy (86% 3-year relapse-free survival) of current standard therapy
* To evaluate the late neurotoxic effects of low-dose craniospinal radiotherapy, in terms of cognitive, endocrinologic, and auditory function, in these patients.

OUTLINE: This is a multi center study of reduced dose craniospinal radiotherapy and chemotherapy in patients ages 3 - 30 years with newly diagnosed average risk medulloblastoma.

* Induction chemoradiotherapy: Beginning within 28 days after complete surgical resection, patients undergo radiotherapy to the craniospinal axis (1800 centigray (cGy)) followed by conformal radiotherapy to the tumor bed (5400 cGy). Patients receive vincristine weekly for 6 weeks.
* Maintenance chemotherapy: Beginning 4 weeks after the completion of craniospinal radiation therapy, patients receive two 6-week courses of regimen A as outlined below alternating with one 6-week course of regimen B for a total of 9 courses (AABAABAAB).

  * Regimen A: Patients receive oral lomustine and cisplatin on day 0 and vincristine on days 0, 7, and 14.
  * Regimen B: Patients receive cyclophosphamide on days 0 and 1 and etoposide intravenous (IV) on days 0 and 1, followed by oral etoposide on days 14-34.

Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter with surveillance neuroimaging using Magnetic Resonance Imaging Scan (MRI scan) and clinical examination.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study within 3 years.

Eligibility Criteria:
Inclusion Criteria:

1. Histologically confirmed medulloblastoma
2. Standard-risk disease
3. No residual tumor greater than 1.5 cm\^2 after resection by postoperative MRI

   * No tumor in the spinal or cerebral subarachnoid space by MRI
   * No tumor in the subarachnoid space by Cerebrospinal fluid (CSF)
   * No failure to perform staging studies (spine MRI and CSF cytology) preoperatively or postoperatively
4. Must begin radiotherapy on study within 28 days after surgery

Exclusion Criteria:

1. Prior radiotherapy and anti-tumor chemotherapy other than corticosteroids are not allowed.
2. Pregnant females will not be eligible
3. Patients must begin radiotherapy on protocol within 28 days of completion of surgery. Exceptions need to be approved by the Principal Investigator.
4. Patients with the following will not be eligible:

   * \> 1.5cm3 residual tumor following resection as indicated by post-operative MRI.
   * tumor in spinal or cerebral subarachnoid space either by MRI of brain and spine
   * tumor in subarachnoid space by CSF cytology
   * failure to perform staging studies (spine MRI, CSF cytology) either pre- or post- operatively