Chemotherapy and Radiation Therapy After Surgery in Treating Children With Newly Diagnosed Astrocytoma, Glioblastoma Multiforme, Gliosarcoma, or Diffuse Intrinsic Pontine Glioma
Chemotherapy and Radiation Therapy After Surgery in Treating Children With Newly Diagnosed Astrocytoma, Glioblastoma Multiforme, Gliosarcoma, or Diffuse Intrinsic Pontine Glioma
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so
 they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells.
 Giving chemotherapy together with radiation therapy may kill more tumor cells.

 PURPOSE: This phase II trial is studying how well giving chemotherapy together with radiation
 therapy after surgery followed by chemotherapy alone works in children with newly diagnosed
 astrocytoma, glioblastoma multiforme, gliosarcoma, or diffuse intrinsic pontine glioma.
OBJECTIVES:

 -  Compare the event-free survival of patients with newly diagnosed anaplastic astrocytoma,
 glioblastoma multiforme, gliosarcoma, or diffuse intrinsic pontine glioma (DIPG) treated
 with adjuvant temozolomide administered concurrently with postoperative radiotherapy and
 then alone as maintenance therapy vs historical control cohorts treated in prior
 Pediatric Oncology Group and Children's Cancer Group studies.

 -  Determine the toxicity of this regimen in these patients.

 -  Determine the efficacy of this regimen in patients with DIPG.

 -  Determine the toxicity of this regimen in patients with DIPG.

 OUTLINE: This is a multicenter study.

 -  Adjuvant chemoradiotherapy: Beginning within 6 weeks after surgical resection or
 diagnosis*, patients without gross residual disease undergo cranial irradiation 5 days a
 week for 6 weeks. Beginning within 6 weeks after surgical resection, patients with gross
 residual disease undergo radiotherapy as above followed by boost radiotherapy for 1
 week. All patients receive oral temozolomide once daily beginning within 5 days after
 initiation of radiotherapy and continuing for a total of 6 weeks in the absence of
 disease progression or unacceptable toxicity.

 -  Adjuvant maintenance therapy: Beginning 4 weeks after completion of adjuvant
 chemoradiotherapy, patients receive oral temozolomide on days 1-5. Treatment repeats
 every 28 days for a total of 10 courses in the absence of disease progression or
 unacceptable toxicity.

 NOTE: *For patients with diffuse intrinsic pontine glioma only

 Patients are followed every 3-6 months for 4 years and then annually thereafter.

 PROJECTED ACCRUAL: A total of 50-60 patients will be accrued for this study within 12-14
 months.
DISEASE CHARACTERISTICS:

 -  Histologically confirmed newly diagnosed CNS tumor of the following types:

 -  High grade glioma (HGG) of one of the following histologies:

 -  Anaplastic astrocytoma (grade III)

 -  Glioblastoma multiforme (grade IV)

 -  Gliosarcoma

 -  Primary spinal cord malignant glioma

 -  Diffuse intrinsic pontine glioma (DIPG)

 -  Diagnosed by gadolinium-enhanced MRI

 -  At least 2/3 of tumor situated in the pons AND tumor clearly originated in
 the pons

 -  No diffuse leptomeningeal disease

 -  No tumors with features not typical of diffuse intrinsic brainstem glioma,
 including any of the following:

 -  Dorsally exophytic brainstem glioma

 -  Cervico-medullary junction tumor

 -  Focal low-grade glioma of the midbrain or brainstem

 -  No diffuse brainstem enlargement due to neurofibromatosis

 -  No primary brain stem malignant glioma

 -  No M+ disease (CSF positive for tumor or metastatic disease)

 -  Must begin study radiotherapy within 6 weeks after surgical resection (for HGG
 patients) or diagnosis (for DIPG patients)

 PATIENT CHARACTERISTICS:

 Age:

 -  3 to 21

 Performance status:

 -  Karnofsky 50-100% OR

 -  Lansky 50-100%

 Life expectancy:

 -  At least 2 months

 Hematopoietic:

 -  Absolute neutrophil count at least 1,000/mm^3

 -  Platelet count at least 100,000/mm^3*

 -  Hemoglobin at least 10.0 g/dL* NOTE: *Transfusion independent

 Hepatic:

 -  Bilirubin no greater than 1.5 times upper limit of normal (ULN)

 -  SGOT or SGPT less than 2.5 times ULN

 Renal:

 -  Creatinine no greater than 1.5 times ULN

 Other:

 -  No other concurrent malignancy

 -  Concurrent seizure disorder allowed if well controlled on anticonvulsants

 -  Not pregnant or nursing

 -  Negative pregnancy test

 -  Fertile patients must use effective contraception during and for 2 months after
 completion of study treatment

 PRIOR CONCURRENT THERAPY:

 Biologic:

 -  No concurrent routine cytokine support

 Chemotherapy:

 -  Not specified

 Endocrine therapy:

 -  No concurrent corticosteroids except for increased intracranial pressure in patients
 with CNS tumors

 Radiotherapy:

 -  See Disease Characteristics

 Surgery:

 -  See Disease Characteristics

 Other:

 -  No prior therapy for HGG or DIPG