RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether radiation therapy is more effective when given together with or without temozolomide in treating patients with low-grade glioma.

PURPOSE: This randomized phase III trial is studying radiation therapy so see how well it works when given together with or without temozolomide in treating patients with low-grade glioma.

OBJECTIVES:

Primary

• To determine whether the addition of temozolomide to fractionated radiotherapy improves the progression-free survival (PFS) of patients with symptomatic or progressive low-grade gliomas.
• To determine whether the addition of temozolomide to fractionated radiotherapy improves the median overall survival (OS) of these patients.

Secondary

• To determine whether combination therapy with temozolomide and radiotherapy improves or maintains cognition and quality of life compared to radiotherapy alone.
• To compare the toxicities (severe or worse [≥ grade 3]) of radiotherapy with vs without temozolomide in these patients.
• To assess the impact of the presence or absence of 1p and 19q deletion on PFS and OS.
• To determine the impact of 1p and 19q status on PFS and OS of patients treated with temozolomide.
• To create a tumor and tissue bank, including plasma and germ line DNA, within the ECOG Pathology Coordinating Office.

OUTLINE: This is a multicenter study. Patients are stratified according to age (< 40 years vs ≥ 40 years), 1p and 19q status (both deleted vs either/both intact vs undeterminable), pre-operative maximum tumor diameter (< 6 cm vs ≥ 6 cm [based on T2 or FLAIR MRI]), Karnofsky performance status (60-70% vs 80-100%), and contrast enhancement on pre-treatment MRI scan (present vs absent). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients undergo 3-dimensional conformal or intensity-modulated radiotherapy once daily 5 days a week for 5½ weeks (28 fractions).
• Arm II: Patients undergo radiotherapy as in arm I and receive concurrent oral temozolomide once daily for 5½ weeks. Beginning 28 days after completion of chemoradiotherapy, patients receive oral temozolomide alone once daily on days 1-5. Treatment with temozolomide repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.

Some patients undergo quality-of-life and neurocognitive (e.g., visual scanning speed, divided attention, language, memory, and fine motor skills) assessments at baseline, annually until disease progression, and at the time of disease progression.

Tumor tissue samples are collected at baseline for confirmation of diagnosis and determination of 1p and 19q deletion status. Peripheral blood, serum, and additional tumor tissue samples may be collected for further research studies.

After completion of study treatment, patients are followed up periodically for up to 15 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed* supratentorial low-grade glioma, including 1 of the following:

  • Grade 2 astrocytoma
  • Grade 2 oligodendroglioma
  • Grade 2 oligoastrocytoma (mixed glioma containing astrocytoma and oligodendroglioma)

• NOTE: *If the pathology from multiple procedures supports the diagnosis of a brain tumor, the qualifying pathology of grade 2 astrocytoma, oligodendroglioma, or oligoastrocytoma must be the most recent pathological diagnosis; no pathological diagnosis of grade 3 or 4 glioma at any time

• Paraffin-embedded tumor specimen available for submission for confirmation of pathological review and determination of 1p and 19q deletion status

• Patients must currently meet ≥ 1 of the following criteria*:

  • Uncontrolled symptoms, defined as any of the following:

    • Headaches associated with mass effect
    • Uncontrolled seizures despite two different antiepileptic drug regimens (i.e., two antiepileptic drugs tested either sequentially or in combination)
    • Focal neurological symptoms
    • Cognitive symptoms or deficits

  • Tumor progression by serial MRIs, defined as any of the following:

    • New or progressive enhancement
    • New or progressive T2 or FLAIR signal abnormality

  • Age ≥ 40 years

• NOTE: *Patients < 40 years of age whose only symptom of low-grade glioma is seizures that are well-controlled on antiepileptic drugs AND who have no evidence of radiographic progression are not eligible.

• Patients who have undergone gross total resection and have no detectable residual disease are eligible

• No pilocytic astrocytoma, ganglioglioma, pleomorphic xanthoastrocytoma, or dysembryoplastic neuroepithelial tumors

PATIENT CHARACTERISTICS:

• Karnofsky performance status 60-100%
• WBC ≥ 3,000/mm^3
• ANC ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hematocrit ≥ 30%
• Bilirubin ≤ 2 times upper limit of normal (ULN)
• AST and ALT ≤ 3 times ULN
• Creatinine ≤ 2.0 times ULN
• Not pregnant or nursing
• Negative pregnancy test
• Able to undergo MRI with and without contrast
• No other malignancy within the past 5 years, except for nonmelanoma skin cancer or cervical carcinoma in situ
• No uncontrolled infection
• No known HIV positivity
• No medical disorder that would increase risks associated with radiotherapy and temozolomide
• No other disorder that would limit life expectancy to < 5 years

PRIOR CONCURRENT THERAPY:

• No prior radiotherapy, cytotoxic chemotherapy, radiosurgery, or investigational therapy directed at the brain tumor

  • Any number of prior surgical procedures for the brain tumor allowed

• No prior radiotherapy to the head unless the radiotherapy ports entirely excluded the brain

• At least 2 weeks since any prior brain surgery (e.g., stereotatic biopsy, open biopsy, or resection)

• At least 6 weeks since prior MRI and chest x-ray

  • If resection is performed, an MRI after surgery is required