Inclusion Criteria:

• Histopathologically confirmed WHO grade IV astrocytoma (GBM), tumor can be supra- or infra-tentorial in location but not located in the brain stem.
• Solitary or multifocal tumor.
• Tumor can be biopsied or resected, either totally or sub-totally.
• A pre-radiation therapy brain MRI is mandatory. Patients with contraindications for MRI scanning are ineligible for this study.
• Surgical cavity or surgical cavity + T1 enhancing residual tumor ≤ 6 cm in the largest diameter on the pre-radiation therapy MRI. In the case of multifocal tumor, the combined largest diameter of T1 enhancing tumor + surgical cavity ≤ 6 cm.
• Placement of BCNU wafers at the time of surgery is allowed.
• Age > 18 years at time of registration.
• Estimated survival of at least 3 months.
• Zubrod Performance Scale of 0-2 (Karnofsky performance scale ≥ 60).
• Hgb > 9 gm; ANC (absolute neutrophil count) > 1500/ul; platelets > 100,000; Creatinine < 1.5 times the upper limit of laboratory normal value; Bilirubin < 2 times the upper limit of laboratory normal value; SGPT or SGOT < 3 times the upper limit of laboratory normal value.
• Patients cannot be treated on any other clinical protocols within 30 days prior to study entry or during participation in the study.
• Patients must sign study-specific informed consent form prior to registration.
• Men and women and members of all ethnic groups are eligible for this trial.
• No active connective tissue disorders, such as active lupus or scleroderma.
• Radiation therapy and chemotherapy must start within 8 weeks of tumor resection or biopsy

Exclusion Criteria:

• prior temozolomide chemotherapy.
• prior brain irradiation.
• evidence of severe or uncontrolled psychiatric or systemic disease (e.g., unstable or uncompensated respiratory, cardiac, hepatic, or renal disease) that would interfere with study protocol as judged by the investigator.
• Acquired Immune Deficiency (HIV (+)/AIDS)
• pregnant women or breast feeding women. Women of childbearing potential must practice medically approved contraceptive precautions. Men should be counseled and agreeable to follow acceptable birth control methods.
• concurrent active malignancy at other sites.
• frequent vomiting of medical condition which could interfere with oral medication intake (e.g. partial bowel obstruction).