A Dose Per Fraction Escalation Trial of Hypofractionated IMRT With Temozolomide for Newly Diagnosed Glioblastoma

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. * 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 bis-chloronitrosourea (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; absolute neutrophil count (ANC) \> 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; serum glutamate pyruvate transaminase (SGPT) or serum glutamate oxaloacetate transaminase (SGOT) \< 3 times the upper limit of laboratory normal value. * 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. * Radiation therapy and chemotherapy must start within 8 weeks of tumor resection or biopsy Exclusion Criteria: * Patients with contraindications for MRI scanning. * 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) * Patients being treated on any other clinical protocols within 30 days prior to study entry or during participation in the study. * 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. * Active connective tissue disorders, such as active lupus or scleroderma. * Concurrent active malignancy at other sites. * Frequent vomiting of medical condition which could interfere with oral medication intake (e.g. partial bowel obstruction).