Trial to determine the safety of neoadjuvant treatment with concurrent temozolomide and radiation therapy, followed by surgery and then further temozolomide.

Prior to any definitive treatment and after enrollment, the patient will undergo stereotactic biopsy of the lesion to confirm the histology of the lesion and to determine methylated methylguanine methyltransferase (MGMT) status. Standard image-guided stereotactic technique will be used. Patients will be treated with conformal radiation therapy. Temozolomide will be given from the day prior to radiation therapy through the last day of radiation therapy. 4-6 weeks after radiation therapy the patient will undergo craniotomy and maximal safe resection. Temozolomide will continue beginning 4 weeks after surgery.

Imaging:

MRI within 2 weeks prior to the start of the protocol. MRI at 4 weeks after chemoradiation therapy and prior to surgery. MRI within 48 hours after surgery.

MRI after every 2 cycles of chemotherapy and then every 2 months until progression, up to 2 years.

Inclusion Criteria:

• MRI lesions of the brain that have a high probability of being glioblastoma in a potentially resectable location in the brain (the primary study population)
• WHO performance status 0-2 (to allow comparison to historical controls)
• Adequate hematological parameters: (for safety because of neutropenia from the temozolomide)
• Consent can be obtained from the patient, and if the patient cannot give consent then from the medical power of attorney and if one is not assigned, then the nearest relative (required to obtain consent)
• Able to have MRI scans (secondary endpoint is MRI scan characteristics)
• Willing to have radiation treatment at a participating center (homogeneity of treatment parameters)
• Ages 18-80

Exclusion Criteria:

• Unresectable tumor
• Absolute neutrophil count (ANC) less than 1,200/μL
• Hemoglobin less than 9.0g/dL
• Platelet count less than 100,000/μL