Dose Escalated MRSI Guided Radiation Therapy in Glioblastoma

Inclusion Criteria:

1. Histologically proven diagnosis of glioblastoma (WHO grade IV). Since gliosarcoma is a variant of glioblastoma, gliosarcoma is also an eligible diagnosis.
2. The tumor must have a supratentorial component
3. Patients must have recovered from the effects of surgery, postoperative infection and other complications
4. Karnofsky performance status \> 70
5. Age \> 18 years
6. Adequate bone marrow function defined as follows:

   * Absolute neutrophil count (ANC) \>/= 1500 cells/mm\^3
   * Platelet count \> 100,000 cells/mm\^3
   * Hemoglobin \> 10.0 g/dL (Note: the use of transfusion or other intervention to achieve Hgb \> 10.0 g/dL is acceptable.)
7. Patients on full-dose anticoagulants (e.g., warfarin or low-molecular weight (LMW) heparin) must meet both of the following criteria:

   * No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)
   * In-range international normalized ratio (INR) (usually between 2 and 3) on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin
8. Adequate renal function, defined as follows:

   * Blood urea nitrogen (BUN) \< 30 mg/dL
   * Serum creatinine \< 1.5 x upper limit of normal (ULN)
9. Adequate hepatic function, as defined below:

   * Bilirubin \< 1.5 normal range
   * Alanine transaminase (ALT) \< 3x normal range
   * Aspartate transaminase (AST) \< 3x normal range
10. Patients must not be pregnant (positive pregnancy test) or breast feeding; pregnancy test must be done within 7 days prior to registration. Effective contraception (men and women) must be used in patients of child-bearing potential while on study treatment and for 6 months after.
11. Ability to understand and the willingness to sign a written informed consent document
12. Ability to have MRI Scans
13. Ability to swallow capsules

Exclusion Criteria:

1. Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years (for example, carcinoma in situ of the breast, oral cavity or cervix are all permissible)
2. Recurrent malignant glioma or evidence of leptomeningeal spread
3. Metastases detected below the tentorium or beyond the cranial vault
4. Prior use of Gliadel wafers or any other intratumoral or intracavitary treatment
5. Prior radiotherapy to the head or neck (except for T1 glottic cancer), resulting in overlap of radiation therapy fields
6. Prior radiation therapy or chemotherapy for glioblastoma
7. Severe, active co-morbidity, defined as follows:

   * Symptomatic congestive heart failure of New York heart Association Class III or IV
   * Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within the last 6 months, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease
   * Severely impaired lung function as defined as spirometry and diffusing capacity of the lung for carbon monoxide (DLCO) that is 50% of the normal predicted value and/or 02 saturation that is 88% or less at rest on room air
   * Uncontrolled diabetes as defined by fasting serum glucose \>1.5 x ULN
   * Active (acute or chronic) or uncontrolled severe infections requiring intravenous antibiotics
   * Liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis
   * Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition or known HIV seropositivity. Note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with HIV/AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive.
   * Active connective tissue disorders, such as lupus or scleroderma, that in the opinion of the treating physician may put the patient at high risk for radiation toxicity
   * Other major medical illnesses or psychiatric impairments that in the investigator's opinion will prevent administration or completion of protocol therapy
8. Pregnancy
9. Women who are breast feeding
10. Prior allergic reaction to temozolomide
11. Treatment on any other therapeutic clinical protocol
12. Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter their absorption of temozolomide (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)
13. Contraindications to MRI including but not limited to, pacemaker, aneurysm clips, neurostimulators, cochlear implants, metal in eyes, steelworker or other implants
14. Need to continue treatment with any prohibited medication (e.g. antioxidants) or have not completed the appropriate washout period.