This study is being done to compare standard radiation therapy with hypofractionated radiation therapy for patients with newly diagnosed glioblastoma

Hypofractionated radiation therapy (RT) in the treatment of patients with glioblastoma, 18 - 70 years of age with good performance status (ECOG 0 - 2), will be well tolerated and yield survival non-inferior to conventional fractioned RT, allowing significant abbreviation of the length of the radiation course required for these patients with limited survival. The importance of hypofractionation is, therefore, not in improving survival, but rather to shorten RT duration to improve patient comfort and convenience. This approach is pertinent given the limited life expectancy of glioblastoma and has been used in patients with prolonged survival including breast and prostate cancers.

Inclusion Criteria:

1. Newly-diagnosed, histologically proven, intracranial glioblastoma or gliosarcoma treated with maximal safe resection, which may be biopsy alone if resection is not possible.

2. History and physical examination, including neurological examination, within 14 days prior to randomization.

3. Age between 18 and 70 years, inclusive.

4. ECOG performance score 0-2.

5. Stable or decreasing dose of corticosteroids for at least 14 days prior to randomization (Stupp et al.).

6. Laboratory evaluation obtained within 7 days prior to randomization, with adequate function as defined below: (Stupp et al.)

   1. ANC ≥ 1.5 x 10^9/L
   2. Platelets ≥ 100 x 10^9/L
   3. Serum creatinine ≤ 1.5 times ULN
   4. Total serum bilirubin ≤ 1.5 times ULN
   5. ALT < 3 times ULN
   6. AST < 3 times ULN
   7. Alkaline phosphatase < 3 times ULN

7. Patients must sign a study-specific informed consent prior to study registration and must be willing to comply with study treatment, questionnaire completion and follow-up.

Exclusion Criteria:

1. Recurrent or multifocal malignant gliomas. Multicentric gliomas, defined as multiple, discrete areas of enhancement on T1 weighted MRI sequences with contrast all contained within one connected region of abnormality on T2 weighted/FLAIR MRI sequences, are allowed to enroll on this study.

2. Prior invasive malignancy (except for non-melanomatous skin cancer) unless expected survival from prior malignancy is ≥ 5 years.

3. Prior head or neck RT (except for T1 glottic cancer), or systemic therapy precluding delivery of concurrent and adjuvant temozolomide

4. Treatment with any other therapeutic clinical protocol within 30 days prior to study registration or during participation in the study.

5. Severe, active co-morbidity, defined as follows:

   1. Unstable angina and/or congestive heart failure requiring hospitalization
   2. Transmural myocardial infarction within the last 6 months
   3. Acute bacterial or fungal infection requiring intravenous antibiotics at the time of study registration
   4. Any severe, active co-morbidity precluding delivery of temozolomide.

6. Women of child-bearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception.

7. Pregnant or lactating women, due to possible adverse effects on the developing fetus or infant due to temozolomide.