Targeted High Dose Radiation Therapy and Temozolomide in Treating Participants with Newly Diagnosed Glioblastoma

Inclusion Criteria

• Ability to understand and willingness to provide informed consent.
• Newly diagnosed, histologically-confirmed supratentorial World Health Organization (WHO) grade IV gliomas including glioblastoma (all variants) and gliosarcoma.
• Karnofsky performance status >= 70.
• Minimal life expectancy of 12 weeks.
• Hemoglobin >= 10 g/dL. Eligibility level for hemoglobin may be reached by transfusion.
• Absolute neutrophils >= 1500/mm^3.
• Platelet count >= 100,000/mm^3.
• Total bilirubin =< 2 x upper limit of normal (ULN) (unless elevated bilirubin is related to Gilbert syndrome).
• Alanine aminotransferase/aspartate aminotransferase (ALT/AST) =< 5 x ULN.
• Serum creatinine =< 2.0 mg/dL within 21 days of RT fraction 1.
• Maximal contiguous volume of tumor based on high b-value diffusion MRI and perfusion MRI < 1/3 volume of brain.
• Patients must be treated within 6 weeks of most recent resection.
• Evidence of cerebrospinal fluid (CSF) dissemination (positive CSF cytology for malignancy or MRI findings consistent with CSF dissemination).

Exclusion Criteria

• Recurrent glioma, or tumor involving the brainstem or cerebellum. Prior low-grade glioma without prior RT, now with malignant progression are eligible.
• Prior use of Gliadel wafers or any other intratumoral or intracavitary treatment is not permitted. Prior chemotherapy for a different cancer is allowable if interval since last treatment cycle completion is > 3 years.
• Multifocal disease (> 1 lobe of involvement) of discontiguous, contrast enhancing disease as seen on conventional MRI.
• Evidence of severe concurrent disease requiring treatment.
• Known active malignancy as determined by treating medical and radiation oncologist.
• Patients unable to undergo MRI exams.
• Patients treated with previous cranial or head/neck radiotherapy leading to significant radiation field overlap.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring inpatient hospitalization or delay treatment, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements or compromise subject safety.
• Pregnant women are excluded from this study because ionizing radiation is a known teratogen, and temozolomide is a class D agent with the potential for teratogenic or abortifacient effects.
• Nursing mothers declining to discontinue breastfeeding are excluded because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with temozolomide.
• Patients with reproductive potential declining to use an effective contraceptive method during treatment are excluded from this study.