A Study of High-Dose Chemoradiation Using Biologically-Based Target Volume Definition in Patients With Glioblastoma

Inclusion Criteria: * Newly diagnosed histologically-confirmed supratentorial World Health Organization (WHO) grade IV gliomas including glioblastoma multiforme and gliosarcoma * Age 18 or older * Karnofsky performance status (a measure to quantify general well being and activities of daily life; scale ranges from 0 to 100 where 100 is perfect health) of greater than or equal to 70 * Life expectancy of at least 12 weeks * Adequate bone marrow reserve (hemoglobin greater than or equal to 10, absolute neutrophil count greater than or equal to 1500, platelets greater than or equal to 100,000); acceptable liver function (total bilirubin less than or equal to 2.0 mg/dl, ALT (Alanine Aminotransferase)/AST (Aspartate Aminotransferase) less than or equal to 5 times the normal range); acceptable renal function (serum creatinine less than or equal to 2.0 mg/dl). Eligibility level for hemoglobin may be reached by transfusion. * Maximal contiguous volume of tumor based on high b-value diffusion MRI \< 1/3 volume of brain * Patients must be registered within 6 weeks of most recent resection. * Patients must have signed a study-specific informed consent. 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, except for Temozolomide or Bevacizumab. * Evidence of cerebrospinal fluid dissemination (positive cerebrospinal fluid cytology for malignancy or MRI findings consistent with CSF dissemination) * Evidence of severe concurrent disease requiring treatment * Prior invasive malignancy (except non-melanoma skin cancer) unless disease-free for a minimum of 3 years (for example, carcinoma in situ of breast, oral cavity or cervix are all permissible) * Patients unable to undergo Magnetic Resonance Imaging exams (MRI) (i.e. patients with non-compatible devices such as cardiac pacemakers, other implanted electronic devices, metallic prostheses, or ferromagnetic prostheses (e.g. pins in artificial joints and surgical pins/clips) or unable to receive gadolinium for MRI, as per the standard UM Department of Radiology MRI screening criteria) * Patients treated with previous cranial or head/neck radiotherapy leading to radiation field overlap * Females of child-bearing potential must have a negative pregnancy test within 14 days prior to registration. Patients with reproductive potential must agree to use an effective contraceptive method during treatment.