Multiparametric MR-Guided High Dose Adaptive Radiotherapy With Concurrent Temozolomide in Patients With Newly Diagnosed Glioblastoma

Inclusion Criteria: * Provision of signed and dated informed consent form * Stated willingness to comply with all study procedures and availability for the duration of the study * Newly diagnosed, histologically-confirmed supratentorial WHO grade IV gliomas including glioblastoma (all variants) and gliosarcoma. Prior low-grade glioma without prior RT, now with malignant progression are eligible. * Karnofsky performance status \>=70 * Minimal life expectancy of 12 weeks * Adequate bone marrow reserve (Hemoglobin ≥ 10 g/dL, absolute neutrophils ≥ 1500/mm3, platelet count ≥ 100,000/mm3), acceptable liver function (total bilirubin ≤ 2 x upper limit of normal (ULN) (unless elevated bilirubin is related to Gilbert syndrome), and ALT/AST ≤ 5 x ULN) and renal function (serum creatinine ≤ 2.0 mg/dL) within 14 day prior to registration. Eligibility level for hemoglobin may be reached by transfusion. * Maximal contiguous diameter of tumor based on high b-value diffusion MRI and DCE perfusion MRI ≤5 cm * Patients must be registered within 6 weeks of most recent resection * 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 and study participation. Exclusion Criteria: * Recurrent glioma, or tumor involving the brainstem or cerebellum * 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. * Evidence of CSF dissemination (positive CSF 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 or non-life limiting invasive malignancy that may not require treatment, such as low-risk prostate 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 MRI exams (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 Department of Radiology MRI screening criteria) * Patients treated with previous cranial or head/neck radiotherapy leading to significant radiation field overlap as determined by treating physician * Multifocal disease (\>1 lobe of involvement) of discontiguous contrast enhancing disease as seen on conventional MRI * Pregnancy or lactation