Clinical Trial Finder

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

Arms

Experimental: Patients with Newly Diagnosed Glioblastoma

Patients will receive dose-intensified, adaptive photon radiation therapy

Interventions

Radiation: - Dose-Intensified Radiotherapy

Adaptive, dose-intensified radiotherapy targeting an advanced imaging signature, with a target, nominal radiotherapy dose of 80 Gy.

Drug: - Temozolomide

Temozolomide chemotherapy (75 mg/m2 daily for 6 weeks)

Drug: - Adjuvant temozolomide

Adjuvant temozolomide will be delivered at 150-200 mg/m2 days 1-5 every 28 days for 6 cycles, with additional cycles delivered at the discretion of the investigator.