UNIty-Based MR-Linac Guided Adaptive RadioThErapy for High GraDe Glioma-3 (UNITED-3)

The goal of this study is to test whether an adaptive radiation therapy (RT), two-phase approach in participants with glioblastoma impacts local control compared to standard non-adaptive RT approach. The main questions of the study are to see how this adaptive, two-phase RT approach compares to standard RT in terms of:Local controlOverall and progression-free survivalPatterns of failureToxicity, Neurological Function, and Quality of Life

Inclusion Criteria:Histopathologically confirmed, based on biopsy or surgical resection, glioblastoma, or grade 4 astrocytoma, as defined by the World Health Organization (WHO)Deemed clinically appropriate for long course radiation therapy concurrent with systemic therapyBiopsy or surgical resection performed ≤ 12 weeks prior to study entryAdequate hematological, renal and hepatic functions as defined by the following required laboratory values obtained within 14 days prior to study entry:Absolute granulocyte count (AGC) > 1.5 x 109/L (1,500 cells/mm3)Platelet count > 100x109/L (100,000 cells/mm3)Serum creatinine < 1.5 times the upper limit of normalTotal serum bilirubin < 1.5 times the upper limit of normalAlanine Aminotransferase (ALT, or formerly serum glutamic-pyruvic transaminase (SGPT)) < 2.5 times the upper limit of normaland/or aspartate aminotransferase (AST, or serum glutamic-oxaloacetic transaminase (SGOT)) < 2.5 times the upper limit of normalExpected survival ≥ 12 weeksEastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2Able (sufficiently fluent in English) and willing to complete quality of life questionnaires; however, inability to complete the questionnaires will not make the patient ineligible for the studySufficient estimated glomerular filtration rate (eGFR) of ≥ 30 mL / min/1.73 m2 to allow administration of gadolinium-based contrast agent; patients with eGFR < 30 mL/min/1.73 m2 not on dialysis may be allowed on the study after discussion of risks and benefits and approval by study neuroradiologist(s)Completed written informed consentPatient must be accessible for treatment and follow-upExclusion Criteria:Contraindications to MRI examination as per standard MRI screening policyContraindication to Gadolinium-based contrast mediaInability to lie flat in a supine position for at least 30 minutesInability to tolerate immobilization in a head thermoplastic maskPatients > 140 kg and/or a circumference > 60 cmPrior therapeutic cranial irradiationLeptomeningeal dissemination of diseaseHistory of other malignancies with the exception of adequately treated non-melanoma skin cancer, or curatively treated other solid tumours with no evidence of disease for ≥ 2 yearsPatients with any condition (e.g. psychological, geographical, etc.) that does not permit compliance with the protocol