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

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 therapy Biopsy or surgical resection performed ≤ 12 weeks prior to study entry Adequate 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 normal Total serum bilirubin < 1.5 times the upper limit of normal Alanine Aminotransferase (ALT, or formerly serum glutamic-pyruvic transaminase (SGPT)) < 2.5 times the upper limit of normal and/or aspartate aminotransferase (AST, or serum glutamic-oxaloacetic transaminase (SGOT)) < 2.5 times the upper limit of normal Expected survival ≥ 12 weeks Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 Able (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 study Sufficient 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 consent Patient must be accessible for treatment and follow-up Exclusion Criteria: Contraindications to MRI examination as per standard MRI screening policy Contraindication to Gadolinium-based contrast media Inability to lie flat in a supine position for at least 30 minutes Inability to tolerate immobilization in a head thermoplastic mask Patients > 140 kg and/or a circumference > 60 cm Prior therapeutic cranial irradiation Leptomeningeal dissemination of disease History 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 years Patients with any condition (e.g. psychological, geographical, etc.) that does not permit compliance with the protocol