UNIty-Based MR-Linac Guided Adaptive RadioThErapy for High GraDe Glioma-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 withsystemic therapy

• Biopsy or surgical resection performed ≤ 12 weeks prior to study entry

• Adequate hematological, renal and hepatic functions as defined by the followingrequired 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-oxaloacetictransaminase (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 lifequestionnaires; however, inability to complete the questionnaires will not make thepatient ineligible for the study

• Sufficient estimated glomerular filtration rate (eGFR) of ≥ 30 mL / min/1.73 m2 toallow administration of gadolinium-based contrast agent; patients with eGFR < 30mL/min/1.73 m2 not on dialysis may be allowed on the study after discussion of risksand 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-melanomaskin cancer, or curatively treated other solid tumours with no evidence of diseasefor ≥ 2 years

• Patients with any condition (e.g. psychological, geographical, etc.) that does notpermit compliance with the protocol