Patients with GBM, who were deemed ineligible for any active protocols at our centre, received accelerated hypofractionation EBRT if 60Gy/20Fx using an IMRT technique with conventional dose of concomitant and adjuvant TMX as per the STUPP's TMZ schedule. Thirty five patients, 15 females and 20 males with a median age of 63 (range 31-78) were treated with a median KPS of 90 (range 50-100). Four patients had multicentric disease at presentation. Eight patients had biopsy only while the rest had a near total resection (n=14) and partial resection (n=13) with a median follow-up of 12.1 months, the median survival was 14.4 months.

In this proposal, the total cumulative dose of TMZ is unchanged as compared to the doses used in the Stupp protocol. In this proposal, the dose of TMZ is the same, with the sole difference that TMZ will be given in a neo-adjuvant setting for two weeks and then continued at the same dose concurrently with the accelerated hypofractionated EBRT delivering 60Gy in 4 weeks. The adjuvant component of TMZ remains unchanged from current standard practice.

Inclusion Criteria:

• Age: 18 years or older
• Histological confirmation of supratentorial GBM
• KPS > 60
• Neurological function 0 or 1
• Adequate bone marrow as defined below:
• absolute neutrophil count (ANC) > 1500 cells/mm3
• platelets > 100,000 cells/mm3
• hemoglobin > 10g/dl
• Adequate renal function as defined below:
• BUN < 25mg/dl within 14 days prior to study registration
• creatinine of 63 to 103 umol/L within 14 days prior to study registration
• Adequate hepatic function as defined below:
• Bilirubin of 3 to 21 umol/L within 14 days prior to study registration
• ALT & AST < 3xnormal range within 14 days prior to study registration
• Neoadjuvant TMZ to start within 3 weeks of surgery/biopsy if no resection was deemed feasible
• A diagnostic contrast-enhanced MRI or CT scan of the brain must be performed preoperatively and postoperatively.
• History, physical and neurological examination within 14 days prior to study registration.
• For females of child-bearing potential, negative pregnancy test within 72 hours prior to starting TMZ.
• Able to sign an informed study-specific consent

Exclusion Criteria:

• Margin of contrast-enhanced residual mass closer than 15mm from the optic chiasm or optic nerves.
• Prior invasive malignancy, unless disease-free for >3years
• Recurrent or multifocal GBM
• Severe co-morbidities such as
• unstable angina
• transmural myocardial infarction within 6 months
• COPD at the time of registration
• Hepatic insufficiency
• Bacterial or fungal infection requiring IV antibiotics at the time of registration
• Acquired Immune Deficiency Syndrome (AIDS)
• Major medical illnesses or psychiatric impairments
• Pregnant women or lactating women