This is a multi-centre prospective, non-inferiority trial. Patients will be randomized to two treatment groups in a 1:1 ratio and will be stratified by age, Karnofsky Performance Status and extent of the surgical resection.

This study will assess the effect of a one-week radiotherapy regimen in comparison with a three-week radiotherapy regimen on the survival of elderly and/or frail patients with glioblastoma multiforme (Frail: ≥>50 years old and with a KPS of 50% or less50%-70%; Elderly and frail: ≥65 years and with a KPS of 50% - 70%; Elderly: ≥65 years and with a KPS of 80% - 100%).

This is a multi-centre prospective, non-inferiority trial. Patients will be randomized to two treatment groups in a 1:1 ratio and will be stratified by:

• Age (<65 and ≥65 years old)
• Karnofsky Performance Status (≤70 and > 7050 or higher)
• Extent of the resection at surgery (biopsy only versus complete/near total and gross total or incomplete /partial resection)

Randomization:

Patients will be randomized to receive one of the two following treatments:

Arm 1:

• Short Radiotherapy
• 25 Gy/5 fractions
• 1 week (5 fractions per week)

Arm 2:

• Regular Radiotherapy
• 40 Gy/15 fractions
• 3 weeks (5 fractions per week)

Inclusion Criteria:

• Histopathologically confirmed newly diagnosed glioblastoma multiforme (GBM, WHO grade IV). The histological diagnosis must have been made locally after biopsy or neurosurgical tumour resection.
• Initial surgery/biopsy at diagnosis performed < 6 weeks (42 days) prior to randomization.
• Patient's age is 50 years or older.
• Karnofsky performance status is 50% or higher.
• Patients may have received and continue to receive corticosteroids, but they have to be on a stable or decreasing dose for at least 14 days prior to randomization.
• Patients must not have received prior chemotherapy or radiotherapy.
• Patient is able (i.e. sufficiently fluent) and willing to complete the quality of life questionnaires in either English or any other language the questionnaire is officially translated into. The baseline assessment (prior to start of radiotherapy) must already have been completed. Inability (illiteracy, loss of sight, or other equivalent reason) to complete the questionnaires will not make the patient ineligible for the study. In centres where patients are not able to read or write, proxy interviews will be conducted in-person or via telephone by the nurse at that particular centre.
• Patient consent must be obtained according to local institutional policy. It will be the responsibility of the local participating investigators to obtain the necessary local clearance, and to indicate in writing to the IAEA Study Coordinator that such clearance has been obtained, before the trial can commence in that centre. A copy of the initial full board ERB approval and approved consent form must be sent to the Project Officer at IAEA. The patient must sign the consent form prior to randomization or registration.
• Patients must be accessible for treatment and follow-up. Investigators must assure themselves the patients randomized on this trial will be available for complete documentation of the treatment, adverse events, and follow-up.
• Protocol treatment is to begin within 2 weeks of patient randomization.

Exclusion Criteria:

• Patients with a history of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for 3 or more years.
• Patients with a serious active infection or other serious underlying medical conditions that would impair the ability of the patient to receive protocol treatment or comply with protocol.