The trial is designed as a multicenter randomized controlled study. 246 patients with presumed Glioblastoma Multiforme in eloquent areas on diagnostic MRI will be selected by the neurosurgeons according the eligibility criteria (see under). After written informed consent is obtained, the patient will be randomized for an awake craniotomy (AC) (+/-123 patients) or craniotomy under general anesthesia (GA) (+/-123 patients), with 1:1 allocation ratio. Under GA the amount of resection of the tumour has to be performed within safe margins as judged by the surgeon during surgery. The second group will be operated with an awake craniotomy procedure where the resection boundaries for motor or language functions will be identified by direct cortical and subcortical stimulation. After surgery, the diagnosis of GBM will have to be histologically confirmed. If GBM is not histologically confirmed, patients will be considered off-study and withdrawn from the study. These patients will be followed-up according to standard practice. Thereafter, patients will receive the standard treatment with concomitant Temozolomide and radiation therapy and standard follow up. Total duration of the study is 5 years. Patient inclusion is expected to take 4 years. Follow-up is 1 year after surgery. Statistical analysis, cost benefit analysis and article writing will take 3 months.
Age ≥18 years and ≤ 90 years
Tumor diagnosed as Glioblastoma Multiforme on MRI with distinct ring-like pattern of contrast enhancement with thick irregular walls and a core area reduced signal suggestive of tumour necrosis as assessed by the surgeon
Tumors situated in or near eloquent areas; motor cortex, sensory cortex, subcortical pyramidal tract or speech areas as indicated on MRI (Sawaya Grading II and II)
The tumor is suitable for resection (according to neurosurgeon)
Tumors of the cerebellum, brain stem or midline
Multifocal contrast enhancing lesions
Substantial non-contrast enhancing tumor areas suggesting low grade gliomas with malignant transformation
Medical reasons precluding MRI (eg, pacemaker)
Parallel
Awake craniotomy
Procedure/SurgeryAwake craniotomy
Craniotomy under general anesthesia
Procedure/SurgeryCraniotomy under general anesthesia
Postoperative neurological morbidity
Proportion of patients with NIHSS (National Institute of Health Stroke Scale) deterioration at 6 weeks post-surgery, where deterioration is defined as at least one point increase in total NIHSS score compared to baseline
Proportion of gross-total resections
Proportion of patients without residual contrast-enhancing tumour on postoperative MRI, where residual tumour is defined as contrast-enhancement with a volume more than 0.175 cm3.
Health-related quality of life assessed by EQ-5D questionnaire
Health related quality of life (HRQoL) at 6 weeks, 3 and 6 months after operation, where HRQol is measured with the EQ-5D questionnaire
Health-related quality of life assessed by EORTC-QLQ-BN20 questionnaire
Health related quality of life (HRQoL) at 6 weeks, 3 and 6 months after operation, where HRQol is measured with the EORTC QLQ-BN20 questionnaire
Health-related quality of life assessed by EORTC-QLQ-C30 questionnaire
Health related quality of life (HRQoL) at 6 weeks, 3 and 6 months after operation, where HRQol is measured with the EORTC-QLQ-C30 questionnaire
Progression-free survival
Progression-free survival (PFS) at 12 months defined as time from diagnosis to disease progression (occurrence of a new tumour lesion with a volume greater than 0.175 cm3, or an increase in residual tumour volume of more than 25%) or death, whichever comes first
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Jasper Gerritsen
Lead sponsor
Erasmus Medical Center
Sponsor institution
Elisabeth-TweeSteden Ziekenhuis
Collaborator
University Medical Center Groningen
Collaborator
Medical Center Haaglanden
Collaborator
University Hospital, Ghent
Collaborator
