The SAFE-trial: Safe surgery for glioblastoma multiforme: Awake craniotomy versus surgery under general anesthesia. Study protocol for a multicenter prospective randomized controlled trial.

BACKGROUND: Surgery of GBM nowadays is usually performed under general anesthesia (GA) and resections are often not as aggressive as possible, due to the chance of seriously damaging the patient with a rather low life expectancy. A surgical technique optimizing resection of the tumor in eloquent areas but preventing neurological deficits is necessary to improve survival and quality of life in these patients. Awake craniotomy (AC) with the use of cortical and subcortical stimulation has been widely implemented for low-grade glioma resections (LGG), but not yet for GBM. AC has shown to increase resection percentage and preserve quality of life in LGG and could thus be of important value in GBM surgery.

METHODS/DESIGN: This study is a prospective, multicenter, randomized controlled trial (RCT). Consecutive patients with a glioblastoma in or near eloquent areas (Sawaya grading II/III) will be 1:1 randomized to awake craniotomy or craniotomy under general anesthesia. 246 patients will be included in neurosurgical centers in the Netherlands and Belgium. Primary end-points are: 1) Postoperative neurological morbidity and 2) Proportion of patients with gross-total resections. Secondary end-points are: 1) Health-related quality of life; 2) Progression-free survival (PFS); 3) Overall survival (OS) and 4) Frequency and severity of Serious Adverse Effects in each group. Also, a cost-benefit analysis will be performed. All patients will receive standard adjuvant treatment with concomitant chemoradiotherapy.

DISCUSSION: This RCT should demonstrate whether AC is superior to craniotomy under GA on neurological morbidity, extent of resection and survival for glioblastoma resections in or near eloquent areas.

TRIAL REGISTRATION: Clinicaltrials.gov: NCT03861299 Netherlands Trial Register (NTR): NL7589.