About this trial
A greater extent of resection of the contrast-enhancing (CE) tumor part has been associated with improved outcomes in high-grade glioma patients. Recent results suggest that resection of the non-contrast-enhancing (NCE) part might yield even better survival outcomes (supramaximal resection, SMR). Therefore, this study evaluates the efficacy and safety of SMR with and without mapping techniques in HGG patients in terms of survival, functional, neurological, cognitive, and quality of life outcomes. Furthermore, it evaluates which patients benefit the most from SMR, and how they could be identified preoperatively.
This study is an international, multicenter, prospective, 2-arm cohort study of observational nature. Consecutive HGG patients will be operated with supramaximal resection or maximal resection at a 1:3 ratio. Primary endpoints are: 1) overall survival and 2) proportion of patients with NIHSS (National Institute of Health Stroke Scale) deterioration at 6 weeks, 3 months, and 6 months postoperatively. Secondary endpoints are 1) residual CE and NCE tumor volume on postoperative T1-contrast and FLAIR MRI scans 2) progression-free survival; 3) onco-functional outcome, and 4) quality of life at 6 weeks, 3 months, and 6 months postoperatively.
The study will be carried out by the centers affiliated with the European and North American Consortium and Registry for Intraoperative Mapping (ENCRAM).
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age ≥18 years and ≤90 years
Tumor diagnosed as HGG (WHO grade III/IV) on MRI as assessed by the neurosurgeon
Written informed consent
Disqualifiers
Tumors of the cerebellum, brainstem or midline
Multifocal contrast enhancing lesions
Medical reasons precluding MRI (e.g. pacemaker)
Inability to give written informed consent
Trial population
Patients with primary high-grade glioma will be recruited from the neurosurgical or neurological outpatient clinic or through referral from general hospitals of the participating neurosurgical hospitals, located in Europe and the United States. The study is carried out by centers from the ENCRAM Consortium.
Trial design
Cohort
Prospective
Treatments tested in this trial
Supramaximal resection
Procedure/SurgerySupramaximal resection. Tumor resection continues until either the FLAIR abnormalities have been resected based on the neuronavigation (after updating the navigation intraoperatively), or when subcortical tracts are identified with intraoperative stimulation.
Maximal safe resection
Procedure/SurgeryMaximal safe resection. Tumor resection continues until maximal safe resection has been achieved as by the neurosurgeon's opinion.
Treatment groups
Trial outcomes
Primary outcomes
Overall survival
Time from diagnosis to death from any cause
Neurological morbidity at 6 weeks
NIHSS deterioration of 1 point or more at 6 weeks after surgery
Secondary outcomes
Neurological morbidity at 3 months
NIHSS deterioration of 1 point or more at 3 months after surgery
Neurological morbidity at 6 months
NIHSS deterioration of 1 point or more at 6 months after surgery
Progression-free survival
Time from diagnosis to disease progression (occurrence of a new tumor lesions with a volume greater than 0.175 cm3, or an increase in residual tumor volume of more than 25%) or death, whichever comes first
Residual tumor volume
Residual tumor volume of the contrast-enhancing and non-contrast enhancing part, as assessed by a neuroradiologist on postoperative MRI scan (T1 with contrast and FLAIR sequences) using manual or semi-automatic volumetric analyses (Brainlab Elements iPlan CMF Segmentation, Brainlab AG, Munich, Germany; or similar software)
Sponsors and contacts
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Jasper Gerritsen
Lead sponsor
Erasmus Medical Center
Sponsor institution
Haaglanden Medical Centre
Collaborator
Universitaire Ziekenhuizen KU Leuven
Collaborator
University Hospital Heidelberg
Collaborator
Technical University of Munich
Collaborator
Insel Gruppe AG, University Hospital Bern
Collaborator
Massachusetts General Hospital
Collaborator
University of California, San Francisco
Collaborator