Previous evidence has indicated that resection for recurrent glioblastoma might benefit the prognosis of these patients in terms of overall survival. However, the demonstrated safety profile of this approach is contradictory in the literature and the specific benefits in distinct clinical and molecular patient subgroups remains ill-defined. The aim of this study, therefore, is to compare the effects of resection and best oncological treatment for recurrent glioblastoma as a whole and in clinically important subgroups.
This study is an international, multicenter, prospective observational cohort study. Recurrent glioblastoma patients will undergo tumor resection or best oncological treatment at a 1:1 ratio as decided by the tumor board. Primary endpoints are: 1) proportion of patients with NIHSS (National Institute of Health Stroke Scale) deterioration at 6 weeks after surgery and 2) overall survival. Secondary endpoints are: 1) progression-free survival (PFS), 2) NIHSS deterioration at 3 months and 6 months after surgery, 3) health-related quality of life (HRQoL) at 6 weeks, 3 months, and 6 months after surgery, and 4) frequency and severity of Serious Adverse Events (SAEs) in each arm. Estimated total duration of the study is 5 years. Patient inclusion is 4 years, follow-up is 1 year.
The study has been approved by the Medical Ethics Committee (METC Zuid-West Holland/Erasmus Medical Center; MEC-2020-0812). The results will be published in peer-reviewed academic journals and disseminated to patient organisations and media.
Age ≥18 years and ≤90 years
Tumor recurrence according to the RANO criteria of a previously diagnosed glioblastoma based on the WHO 2021 classification for glioma
The tumor is suitable for resection (according to neurosurgeon)
Written informed consent
Tumors of the cerebellum, brainstem, or midline
Medical reasons precluding MRI (e.g., pacemaker)
Inability to give written informed consent
Secondary high-grade glioma due to malignant transformation from low-grade glioma
Patients with recurrent glioblastoma 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.
Cohort
Prospective
Re-resection
Procedure/SurgeryResection of the recurrent tumor
Temozolomide
DrugRe-challenge Temozolomide chemotherapy
Lomustine
DrugSecond line chemotherapy with Lomustine
Re-irradiation
RadiationRe-irradiation with single dose, fractionated, or hypofractionated radiation of the recurrent tumor
Experimental therapy
Procedure/SurgeryExperimental phase I therapy with oncolytic virotherapy or immunotherapy (this list is not exhaustive)
Best supportive care
Other interventionBest supportive care, focused on alleviating symptoms
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
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)
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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
