Clinical trials

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.

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).

There is no consensus on the optimal treatment of patients with high-grade glioma, especially when patients have limited functioning performance at presentation (KPS ≤70). Therefore, there are varied practice patterns around pursuing biopsy, resection, or palliation (best supportive care). This study aims to characterize the impact of palliative care versus biopsy versus resection on survival and quality of life in these patients. Also, it will aim to determine if there is a subset of patients that benefit the most from resection or biopsy, for which outcome, and how they could be identified preoperatively. This study is an international, multicenter, prospective, 3-arm cohort study of observational nature. Consecutive HGG patients will be treated with palliative care, biopsy, or resection at a 1:3:3 ratio. Primary endpoints are: 1) overall survival, and 2) quality of life at 6 weeks, 3 months and 6 months after initial presentation based on the EQ-5D, EORTC QLQ C30 and EORTC BN 20 questionnaires. Total duration of the study is 5 years. Patient inclusion is 4 years, follow-up is 1 year.

There are no guidelines or prospective studies defining the optimal surgical treatment for gliomas of older patients (≥70 years) or those with limited functioning performance at presentation (KPS ≤70). Therefore, the decision between resection and biopsy is varied, amongst neurosurgeons internationally and at times even within an instiutition. This study aims to compare the effects of maximal tumor resection versus tissue biopsy on survival, functional, neurological, and quality of life outcomes in these patient subgroups. Furthermore, it evaluates which modality would maximize the potential to undergo adjuvant treatment. This study is an international, multicenter, prospective, 2-arm cohort study of observational nature. Consecutive HGG patients will be treated with resection or biopsy at a 3:1 ratio. Primary endpoints are: 1) overall survival (OS) and 2) proportion of patients that have received adjuvant treatment with chemotherapy and radiotherapy. Secondary endpoints are 1) proportion of patients with NIHSS (National Institute of Health Stroke Scale) deterioration at 6 weeks, 3 months and 6 months after surgery 2) progression-free survival (PFS); 3) quality of life at 6 weeks, 3 months and 6 months after surgery and 4) frequency and severity of Serious Adverse Events (SAEs). Total duration of the study is 5 years. Patient inclusion is 4 years, follow-up is 1 year.

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.