The PROGRAM-study: Awake Mapping Versus Asleep Mapping Versus No Mapping for Glioblastoma Resections

Study Overview
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Brief Summary
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The study is designed as an international, multicenter prospective cohort study. Patients with presumed glioblastoma (GBM) in- or near eloquent areas on diagnostic MRI will be selected by neurosurgeons. Patients will be treated following one of three study arms: 1) a craniotomy where the resection boundaries for motor or language functions will be identified by the awake mapping technique (awake craniotomy, AC); 2) a craniotomy where the resection boundaries for motor functions will be identified by asleep mapping techniques (MEPs, SSEPs, continuous dynamic mapping); 3) a craniotomy where the resection boundaries will not be identified by any mapping technique (no mapping group). All patients will receive follow-up according to standard practice.

Official Title
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The PROGRAM-study: Awake Mapping Versus Asleep Mapping Versus No Mapping for Glioblastoma Resections

Conditions
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Glioblastoma

Intervention / Treatment
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* Procedure: Awake mapping under local anesthesia
* Procedure: Asleep mapping under general anesthesia
* Procedure: Resection under general anesthesia without mapping


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years and ≤ 90 years Tumor diagnosed as GBM on MRI as assessed by the neurosurgeon Tumors situated in or near eloquent areas; motor cortex, sensory cortex, subcortical pyramidal tract, speech areas or visual areas as indicated on MRI (Sawaya Grading II and II) The tumor is suitable for resection (according to neurosurgeon) Written informed consent Exclusion Criteria: Tumors of the cerebellum, brain stem or midline Multifocal contrast enhancing lesions Medical reasons precluding MRI (e.g. pacemaker) Inability to give written informed consent (e.g. because of severe language barrier) Second primary malignancy within the past 5 years with the exception of adequately treated in situ carcinoma of any organ or basal cell carcinoma of the skin

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Awake mapping under local anesthesia<br> | Procedure: Awake mapping under local anesthesia<br>* During an awake craniotomy, the patient is awake and cooperative during the resection of the tumor while the surgeon uses electro(sub)cortical mapping to prevent damage to eloquent areas.<br>|
| Asleep mapping under general anesthesia<br> | Procedure: Asleep mapping under general anesthesia<br>* During asleep mapping under general anesthesia, the surgeon uses electro(sub)cortical mapping with evoked potentials (MEPs, SSEPs or continuous dynamic mapping) to prevent damage to eloquent areas.<br>|
| Resection under general anesthesia without mapping<br> | Procedure: Resection under general anesthesia without mapping<br>* During resection under general anesthesia without mapping, the surgeon does not use any intraoperative stimulation mapping techniques to identify eloquent areas.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neurological morbidity | NIHSS deterioration of 1 point or more as compared to baseline value. | Between baseline and 6 weeks/3 months/6 months postoperatively | 
| Extent of resection | Resection percentage as assessed by an independent neuroradiologist on MRI contrast images with volumetric analysis | Assessed within 72 hours on postoperative MRI scan | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | Progression-free survival (PFS) 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. | Between surgery and 12 months postoperatively | 
| Overall survival | Overall survival (OS) defined as time from diagnosis to death from any cause. | Between surgery and 12 months postoperatively | 
| Onco-functional outcome | 2D coordinate based on extent of resection (or residual tumor volume) on the x-axis and NIHSS score on the y-axis | Between baseline and 6 weeks/3 months/6 months postoperatively | 
| Frequency and severity of Serious Adverse Events (SAEs) | Infections, intracerebral bleeding, epilepsy, aphasia, paresis/paralysis in arms or/and legs (this is not an exhaustive list). | Between surgery and 6 weeks postoperatively | 
| Residual tumor volume | Postoperative tumor volume in mm3 as assessed by an independent neuroradiologist on MRI contrast images with volumetric analysis | Assessed within 72 hours on postoperative MRI scan | 
| MRC deterioration (for motor gliomas) | MRC deterioration of 1 point or more as compared to baseline value. | Between baseline and 6 weeks/3 months/6 months postoperatively |