Impact of iMRI on the Extent of Resection in Patients With Newly Diagnosed Glioblastomas
Study Details
Study Description
Brief Summary
Standard treatment of glioblastomas (GBMs) consists of microsurgical resection followed by concomitant chemoradiation. The extent of resection is one of the most important prognostic factors with significant influence on the survival of patients. State of the art technique to achieve the most radical resection possible in conventional surgery is fluorescence-guidance with 5-aminolevulinic acid (5-ALA). If available, intraoperative MRI (iMRI)-guided tumor resection enables an intraoperative resection control and subsequent continuation of surgery if contrast enhancing tumor remnants are found. Therefore a more radical resection and longer survival of patients might be possible. To date no comparison of these two leading technologies for GBM-surgery is available to identify the best surgical therapy of this fatal disease and to justify significant healthcare-economic differences between both technologies.
Goal of this study is to assess the value of iMRI guidance in the resection of GBMs in comparison to conventional 5-ALA microsurgery. Primary endpoint is the number of total resections (no residual contrast enhancement) in the postoperative MRI (T1+CM within 48 hours after surgery) in each group. Secondary endpoints are perioperative clinical data, progression free survival, patients' clinical condition and overall survival.
The study design was chosen to be a parallel-group approach to compare iMRI and 5-ALA centers (n=13) to exclude possible bias which might be found by randomizing patients within individual iMRI centers and to have surgeons with the most experience possible in use of each respective technology.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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N/A |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: iMRI-guided surgery Resection of Glioblastomas with iMRI-guidance |
Device: iMRI-guided surgery
For iMRI-guided glioma resections the surgery can be paused and a direct intraoperative resection control is possible by performing an intraoperative MRI scan. If residual tumor is found, the resection might be continued.
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| Active Comparator: 5-ALA-guided surgery Resection of Glioblastomas with 5-ALA-fluorescence-guidance |
Drug: 5-ALA-guided surgery
For 5-ALA guided glioma resections patients have to drink 100ml of a solution with 5-Aminolevulinic acid 4-6 hours before surgery. Intraoperatively the light source of the surgical microscope can be switched to a certain wave length to enable fluorescence of the glioma cells, which helps resecting the tumor as radical as possible.
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Outcome Measures
Primary Outcome Measures
- Complete resections in the postoperative MRI (T1+/-CM) within 48 hours after surgery [48 hour]
Completeness of resection in the postoperative MRI within 48h after surgery. Blinded analysis by an independent radiologist.
Secondary Outcome Measures
- Patients' clinical condition (KPS) [preoperative (day before surgery), 1 week, 3Months, 6Months, 9Months, 12Months after surgery]
-KPS clinical scoring
- Patients' clinical condition (NIHSS) [preoperative (day before surgery), 1 week, 3Months, 6Months, 9Months, 12Months after surgery]
-NIHSS stroke score
- Patients' clinical condition (QoL) [preoperative (day before surgery), 1 week, 3Months, 6Months, 9Months, 12Months after surgery]
-quality of life (EORTC) questionnaire
- ICU and hospital stay after surgery [Time of hospital stay (average 7days)]
-ICU and overall hospital stay after surgery
- Patients' adjuvant treatment [3Months, 6Months, 9Months, 12Months after surgery]
-adjuvant treatment each patient has received
- Recurrent tumor growth (RANO criteria) [3Months, 6Months, 9Months, 12Months after surgery]
-recurrent tumor growth (RANO criteria) according to local tumor boards and independent blinded analysis
- Follow-up imaging [3Months, 6Months, 9Months, 12Months after surgery]
-follow-up imaging 3, 6, 9, 12 months postoperative incl. independent blinded analysis
- Histology [1 week after surgery]
Histological analysis
- MGMT (O6-methylguanine-DNA-methyltransferase) analysis [1 week after surgery]
MGMT promoter analysis (Routine molecular diagnostics)
- IDH-1 (isocitrate dehydrogenase) analysis [1 week after surgery]
IDH-1 mutation analysis (Routine molecular diagnostics)
- Progression-free survival (PFS) [Day of surgery - 6 months - 12 months]
6M&12M-PFS
- Overall survival (OS) [Day of surgery - Death of patient (Max. 10 years follow-up)]
OS of patients
Other Outcome Measures
- Preoperative tumor localization and resectability concerning eloquent regions [Blinded analysis of preoperative imaging (not older than 3 days prior to surgery)]
Independent blinded analysis of the preoperative imaging data by a blinded neurosurgeon with extensive experience in the resection of gliomas. Analysis will be done before the final evaluation of results. (Within 12 months)
Eligibility Criteria
Criteria
Inclusion Criteria:
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In MRI suspected primary singular untreated GBM
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Planned total resection of the tumor according to the surgeon
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Patient ≥18 years, ≤80 years
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Preoperative KPS ≥ 60%, American Society of Anesthesiologists (ASA) score 1 and 2
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Patients' informed consent
Exclusion Criteria:
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Tumors of the midline, basal ganglia, cerebellum, brain stem, eloquent areas
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Multifocal glioblastoma
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Substantial (>50%), non-contrast enhancing tumor areas suggesting low-grade glioma with malignant transformation
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Contraindications to MRI
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Inability to give consent because of language barrier or dysphasia
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Histological diagnosis other than Glioblastoma multiforme WHO °IV
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Increased risk of thrombosis (e.g. Factor V Leiden)
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Pregnancy or breast feeding
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Hypersensibility for 5-ALA oder porphyrins
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Acute or chronic Porphyria
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Renal insufficiency
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Hepatic insufficiency
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High likelihood of inability to receive adjuvant therapy
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Department of Neurosurgery, Universitätsklinikum Bonn, Bonn, Germany | Bonn | Germany | ||
| 2 | Department of Neurosurgery, Universität zu Köln, Köln, Germany | Cologne | Germany | ||
| 3 | Städtisches Klinikum Dresden Friedrichstadt | Dresden | Germany | ||
| 4 | Department of Neurosurgery, Heinrich-Heine-Universität Düsseldorf, Düsseldorf | Düsseldorf | Germany | ||
| 5 | Department of Neurosurgery, Friedrich-Alexander-University Erlangen-Nürnberg | Erlangen | Germany | ||
| 6 | Department of Neurosurgery, Johann Wolfgang Goethe-University Frankfurt am Main | Frankfurt a.M. | Germany | ||
| 7 | Department of Neurosurgery, Georg-August-Universität Göttingen, Göttingen, | Göttingen | Germany | ||
| 8 | Department of Neurosurgery, University of Ulm, Hospital Günzburg, | Günzburg | Germany | ||
| 9 | Asklepios Klinik Hamburg, Klinik für Neurochirurgie | Hamburg | Germany | ||
| 10 | International Neuroscience Institute Hannover, Hannover, Germany | Hannover | Germany | ||
| 11 | Department of Neurosurgery, Ruprecht-Karls-University Heidelberg | Heidelberg | Germany | ||
| 12 | Department of Neurosurgery, University of Schleswig-Holstein, Kiel, Germany | Kiel | Germany | ||
| 13 | Department of Neurosurgery, Westfälische Wilhelms-Universität Münster, Münster, Germany | Münster | Germany | ||
| 14 | Department of Neurosurgery, Eberhard Karls University, Tübingen, | Tübingen | Germany | ||
| 15 | Department of Neurosurgery, Julius-Maximilians-Universität Würzburg | Würzburg | Germany |
Sponsors and Collaborators
- University Hospital Tuebingen
Investigators
- Principal Investigator: Constantin Roder, Dr., University Hospital Tuebingen, Department of Neurosurgery
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- Nch1