Intraoperative Sonographically Versus Fluorescence-guided Resection of Contrast-enhancing Gliomas and Brain Metastases

Study Overview
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Brief Summary
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Objective of the study is to determine whether intraoperative ultrasound guided resection of gliomas with contrast enhancement in magnetic resonance imaging and brain metastases can achieve as high rate of gross total resection as fluorescence-guided surgery with 5-aminolevulinic acid

Detailed Description
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Fluorescence with 5-aminolevulinic acid, fluorescein and intraoperative magnetic resonance imaging (MRI) are the most common modalities used to intraoperatively rate extent of brain tumor resection. Intraoperative sonography is another promising method of intraoperative visualization. It's advantages include possibility of real-time estimation of tumor remnants without disturbing of surgical workflow, opportunity to discover residual tumor under normal brain tissue and chipper cost. At this time there are no published results of randomized control trials comparing ultrasound and fluorescence-guided brain tumor resection. Objective of this study is to determine whether intraoperative ultrasound guided resection of gliomas with contrast enhancement in magnetic resonance imaging and brain metastases can achieve as high rate of gross total resection as 5-aminolevulinic acid fluorescence-guided surgery. Participants of the study will be randomly operated using intraoperative ultrasound or fluorescence with 5-aminolevulinic acid. Extent of resection will be assessed in postoperative MRI by blinded radiologists

Official Title
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Intraoperative Sonographically Guided Versus 5-Aminolevulinic Acid Fluorescence Guided Resection of Gliomas and Brain Metastases Enhancing Contrast Agent in Magnetic Resonance Imaging: a Randomised, Controlled, Noninferiority Trial

Conditions
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Gliomas, Malignant, Metastases to Brain

Intervention / Treatment
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* Device: Ultrasound guided brain tumor resection
* Device: 5-aminolevulinic acid fluorescence-guided brain tumor resection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: single gliomas with contrast enhancement in preoperative magnetic resonance imaging (presumed high-grade gliomas) one or several brain metastases newly diagnosed Karnofsky Performance Status 60-100% age 18-79 years performed magnetic resonance imaging with contrast enhancement Exclusion Criteria: tumor spreading to basal ganglia, corpus callosum or brainstem previously performed brain radiotherapy planned supratotal tumor resection until neurophysiologically revealed eloquent areas known hypersensibility to 5-aminolevulinic or to porphyrin hepatic or renal insufficiency porphyria pregnancy breast feeding

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 79 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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ultrasound<br>Intraoperative extent of tumor resection will be assessed using sonography | Device: Ultrasound guided brain tumor resection<br>* Surgeon intraoperatively assesses extent of tumor resection using ultrasound<br>|
| Active Comparator: Fluorescence<br>Intraoperative extent of tumor resection will be assessed using fluorescence with 5-aminolevulinic acid | Device: 5-aminolevulinic acid fluorescence-guided brain tumor resection<br>* Surgeon intraoperatively assesses extent of tumor resection observing it's fluorescence in microscope<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gross total resection (Yes or No) | No residual contrast enhancement in postoperative T1-weighted magnetic resonance imaging | within 48 hours after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Extent of resection (in percents) | Extent of resection = (preoperative tumor volume - postoperative tumor volume) / preoperative tumor volume x 100 | within 48 hours after surgery | 
| Motor function (in grades) | Motor function is assessed in Medical Research Council scale | within 10 days after surgery | 
| Speech function (in grades) | Speech function is assessed in Hendrix scale (2017) | within 10 days after surgery | 
| Karnofsky performance status (in percents) | Assesses patients' possibilities to self-service in Karnofsky Performance Status scale | within 10 days after surgery | 
| Cerebral complications | Which cerebral complications arose after surgery | From admission to intensive care unit after surgery till hospital discharge, up to 365 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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5-ALA, sonography, contrast-enhancing glioma, brain metastasis, ultrasound, fluorescence, 5-aminolevulinic acid