Concurrent Fluorescence and Sonographically Guided Eradication of Contrast-enhancing Gliomas and Metastases

Study Overview
=================
Brief Summary
-----------------
Objective of the study is to determine whether combined use of intraoperative fluorescence with 5-aminolevulinic acid (5-ALA) and sonography can achieve higher rate of gross total resection of contrast-enhancing gliomas and brain metastases compared to intraoperative fluorescence with 5-ALA alone.

Detailed Description
-----------------
Fluorescence-guided resection of contrast-enhancing gliomas and metastases increases extent of tumor resection. But the main drawback of this method is an inability to observe tumor fluorescence while it is covered with normal brain. Ultrasound can resolve this problem, allowing to reveal such tumor remnants. By the time there are published results of randomized control trials comparing these two technics. Objective of the study is to determine whether combined use of intraoperative fluorescence with 5-aminolevulinic acid (5-ALA) and sonography can achieve higher rate of gross total resection of contrast-enhancing gliomas and brain metastases compared to intraoperative fluorescence with 5-ALA alone. Participants of the study will be randomly operated using both fluorescence with 5-ALA and intraoperative ultrasound versus fluorescence with 5-ALA alone. Extent of resection will be assessed in postoperative MRI by blinded radiologists.

Official Title
-----------------
Concurrent Fluorescence and Sonographically Guided Eradication of Gliomas and Metastases Enhancing Contrast Agent in Magnetic Resonance Imaging: a Randomised, Controlled Trial

Conditions
-----------------
Glioma, Malignant, Metastases to Brain

Intervention / Treatment
-----------------
* Device: Combined ultrasound and fluorescence-guided brain tumor resection
* Device: Fluorescence-guided brain tumor resection


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: single gliomas with contrast enhancement in preoperative magnetic resonance imaging (presumed high-grade gliomas) one or several brain metastases from any cancer 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
-----------------
Minimum Age: 18 Years
Maximum Age: 79 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fluorescence and Ultrasound<br>Extent of tumor resection will be intraoperatively assessed using both fluorescence with 5-aminolevulinic acid and sonography | Device: Combined ultrasound and fluorescence-guided brain tumor resection<br>* Surgeon intraoperatively assesses extent of tumor resection observing it's fluorescence in microscope and performing sonography<br>|
| Active Comparator: Fluorescence<br>Extent of tumor resection will be intraoperatively assessed using fluorescence with 5-aminolevulinic acid | Device: 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?
-----------------
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
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
contrast-enhancing glioma, brain metastasis, sonography, ultrasound, fluorescence, 5-aminolevulinic acid, 5-ALA