Intraoperative MRI-guidance in Frameless Stereotactic Biopsies

January 17, 2016 updated by: Marcin Czyz, Wroclaw Medical University

The Safety and Effectiveness of Low Field Intraoperative MRI-guidance in Frameless Stereotactic Biopsies of Brain Tumours - a Prospective Randomized Trial

Background: The aim of the study was to assess the safety and effectiveness of stereotactic brain tumour biopsy (STx biopsy) guided by low-field intraoperative MRI (iMRI) in comparison with its frameless classic analogue based on a prospective randomized trial.

Patients are prospectively randomized into a low-field iMRI group and a control group that undergo a frameless STx biopsy. The primary endpoints of the analysis are: postoperative complication rate and diagnostic yield, and the secondary endpoints: length of hospital stay and duration of operation.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

INTRODUCTION Stereotactic brain biopsy (STx biopsy) offers a relatively straightforward, accurate and safe method of obtaining diagnostic tissue. Frameless computer-based neuronavigation is now widely used in brain tumor surgery. It has many advantages over frame-based techniques and provides similar accuracy to the rigid frame. One of the methods applied to improve diagnostic yield and safety is the usage of intraoperative magnetic resonance imaging (iMRI), proposed by Bernays et al. in 2002.

Besides the obvious indications given in previous papers, including STx biopsy of very small, deeply localized or cystic lesions, iMRI guidance is particularly useful in two cases. The first one is when a satisfactory 3D volume modality cannot be obtained during preoperative high-field diagnostic MR imaging. When using iMRI there is no need to perform preoperative 3D imaging of any kind and manually register the patient's head in a neuronavigation system before the operation, which helps to significantly improve the workflow. In our study the total amount of patients with insufficient neuroimaging - admitted from outside medical centers - is over 30%. The second case is for teaching purposes - frameless iMRI guided STx biopsy, is relatively uncomplicated and technically straightforward and can be introduced as the first procedure during training in neurosurgical intraoperative imaging.

Although the usefulness of ultra-low-field iMRI in STx biopsy was subsequently confirmed by other authors, according to our knowledge no previous published studies have compared iMRI to preoperative MRI for brain tumor biopsy according to evidence-based medicine guidelines (EBM). Though this method has been subject to slight criticism, it has been consequently applied in neurosurgical daily practice in recent years.

The aim of our study was to verify the safety and effectiveness of the STx biopsy guided by low-field iMRI in comparison with its frameless classic analogue basing on a prospective randomized parallel-group, controlled trial. In the current paper we present the study design and results of the interim analysis.

MATERIAL AND METHODS

Patients Patients who are - following contemporary recommendations - scheduled to undergo STx biopsy, are prospectively recruited for the study. Each patient sign a written consent to participate in the study.

Inclusion criteria The inclusion criteria were as follows: male and female patients ≥ 18 years with supratentorial brain tumor scheduled to undergo STx biopsy. The estimated number of patients needed to reveal the difference of over 5% between primary endpoints' - diagnostic yield and complications ratio - at the level of significance 0.05 and power 80% was 465 per each arm.

Exclusion criteria Patients unable to provide informed consent and those with metal implants which could prevent or influence the head MR study were excluded from the study.

Allocation Patients were prospectively allocated by minimization according to demographic (gender, age) and epidemiologic data (preoperative Eastern Cooperative Oncology Group Performance Status-ECOG- a scale providing information about neurological and social status of a patient with oncological disease, maximum tumor diameter, presence of contrast enhancement, independent risk factors of hemorrhage - basal and thalamic localization and preoperative diabetes) into the iMRI and the control group.

Intervention After being transferred to the operating room each patient was sedated with an intravenous infusion of Remifentanil with passive oxygen therapy and monitoring of vital functions. Additionally, the sites of head holder pins and skin incision were anaesthetized with 1% Lignocaine. All biopsies in both groups were performed via a 6 mm burr-hole with the use of the Vertec system (Medtronic Navigation, Louisville, CO, USA). A passively navigated side cut 2.2 mm biopsy needle was used. All operations were performed by one of the three first authors.

In the iMRI-guided group the head of each patient was immobilized with a 3-pin iMRI-compatible head holder. The PoleStar N20 iMRI system (Medtronic Navigation, Louisville, CO, USA) with a 0.15-T constant magnet was used in all procedures. Subsequently, after the patient's positioning, the preoperative reference examination was routinely carried out (T1+gadolinum, T2 or FLAIR weighted - depending on the pathology, axial 4 mm scans). Images were automatically transferred into the neuronavigation system (StealthStation, Medtronic Navigation, Louisville, CO, USA). The entry point, target and optimal biopsy trajectory were then defined by the operator on the basis of the obtained iMRI images. Serial tissue samples (4 from the central and another 4 from the marginal part of the tumor) were collected according to the modified protocol described by Shooman et al., which made use of intraoperative histopathological examination obsolete. Following each operation, a control iMRI (T1-weighted, axial, 4 mm scan examination) was routinely performed to confirm and document the proper targeting and - as proposed by Bernays et al. - to exclude postoperative hyperacute intraparenchymal bleeding.

A frameless STx biopsy was performed for each patient from the control group with the use of a neuronavigation system. The entry point, target and optimal biopsy trajectory were defined by the operator before the operation on the basis of the preoperatively obtained high-field MR images with the use of a neuronavigation workstation (Cranial 5, StealthStation Application Software, Medtronic Navigation, Louisville, CO, USA). Following surgery the specimens were sent for independent histopathological analysis.

Postoperative care Postoperative care was conducted according to standard protocols and clinical guidelines. A postoperative follow-up head CT was subsequently performed 4 to 6 hours after each procedure. All patients were followed up with a clinical examination 2 weeks postoperatively performed by an independent and blinded for the allocation investigator.

Data collection Demographic and epidemiological data were collected prospectively. The primary endpoints were: the ratio of acute postoperative complications and the diagnostic yield. The presence of acute postoperative complication was noted if any of following findings was noted: (wound site infection up to two weeks after the operation, a new neurological deficit developed up to 24 hours following the operation and present in a follow up clinical examination 2 weeks postoperatively), intraparenchymal hematoma with radiological or clinical signs of the intracranial expansion.) and the diagnostic yield. The diagnostic yield was expressed according to the literature as a percentage of patients in whom the histopathological diagnosis was possible on the basis of the biological material obtained during the operation. Secondary endpoints included: the preoperative (LOSpre), postoperative (LOSpost) and total length of hospital stay (LOS) as well as the preparation (Tprep), operation (Top) and total operating room (TOR) time. The LOS and T were routinely measured and recorded in the central hospital files by the independent staff.

Study Type

Interventional

Enrollment (Actual)

42

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Poland
      • Wroclaw, Poland, 50-556
        • Department of Neurosurgery, Wroclaw Medical University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • male and female patients ≥ 18 years
  • supratentorial brain tumour
  • scheduled to undergo STx biopsy

Exclusion Criteria:

  • patients unable to provide informed consent
  • metal implants which could prevent or influence the head MR study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: iMRI-guided
Intervention: iMRI-guided brain tumour biopsy. The PoleStar N20 iMRI system (Medtronic Navigation, Louisville, CO, USA) with a 0.15-T constant magnet imager will be used in all cases. After the patient's positioning, the preoperative reference examination is routinely carried out. The entry point, target and optimal biopsy trajectory are then defined by the operator on the basis of the obtained iMRI images. Serial tissue samples are collected. Following each operation, a control iMRI (T1-weighted, axial, 4 mm scan examination) is routinely performed to confirm and document the proper targeting and to exclude postoperative hyperacute intraparenchymal bleeding.
Device: iMRI-guided brain tumour biopsy
The PoleStar N20 iMRI system (Medtronic Navigation, Louisville, CO, USA) with a 0.15-T constant magnet was used in all procedures.
Other Names:
  • iMRI
Active Comparator: non-iMRI
Intervention: Stereotactic frameless brain tumour biopsy. A frameless STx biopsy is performed for each patient from the control group with the use of a neuronavigation system. The entry point, target and optimal biopsy trajectory are defined by the operator before the operation on the basis of the preoperatively obtained high-field MR images with the use of a neuronavigation workstation (Cranial 5, StealthStation Application Software, Medtronic Navigation, Louisville, CO, USA).
Device: Stereotactic frameless brain tumour biopsy
The entry point, target and optimal biopsy trajectory were defined by the operator before the operation on the basis of the preoperatively obtained high-field MR images with the use of a neuronavigation workstation (Cranial 5, StealthStation Application Software, Medtronic Navigation, Louisville, CO, USA).
Other Names:
  • Neuronavigation
  • Non-iMRI

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants Presenting With Complications
Time Frame: Patients were followed for the duration of hospital stay (average 2 days) and again 2 weeks after the operation.
The presence of acute postoperative complication is noted if any of following findings is present: wound site infection up to two weeks after the operation, a new neurological deficit developed up to 24 hours following the operation and present in a follow up clinical examination 2 weeks postoperatively, intraparenchymal hematoma with radiological or clinical signs of the intracranial expansion.
Patients were followed for the duration of hospital stay (average 2 days) and again 2 weeks after the operation.
Diagnostic Yield
Time Frame: For each patient 2 weeks after the operation
The diagnostic yield is expressed as the number of patients in whom the histopathological diagnosis was made based of the biological material obtained during the operation.
For each patient 2 weeks after the operation

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Length of Hospital Stay
Time Frame: From date of hospitalization until the date of discharge, assessed up to 2 days.
The preoperative (LOSpre), postoperative (LOSpost) and total length of hospital stay (LOS)
From date of hospitalization until the date of discharge, assessed up to 2 days.
Time
Time Frame: From moment of the transfer to the OR until the moment of transfer out of it, assessed on the day of operation.
the preparation (Tprep), operation (Top) and total operating room (TOR) time
From moment of the transfer to the OR until the moment of transfer out of it, assessed on the day of operation.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Wroclaw Medical University

Investigators

  • Study Chair: Wlodzimierz Jarmundowicz, Professor, Wroclaw Medical University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2009

Primary Completion (Actual)

October 1, 2015

Study Completion (Actual)

October 1, 2015

Study Registration Dates

First Submitted

January 15, 2013

First Submitted That Met QC Criteria

January 29, 2013

First Posted (Estimate)

January 30, 2013

Study Record Updates

Last Update Posted (Estimate)

February 15, 2016

Last Update Submitted That Met QC Criteria

January 17, 2016

Last Verified

January 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STAT2009

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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