Intraoperative MRI-guidance in Frameless Stereotactic Biopsies

Primary Brain Tumour Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01779219
• Other study ID #: STAT2009
• Status: Terminated
• Phase: N/A
• First received: January 15, 2013
• Last updated: January 17, 2016
• Start date: June 2009
• Est. completion date: October 2015

Study information

• Verified date: January 2016
• Source: Wroclaw Medical University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Poland: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 42
• Est. completion date: October 2015
• Est. primary completion date: October 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Brain Neoplasms
• Primary Brain Tumour

Intervention

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.
• 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).

Locations

Country	Name	City	State
Poland	Department of Neurosurgery, Wroclaw Medical University	Wroclaw

Sponsors (1)

Lead Sponsor	Collaborator
Wroclaw Medical University

Country where clinical trial is conducted

Poland, 

References & Publications (13)

Bernays RL, Kollias SS, Khan N, Brandner S, Meier S, Yonekawa Y. Histological yield, complications, and technological considerations in 114 consecutive frameless stereotactic biopsy procedures aided by open intraoperative magnetic resonance imaging. J Neurosurg. 2002 Aug;97(2):354-62. — View Citation

Czyz M, Tabakow P, Jarmundowicz W, Lechowicz-Glogowska B. Intraoperative magnetic resonance-guided frameless stereotactic biopsies - initial clinical experience. Neurol Neurochir Pol. 2012 Mar-Apr;46(2):157-60. — View Citation

Frati A, Pichierri A, Bastianello S, Raco A, Santoro A, Esposito V, Giangaspero F, Salvati M. Frameless stereotactic cerebral biopsy: our experience in 296 cases. Stereotact Funct Neurosurg. 2011;89(4):234-45. doi: 10.1159/000325704. Epub 2011 Jul 21. — View Citation

Han B, Enas NH, McEntegart D. Randomization by minimization for unbalanced treatment allocation. Stat Med. 2009 Nov 30;28(27):3329-46. doi: 10.1002/sim.3710. — View Citation

Isaacs D, Fitzgerald D. Seven alternatives to evidence based medicine. BMJ. 1999 Dec 18-25;319(7225):1618. — View Citation

Kundt G. Comparative evaluation of balancing properties of stratified randomization procedures. Methods Inf Med. 2009;48(2):129-34. doi: 10.3414/ME0538. Epub 2009 Feb 18. — View Citation

Langen HJ, Kugel H, Ortmann M, Noack M, de Rochemont RM, Landwehr P. [Functional capacity of MRI-compatible biopsy needles in comparison with ferromagnetic biopsy needles. In vitro studies]. Rofo. 2001 Jul;173(7):658-62. German. — View Citation

McGirt MJ, Woodworth GF, Coon AL, Frazier JM, Amundson E, Garonzik I, Olivi A, Weingart JD. Independent predictors of morbidity after image-guided stereotactic brain biopsy: a risk assessment of 270 cases. J Neurosurg. 2005 May;102(5):897-901. — View Citation

Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982 Dec;5(6):649-55. — View Citation

Schulder M, Spiro D. Intraoperative MRI for stereotactic biopsy. Acta Neurochir Suppl. 2011;109:81-7. doi: 10.1007/978-3-211-99651-5_13. — View Citation

Senft C, Bink A, Franz K, Vatter H, Gasser T, Seifert V. Intraoperative MRI guidance and extent of resection in glioma surgery: a randomised, controlled trial. Lancet Oncol. 2011 Oct;12(11):997-1003. doi: 10.1016/S1470-2045(11)70196-6. Epub 2011 Aug 23. — View Citation

Shooman D, Belli A, Grundy PL. Image-guided frameless stereotactic biopsy without intraoperative neuropathological examination. J Neurosurg. 2010 Aug;113(2):170-8. doi: 10.3171/2009.12.JNS09573. — View Citation

Weaver CS, Leonardi-Bee J, Bath-Hextall FJ, Bath PM. Sample size calculations in acute stroke trials: a systematic review of their reporting, characteristics, and relationship with outcome. Stroke. 2004 May;35(5):1216-24. Epub 2004 Mar 18. Review. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Presenting With Complications	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.	Yes
Primary	Diagnostic Yield	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	No
Secondary	Length of Hospital Stay	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.	No
Secondary	Time	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.	No