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
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.
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.
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Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Diagnostic
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Recruiting |
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