Is There an Indication for Intraoperative MRI in Subtotal Resection of Glioblastoma? A Multicenter Retrospective Comparative Analysis

doi:10.1016/j.wneu.2017.11.015

World Neurosurgery

Volume 110, February 2018, Pages e389-e397

Parts of these data have been presented as a talk at the Intraoperative Imaging Society 6th Biennial Meeting, February 23–26, 2017, in Hannover, Germany.

https://doi.org/10.1016/j.wneu.2017.11.015 Get rights and content

Objective

Surgery in patients with highly eloquent glioblastoma (GB) remains challenging. The aim of this study was to evaluate influence of use of intraoperative magnetic resonance imaging (iMRI) on extent of resection (EOR), clinical outcome, and survival in patients with preoperatively intended subtotal resection of GB.

Methods

Retrospective assessment was performed in 3 neurosurgical centers (2008–2013). All patients with primary GB, unilocular growth, and adjuvant radiochemotherapy in whom subtotal resection was intended were included. Imaging data were pseudonymized and volumetrically assessed by a central reviewer. Clinical outcome was evaluated based on complications, new permanent neurologic deficits, and survival. Based on subtraction of potential EOR (as defined by reviewer) from effective EOR, EOR change (ΔEOR) was calculated for each case. We calculated multivariate linear regressions to assess influence on effective EOR and ΔEOR, binary regressions to assess influence on complications and new permanent neurologic deficits, and Cox regression models to assess survival.

Results

Assessment included 70 patients. In iMRI group, a significantly lower ΔEOR (4% vs. 22%, P = 0.008) was found. In linear regression model controlling for age, tumor volume, neurophysiologic mapping, and iMRI, only iMRI influenced ΔEOR significantly (P = 0.03, odds ratio 0.27). In binary regression model controlling for age, tumor volume, effective EOR, neurophysiologic mapping, and iMRI, none of the variables showed a significant difference concerning complications and new permanent neurologic deficits. Overall survival was significantly influenced by age (P = 0.03, odds ratio 1.02) and iMRI (P = 0.026, odds ratio 0.51).

Conclusions

Maximum safe resection is an important prognostic factor for patients with eloquent GBs. iMRI seems to be a relevant tool to achieve this goal.

Introduction

The present literature on glioblastoma (GB) surgery shows a strong benefit of gross total resection (GTR) on overall survival (OS).¹ Still, counseling patients with highly eloquent GBs amenable only to subtotal resection (STR) remains challenging. Based on the current level of evidence, definitive conclusions concerning the oncologic benefit of STR are not possible. Although explicit data on this group of patients are scarce, a large meta-analysis demonstrated that STR shows a significant benefit for OS compared with biopsy alone without increased morbidity.² Data from Marko et al.³ showed that there might by a linear association of resected tumor volume and survival promoting the strategy of a maximum safe resection in GB surgery. The additional use of intraoperative imaging methods, such as 5-aminolevulinic acid and intraoperative magnetic resonance imaging (iMRI), was shown to be beneficial to increase GTR rate in lesions eligible for complete removal of contrast enhancement.4, 5 Based on rates of residual tumor volume and thresholds of extent of resection (EOR) to influence survival published by Chaichana et al.,⁶ there might be a beneficial role of intraoperative imaging in lesions primarily amenable only to STR. High-field iMRI with field strength of ≥1.5T allows for an intraoperative update of neuronavigation and diffusion tensor imaging (DTI) data for fiber tracking.⁷ Thus, iMRI provides useful information on eloquent areas in addition to intraoperative mapping/monitoring (IOM). The aim of the present study was to assess the influence of use of iMRI on EOR in preoperatively intended STR of GB involving eloquent areas. Furthermore, we assessed clinical outcome and progression-free survival (PFS) and OS in this cohort.

Section snippets

Study Design

We performed a retrospective multicenter study in 3 neuro-oncologic centers (Klinikum Stuttgart/Katharinenhospital, University Medical Center Mainz, and University Medical Center Ulm/Günzburg) to evaluate patients undergoing STR with regard to clinical outcomes from 2008 to 2013. Ethical approval was received by the ethical board of Ulm University (No: 316/16). Owing to the retrospective nature of the study, no patient consent was required for this study. Inclusion criteria were age >18 years;

General Assessment

Our assessment included 70 patients with a GB diagnosis (World Health Organization grade IV); 33 patients underwent surgery with iMRI, and 37 patients underwent surgery without MRI. Table 1 presents the details of both cohorts. All patients had a complete follow-up. Except for the higher prevalence of patients with MGMT promoter methylation in the iMRI cohort and the higher number of unassessed MGMT promoter methylation status in the non-iMRI group, both cohorts showed similar general

Discussion

iMRI has been used for the past 20 years to assist surgery for various intracranial pathologies.9, 10, 11, 12, 13, 14, 15, 16 This technology was developed primarily to control for the significant shift of brain structures during the course of surgery (brain shift).17, 18 Based on the direct visualization of residual tumor and the option to update the imaging information of the neuronavigation system, iMRI has been shown to improve EOR compared with neuronavigation alone.⁴ The development of

Conclusions

Maximal safe resection is an important prognostic factor for patients with eloquent GBs. iMRI seems to be a relevant tool to achieve this goal. We recommend the mandatory use of IOM during all intended STRs.

Acknowledgments

We thank the Institute for Epidemiology and Medical Biometrics of Ulm University for extensive statistical counseling.

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Effect of high-field iMRI guided resection in cerebral glioma surgery: A randomized clinical trial
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Extent of resection (EOR) in glioma contributes to longer survival. The purpose of NCT01479686 was to prove whether intraoperative magnetic resonance imaging (iMRI) increases EOR in glioma surgery and benefit survival.
Patients were randomized (1:1) to receive the iMRI (n = 161) or the conventional neuronavigation (n = 160). The primary endpoint was gross total resection (GTR); secondary outcomes reported were progression-free survival (PFS), overall survival (OS), and safety.
188 high-grade gliomas (HGGs) and 133 low-grade gliomas (LGGs) were enrolled. GTR was 83.85% in the iMRI group vs. 50.00% in the control group (P < 0.0001). In 321 patients, the median PFS (mPFS) was 65.12 months in the iMRI group and 61.01 months in the control group (P = 0.0202). For HGGs, mPFS was improved in the iMRI group (19.32 vs. 13.34 months, P = 0.0015), and a trend of superior OS compared with control was observed (29.73 vs. 25.33 months, P = 0.1233). In the predefined eloquent area HGG subgroup, mPFS, and mOS were 20.47 months and 33.58 months in the iMRI vs. 12.21 months and 21.16 months in the control group (P = 0.0098; P = 0.0375, respectively). From the exploratory analyses of HGGs, residual tumor volume (TV) < 1.0 cm³ decreased the risk of survival (mPFS: 18.99 vs. 9.43 months, P = 0.0055; mOS: 29.77 vs. 18.10 months, P = 0.0042). LGGs with preoperative (pre-OP) TV > 43.1 cm³ and postoperative (post-OP) TV > 4.6 cm³ showed worse OS (P= 0.0117)
It showed that iMRI significantly increased EOR and indicated survival benefits for HGGs, particularly eloquent HGGs. Residual TV in either HGGs or LGGs is a prognostic factor for survival.
Intraoperative Magnetic Resonance Imaging (MRI)-Guided Resection of Glioblastoma: A Meta-Analysis of 1,847 Patients
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Intraoperative Magnetic Resonance Imaging for Low-Grade and High-Grade Gliomas: What Is the Evidence? A Meta-Analysis
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Citation Excerpt :
Partial resection and debulking (presumably for the purpose of mass effect reduction and possibly cytoreduction) might be performed solely based on preoperative MRI and neuronavigation, without a need to acquire a new MRI during surgery. For planned subtotal resection of extensive gliomas in patients in whom there were significant brain shifts, iMRI would be invaluable to guide maximal safe resection and to allow biopsy of specific regions.42 Three different iMRI setups were described in the included studies: an integrated OR with iMRI in the same room,12,27 iMRI located in a separated OR,10,26,28,30,31,35 or as a mobile ultralow-field iMRI scanner that did not require a dedicated OR.25,29,33,36
The benefit of intraoperative magnetic resonance imaging (iMRI) in gliomas remains unclear. We performed a meta-analysis of outcomes with iMRI-guided surgery in high-grade gliomas (HGGs) and low-grade gliomas (LGGs).
Databases were searched until November 29, 2018 for randomized controlled trials (RCTs) and observational studies (OBS) comparing iMRI use with conventional neurosurgery. Pooled risk ratios (RRs) or hazard ratios were evaluated with the random-effects model. Outcomes included extent of resection (EOR), gross total resection (GTR), progression-free survival (PFS), overall survival (OS), and length of surgery (LOS), stratified by study design and glioma grade.
Fifteen articles (3 RCTs and 12 OBS) were included. In RCTs, GTR was higher in iMRI compared with conventional neurosurgery (RR, 1.42; 95% confidence interval [CI], 1.17–1.73; I², 7%) overall, for LGGs (1.91; 95% CI, 1.19–3.06), but not HGGs (1.24; 95% CI, 0.89–1.73), with no difference in EOR, PFS, OS, and LOS. For OBS, GTR was higher (RR, 1.65; 95% CI, 1.43–1.90; I², 4%) overall, and for LGGs (1.63; 95% CI, 1.17–2.28; I², 0%) and HGGs (1.62; 95% CI, 1.36–1.92; I², 19%). EOR was greater with iMRI (6%; 95% CI, 4%–8%; I², 44%) overall, in LGGs (5%; 95% CI, 2%–8%; I², 37%) and HGGs (7%; 95% CI, 4%–10%; I², 13%). There was no difference in PFS, OS, and LOS with iMRI.
IMRI use improved GTR in gliomas, including LGGs. However, no PFS and OS benefit was shown in the meta-analysis.
Anesthetic challenges and outcomes for procedures in the intraoperative magnetic resonance imaging suite: A systematic review
2019, Journal of Clinical Anesthesia
Citation Excerpt :
Introduction of a magnetic field within the surgical environment also necessitates modifications to the physical space and equipment, resulting in multiple changes to the usual workflow, communication, and patient care. The use of iMRI technology is supported by the available evidence, suggesting a benefit to neurosurgical patients undergoing intracranial tumor resections [9–12]. Several other applications are being investigated, including epilepsy and breast cancer surgery [13,14].
Hybrid operating room suites with intraoperative magnetic resonance imaging enable image guided surgery in a fully functional operating room environment. While this environment creates challenges to anesthetic care, the effects on anesthetic adverse events and outcomes are largely unknown. This systematic scoping review aims to map the existing knowledge about anesthetic care in advanced imaging hybrid operating rooms.
A broad-based literature search was performed using the PubMed (Medline), Embase, Cochrane Library, Web of Science, and Google Scholar databases. References published in English between January 1994 and August 2017 were included. Quality of evidence was assessed using the GRADE guidelines.
Forty-seven manuscripts were eligible for data collection. Adverse events were heterogeneously defined across 17 manuscripts and occurred in 0 to 100% (quality of evidence mostly very low). Monitoring difficulty was reported in 4 manuscripts of very low data quality. Interference between the magnet and the electrocardiogram was investigated in 2 manuscripts (quality of evidence low and very low, respectively). None of the reported events appeared to result in long-term patient harm. Author recommendations or a narrative review of the literature were provided in 40 manuscripts. Common safety concerns included lower equipment reliability, inaccessibility of the patient and airway, and the relative isolation of the suite (in relationship to other anesthesia care areas). Most authors also emphasized the importance of safety checklists, protocols, and provider training.
While intraoperative magnetic resonance imaging hybrid operating rooms are increasingly utilized, the existing literature does not allow estimating adverse event rates in this location. Prospective studies quantifying the effect of the environment on anesthesia outcomes are lacking. Despite this, there is a broad consensus regarding the anesthetic and safety concerns. More research is needed to inform practice standards and training requirements for this challenging environment.
Counseling Patients with a Glioblastoma Amenable Only for Subtotal Resection: Results of a Multicenter Retrospective Assessment of Survival and Neurologic Outcome
2018, World Neurosurgery
Citation Excerpt :
Data of our group from a retrospective multicenter series assessing exclusively patients with GB amenable only for stereotactic biopsy or for STR show that, especially in the latter group of patients, potential extent of resection (EoR) is mainly underestimated.7 Furthermore, we found that patients with GB amenable for a STR operated with intraoperative magnetic resonance imaging (iMRI) showed an improved OS compared with resection without use of additional intraoperative imaging.8 This finding might support the theory of a maximum safe resection approach in patients with an intended STR.
Patients with a glioblastoma (GB) amenable only for subtotal resection (STR) represent a challenge in patient counseling. Our objective was to assess impact of extent of resection (EoR) on survival and clinical outcome of these patients.
We performed a retrospective multicenter assessment. Patients receiving an intended STR in 3 centers with unilocular, primary, highly eloquent GB who received the same adjuvant treatment were included. We assessed EoR, neurologic outcome, and rate of complications. Progression-free survival (PFS) and overall survival (OS) were calculated with Kaplan–Meier estimations. We used 1% EoR and 1-cm³ steps to detect a threshold for a minimal EoR and residual tumor volume (RV) to be beneficial for survival and performed multivariate Cox regression models to assess its influence on PFS and OS.
In total, 67 patients were included. EoR and RV were not significantly associated with PFS in multivariate Cox regression. Multivariate Cox regression model for OS revealed that volumetric EoR is a significant predictor for OS (P = 0.002, OR 0.982), same as RV (P = 0.007, OR 1.03), controlling for age, preoperative tumor volume, sex, and recurrent surgery. We found a significant benefit for OS if an EoR >60% or a RV <8 cm³ was reached. In the aforementioned multivariate Cox regression models, an EoR ≤60% and a RV ≥8 cm³ independently showed a significantly negative association with OS (P = 0.044, OR 1.96/P = 0.024, OR 2.07).
In highly eloquent GB, EoR significantly matters for patients' OS. Also, potential RV should be considered when treating these patients. In cases with an expected RV above or an EoR below the aforementioned thresholds, open surgery should be carefully considered.
Review of Intraoperative Adjuncts for Maximal Safe Resection of Gliomas and Its Impact on Outcomes
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: Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Original ArticleIs There an Indication for Intraoperative MRI in Subtotal Resection of Glioblastoma? A Multicenter Retrospective Comparative Analysis

Objective

Methods

Results

Conclusions

Introduction

Section snippets

Study Design

General Assessment

Discussion

Conclusions

Acknowledgments

Lancet Oncol

Lancet Oncol

Lancet Oncol

Acad Radiol

World Neurosurg

Ann Oncol

Int J Radiat Oncol Biol Phys

Association of the extent of resection with survival in glioblastoma: a systematic review and meta-analysis

JAMA Oncol

Biopsy versus partial versus gross total resection in older patients with high-grade glioma: a systematic review and meta-analysis

Neuro Oncol

Extent of resection of glioblastoma revisited: personalized survival modeling facilitates more accurate survival prediction and supports a maximum-safe-resection approach to surgery

J Clin Oncol

Establishing percent resection and residual volume thresholds affecting survival and recurrence for patients with newly diagnosed intracranial glioblastoma

Neuro Oncol

Preoperative and intraoperative diffusion tensor imaging-based fiber tracking in glioma surgery

Neurosurgery

Intraoperative diagnostic and interventional MRI in neurosurgery: first experience with an “open MR” system

Craniotomy for tumor treatment in an intraoperative magnetic resonance imaging unit

Neurosurgery

Original Article
Is There an Indication for Intraoperative MRI in Subtotal Resection of Glioblastoma? A Multicenter Retrospective Comparative Analysis