Intraoperative MRI Guided Resection for Glioblastoma Results in Increased Short-term Survival Compared to Conventional Surgery
Mark Oswood1,2, Bridget Ho3, Aditi Gupta4, Todd DeFor5, and Nilanjana Banerji4

1Radiology, HCMC, Minneapolis, MN, United States, 2Radiology, University of Minnesota, Minneapolis, MN, United States, 3John Nasseff Neuroscience Institute, Allina Health, St. Paul, MN, United States, 4John Nasseff Neuroscience Institute, Allina Health, Minneapolis, MN, United States, 5MCC Biostatistics Core, University of Minnesota, Minneapolis, MN, United States

Synopsis

A retrospective analysis of survival after resection of glioblastoma was performed comparing use of intraoperative MRI with conventional surgery. There was a significant difference in extent of resection, with more gross total resections achieved with iMRI. There was a significant improvement in overall survival at 6 months with iMRI. The groups had equivalent survival from 12-36 months. Younger age was correlated with longer overall survival.

Purpose

Intraoperative MRI (iMRI) has increasingly been used for image-guided resection of glioblastoma. Survival for glioblastoma with current therapy has been poor, averaging 15 months1. Prior studies have demonstrated increased extent of resection with the use of iMRI in glioblastoma2, 3. Other studies have also demonstrated increased overall survival with increased extent of resection4. Few studies to date have examined MRI guided resection as an independent predictor of overall survival for glioblastoma, with published series limited by small sample size or inclusion of lower grade tumors5-7. We retrospectively analyzed 161 cases of glioblastoma treated at a single institution to determine the effect of resection with iMRI on outcomes in patients with glioblastoma.

Methods

Approval for the study was obtained from the hospital IRB. We performed a chart review to identify 161 subjects with initial resection of glioblastoma at our institution over a seven-year period. We identified 68 subjects who had conventional surgery using pre-operative stereotactic MRI and 93 subjects where additional intraoperative MR imaging was performed during resection. Intraoperative imaging was performed on a 1.5T MRI scanner (IMRIS, Minneapolis, Minnesota, USA) using T1, T2, and gadolinium enhanced T1 weighted sequences. Baseline demographics and outcomes were obtained on all subjects. Statistical comparisons across type of brain surgery by various demographic/characteristics were performed by a chi-square test for categorical data and the general Wilcoxon test for continuous data. Kaplan-Meier curves were used to estimate the probability of survival8. The log-rank test was used to complete comparisons. Cox regression was used to look at the independent effect of iMRI on survival. All reported p-values were 2-sided. All analyses were performed using SAS version 9.3 (SAS Institute, Cary, NC).

Results

There were no significant demographic differences between the iMRI and conventional surgery groups (Table 1). Recipients of iMRI in our study had a higher probability of gross total resection than did recipients of conventional surgery (63% [95% CI, 54-73%]) vs 41% [95% CI, 29-53%]; p < 0.01). When restricted to a follow-up of 6 months after the procedure (Table 2), overall survival (OS) among the iMRI group showed a statistically significant benefit as well (89% [95% CI, 81-94%] versus 78% [95% CI, 66-86%]; p=0.04). However, after extending the follow-up (Figure 1), there did not appear to be a difference in median time to OS between iMRI and conventional therapy (17 months vs 15 respectively, p=0.59). OS was longer for younger age groups, p=0.03 (Table 3), as has been reported in prior studies 9.

Discussion

Our research confirmed the advantage to iMRI in achieving a greater number of gross total resections. We found that there is a short-term OS advantage to iMRI at 6 months. No statistically significant survival benefit was noticed at long term follow-up. These findings may be due to the heterogeneous genetic makeup of glioblastoma 10. A subgroup of subjects may gain a short-term advantage from greater extent of resection. Long term survival may be determined by genetic susceptibility to chemotherapy and radiotherapy, and therefore extent of resection may be less influential in the long term. Analysis of genetic mutations is not available for our study group. Future studies including survival analysis with subgroups analyzed for specific chromosome or gene mutations may provide more information.

Conclusion

Use of iMRI for initial resection of glioblastoma provides greater extent of resection as well as a short-term survival benefit. Conventional surgery and iMRI groups demonstrated equivalent survival between 12-36 months. Limitations of the study include retrospective data collection and lack of availability of information on molecular profiles of the tumors as well as functional status of patients. Additional prospective studies are warranted to better appreciate the overall effect of iMRI in patients with glioblastoma.

Acknowledgements

This work was supported by a grant from the Abbott-Northwestern Hospital Foundation.

References

[1] Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005;352(10):987-996.

[2] Olubiyi OI, Ozdemir A, Incekara F, et al. Intraoperative Magnetic Resonance Imaging in Intracranial Glioma Resection: A Single-Center, Retrospective Blinded Volumetric Study. World Neurosurg 2015;84(2):528-536.

[3] Senft C, Bink A, Franz K, et al. Intraoperative MRI guidance and extent of resection in glioma surgery: a randomised, controlled trial. Lancet Oncol 2011;12(11):997-1003.

[4] Coburger J, Wirtz CR, König RW Impact of extent of resection and recurrent surgery on clinical outcome and overall survival in a consecutive series of 170 patients for glioblastoma in intraoperative high field iMRI. J Neurosurg Sci 2015

[5] Kubben PL, ter Meulen KJ, Schijns OE, et al. Intraoperative MRI-guided resection of glioblastoma multiforme: a systematic review. Lancet Oncol 2011;12(11):1062-1070.

[6] Kuhnt D, Ganslandt O, Schlaffer SM, et al. Quantification of glioma removal by intraoperative high-field magnetic resonance imaging: an update. Neurosurgery 2011;69(4):852-62; discussion 862.

[7] Kubben PL, Scholtes F, Schijns OE, et al. Intraoperative magnetic resonance imaging versus standard neuronavigation for the neurosurgical treatment of glioblastoma: A randomized controlled trial. Surg Neurol Int 2014;570.

[8] Kaplan EL, Meier P Nonparametric estimation from incomplete observations Journal of the American statistical association 1958;53(282):457-481.

[9] Visser O, Ardanaz E, Botta L, et al. Survival of adults with primary malignant brain tumours in Europe; Results of the EUROCARE-5 study. Eur J Cancer 2015

[10] Verhaak RG, Hoadley KA, Purdom E, et al. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 2010;17(1):98-110.

Figures

Figure 1: Kaplan-Meier curve showing overall survival for glioblastoma after resection with intraoperative MRI or conventional surgery. There was a significant difference in survival at 6 months following resection.

Table 1: There are no significant demographic differences between the iMRI and conventional surgery groups. Extent of resection and operative time are significantly greater for the iMRI group.

Table 2: Overall survival at 6 months shows significant improvement with iMRI compared to conventional surgery.

Table 3: Differences in overall survival between iMRI and conventional surgery do not reach statistical significance with followup extended to 36 months. Younger age is significantly correlated with longer survival.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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