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Table of Contents
ABHIJIT GUHA ORATION, ISNOCON 2018
Year : 2018  |  Volume : 1  |  Issue : 1  |  Page : 11-13

Extent of resection in glioblastoma – Where to draw the line?


Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Date of Web Publication14-Nov-2018

Correspondence Address:
Prof. Raymond Sawaya
Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 442, Houston, TX 77030-4009
USA
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/IJNO.IJNO_9_18

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How to cite this article:
Sawaya R. Extent of resection in glioblastoma – Where to draw the line?. Int J Neurooncol 2018;1:11-3

How to cite this URL:
Sawaya R. Extent of resection in glioblastoma – Where to draw the line?. Int J Neurooncol [serial online] 2018 [cited 2019 Mar 20];1:11-3. Available from: http://www.Internationaljneurooncology.com/text.asp?2018/1/1/11/245367



The field of neurosurgical oncology has greatly benefited from the contributions of Dr. Abhijit Guha, and we have been enriched by his dedication to patient care, research, and education. It is thus an honor to deliver an oration that bears his name [Figure 1].
Figure 1: Picture of Abhijit Guha, MD, PhD, and his dates of birth and death

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Some years ago, the role that extent of tumor resection played in prolonging the survival of patients with glioblastoma (GBM) was put into question owing to the lack in the literature of scientifically valid data[1] positively correlating survival time with extent of resection. In a critical summary addressing this controversy, four key variables were identified as contributing to it.[2] First was a lack of imaging confirmation of the degree of resection, with surgeons basing their assessment on subjective evaluations. Second, most patients underwent partial resections, with very few of them benefitting from more extensive resections. Third, the term malignant glioma was applied to a mixture of tumors ranging from GBM, to anaplastic astrocytoma, to anaplastic oligodendroglioma. This resulted in a histologic “contamination” in the published series, which failed to provide the ability to separate these subgroups. A greater participation of patients with anaplastic astrocytomas in a given series would skew the survival results in a more favorable direction than would a series comprising only GBM patients, thus masking the potential influence of more extensive resections on patients' survival. Finally, the statistical methods employed were inadequate due to lack of sufficient statistical power or inadequate adjustments for factors known to affect survival, such as a patient's age, Karnofsky Performance Scale score, or tumor grade.

Unfortunately, these inadequacies continued well into the 1990s, as documented by Hess.[3] This was surprising since most of the imaging and surgical technical advances that we currently benefit from had already been introduced into our neurosurgical practices.

This brings us to the current millennium and the increased appreciation that GBM, with its highly resistant nature to ionizing radiation and alkylating agents, could benefit from more extensive resections, giving the patients potentially greater remission periods.

The first publication on this topic in this millennium, which has garnered the most attention and citations, is by Lacroix et al.[4] This is because of the attention paid by the authors to the prior deficiencies enumerated above and also because they relied on computerized volumetric measurements when assessing the extent of resection instead of the subjective and hard-to-define descriptions by neurosurgeons, who used terms such as partial and subtotal resection. Even the often used term gross-total resection did not necessarily equate to a complete resection of the enhancing mass. The findings in this study emphasized the advantage of resections that exceeded 90% of the volume of the mass, achieving the maximal benefit to prolonging a patient's survival when 98% or more of the mass was removed. Many subsequent studies have confirmed or built upon these results,[5] and in a meta-analysis, Brown et al. concluded that the weight of evidence in the modern literature indicates that maximal resections do indeed have a beneficial effect on survival.[6]

As an extension of this realization, a hypothesis was generated by Li et al. that posits that if 100% resection of the contrast-enhancing GBM mass leads to improved survival relative to lesser resection volumes, could not additional resections of tissues from the surrounding fluid-attenuated inversion recovery (FLAIR) signal (nonenhancing on T1 MR images) provide further gains in survival?[7] In support of this hypothesis are the multitude of clinical studies indicating that 75% of GBM recurrences occur within 2 cm of the resection margin and autopsy studies showing that the highest concentration of infiltrating tumor cells are in this peritumoral brain tissue. This hypothesis was tested in a series of 1229 GBM patients in whom the degree of peritumoral tissue resected was volumetrically measured. The results of the study showed that on multivariate analysis, in patients who had undergone resection of 100% of their tumor, the additional resection of over 50% of the FLAIR tissue (hyperintense on T2 MR images) surrounding the mass resulted in median survival times beyond 23 months, significantly greater than the median survival of patients with lesser volumetric resections.

[Figure 2] and [Figure 3] demonstrate an example of how, with modern imaging and mapping techniques, wide resection of the GBM mass, including the surrounding tissue immediately adjacent to it, can be safely performed.
Figure 2: Functional magnetic resonance imaging showing a left temporal glioblastoma (M) surrounded by the arcuate fasciculus (AF)

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Figure 3: Preoperative (left upper) and postoperative (left lower) contrast-enhanced magnetic resonance imaging of a left temporal glioblastoma resected (specimen in center image) in a perilesional fashion, plus preoperative (right upper) and postoperative (right lower) magnetic resonance imaging showing resection of the surrounding fluid-attenuated inversion recovery signal region

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In conclusion, it is now well established that maximal safe resection of the contrast-enhancing region of a GBM results in a significant survival advantage relative to performing less extensive resections. However, the more recent observation that additional resection of the surrounding infiltrated brain tissue may confer an added survival advantage deserves further assessment. Thus, it is imperative that when neurosurgeons evaluate patients before surgery, they base their decision judiciously after careful clinical and imaging analyses, and that they employ all the appropriate state-of-the-art surgical tools and techniques in order to achieve the most beneficial outcomes.



 
  References Top

1.
Nazzaro JM, Neuwelt EA. The role of surgery in the management of supratentorial intermediate and high-grade astrocytomas in adults. J Neurosurg 1990;73:331-44.  Back to cited text no. 1
    
2.
Sawaya R. Extent of resection in malignant gliomas: A critical summary. J Neurooncol 1999;42:303-5.  Back to cited text no. 2
    
3.
Hess KR. Extent of resection as a prognostic variable in the treatment of gliomas. J Neurooncol 1999;42:227-31.  Back to cited text no. 3
    
4.
Lacroix M, Abi-Said D, Fourney DR, Gokaslan ZL, Shi W, DeMonte F, et al. A multivariate analysis of 416 patients with glioblastoma multiforme: Prognosis, extent of resection, and survival. J Neurosurg 2001;95:190-8.  Back to cited text no. 4
    
5.
Sanai N, Polley MY, McDermott MW, Parsa AT, Berger MS. An extent of resection threshold for newly diagnosed glioblastomas. J Neurosurg 2011;115:3-8.  Back to cited text no. 5
    
6.
Brown TJ, Brennan MC, Li M, Church EW, Brandmeir NJ, Rakszawski KL, et al. Association of the extent of resection with survival in glioblastoma: A systematic review and meta-analysis. JAMA Oncol 2016;2:1460-9.  Back to cited text no. 6
    
7.
Li YM, Suki D, Hess K, Sawaya R. The influence of maximum safe resection of glioblastoma on survival in 1229 patients: Can we do better than gross-total resection? J Neurosurg 2016;124:977-88.  Back to cited text no. 7
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]



 

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