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Table of Contents    
COMMENTARY
Year : 2017  |  Volume : 65  |  Issue : 6  |  Page : 1302-1303

Outcome assessment in gliomas – the way forward


Neuro Oncology Disease Management Group, Tata Memorial Centre, Mumbai, Maharashtra, India

Date of Web Publication10-Nov-2017

Correspondence Address:
Dr. Rakesh Jalali
Neuro Oncology Disease Management Group, Tata Memorial Centre, Mumbai, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.217990

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How to cite this article:
Moiyadi A, Jalali R. Outcome assessment in gliomas – the way forward. Neurol India 2017;65:1302-3

How to cite this URL:
Moiyadi A, Jalali R. Outcome assessment in gliomas – the way forward. Neurol India [serial online] 2017 [cited 2018 Dec 16];65:1302-3. Available from: http://www.neurologyindia.com/text.asp?2017/65/6/1302/217990


Bose et al., deserve to be congratulated for reporting on a consecutive series of gliomas treated at a single centre in the present issue of the journal. This is a large cohort of gliomas from a tertiary level neurosurgical centre. 471 gliomas (of all types) were treated by an experienced team over a five-year period. The findings reinforce what is known about gliomas – glioblastomas have the worst prognosis (in spite of multimodality therapy); younger patients do better as do those with a higher Karnofsky's performance score (KPS). This is per se not ground-breaking information. Nonetheless, it reinforces the prognostic value of age-old, time-tested prognostic factors, confirmed in a contemporary cohort of patients.

The strength of the study is in its numbers and authors need to be commended for that. As with all studies using survival as an endpoint (and it is indeed the most appropriate and hardest endpoint to use), meticulous follow up and stratification for known prognostic variables is the key and may be a major limitation of this report as well. In that respect, there are limitations to the data and its analysis (a function, of course of the retrospective nature of the analysis) which to some extent hamper the eventual conclusions. The inadequacy of the follow up, although not unexpected in these type of audits, is reflected in the rather wide confidence intervals of the survival figures (1 day to 62 months). The mean survival of only 14 months in the entire cohort comprising of all grades of gliomas may also seem low but probably could be attributed to the inclusion of high grade gliomas as a major tumour entity and also a reflection of lack of robust follow up. This also reinforces the importance of prospective collection of data and meticulous documentation of outcomes. Only then will we be able to replicate (or rightly negate) the so called “successes” of clinical trials in real-world scenarios. Notwithstanding these points, there are still possible lessons to be learnt from this report. Prospective data accrual, preferably as part of collaborative efforts led by large volume tertiary care centres in concert with national societies such as the ISNO (Indian Society of Neuro-Oncology) may yield more practically relevant and relatable outcomes.

As the authors rightly point out, little has changed with respect to outcomes in glioblastomas. However, there has been a revolution of sorts in certain aspects related to glioma management over the past decade which merit discussion. The addition of adjuvant radio-chemotherapy has improved survival in glioblastomas and has been replicated in the Indian scenario, as well.[1],[2],[3] The extent of resection has emerged as a robust and important prognostic marker, not only in low-grade gliomas but also in high-grade gliomas, paving the way for a conceptual shift towards the aim of achieving supra-radical resections.[4],[5] This has been facilitated by increasing adoption and the widespread use of technical adjuncts (intraoperative ultrasound/magnetic resonance imaging, fluorescence, functional mapping and monitoring) during glioma surgery [6],[7],[8] in order to achieve the Holy Grail (in the author's own words) of “safe maximal resection.” Here again, the authors had an excellent opportunity to evaluate the utility of these adjuncts (they have used intraoperative magnetic resonance (IOMR) imaging scan, fluorescence, and probably some functional mapping techniques, though all details are not provided) and provide novel insights into the utility of such combined multi-modality strategies during glioma surgery. Interestingly they found that the use of IOMR was not beneficial. However, it was used only in a relatively small subset of patients (76 out of a total of 471 cases) and these could possibly have been the more difficult cases leading to the equivocal results. Absence of objective data assessing the extent of resection is a limitation of the study which could have confounded the results. It has been shown that even resections short of gross total may confer prognostic benefit when combined with other risk factors.[9]

What comes across as most surprising, however, is the lack of significant difference in outcomes amongst different grades of the non-glioblastoma gliomas. There is now, unequivocal (and rather voluminous) data in literature attesting to the prognostic importance of tumor grade. One of the major reasons for this discordance in the results reported by Bose et al., could be either due to sampling errors in reporting by an experienced neuropathologist but also likely due to lack of molecular stratification. It is being increasingly recognised for example, that lower grade gliomas but harbouring isocitrate dehydrogenase (IDH) wild type do poorly (in fact, these are sometimes equated with glioblastomas in terms of survival). Similarly, patients with 1p, 19q co-deletion in oligodendroglial tumours have significantly superior outcomes than non-co-deleted tumours and astrocytomas. Addition of adjuvant radiation and chemotherapy in aggressive/high-risk low grade gliomas, which has resulted in increased survival outcomes, may also not have been practiced uniformly in the study cohort. Presence of such tumors within the grade 2/3 gliomas could lead to lack of difference in survival estimates as reported by the authors. This reinforces the importance of incorporation of molecular testing in routine neuropathological reporting in gliomas, as has been stipulated in the recent 2016 update of the World Health Organisation classification of brain tumors.[10]

Moving ahead, the 'take home' message for future studies in glioma outcomes would be to have meticulously collected prospective data; volumetric and objective assessment of extent of resection; careful documentation of the indications and use of specialized intraoperative adjuncts; thorough molecular characterization of the tumor types, careful recording of adjuvant and salvage therapies offered, and an overall appropriate stratification for known prognostic markers. As mentioned, the present report collected from a large cohort of patients would act as a suitable benchmark for conducting collaborative efforts undertaken in a systematic way. This will ensure that the future studies are more robust and productive.

 
  References Top

1.
Stupp R, Mason WP, van den Bent MJ, Weller, Fisher M, Taphoorn MB, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. New Eng J Med 2005;352:987-96.  Back to cited text no. 1
    
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Gupta T, Mohanty S, Moiyadi A, Jalali R. Factors predicting temozolomide induced clinically significant acute hematologic toxicity in patients with high-grade gliomas: A clinical audit. Clin Neurol Neurosurg2013;115:1814-19.  Back to cited text no. 2
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3.
Jalali R, Basu A, Gupta T, Munshi A, Menon H, Sarin R, et al. Encouraging experience of concomitant temozolomide with radiotherapy followed by adjuvant temozolomide in newly diagnosed glioblastoma multiforme: Single institution experience. Br J Neurosurg2007;21:583-7.  Back to cited text no. 3
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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 Neurosurg2016;124:977-88.  Back to cited text no. 4
    
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Duffau H, Mandonnet E. The “onco-functional balance” in surgery for diffuse low-grade glioma: Integrating the extent of resection with quality of life. Acta Neurochir 2013;155:951-7.  Back to cited text no. 5
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Moiyadi AV, Kannan S, Shetty P. Navigated intraoperative ultrasound for resection of gliomas: Predictive value, influence on resection and survival. Neurol India 2015;63:727-35.  Back to cited text no. 6
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Moiyadi AV, Stummer W. delta-Aminolevulinic acid-induced fluorescence-guided resection of brain tumors. Neurol India2015;63:155-65.  Back to cited text no. 7
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Senft C BA, 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;12:997-1003.  Back to cited text no. 8
    
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Marko NF, Weil RJ, Schroeder JL, Lang FF, Suki D, Sawaya RE. 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 Oncol2014;32:774-82.  Back to cited text no. 9
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Louis DN, Perry A, Reifenberger G, von Deimling, A, Figarella-Branger D, Cavenee W. K, et al. The 2016 World Health Organization classification of tumors of the central nervous system: A summary. Acta Neuropath 2016;131:803-20.  Back to cited text no. 10
    




 

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