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Table of Contents    
COMMENTARY
Year : 2019  |  Volume : 67  |  Issue : 1  |  Page : 183-184

The Indian Society of Neuro-oncology guidelines: A “personalized” approach to treating adult diffuse gliomas


Department of Neurosurgery, UT MD Anderson Cancer Center; Department of Neurosurgery, Baylor College of Medicine, Houston, Texas, USA

Date of Web Publication7-Mar-2019

Correspondence Address:
Dr. Sujit S Prabhu
Department of Neurosurgery, UT MD Anderson Cancer Center, Houston, Texas TX, 2008 – 2013
USA
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.253602

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How to cite this article:
Prabhu SS. The Indian Society of Neuro-oncology guidelines: A “personalized” approach to treating adult diffuse gliomas. Neurol India 2019;67:183-4

How to cite this URL:
Prabhu SS. The Indian Society of Neuro-oncology guidelines: A “personalized” approach to treating adult diffuse gliomas. Neurol India [serial online] 2019 [cited 2019 May 23];67:183-4. Available from: http://www.neurologyindia.com/text.asp?2019/67/1/183/253602




The article on the Indian Society of Neuro-oncology (ISNO) guidelines is a very timely and thoughtful manuscript outlining the management of adult diffuse gliomas. The authors recognize the challenges facing the specialty of neuro-oncology in India; however, doing what is right to provide the best patient care is an overriding theme of these guidelines.[1] My hope is that as this information is widely disseminated, more practitioners in the field of neuro-oncology will understand the importance of these guidelines.

The authors correctly point out to the financial burden that these guidelines may impose on individual patients. However, as insurance coverage gets more widespread in the Indian subcontinent, the individual payers (Insurance companies) will see the benefits of using these guidelines in everyday practice. The World Health Organization (WHO) 2016 classification of diffuse gliomas does represent a major paradigm shift in our understanding and management of these malignant tumors. In doing so, the classification facilitates a more precise diagnosis of well-understood entities and a clearer designation of less-understood entities, which will in turn allow further studies and likely future advances in their classifications. We are now able to understand their biological behaviour and critically prognosticate individual patient outcomes based on the molecular profile of these tumors. There is increasing evidence to support the role of maximal safe resection and re-resection, if necessary, especially in isocitrate dehydrogenase (IDH) mutant tumors.[2],[3],[4] However, recent studies confirm the benefit if chemotherapy is added to the radiation therapy (RT) regimen compared with RT alone or observation in Grade II tumors. This study also showed that histology, molecular grouping and extent of resection were significantly associated with progression free survival (PFS) and overall survival (OS) in a multivariate analysis.[2] Tumors, however, with the 1p 19 q co-deletion with a classic oligodendroglioma morphology can be effectively treated with temozolomide or a combination of procarbazine, lomustine, and vincristine (PCV) after a safe maximal resection has been achieved. Patients with an oligodendroglioma diagnosis clearly benefit from safe maximal resection and a combination of chemo-radiation [median overall survival (OS) 17.2 years and progression free survival (PFS) 15.2 years, respectively]. There is also a protocol to use “neoadjuvant” temozolomide or PCV in patients with the “integrated” diagnosis of oligodendroglioma. The authors in this paper had a limited number of patients; yet they showed some compelling data on the concept of using first line chemotherapeutic agents upfront with the aim of either reducing the tumor size making them more amenable to surgical resection, or stopping the growth of the tumors.[5] This concept can be applied to deep seated tumors, especially insular gliomas, where the surgical morbidity is higher compared to other supratentorial tumors. Hence, all these reports confirm the urgency in knowing the “integrated diagnosis” so as to permit the clinicians to make the best treatment choices for the patients.

The authors have gone to great lengths to explain how tumors with either an astrocytic or oligodendroglioma lineage not otherwise specified (NOS) can be managed clinically, though this entity is becoming more or less obsolete. This also begs the question of providing adequate tissue at the time of surgery to the pathologists to make a meaningful and impactful diagnosis in all or most cases.[6] This process can be a learning curve for many neurosurgeons who practice neuro-oncology. Tissue banking is of paramount importance in this endeavor to make an impactful diagnosis in every case and there should be a major emphasis among treating physicians to provide adequate tissue samples to the pathologist in this regard. The present guidelines also emphasize the challenges faced in assigning tumors as “oligoastrocytoma”, as this diagnosis becomes “the no man's land” on how this entity is managed clinically. However, as the authors point out, following histology and immunohistochemistry (IHC) with two markers, IDH1 (R132H) and ATRX, they can further define groups of diffuse glioma which are clinically relevant in the management. This practical and pragmatic approach has also been clarified by cIMPACT-NOW (the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy). The goal of cIMPACT-NOW is to facilitate input and consensus review of novel diagnostically relevant data and determine how such information can be practically incorporated into future central nervous system (CNS) tumor classifications. While it is understood that the major impact on international brain tumor classification comes about through the World Health Organization (WHO) classification update process, it is anticipated that the cIMPACT-NOW initiative will “see impact” in selected tumor types and in time periods between the WHO classification updates. There have been significant updates in our understanding of the molecular basis of gliomas and the cIMPACT-NOW will fill that void. The authors point out that in India, whilst IHC for IDH1R132H, ATRX and P53 is available in most of the diagnostic histopathology laboratories, FISH and DNA sequencing techniques are offered mostly in major diagnostic/research centers. Also, the cost of these tests is generally not affordable by patients from the lower economic strata. Though these can be real challenges, creating affordable “packages” for patients incorporating the various IHC and molecular testing will be a challenge to the scientific community as a whole.

The possibility to test H3K27M mutant tumor using these guidelines is a big step to further understanding and treating the tumors closer to the midline, e.g., thalamic and brainstem gliomas. Unfortunately, these tumors behave biologically like high grade gliomas, and hence, there is a significant risk-to-benefit ratio in knowing the molecular diagnosis of these tumors upfront prior to their resection, which can result in significant morbidity to the patient.

The management of glioblastomas in the elderly can be particularly challenging. These guidelines outline the important and thoughtful considerations of using a cut-off with age and methylation profile in the management of glioblastomas in the elderly patients.[1] Increasingly, we are seeing the elderly population present with glioblastomas with a good Karnofsky performance score. A number of clinical studies have shown the value of safe maximal resection in the elderly, which is essential for the adjuvant treatments like RT and chemotherapy to be effective. The Indian Society of Neuro-oncology guidelines have come up with a very straight forward and “personalized” approach to treating these tumors based on the age and the methylation status. Maybe in the future, they will also have set the stage for more elaborate clinical trials to test these different management approaches.

In conclusion, these guidelines framed by this expert and well-respected panel of clinician scientists will set a precedence to achieve excellence in the practice of neuro-oncology in the subcontinent.



 
  References Top

1.
Santosh V, Sravya P, Gupta T, Muzumdar D, Chacko G, Suri V, et al. ISNO consensus guidelines for practical adaptation of the WHO 2016 classification of adult diffuse gliomas. Neurol India 2019:67:173-82.  Back to cited text no. 1
    
2.
Youland RS, Kreofsky CR, Schomas DA, Brown PD, Buckner JC, Laack NN. The impact of adjuvant therapy for patients with high-risk diffuse WHO grade II glioma. J Neurooncol 2017;135:535-43.  Back to cited text no. 2
    
3.
Tateishi K, Wakimoto H, Cahill D. IDH1 mutation and World Health Organization 2016 diagnostic criteria for adult diffuse gliomas: Advances in surgical strategy. Neurosurgery 2017;138:134-8.  Back to cited text no. 3
    
4.
Beiko J, Suki D, Hess KR, Fox BD, Cheung V, Cabral M, et al. IDH1 mutant malignant astrocytomas are more amenable to surgical resection and have a survival benefit associated with maximal surgical resection. Neuro Oncol 2014;16:81-91.  Back to cited text no. 4
    
5.
Blonski, M, Pallud J, Goze'C, Mandonnet E, Rigau V, Bauchet L, et al. Neoadjuvant chemotherapy may optimize the extent of resection of World Health Organization grade II gliomas: A case series of 17 patients. J Neurooncol 2013;113:267-75.  Back to cited text no. 5
    
6.
Kim BYS, Jiang W, Beiko J, Prabhu SS, DeMonte F, Gilbert MR et al. Diagnostic discrepancies in malignant astrocytoma due to limited small pathological tumor sample can be overcome by IDH1 testing. J Neurooncol 2014;118:405-12.  Back to cited text no. 6
    




 

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