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Subgroup stratification of adult diffuse gliomas and outcomes: an adaptation of the updated WHO classification in a resource-constrained environment

Published online by Cambridge University Press:  20 December 2019

T. Naveen ,
A. S. Uday Krishna Open the ORCID record for A. S. Uday Krishna [Opens in a new window] ,
Vani Santosh ,
A. Arivazhagan  and
V. Lokesh
T. Naveen
Affiliation:
1Department of Radiation Oncology, Kidwai Memorial Institute of Oncology, Bangalore, India
A. S. Uday Krishna*
Affiliation:
1Department of Radiation Oncology, Kidwai Memorial Institute of Oncology, Bangalore, India
Vani Santosh
Affiliation:
2Department of Neuropathology, NIMHANS, Bangalore, India
A. Arivazhagan
Affiliation:
3Department of Neurosurgery, NIMHANS, Bangalore, India
V. Lokesh
Affiliation:
1Department of Radiation Oncology, Kidwai Memorial Institute of Oncology, Bangalore, India
*
Author for correspondence: A. S. Uday Krishna, Kidwai Memorial Institute of Oncology, Bangalore, Karnataka, India. E-mail: [email protected]
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Abstract

Introduction:

The updated World Health Organization 2016 classification of central nervous system tumours recommends the addition of molecular parameters to histological diagnosis. In a resource-constrained setting, molecular testing such as gene sequencing and fluorescence in situ hybridisation is not feasible for all the patients. We assessed the utility of immunohistochemistry (IHC) for isocitrate dehydrogenase (IDH1/R132H) gene and alpha thalassemia/mental retardation syndrome X linked gene (ATRX) to stratify adult diffuse gliomas into subgroups and analysed the outcomes.

Materials/Methods:

Fifty-eight patients with grades III/IV astrocytic gliomas were tested by IHC for IDH1/R132H and ATRX mutation as per the standard protocol and were later stratified into three subgroups based on IHC. IDH1/R132H positive/ATRX retained gliomas were stratified as group 1 (G1), IDH1/R132H positive/ATRX lost were grouped as G2 and IDH1/R132H negative (with or without ATRX loss) as G3. All patients underwent adjuvant therapy as per the Stupp regimen. Outcomes and survival were analysed by Kaplan–Meier analysis using SPSS 21.v.

Results:

Median age of the cohort of 58 patients (male: 39, female: 19) was 40 years. Histologically, glioblastoma multiforme (GBM), anaplastic astrocytoma (AA) and anaplastic oligodendroglioma (AOD) were seen in 23:17:18 patients. Forty-eight percent were tested positive for IDH1/R132H, 62% had retained ATRX protein stratifying patients into three subgroups (G1:14, G2:14, G3:30). The G3 group contained both AA and GBM cases. At median follow-up of 18 months, overall survival (OS) of the entire cohort was 76%, higher in G1, compared to G2 and G3 (log-rank p = 0·01). In comparison to various factors such as age, gender, location of the lesion and presenting symptom on survival among various groups, we found that gender of the patient in group I (men vs. women, p = 0·02), laterality of the tumour in group II (right vs. left, p = 0·07) and age of the patient in group III (<45 vs. >45, p = 0·01) demonstrated significant impact on OS.

Conclusion:

Subgroup stratification of adult diffuse gliomas based on IHC for IDH/R132H and ATRX demonstrates that group 1 was the most favourable prognostic factor. In a resource-constrained environment, IHC alone may guide appropriate management decision for the majority of adult diffuse gliomas, gene sequencing reserved for IDH1/R132H negative GBM in patients less than 45 years of age.

Keywords

IDHATRXsubgroupsgliomas
Type
Original Article
Information
Journal of Radiotherapy in Practice , Volume 20 , Issue 1 , March 2021 , pp. 55 - 58
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Copyright
© Cambridge University Press 2019

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References

Louis, D N, Perry, A, Reifenberger, G et al. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol 2016; 131 (6): 803–820.CrossRefGoogle ScholarPubMed
Parsons, D W, Jones, S, Zhang, X et al. An integrated genomic analysis of human glioblastoma multiforme. Science 2008; 321 (5897): 1807–1812.CrossRefGoogle ScholarPubMed
Santosh, V, Pallavalasa, S, Gupta, T et al. ISNO consensus guidelines for practical adaptation of the WHO 2016 classification of adult diffuse gliomas. Neurol India 2019; 67: 173–182.Google ScholarPubMed
Stupp, R, Mason, W P, van den Bent, M J et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005; 352 (10): 987–996.CrossRefGoogle ScholarPubMed
Van den Bent, M J, Baumert, B, Erridge, S C et al. Interim results from the CATNON trial (EORTC study 26053-22054) of treatment with concurrent and adjuvant temozolomide for 1p/19q non-co-deleted anaplastic glioma: a phase 3, randomised, open-label intergroup study. Lancet 2017; 390 (10103): 1645–1653.CrossRefGoogle ScholarPubMed
Agarwal, S, Sharma, S C, Sarkar, C et al. Comparative study of IDH1 mutations in gliomas by immunohistochemistry and DNA sequencing. Neuro-Oncology 2013; 15 (6): 718–726.CrossRefGoogle ScholarPubMed
Wiestler, B, Capper, D, Wick, W et al. ATRX loss refines the classification of anaplastic gliomas and identifies a subgroup of IDH mutant Astrocytic tumours with better prognosis. Acta Neurpathol. 2013; 126 (3): 443–451.CrossRefGoogle ScholarPubMed
Louis, D N, Perry, A, Reifenberger, G et al. International Society of Neuropathology–Haarlem consensus guidelines for nervous system tumor classification and grading. Brain Pathol 2014; 4 (5): 429–435.CrossRefGoogle Scholar
Rajmohan, S, Arivazhagan, A, Santosh, V et al. Prognostic significance of histo-molecular subgroups of adult anaplastic (WHO Grade III) gliomas: applying the ‘integrated’ diagnosis approach. J Clin Pathol 2016; 69 (8): 686–694.CrossRefGoogle Scholar
Rajeswarie, RT, Rao, S, Santosh, V et al. A simple algorithmic approach using histology and immunohistochemistry for the current classification of adult diffuse glioma in a resource-limited set-up. J Clin Pathol 2017; 71 (4): 323–329. doi: 10.1136/jclinpath-2017-204638 CrossRefGoogle Scholar