Journal of Neuro-Oncology

, Volume 141, Issue 1, pp 223–233 | Cite as

Surgical management of lower-grade glioma in the spotlight of the 2016 WHO classification system

  • Daniel DelevEmail author
  • Dieter Henrik Heiland
  • Pamela Franco
  • Peter Reinacher
  • Irina Mader
  • Ori Staszewski
  • Silke Lassmann
  • Stefan Grau
  • Oliver Schnell
Clinical Study



According to the 2016 WHO classification lower-grade gliomas consist of three groups: IDH-mutated and 1p/19q co-deleted, IDH-mutated and IDH-wildtype tumors. The aim of this study was to evaluate the impact of surgical therapy for lower-grade gliomas with a particular focus on the molecular subgroups.


This is a bi-centric retrospective analysis including 299 patients, who underwent treatment for lower-grade glioma between 1990 and 2016. All tumors were re-classified according to the 2016 WHO classification. Data concerning baseline and tumor characteristics, overall survival, different treatment modalities and functional outcome were analyzed.


A total of 112 (37.5%) patients with IDH-mutation and 1p/19q co-deletetion, 86 (28.8%) patients with IDH-mutation and 101 (33.8%) patients with IDH-wildtype tumors were identified. The median overall survival (mOS) differed significantly between the groups (p < 0.001). Surgical resection was performed in 226 patients and showed significantly improved mOS compared to the biopsy group (p = 0.001). Gross total resection (GTR) was associated with better survival (p = 0.007) in the whole cohort as well as in the IDH-mutated and IDH-wildtype groups compared to partial resection or biopsy. IDH-wildtype patients presented a significant survival benefit after combined radio-chemotherapy compared to radio- or chemotherapy alone (p = 0.02). Good clinical status (NANO) was associated with longer OS (p = 0.001).


The impact of surgical treatment on the outcome of lower-grade gliomas depends to a great extent on the molecular subtype of the tumors. Patients with more aggressive tumors (IDH-wildtype) seem to profit from more intensive treatment like GTR, multiple resections and combined radio-/chemotherapy.


Lower-grade gliomas Oligodendroglioma Astrocytoma WHO-classification IDH-mutation 1p/19q Gross total resection 



This research did not receive any financial or material support from funding agencies in the public, commercial, or not-for-profit sectors.

Compliance with ethical standards

Conflict of interest

The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

Supplementary material

11060_2018_3030_MOESM1_ESM.png (488 kb)
Supplementary figure 1 Kaplan Meier Curves showing the overall survival according to extent of resection, comparing patients with at least one gross total resection (GTR) to those with biopsy or partial resection after molecular subgroup stratification (PNG 487 KB)
11060_2018_3030_MOESM2_ESM.png (481 kb)
Supplementary figure 2 Kaplan Meier Curves showing the overall survival according to WHO grade after molecular subgroup stratification (PNG 480 KB)


  1. 1.
    Louis DN, Perry A, Reifenberger G et al (2016) The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol 131:803–820. CrossRefGoogle Scholar
  2. 2.
    The Cancer Genome Atlas Research Network (2015) Comprehensive, integrative genomic analysis of diffuse lower-grade gliomas. N Engl J Med 372:2481–2498. CrossRefGoogle Scholar
  3. 3.
    Leeper HE, Caron AA, Decker PA et al (2015) IDH mutation, 1p19q codeletion and ATRX loss in WHO grade II gliomas. Oncotarget 6:30295–30305. CrossRefGoogle Scholar
  4. 4.
    Weller M, Weber RG, Willscher E et al (2015) Molecular classification of diffuse cerebral WHO grade II/III gliomas using genome- and transcriptome-wide profiling improves stratification of prognostically distinct patient groups. Acta Neuropathol 129:679–693. CrossRefGoogle Scholar
  5. 5.
    Weller M, Felsberg J, Hartmann C et al (2009) Molecular predictors of progression-free and overall survival in patients with newly diagnosed glioblastoma: a prospective translational study of the German Glioma Network. J Clin Oncol 27:5743–5750. CrossRefGoogle Scholar
  6. 6.
    Buckner J, Giannini C, Eckel-Passow J et al (2017) Management of diffuse low-grade gliomas in adults—use of molecular diagnostics. Nat Publ Group 1–12.
  7. 7.
    Cahill DP, Sloan AE, Nahed BV et al (2015) The role of neuropathology in the management of patients with diffuse low grade glioma. J Neurooncol 125:531–549. CrossRefGoogle Scholar
  8. 8.
    Olar A, Wani KM, Alfaro-Munoz KD et al (2015) IDH mutation status and role of WHO grade and mitotic index in overall survival in grade II–III diffuse gliomas. Acta Neuropathol 129:585–596. CrossRefGoogle Scholar
  9. 9.
    Sanai N, Chang S, Berger MS (2011) Low-grade gliomas in adults. J Neurosurg 115:948–965. CrossRefGoogle Scholar
  10. 10.
    Potts MB, Smith JS, Molinaro AM, Berger MS (2012) Natural history and surgical management of incidentally discovered low-grade gliomas. J Neurosurg 116:365–372. CrossRefGoogle Scholar
  11. 11.
    Capelle L, Fontaine D, Mandonnet E et al (2013) Spontaneous and therapeutic prognostic factors in adult hemispheric World Health Organization Grade II gliomas: a series of 1097 cases: clinical article. J Neurosurg 118:1157–1168. CrossRefGoogle Scholar
  12. 12.
    Englot DJ, Chang EF, Vecht CJ (2016) Epilepsy and brain tumors. Handb Clin Neurol 134:267–285. CrossRefGoogle Scholar
  13. 13.
    Englot DJ, Berger MS, Barbaro NM, Chang EF (2011) Predictors of seizure freedom after resection of supratentorial low-grade gliomas. J Neurosurg 115:240–244. CrossRefGoogle Scholar
  14. 14.
    Duffau H (2014) Diffuse low-grade gliomas andneuroplasticity. Diagn Interv Imaging 95:945–955. CrossRefGoogle Scholar
  15. 15.
    Weller M, van den Bent M, Tonn JC et al (2017) European Association for Neuro-Oncology (EANO) guideline on the diagnosis and treatment of adult astrocytic and oligodendroglial gliomas. Lancet Oncol 18:e315–e329. CrossRefGoogle Scholar
  16. 16.
    Roelz R, Strohmaier D, Jabbarli R et al (2016) Residual tumor volume as best outcome predictor in low grade glioma—a nine-years near- randomized survey of surgery vs. biopsy. Nat Publ Group Google Scholar
  17. 17.
    Duffau H (2017) The role of surgery in low-grade gliomas: do timing and extent of resection matter? CNS Oncol 6:179–183. CrossRefGoogle Scholar
  18. 18.
    Michaud K, Duffau H (2016) Surgery of insular and paralimbic diffuse low-grade gliomas: technical considerations. J Neurooncol 130:289–298. CrossRefGoogle Scholar
  19. 19.
    Eseonu CI, ReFaey K, Garcia O et al (2017) Original article. World Neurosurg 103:265–274. CrossRefGoogle Scholar
  20. 20.
    Gousias K, Schramm J, Simon M (2013) Extent of resection and survival in supratentorial infiltrative low-grade gliomas: analysis of and adjustment for treatment bias. Acta Neurochir (Wien) 156:327–337. CrossRefGoogle Scholar
  21. 21.
    Englot DJ, Han SJ, Berger MS et al (2012) Extent of surgical resection predicts seizure freedom in low-grade temporal lobe brain tumors. Neurosurgery 70:921–928. CrossRefGoogle Scholar
  22. 22.
    Sanai N, Berger MS (2008) Glioma extent of resection and its impact on patient outcome. Neurosurgery 62:753–764. (discussion 264–6).CrossRefGoogle Scholar
  23. 23.
    Smith JS, Chang EF, Lamborn KR et al (2008) Role of extent of resection in the long-term outcome of low-grade hemispheric gliomas. J Clin Oncol 26:1338–1345. CrossRefGoogle Scholar
  24. 24.
    Jakola AS, Myrmel KS, Kloster R et al (2012) Comparison of a strategy favoring early surgical resection vs a strategy favoring watchful waiting in low-grade gliomas. JAMA 308:1881. CrossRefGoogle Scholar
  25. 25.
    Jakola AS, Skjulsvik AJ, Myrmel KS et al (2017) Surgical resection versus watchful waiting in low-grade gliomas. Ann Oncol. Google Scholar
  26. 26.
    Eseonu CI (2017) Comparative volumetric analysis of the extent of resection of molecularly and histologically distinct low grade gliomas and its role on survival. J Neurooncol 134:65–74. CrossRefGoogle Scholar
  27. 27.
    van den Bent MJ, Wefel JS, Schiff D et al (2011) Response assessment in neuro-oncology (a report of the RANO group): assessment of outcome in trials of diffuse low-grade gliomas. Lancet Oncol 12:583–593. CrossRefGoogle Scholar
  28. 28.
    Weller M, van den Bent M, Hopkins K et al (2014) EANO guideline for the diagnosis and treatment of anaplastic gliomas and glioblastoma. Lancet Oncol 15:e395–e403. CrossRefGoogle Scholar
  29. 29.
    Nayak L, DeAngelis LM, Brandes AA et al (2017) The Neurologic Assessment in Neuro-Oncology (NANO) scale: a tool to assess neurologic function for integration into the Response Assessment in Neuro-Oncology (RANO) criteria. Neurooncology 19:625–635. Google Scholar
  30. 30.
    Wick W, Roth P, Hartmann C et al (2016) Long-term analysis of the NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with PCV or temozolomide. Neuro-Oncology. Google Scholar
  31. 31.
    van den Bent MDPMJ, MD BB, MD SCE et al (2017) 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. Google Scholar
  32. 32.
    Baumert BG, Hegi ME, van den Bent MJ et al (2016) Temozolomide chemotherapy versus radiotherapy in high-risk low-grade glioma (EORTC 22033–26033): a randomised, open-label, phase 3 intergroup study. Lancet Oncol 17:1521–1532. CrossRefGoogle Scholar
  33. 33.
    Wijnenga MMJ, French PJ, Dubbink HJ et al (2017) The impact of surgery in molecularly defined low-grade glioma: an integrated clinical, radiological, and molecular analysis. Neurooncology 20:103–112. Google Scholar
  34. 34.
    Kawaguchi T, Sonoda Y, Shibahara I et al (2016) Impact of gross total resection in patients with WHO grade III glioma harboring the IDH 1/2 mutation without the 1p/19q co-deletion. J Neurooncol 129:505–514. CrossRefGoogle Scholar
  35. 35.
    Rahman M, Abbatematteo J, De Leo EK et al (2017) The effects of new or worsened postoperative neurological deficits on survival of patients with glioblastoma. J Neurosurg 127:123–131. CrossRefGoogle Scholar
  36. 36.
    Duffau H, Taillandier L (2014) New concepts in the management of diffuse low-grade glioma: proposal of a multistage and individualized therapeutic approach. Neurooncology. Google Scholar
  37. 37.
    Aibaidula A, Chan AK-Y, Shi Z et al (2017) Adult IDH wild-type lower-grade gliomas should be further stratified. Neurooncology 19:1327–1337. Google Scholar
  38. 38.
    Appin CL, Brat DJ (2014) Molecular genetics of gliomas. Cancer J 20:66–72. CrossRefGoogle Scholar
  39. 39.
    van den Bent MJ, Smits M, Kros JM, Chang SM (2017) Diffuse infiltrating oligodendroglioma and astrocytoma. J Clin Oncol 35:2394–2401. CrossRefGoogle Scholar
  40. 40.
    van den Bent MJ, Weller M, Wen PY et al (2017) A clinical perspective on the 2016 WHO brain tumor classification and routine molecular diagnostics. Neurooncology 19:614–624. Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of NeurosurgeryMedical CenterFreiburgGermany
  2. 2.Department of Stereotactic and Functional NeurosurgeryMedical CenterFreiburgGermany
  3. 3.Department of NeuroradiologyMedical CenterFreiburgGermany
  4. 4.Institute of NeuropathologyFreiburg University Medical CenterFreiburgGermany
  5. 5.Institute of PathologyUniversity of FreiburgFreiburgGermany
  6. 6.Department of NeurosurgeryUniversity Hospital CologneCologneGermany
  7. 7.Medical FacultyFreiburg UniversityFreiburgGermany

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