Skip to main navigation menu Skip to main content Skip to site footer

Review article: Biomedical intelligence

Vol. 150 No. 2324 (2020)

A contemporary perspective on the diagnosis and treatment of diffuse gliomas in adults

DOI
https://doi.org/10.4414/smw.2020.20256
Cite this as:
Swiss Med Wkly. 2020;150:w20256
Published
18.06.2020

Summary

Gliomas are intrinsic brain tumours, which are classified by the World Health Organization (WHO) into different grades of malignancy, with glioblastoma being the most frequent and most malignant subtype (WHO grade IV). Mutations in the isocitrate dehydrogenase (IDH) 1 or 2 genes are frequent in lower (WHO II/III) grade tumours but typically absent in classical glioblastoma. IDH mutations are associated with a better prognosis compared with IDH wild-type tumours of the same WHO grade. Following detection of a tumour mass by imaging, maximum safe surgery as feasible is commonly performed to reduce mass effect and to obtain tissue allowing histopathological diagnosis and molecular assessment. Radiotherapy has been the mainstay in the treatment of diffuse gliomas for several decades. It provides improved local control, but is not curative. Furthermore, several randomised trials have shown that the addition of alkylating chemotherapy, either temozolomide or nitrosourea-based regimens, to radiotherapy results in prolonged survival. Tumour-treating fields (TTFields) have emerged as an additional treatment option in combination with maintenance temozolomide treatment for patients with newly diagnosed glioblastoma. Treatment at recurrence is less standardised and depends on the patient’s performance status, symptom burden and prior treatments. Bevacizumab prolongs progression-free survival in newly diagnosed and recurrent glioblastoma, but does not impact overall survival. However, in Switzerland and some other countries, it is still considered a valuable treatment option to reduce clinical symptom burden. Given the generally poor outcome for these patients, various novel treatment approaches are currently being explored within clinical trials including immunotherapeutic strategies such as immune checkpoint inhibition and the brain-penetrant proteasome inhibitor marizomib.

References

  1. Weller M, van den Bent M, Tonn JC, Stupp R, Preusser M, Cohen-Jonathan-Moyal E, et al.; European Association for Neuro-Oncology (EANO) Task Force on Gliomas. European Association for Neuro-Oncology (EANO) guideline on the diagnosis and treatment of adult astrocytic and oligodendroglial gliomas. Lancet Oncol. 2017 b;18(6):e315–29. doi:.https://doi.org/10.1016/S1470-2045(17)30194-8
  2. Hartmann C, Meyer J, Balss J, Capper D, Mueller W, Christians A, et al. Type and frequency of IDH1 and IDH2 mutations are related to astrocytic and oligodendroglial differentiation and age: a study of 1,010 diffuse gliomas. Acta Neuropathol. 2009;118(4):469–74. doi:.https://doi.org/10.1007/s00401-009-0561-9
  3. Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, et al. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol. 2016;131(6):803–20. doi:.https://doi.org/10.1007/s00401-016-1545-1
  4. Meyronet D, Esteban-Mader M, Bonnet C, Joly MO, Uro-Coste E, Amiel-Benouaich A, et al. Characteristics of H3 K27M-mutant gliomas in adults. Neuro-oncol. 2017;19(8):1127–34. doi:.https://doi.org/10.1093/neuonc/now274
  5. Brat DJ, Aldape K, Colman H, Holland EC, Louis DN, Jenkins RB, et al. cIMPACT-NOW update 3: recommended diagnostic criteria for “Diffuse astrocytic glioma, IDH-wildtype, with molecular features of glioblastoma, WHO grade IV”. Acta Neuropathol. 2018;136(5):805–10. doi:.https://doi.org/10.1007/s00401-018-1913-0
  6. Shirahata M, Ono T, Stichel D, Schrimpf D, Reuss DE, Sahm F, et al. Novel, improved grading system(s) for IDH-mutant astrocytic gliomas. Acta Neuropathol. 2018;136(1):153–66. doi:.https://doi.org/10.1007/s00401-018-1849-4
  7. Capper D, Jones DTW, Sill M, Hovestadt V, Schrimpf D, Sturm D, et al. DNA methylation-based classification of central nervous system tumours. Nature. 2018;555(7697):469–74. doi:.https://doi.org/10.1038/nature26000
  8. Wen PY, Macdonald DR, Reardon DA, Cloughesy TF, Sorensen AG, Galanis E, et al. Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol. 2010;28(11):1963–72. doi:.https://doi.org/10.1200/JCO.2009.26.3541
  9. Albert NL, Weller M, Suchorska B, Galldiks N, Soffietti R, Kim MM, et al. Response Assessment in Neuro-Oncology working group and European Association for Neuro-Oncology recommendations for the clinical use of PET imaging in gliomas. Neuro-oncol. 2016;18(9):1199–208. doi:.https://doi.org/10.1093/neuonc/now058
  10. Robinson C, Kleinschmidt-DeMasters BK. IDH1-Mutation in Diffuse Gliomas in Persons Age 55 Years and Over. J Neuropathol Exp Neurol. 2017;76(2):151–4. doi:.https://doi.org/10.1093/jnen/nlw112
  11. Wiestler B, Capper D, Holland-Letz T, Korshunov A, von Deimling A, Pfister SM, et al. ATRX loss refines the classification of anaplastic gliomas and identifies a subgroup of IDH mutant astrocytic tumors with better prognosis. Acta Neuropathol. 2013;126(3):443–51. doi:.https://doi.org/10.1007/s00401-013-1156-z
  12. Cocco E, Scaltriti M, Drilon A. NTRK fusion-positive cancers and TRK inhibitor therapy. Nat Rev Clin Oncol. 2018;15(12):731–47. doi:.https://doi.org/10.1038/s41571-018-0113-0
  13. Nayak L, DeAngelis LM, Brandes AA, Peereboom DM, Galanis E, Lin NU, et al. 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. Neuro-oncol. 2017;19(5):625–35. doi:.https://doi.org/10.1093/neuonc/nox029
  14. Stummer W, Pichlmeier U, Meinel T, Wiestler OD, Zanella F, Reulen HJ ; ALA-Glioma Study Group. Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. Lancet Oncol. 2006;7(5):392–401. doi:.https://doi.org/10.1016/S1470-2045(06)70665-9
  15. Senft C, Bink A, 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(11):997–1003. doi:.https://doi.org/10.1016/S1470-2045(11)70196-6
  16. Walker MD, Strike TA, Sheline GE. An analysis of dose-effect relationship in the radiotherapy of malignant gliomas. Int J Radiat Oncol Biol Phys. 1979;5(10):1725–31. doi:.https://doi.org/10.1016/0360-3016(79)90553-4
  17. van den Bent MJ, Afra D, de Witte O, Ben Hassel M, Schraub S, Hoang-Xuan K, et al., EORTC Radiotherapy and Brain Tumor Groups and the UK Medical Research Council. Long-term efficacy of early versus delayed radiotherapy for low-grade astrocytoma and oligodendroglioma in adults: the EORTC 22845 randomised trial. Lancet. 2005;366(9490):985–90. doi:.https://doi.org/10.1016/S0140-6736(05)67070-5
  18. Roa W, Brasher PM, Bauman G, Anthes M, Bruera E, Chan A, et al. Abbreviated course of radiation therapy in older patients with glioblastoma multiforme: a prospective randomized clinical trial. J Clin Oncol. 2004;22(9):1583–8. doi:.https://doi.org/10.1200/JCO.2004.06.082
  19. Brada M, Sharpe G, Rajan B, Britton J, Wilkins PR, Guerrero D, et al. Modifying radical radiotherapy in high grade gliomas; shortening the treatment time through acceleration. Int J Radiat Oncol Biol Phys. 1999;43(2):287–92. doi:.https://doi.org/10.1016/S0360-3016(98)00390-3
  20. Chan JL, Lee SW, Fraass BA, Normolle DP, Greenberg HS, Junck LR, et al. Survival and failure patterns of high-grade gliomas after three-dimensional conformal radiotherapy. J Clin Oncol. 2002;20(6):1635–42. doi:.https://doi.org/10.1200/JCO.2002.20.6.1635
  21. Karim AB, Maat B, Hatlevoll R, Menten J, Rutten EH, Thomas DG, et al. A randomized trial on dose-response in radiation therapy of low-grade cerebral glioma: European Organization for Research and Treatment of Cancer (EORTC) Study 22844. Int J Radiat Oncol Biol Phys. 1996;36(3):549–56. doi:.https://doi.org/10.1016/S0360-3016(96)00352-5
  22. Shaw E, Arusell R, Scheithauer B, O’Fallon J, O’Neill B, Dinapoli R, et al. Prospective randomized trial of low- versus high-dose radiation therapy in adults with supratentorial low-grade glioma: initial report of a North Central Cancer Treatment Group/Radiation Therapy Oncology Group/Eastern Cooperative Oncology Group study. J Clin Oncol. 2002;20(9):2267–76. doi:.https://doi.org/10.1200/JCO.2002.09.126
  23. Malmström A, Grønberg BH, Marosi C, Stupp R, Frappaz D, Schultz H, et al.; Nordic Clinical Brain Tumour Study Group (NCBTSG). Temozolomide versus standard 6-week radiotherapy versus hypofractionated radiotherapy in patients older than 60 years with glioblastoma: the Nordic randomised, phase 3 trial. Lancet Oncol. 2012;13(9):916–26. doi:.https://doi.org/10.1016/S1470-2045(12)70265-6
  24. Wick W, Platten M, Meisner C, Felsberg J, Tabatabai G, Simon M, et al.; NOA-08 Study Group of Neuro-oncology Working Group (NOA) of German Cancer Society. Temozolomide chemotherapy alone versus radiotherapy alone for malignant astrocytoma in the elderly: the NOA-08 randomised, phase 3 trial. Lancet Oncol. 2012;13(7):707–15. doi:.https://doi.org/10.1016/S1470-2045(12)70164-X
  25. Buckner JC, Shaw EG, Pugh SL, Chakravarti A, Gilbert MR, Barger GR, et al. Radiation plus Procarbazine, CCNU, and Vincristine in Low-Grade Glioma. N Engl J Med. 2016;374(14):1344–55. doi:.https://doi.org/10.1056/NEJMoa1500925
  26. Baumert BG, Hegi ME, van den Bent MJ, von Deimling A, Gorlia T, Hoang-Xuan K, et al. Temozolomide chemotherapy versus radiotherapy in high-risk low-grade glioma (EORTC 22033-26033): a randomised, open-label, phase 3 intergroup study. Lancet Oncol. 2016;17(11):1521–32. doi:.https://doi.org/10.1016/S1470-2045(16)30313-8
  27. Cairncross G, Wang M, Shaw E, Jenkins R, Brachman D, Buckner J, et al. Phase III trial of chemoradiotherapy for anaplastic oligodendroglioma: long-term results of RTOG 9402. J Clin Oncol. 2013;31(3):337–43. doi:.https://doi.org/10.1200/JCO.2012.43.2674
  28. van den Bent MJ, Brandes AA, Taphoorn MJ, Kros JM, Kouwenhoven MC, Delattre JY, et al. Adjuvant procarbazine, lomustine, and vincristine chemotherapy in newly diagnosed anaplastic oligodendroglioma: long-term follow-up of EORTC brain tumor group study 26951. J Clin Oncol. 2013;31(3):344–50. doi:.https://doi.org/10.1200/JCO.2012.43.2229
  29. van den Bent MJ, Baumert B, Erridge SC, Vogelbaum MA, Nowak AK, Sanson M, 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):1645–53. doi:.https://doi.org/10.1016/S0140-6736(17)31442-3
  30. Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, et al.; European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987–96. doi:.https://doi.org/10.1056/NEJMoa043330
  31. Perry JR, Laperriere N, O’Callaghan CJ, Brandes AA, Menten J, Phillips C, et al.; Trial Investigators. Short-Course Radiation plus Temozolomide in Elderly Patients with Glioblastoma. N Engl J Med. 2017;376(11):1027–37. doi:.https://doi.org/10.1056/NEJMoa1611977
  32. Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med. 2005;352(10):997–1003. doi:.https://doi.org/10.1056/NEJMoa043331
  33. Herrlinger U, Tzaridis T, Mack F, Steinbach JP, Schlegel U, Sabel M, et al.; Neurooncology Working Group of the German Cancer Society. Lomustine-temozolomide combination therapy versus standard temozolomide therapy in patients with newly diagnosed glioblastoma with methylated MGMT promoter (CeTeG/NOA-09): a randomised, open-label, phase 3 trial. Lancet. 2019;393(10172):678–88. doi:.https://doi.org/10.1016/S0140-6736(18)31791-4
  34. Chinot OL, Wick W, Mason W, Henriksson R, Saran F, Nishikawa R, et al. Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N Engl J Med. 2014;370(8):709–22. doi:.https://doi.org/10.1056/NEJMoa1308345
  35. Gilbert MR, Dignam JJ, Armstrong TS, Wefel JS, Blumenthal DT, Vogelbaum MA, et al. A randomized trial of bevacizumab for newly diagnosed glioblastoma. N Engl J Med. 2014;370(8):699–708. doi:.https://doi.org/10.1056/NEJMoa1308573
  36. Wirsching HG, Tabatabai G, Roelcke U, Hottinger AF, Jörger F, Schmid A, et al. Bevacizumab plus hypofractionated radiotherapy versus radiotherapy alone in elderly patients with glioblastoma: the randomized, open-label, phase II ARTE trial. Ann Oncol. 2018;29(6):1423–30. doi:.https://doi.org/10.1093/annonc/mdy120
  37. Stupp R, Wong ET, Kanner AA, Steinberg D, Engelhard H, Heidecke V, et al. NovoTTF-100A versus physician’s choice chemotherapy in recurrent glioblastoma: a randomised phase III trial of a novel treatment modality. Eur J Cancer. 2012;48(14):2192–202. doi:.https://doi.org/10.1016/j.ejca.2012.04.011
  38. Stupp R, Taillibert S, Kanner A, Read W, Steinberg D, Lhermitte B, et al. Effect of Tumor-Treating Fields Plus Maintenance Temozolomide vs Maintenance Temozolomide Alone on Survival in Patients With Glioblastoma: A Randomized Clinical Trial. JAMA. 2017;318(23):2306–16. doi:.https://doi.org/10.1001/jama.2017.18718
  39. Taphoorn MJB, Dirven L, Kanner AA, Lavy-Shahaf G, Weinberg U, Taillibert S, et al. Influence of Treatment With Tumor-Treating Fields on Health-Related Quality of Life of Patients With Newly Diagnosed Glioblastoma: A Secondary Analysis of a Randomized Clinical Trial. JAMA Oncol. 2018;4(4):495–504. doi:.https://doi.org/10.1001/jamaoncol.2017.5082
  40. Hundsberger T, Hottinger AF, Roelcke U, Roth P, Migliorini D, Dietrich PY, et al. Patterns of care in recurrent glioblastoma in Switzerland: a multicentre national approach based on diagnostic nodes. J Neurooncol. 2016;126(1):175–83. doi:.https://doi.org/10.1007/s11060-015-1957-0
  41. Gramatzki D, Roth P, Rushing EJ, Weller J, Andratschke N, Hofer S, et al. Bevacizumab may improve quality of life, but not overall survival in glioblastoma: an epidemiological study. Ann Oncol. 2018;29(6):1431–6. doi:.https://doi.org/10.1093/annonc/mdy106
  42. Taal W, Oosterkamp HM, Walenkamp AM, Dubbink HJ, Beerepoot LV, Hanse MC, et al. Single-agent bevacizumab or lomustine versus a combination of bevacizumab plus lomustine in patients with recurrent glioblastoma (BELOB trial): a randomised controlled phase 2 trial. Lancet Oncol. 2014;15(9):943–53. doi:.https://doi.org/10.1016/S1470-2045(14)70314-6
  43. Wick W, Gorlia T, Bendszus M, Taphoorn M, Sahm F, Harting I, et al. Lomustine and Bevacizumab in Progressive Glioblastoma. N Engl J Med. 2017;377(20):1954–63. doi:.https://doi.org/10.1056/NEJMoa1707358
  44. Weller M, Tabatabai G, Kästner B, Felsberg J, Steinbach JP, Wick A, et al.; DIRECTOR Study Group. MGMT Promoter Methylation Is a Strong Prognostic Biomarker for Benefit from Dose-Intensified Temozolomide Rechallenge in Progressive Glioblastoma: The DIRECTOR Trial. Clin Cancer Res. 2015;21(9):2057–64. doi:.https://doi.org/10.1158/1078-0432.CCR-14-2737
  45. Yung WK, Albright RE, Olson J, Fredericks R, Fink K, Prados MD, et al. A phase II study of temozolomide vs. procarbazine in patients with glioblastoma multiforme at first relapse. Br J Cancer. 2000;83(5):588–93. doi:.https://doi.org/10.1054/bjoc.2000.1316
  46. Roth P, Wick W, Weller M. Steroids in neurooncology: actions, indications, side-effects. Curr Opin Neurol. 2010;23(6):597–602. doi:.https://doi.org/10.1097/WCO.0b013e32833e5a5d
  47. Weller M, Stupp R, Wick W. Epilepsy meets cancer: when, why, and what to do about it? Lancet Oncol. 2012;13(9):e375–82. doi:.https://doi.org/10.1016/S1470-2045(12)70266-8
  48. Pace A, Dirven L, Koekkoek JAF, Golla H, Fleming J, Rudà R, et al.; European Association of Neuro-Oncology palliative care task force. European Association for Neuro-Oncology (EANO) guidelines for palliative care in adults with glioma. Lancet Oncol. 2017;18(6):e330–40. doi:.https://doi.org/10.1016/S1470-2045(17)30345-5
  49. Reardon DA, Brandes AA, Omuro A, Mulholland P, Lim M, Wick A, et al. Effect of Nivolumab vs Bevacizumab in Patients With Recurrent Glioblastoma: The CheckMate 143 Phase 3 Randomized Clinical Trial. JAMA Oncol. 2020 May 21. doi:.https://doi.org/10.1001/jamaoncol.2020.1024
  50. Weller M, Butowski N, Tran DD, Recht LD, Lim M, Hirte H, et al.; ACT IV trial investigators. Rindopepimut with temozolomide for patients with newly diagnosed, EGFRvIII-expressing glioblastoma (ACT IV): a randomised, double-blind, international phase 3 trial. Lancet Oncol. 2017 a;18(10):1373–85. doi:.https://doi.org/10.1016/S1470-2045(17)30517-X
  51. van den Bent MJ, French P, Juan Sepulveda M, Walenkamp A, Frenel J-S, Franceschi E, et al. Two-year results of the INTELLANCE 2/EORTC trial 1410 randomized-phase II study on Depatux-M alone, Depatux-M combined with temozolomide (TMZ) and either TMZ or lomustine in reucrrent EGFR amplified glioblastoma. Neuro-oncol. 2018;20(suppl_6):vi20. doi:.https://doi.org/10.1093/neuonc/noy148.072
  52. Kaley T, Touat M, Subbiah V, Hollebecque A, Rodon J, Lockhart AC, et al. BRAF Inhibition in BRAF V600-Mutant Gliomas: Results From the VE-BASKET Study. J Clin Oncol. 2018;36(35):3477–84. doi:.https://doi.org/10.1200/JCO.2018.78.9990
  53. Le Rhun E, Preusser M, Roth P, Reardon DA, van den Bent M, Wen P, et al. Molecular targeted therapy of glioblastoma. Cancer Treat Rev. 2019;80:101896. doi:.https://doi.org/10.1016/j.ctrv.2019.101896

Most read articles by the same author(s)

1 2 > >>