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Anaplastic Glioma: Treatment Approaches in the Era of Molecular Diagnostics

  • Michael W. Ruff
  • Joon Uhm
Neuro-oncology (GJ Lesser, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Neuro-oncology

Opinion statement

The treatment paradigm for anaplastic glioma has shifted, owing to new diagnostic criteria and new phase III clinical trial evidence. In 2016, the WHO classification of brain tumors including diffuse gliomas was redefined to include molecular criteria, often supplanting the morphological appearance of the tumor cells. This was necessary as prognosis is more closely associated with molecular diagnosis than with morphology and grade. Recently, the benefit of adjuvant chemotherapy in addition to radiotherapy has been demonstrated in both anaplastic oligodendroglioma and anaplastic astrocytoma, as well as lower grade gliomas with the most marked benefit evident in IDH-mutated (astrocytoma) and 1p/19q co-deleted (oligodendroglial) tumors. The defining principle of recent breakthroughs has been the benefit of combinatorial therapy (chemo-radiation) as opposed to treatment in series or treatment of either modality after a period of observation upon evidence of progression.

Keywords

Anaplastic glioma Oligodendroglioma Astrocytoma PCV Temozolomide 

Notes

Compliance with Ethical Standards

Conflict of Interest

Michael W. Ruff and Joon Uhm declare they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Cahill DP, Louis DN, Cairncross JG. Molecular background of oligodendroglioma: 1p/19q, IDH, TERT, CIC and FUBP1. CNS Oncol. 2015;4(5):287–94.CrossRefGoogle Scholar
  2. 2.
    •• Loruis D, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee W, et al. The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol. 2016;131(6):803–20 This article summarizes the WHO 2016 revision of brain tumor diagnoses.CrossRefGoogle Scholar
  3. 3.
    • Eckel-Passow JE, Lachance DH, Molinaro AM, Walsh KM, Decker PA, Sicotte H, et al. Glioma groups based on 1p/19q, IDH, and TERT promoter mutations in tumors. N Engl J Med. 2015;372(26):2499–508 Characterizes glioma based on molecular profile, with the demonstration that the genetics of glioma (even low grade) are highly predictive of behavior, and in many cases more important than histological grade.CrossRefGoogle Scholar
  4. 4.
    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.CrossRefGoogle Scholar
  5. 5.
    van den Bent MJ, Brandes AA, Taphoorn MJ, 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.CrossRefGoogle Scholar
  6. 6.
    •• 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 Demonstrated the benefit of adjuvant TMZ in anaplastic astrocytoma.CrossRefGoogle Scholar
  7. 7.
    Cairncross G, Berkey B, Shaw E, et al. Phase III trial of chemotherapy plus radiotherapy compared with radiotherapy alone for pure and mixed anaplastic oligodendroglioma: Intergroup Radiation Therapy Oncology Group Trial 9402. J Clin Oncol. 2006;24:2707–14.CrossRefGoogle Scholar
  8. 8.
    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.CrossRefGoogle Scholar
  9. 9.
    Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987–96.CrossRefGoogle Scholar
  10. 10.
    Medical Research Council Brain Tumor Working Party. Randomized trial of procarbazine, lomustine, and vincristine in the adjuvant treatment of high-grade astrocytoma: a Medical Research Council trial. J Clin Oncol. 2001;19(2):509–18.CrossRefGoogle Scholar
  11. 11.
    Cairncross JG, Wang M, Jenkins RB, Shaw EG, Giannini C, Brachman DG, et al. Benefit from procarbazine, lomustine, and vincristine in oligodendroglial tumors is associated with mutation of IDH. J Clin Oncol. 2014;32(8):783–90.CrossRefGoogle Scholar
  12. 12.
    Co-del-“Radiation Therapy With Concomitant And Adjuvant Temozolomide Versus Radiation Therapy With Adjuvant PCV Chemotherapy In Patients With Anaplastic Glioma Or Low Grade Glioma - Full Text View - Clinicaltrials.Gov.” Clinicaltrials.gov. N. p., 2017. Web. 24 Oct. 2017.
  13. 13.
    • Osswald M, Jung E, Sahm F, Solecki G, Venkataramani V, Blaes J, et al. Brain tumor cells interconnect to a functional and resistant network. Nature. 2015;528(7580):93–8 Demonstrates the implications at a cellular level of the 1p/19q codeletion.PubMedGoogle Scholar
  14. 14.
    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.CrossRefGoogle Scholar
  15. 15.
    • 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 Further demonstrates the benefit of adjuvant PCV chemotherapy in low-grade glioma (IDH-mutated with or without 1p/19q codeletion).CrossRefGoogle Scholar
  16. 16.
    Mellinghoff, IK et al. Phase 1 study of AG-881, an inhibitor of mutant IDH1/IDH2, in patients with advanced IDH-mutant solid tumors, including glioma. J Clin Oncol 36, 2018 (suppl; abstr 2002).CrossRefGoogle Scholar
  17. 17.
    Platten M. A mutation-specific peptide vaccine targeting IDH1R132H in patients with newly diagnosed malignant astrocytomas: a first-in-man multicenter phase I clinical trial of the German Neurooncology Working Group (NOA-16). J Clin Oncol 36, 2018 (suppl; abstr 2001).CrossRefGoogle Scholar

Copyright information

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

Authors and Affiliations

  1. 1.Division of Neuro-Oncology Mayo ClinicRochesterUSA
  2. 2.Division of Medical Oncology Mayo ClinicRochesterUSA

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