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Journal of Neuro-Oncology

, Volume 129, Issue 2, pp 195–199 | Cite as

Clinical ramifications of “genomic staging” of low-grade gliomas

  • Vivek Verma
  • Minesh P. MehtaEmail author
Topic Review

Abstract

“Low-grade gliomas” (LGGs), classification of which is derived from histopathological observations, exhibit significant heterogeneity in clinical behavior. Recently, increasing attention has been paid to genomic analyses of these tumors, to aid in treatment and prognostic decision-making. We discuss herein the recent genomic analysis of gliomas from two major recent publications, and also the results of seminal LGG trials in the context of molecular and genomic stratification, with respect to both prognosis and response to therapy. We also analyze implications of these “molecular classifications”. We propose separating out the worst prognostic subsets, whose outcomes resemble those of glioblastoma patients. Lastly, a brief discussion is provided regarding translating this collective knowledge into the clinic and in treatment decisions; also addressed are some of the many questions that still need to be examined in light of these strong and emerging data.

Keywords

Low-grade glioma Genomics Oligodendroglioma Astrocytoma 

Notes

Compliance with ethical standards

Conflict of interest

MPM has served as a consultant for Abbott, Bristol-Meyers-Squibb, Celldex, Cavion, Elekta, Novartis, Novocure, and Roche; has research funding from Novocure and Cellectar; has served in a leadership capacity on the Pharmacyclics BOD (with stock options); and serves on the Data Monitoring and Safety Board of Monteris.

References

  1. 1.
    WHO Classification of Tumours of the Central Nervous System (2007) Louis DN, Ohgaki H, Wiestler OD, Cavenee WK (eds) IARC Press, LyonGoogle Scholar
  2. 2.
    Eckel-Passow JE, Lachance DH, Molinaro AM et al (2015) Glioma groups based on 1p/19q, IDH, and TERT promoter mutations in tumors. N Engl J Med 372(26):2499–2508CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    The Cancer Genome Atlas Research Network (2015) Comprehensive, integrative genomic analysis of diffuse lower-grade gliomas. N Engl J Med 372(26):2481–2498CrossRefPubMedCentralGoogle Scholar
  4. 4.
    Shaw EG, Wang M, Coons SW et al (2012) Randomized trial of radiation therapy plus procarbazine, lomustine, and vincristine chemotherapy for supratentorial adult low-grade glioma: initial results of RTOG 9802. J Clin Oncol 30(25):3065–3070CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Buckner JC, Shaw EG, Pugh SL et al (2016) Radiation plus procarbazine, CCNU, and vincristine in low-grade glioma. N Engl J Med 374(14):1344–1355CrossRefPubMedGoogle Scholar
  6. 6.
    Buckner J, Shaw E, Pugh S et al (2015) IDH1 R132H mutations in NRG Oncology/RTOG 9802: phase III study of radiation therapy (RT) alone vs RT plus procarbazine, CCNU, and vincristine (PCV) in patients with low grade glioma. Presented at Society for Neuro-oncology 2015 annual meeting, San Antonio, TexasGoogle Scholar
  7. 7.
    Baumert BG, Hegi ME, Mason WP et al (2015) Radiotherapy in relation to temozolomide: subgroup analysis of molecular markers of the randomized phase III study by the EORTC/NCIC-CTG/TROG/MRC-CTU (EORTC 22033-26033) in patients with a high risk low-grade glioma. J Clin Oncol 33:S15Google Scholar
  8. 8.
    Cairncross JG, Wang M, Jenkins RB et al (2014) Benefit from procarbazine, lomustine, and vincristine in oligodendroglial tumors is associated with mutation of IDH. J Clin Oncol 32(8):783–790CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Chang SM, Zhang P, Cairncross JG et al (2015) Results of NRG oncology/RTOG 9813: a phase III randomized study of radiation therapy (RT) and temozolomide (TMZ) versus RT and nitrosourea (NU) therapy for anaplastic astrocytoma (AA). J Clin Oncol 33 (suppl;abstr2002)Google Scholar
  10. 10.
    Yan H, Parsons DW, Jin G et al (2009) IDH1 and IDH2 mutations in gliomas. N Engl J Med 360(8):765–773CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Chang S, Peixin Z, Cairncross GJ et al (2015) Results of NRG Oncology/RTOG 9813: a phase III randomized study of radiation therapy (RT) and temozolomide (TMZ) versus RT and nitrosourea (NU) therapy for anaplastic astrocytoma (AA). J Clin Oncol 2–15;15S:96s (abstract 2002)Google Scholar
  12. 12.
    Agnihotri S, Aldape KD, Zadeh G (2014) Isocitrate dehydrogenase status and molecular subclasses of glioma and glioblastoma. Neurosurg Focus 37:E13CrossRefPubMedGoogle Scholar
  13. 13.
    Ceccarelli M, Barthel FP, Malta TM et al (2016) Molecular profiling reveals biologically discrete subsets and pathways of progression in diffuse glioma. Cell 164:550–563CrossRefPubMedGoogle Scholar
  14. 14.
    Cahill DP, Sloan AE, Nahed BV et al (2015) The role of neuropathology in the management of patients with diffuse low grade glioma: a systematic review and evidence-based clinical practice guideline. J Neurooncol 125:531–549CrossRefPubMedGoogle Scholar
  15. 15.
    Huse JT, Aldape KD (2013) The molecular landscape of diffuse glioma and prospects for biomarker development. Expert Opin Med Diagn 7:573–587CrossRefPubMedGoogle Scholar
  16. 16.
    Huse JT, Wallace M, Aldape KD et al (2014) Where are we now? And where are we going? A report from the Accelerate Brain Cancer Cure (ABC2) low-grade glioma research workshop. Neuro Oncol 16:173–178CrossRefPubMedGoogle Scholar
  17. 17.
    Vogelbaum MA, Hu C, Peereboom DM et al (2015) Phase II trial of pre-irradiation and concurrent temozolomide in patients with newly diagnosed anaplastic oligodendrogliomas and mixed anaplastic oligoastrocytomas: long term results of RTOG BR0131. J Neurooncol 124:413–420CrossRefPubMedGoogle Scholar
  18. 18.
    Fisher BJ, Hu C, Macdonald DR et al (2015) Phase 2 study of temozolomide-based chemoradiation therapy for high-risk low-grade gliomas: preliminary results of Radiation Therapy Oncology Group 0424. Int J Radiat Oncol Biol Phys 91:497–504CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Molenaar RJ, Botman D, Smits MA et al (2015) Radioprotection of IDH1-mutated cancer cells by the IDH1-mutant inhibitor AGI-5198. Cancer Res. doi: 10.1158/0008-5472.CAN-14-3603 PubMedGoogle Scholar
  20. 20.
    Beiko J, Suki D, Hess KR et al (2014) IDH1 mutant malignant astrocytomas are more amenable to surgical resection and have a survival benefit associated with maximal surgical resection. Neuro Oncol 16:81–91CrossRefPubMedGoogle Scholar
  21. 21.
    Duffau HA (2013) New philosophy in surgery for diffuse low-grade glioma (DLGG): oncological and functional outcomes. Neurochirurgie 59:2–8CrossRefPubMedGoogle Scholar
  22. 22.
    Duffau H (2016) Long-term outcomes after supratotal resection of diffuse low-grade gliomas: a consecutive series with 11-year follow-up. Acta Neurochir (Wien). doi: 10.1007/s00701-015-2621-3 Google Scholar
  23. 23.
    Dang L, White DW, Gross S et al (2009) Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature 462:739–744CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    de la Fuente MI, Young RJ, Rubel J et al (2016) Integration of 2-hydroxyglutarate-proton magnetic resonance spectroscopy into clinical practice for disease monitoring in isocitrate dehydrogenase-mutant glioma. Neuro Oncol 18:283–290CrossRefPubMedGoogle Scholar
  25. 25.
    Clinical Trial NCT02465060. NCI-MATCH: Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors or Lymphomas. https://clinicaltrials.gov/ct2/show/NCT02465060. Accessed November 11, 2015

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Department of Radiation OncologyUniversity of Nebraska Medical CenterOmahaUSA
  2. 2.Department of Radiation OncologyMiami Cancer InstituteCoral GablesUSA

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