Opinion statement
Anaplastic oligodendroglial tumors have gained increasing interest with the emerging role of molecular markers and systemic chemotherapy during the past years. The long-term results of two landmark trials, RTOG 9402 and EORTC 26961, have resulted in a reconsideration of the appropriate therapeutic approaches for patients with these tumors. Both trials indicate that patients whose tumors harbor a 1p/19q co-deletion benefit particularly from the addition of procarbazine/lomustine (CCNU)/vincristine (PCV) chemotherapy to radiation therapy (RT). The median survival of patients with co-deleted tumors treated within the RTOG trial with PCV before irradiation was 14.7 years compared with 7.3 years of patients who received RT alone. Median overall survival has not been reached in the RT plus PCV arm of the EORTC trial, but a similar difference can be anticipated after a follow-up of more than 12 years. In contrast, no such benefit was observed for patients with tumors lacking 1p/19q co-deletion. Outside clinical trials, patients with anaplastic oligodendroglial tumors, and 1p/19q co-deletion therefore should be offered a combined treatment modality regimen, including radio- and chemotherapy. PCV, however, is associated with significant hematological toxicity and also nonhematological side effects, which probably translate into reduced quality of life for long-term survivors. Therefore, it might be warranted to replace PCV by temozolomide, which displays a more favorable side effect profile. Data from the NOA-04 study suggest that PCV and temozolomide have similar effects. However, long-term data on the benefit from temozolomide are lacking, making a definite answer on the equivalence of temozolomide and PCV in anaplastic oligodendroglioma (AO) impossible. The current evidence precludes RT alone for AO patients. Neither the RTOG nor the EORTC trial defined the role of chemotherapy alone. A comparison of combined modality treatment with chemotherapy alone followed by RT at progression is pending. Long-term follow-up of NOA-04 patients and results from future trials may help to clarify these questions. With more and more AO patients living 10 years or more, particular attention must be paid to late side effects, such as neurotoxicity, and careful monitoring is required for all treated patients.
Similar content being viewed by others
References and Recommended Reading
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
Louis DN, Ohgaki H, Wiestler OD, et al. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 2007;114:97–109.
Weller M, Pfister SM, Wick W, et al. Molecular neuro-oncology entering clinical practice: a new horizon. Lancet Oncol. 2013; in press. A comprehensive review on molecular markers in neurooncology.
Erdem-Eraslan L, Gravendeel LA, de Rooi J, et al. Intrinsic molecular subtypes of glioma are prognostic and predict benefit from adjuvant procarbazine, lomustine, and vincristine chemotherapy in combination with other prognostic factors in anaplastic oligodendroglial brain tumors: a report from EORTC study 26951. J Clin Oncol. 2013;31:328–36.
van den Bent MJ. Interobserver variation of the histopathological diagnosis in clinical trials on glioma: a clinician's perspective. Acta Neuropathol. 2010;120:297–304.
Reifenberger J, Reifenberger G, Liu L, et al. Molecular genetic analysis of oligodendroglial tumors shows preferential allelic deletions on 19q and 1p. Am J Pathol. 1994;145:1175–90.
Jenkins RB, Blair H, Ballman KV, et al. A t(1;19)(q10;p10) mediates the combined deletions of 1p and 19q and predicts a better prognosis of patients with oligodendroglioma.Cancer Res. 2006;66:9852–61.
Bettegowda C, Agrawal N, Jiao Y, et al. Mutations in CIC and FUBP1 contribute to human oligodendroglioma. Science. 2011;333:1453–5. This publication describes 2 genes which may contribute to the pathogenesis of oligodendroglial tumors.
Weller M, Berger H, Hartmann C, et al. Combined 1p/19q loss in oligodendroglial tumors: predictive or prognostic biomarker? Clin Cancer Res. 2007;13:6933–7.
Stummer W, Pichlmeier U, Meinel T, et al. Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. Lancet Oncol. 2006;7:392–401.
Tsitlakidis A, Foroglou N, Venetis CA, et al. Biopsy versus resection in the management of malignant gliomas: a systematic review and meta-analysis. J Neurosurg. 2010;112:1020–32.
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.
van den Bent MJ, Carpentier AF, Brandes AA, et al. Adjuvant procarbazine, lomustine, and vincristine improves progression-free survival but not overall survival in newly diagnosed anaplastic oligodendrogliomas and oligoastrocytomas: a randomized European Organisation for Research and Treatment of Cancer phase III trial. J Clin Oncol. 2006;24:2715–22.
Wick W, Hartmann C, Engel C, et al. NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with procarbazine, lomustine, and vincristine or temozolomide. J Clin Oncol. 2009;27:5874–80. In this randomized trial radiotherapy or chemotherapy achieved comparable results in patients with anaplastic gliomas.
Walker MD, Alexander Jr E, Hunt WE, et al. Evaluation of BCNU and/or radiotherapy in the treatment of anaplastic gliomas. A cooperative clinical trial. J Neurosurg. 1978;49:333–43.
Gannett DE, Wisbeck WM, Silbergeld DL, Berger MS. The role of postoperative irradiation in the treatment of oligodendroglioma. Int J Radiat Oncol Biol Phys. 1994;30:567–73.
Chan JL, Lee SW, Fraass BA, et al. Survival and failure patterns of high-grade gliomas after three-dimensional conformal radiotherapy. J Clin Oncol. 2002;20:1635–42.
Phillips C, Guiney M, Smith J, et al. A randomized trial comparing 35Gy in ten fractions with 60Gy in 30 fractions of cerebral irradiation for glioblastoma multiforme and older patients with anaplastic astrocytoma. Radiother Oncol. 2003;68:23–6.
Cairncross JG, Macdonald DR. Successful chemotherapy for recurrent malignant oligodendroglioma. Ann Neurol. 1988;23:360–4.
Cairncross JG, Macdonald DR, Ramsay DA. Aggressive oligodendroglioma: a chemosensitive tumor. Neurosurgery. 1992;31:78–82.
Cairncross G, Wang M, Shaw E, et al. Phase III trial of chemoradiotherapy for anaplastic oligodendroglioma: long-term results of RTOG 9402. J Clin Oncol. 2013;31:337–43. The long-term follow-up of RTOG 9402 suggests that the combination of radiation therapy with PCV chemotherapy results in prolonged survival in patients with 1p/19q co-deleted tumors.
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;31:344–50. The long-term follow-up of the EORTC 26951 trial suggests that the combination of radiation therapy with PCV chemotherapy results in prolonged survival in patients with 1p/19q co-deleted tumors.
Abrey LE, Louis DN, Paleologos N, et al. Survey of treatment recommendations for anaplastic oligodendroglioma. Neuro Oncol. 2007;9:314–8.
Panageas KS, Iwamoto FM, Cloughesy TF, et al. Initial treatment patterns over time for anaplastic oligodendroglial tumors. Neuro Oncol. 2012;14:761–7.
Kellie SJ, Barbaric D, Koopmans P, et al. Cerebrospinal fluid concentrations of vincristine after bolus intravenous dosing: a surrogate marker of brain penetration. Cancer. 2002;94:1815–20.
Boyle FM, Eller SL, Grossman SA. Penetration of intra-arterially administered vincristine in experimental brain tumor. Neuro Oncol. 2004;6:300–5.
Swain SM, Arezzo JC. Neuropathy associated with microtubule inhibitors: diagnosis, incidence, and management. Clin Adv Hematol Oncol. 2008;6:455–67.
Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352:987–96.
Yung WK, Prados MD, Yaya-Tur R, et al. Multicenter phase II trial of temozolomide in patients with anaplastic astrocytoma or anaplastic oligoastrocytoma at first relapse. Temodal Brain Tumor Group. J Clin Oncol. 1999;17:2762–71.
Chinot OL, Honore S, Dufour H, et al. Safety and efficacy of temozolomide in patients with recurrent anaplastic oligodendrogliomas after standard radiotherapy and chemotherapy. J Clin Oncol. 2001;19:2449–55.
Taliansky-Aronov A, Bokstein F, Lavon I, Siegal T. Temozolomide treatment for newly diagnosed anaplastic oligodendrogliomas: a clinical efficacy trial. J Neurooncol. 2006;79:153–7.
Lassman AB, Iwamoto FM, Cloughesy TF, et al. International retrospective study of over 1000 adults with anaplastic oligodendroglial tumors. Neuro Oncol. 2011;13:649–59. A comprehensive retrospective analysis of patients with anaplastic oligodendroglial tumors.
Friedman HS, Prados MD, Wen PY, et al. Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol. 2009;27:4733–40.
Taillibert S, Vincent LA, Granger B, et al. Bevacizumab and irinotecan for recurrent oligodendroglial tumors. Neurology. 2009;72:1601–6.
Kreisl TN, Zhang W, Odia Y, et al. A phase II trial of single-agent bevacizumab in patients with recurrent anaplastic glioma. Neuro Oncol. 2011;13:1143–50. This study suggests activity of the VEGF inhibitor bevacizumab in patients with recurrent anaplastic glioma.
Seystahl K, Wiestler B, Hundsberger T, et al. Bevacizumab alone or in combination with irinotecan in recurrent WHO grade II and grade III gliomas. Eur Neurol. 2013;69:95–101.
Chamberlain MC, Johnston S. Bevacizumab for recurrent alkylator-refractory anaplastic oligodendroglioma. Cancer. 2009;115:1734–43.
Conflict of Interest
Patrick Roth is a consultant to MSD and Roche on their advisory boards.
Wolfgang Wick has received honoraria and consulted for MSD and Roche.
Michael Weller is a consultant to Magforce and Antisense Pharma and has received honoraria from MSD and Roche.
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.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Roth, P., Wick, W. & Weller, M. Anaplastic Oligodendroglioma: A New Treatment Paradigm and Current Controversies. Curr. Treat. Options in Oncol. 14, 505–513 (2013). https://doi.org/10.1007/s11864-013-0251-7
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11864-013-0251-7