title: Anaplastic oligodendroglioma: a new treatment paradigm and current controversies.
abstract: 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.
authors.affiliation: Department of Neurology, University Hospital Zurich, Frauenklinikstrasse 26, 8091, Zurich, Switzerland.
authors.forename: Patrick
authors.initials: P
authors.lastname: Roth
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wick
authors.forename: Michael
authors.initials: M
authors.lastname: Weller
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000235:genetics / Q000401:mortality / Q000628:therapy*; D003131:Combined Modality Therapy; D005260:Female; D017353:Gene Deletion; D006801:Humans; D008130:Lomustine / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D009837:Oligodendroglioma / Q000235:genetics / Q000401:mortality / Q000628:therapy*; D018579:Patient Selection; D011344:Procarbazine / Q000008:administration & dosage / Q000009:adverse effects; D011788:Quality of Life; D011882:Radiotherapy, High-Energy; D016019:Survival Analysis; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D011344:Procarbazine; D014750:Vincristine; D008130:Lomustine
references.citation: J Clin Oncol. 2009 Oct 1;27(28):4733-40
references.pmid: 19720927
references.citation: Am J Pathol. 1994 Nov;145(5):1175-90
references.pmid: 7977648
references.citation: J Clin Oncol. 2002 Mar 15;20(6):1635-42
references.pmid: 11896114
references.citation: Science. 2011 Sep 9;333(6048):1453-5
references.pmid: 21817013
references.citation: Ann Neurol. 1988 Apr;23(4):360-4
references.pmid: 3382171
references.citation: J Clin Oncol. 2001 May 1;19(9):2449-55
references.pmid: 11331324
references.citation: Cancer. 2002 Mar 15;94(6):1815-20
references.pmid: 11920545
references.citation: Neuro Oncol. 2007 Jul;9(3):314-8
references.pmid: 17435180
references.citation: Int J Radiat Oncol Biol Phys. 1994 Oct 15;30(3):567-73
references.pmid: 7928487
references.citation: J Clin Oncol. 2006 Jun 20;24(18):2707-14
references.pmid: 16782910
references.citation: Lancet Oncol. 2006 May;7(5):392-401
references.pmid: 16648043
references.citation: Acta Neuropathol. 2010 Sep;120(3):297-304
references.pmid: 20644945
references.citation: J Clin Oncol. 2013 Jan 20;31(3):337-43
references.pmid: 23071247
references.citation: Cancer. 2009 Apr 15;115(8):1734-43
references.pmid: 19197992
references.citation: Clin Adv Hematol Oncol. 2008 Jun;6(6):455-67
references.pmid: 18567992
references.citation: Acta Neuropathol. 2007 Aug;114(2):97-109
references.pmid: 17618441
references.citation: J Neurosurg. 2010 May;112(5):1020-32
references.pmid: 19747048
references.citation: J Clin Oncol. 2009 Dec 10;27(35):5874-80
references.pmid: 19901110
references.citation: Neuro Oncol. 2012 Jun;14(6):761-7
references.pmid: 22661585
references.citation: Neurology. 2009 May 5;72(18):1601-6
references.pmid: 19414728
references.citation: J Clin Oncol. 2013 Jan 20;31(3):328-36
references.pmid: 23269986
references.citation: Radiother Oncol. 2003 Jul;68(1):23-6
references.pmid: 12885448
references.citation: J Neurooncol. 2006 Sep;79(2):153-7
references.pmid: 16855865
references.citation: Clin Cancer Res. 2007 Dec 1;13(23):6933-7
references.pmid: 18056167
references.citation: Neuro Oncol. 2011 Oct;13(10):1143-50
references.pmid: 21865400
references.citation: J Clin Oncol. 1999 Sep;17(9):2762-71
references.pmid: 10561351
references.citation: Neuro Oncol. 2011 Jun;13(6):649-59
references.pmid: 21636710
references.citation: Neuro Oncol. 2004 Oct;6(4):300-5
references.pmid: 15494097
references.citation: Eur Neurol. 2013;69(2):95-101
references.pmid: 23182901
references.citation: J Neurosurg. 1978 Sep;49(3):333-43
references.pmid: 355604
references.citation: J Clin Oncol. 2006 Jun 20;24(18):2715-22
references.pmid: 16782911
references.citation: Cancer Res. 2006 Oct 15;66(20):9852-61
references.pmid: 17047046
references.citation: Neurosurgery. 1992 Jul;31(1):78-82
references.pmid: 1641113
references.citation: N Engl J Med. 2005 Mar 10;352(10):987-96
references.pmid: 15758009
references.citation: J Clin Oncol. 2013 Jan 20;31(3):344-50
references.pmid: 23071237