JOURNAL OF CLINICAL ONCOLOGY R E V I E W A R T I C L E Diffuse Infiltrating Oligodendroglioma and Astrocytoma Martin J. van den Bent, Marion Smits, Johan M. Kros, and Susan M. Chang A B S T R A C T The new 2016 WHO brain tumor classification defines different diffuse gliomas primarily according to the presence or absence of IDH mutations (IDH-mt) and combined 1p/19q loss. Today, the di- agnosis of anaplastic oligodendroglioma requires the presence of both IDH-mt and 1p/19q co- deletion, whereas anaplastic astrocytoma is divided into IDH wild-type (IDH-wt) and IDH-mt tumors. IDH-mt tumors have a more favorable prognosis, and tumors with low-grade histology especially tend evolve slowly. IDH-wt tumors are not a homogeneous entity and warrant further molecular testing because some have glioblastoma-like molecular features with poor clinical outcome. Treatment consists of a resection that should be as extensive as safely possible, radiotherapy, and chemotherapy. Trials of patients with newly diagnosed grade II or III glioma have shown survival benefit from adding chemotherapy to radiotherapy compared with initial treatment using radio- therapy alone. Both temozolomide and the combination of procarbazine, lomustine, and vincristine provide survival benefit. In contrast, trials that compare single modality treatment of chemotherapy alone with radiotherapy alone did not observe survival differences. Currently, for patients with grade II or III gliomas who require postsurgical treatment, the preferred treatment consists of a combi- nation of radiotherapy and chemotherapy. Low-grade gliomas with favorable characteristics are slow-growing tumors. When deciding on the timing of postsurgical treatment with radiotherapy and chemotherapy, both clinical and molecular factors should be taken into account, but a more con- servative approach can be considered initially in some of these patients. The factor that best predicts benefit of chemotherapy in grade II and III glioma remains to be established. J Clin Oncol 35:2394-2401. © 2017 by American Society of Clinical Oncology INTRODUCTION Diffuse grade II and III gliomas traditionally have been separated morphologically into two basic subtypes: oligodendroglioma and astrocytoma, with a third mixed category of oligoastrocytoma for those cases in which tumor morphology showed characteristics of both. The WHO 2016 edition of the classification of glioma has radically changed this, and glioma diagnosis is now pri- marily based on molecular characteristics. 1 Thus, the diagnosis of an anaplastic oligodendroglioma now requires the presence of both 1p/19q co- deletion and mutation of isocitrate dehydrogenase 1 or 2 (IDH1-mt or IDH2-mt). Anaplastic as- trocytoma has both IDH-mt and IDH wild-type (IDH-wt) variants. This new classification of diffuse gliomas is more robust and far more informative for treatment outcome than the classic morphologic approach, but it requires clinicians to digest this new reality and to re- think their approach to diagnostics and treat- ment of these tumors. This review summarizes the currently available clinical data for astrocytoma and oligodendroglioma from the perspective of the new WHO 2016 brain tumor classification. CLINICAL PRESENTATION Each year, in the United States, 4,500 to 5,000 patients are newly diagnosed with a grade II or III astrocytoma or oligodendroglioma. 2 Typically, patients with low-grade gliomas present between 25 and 45 years of age, whereas patients with anaplastic tumors tend to be slightly older. As- trocytoma with IDH-mt is occasionally diagnosed in adolescents (even younger than age 15 years) whereas some 1p/19q co-deleted IDH-mt oligo- dendrogliomas are first diagnosed in patients older than age 65 years. The likelihood of finding an IDH mutation in low-grade and anaplastic diffuse gliomas decreases with increasing age. The clinical presentation of brain tumors depends on tumor localization and growth rate. Most low- grade and anaplastic tumors present with sei- zures; early focal deficits are less common in these tumors. Most cases of low-grade glioma tend to Author affiliations and support information (if applicable) appear at the end of this article. Published at jco.org on June 22, 2017. Corresponding author: Martin J. van den Bent, MD, Brain Tumor Center at Erasmus Medical Center Cancer Institute, Groene Hilledijk 301, 3075EA Rotterdam, the Netherlands; e-mail: m.vandenbent@ erasmusmc.nl. © 2017 by American Society of Clinical Oncology 0732-183X/17/3521w-2394w/$20.00 DOI: https://doi.org/10.1200/JCO.2017. 72.6737 2394 © 2017 by American Society of Clinical Oncology VOLUME 35 • NUMBER 21 • JULY 20, 2017 Downloaded from ascopubs.org by 52.73.204.196 on May 12, 2022 from 052.073.204.196 Copyright © 2022 American Society of Clinical Oncology. All rights reserved.