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  • Updated 03.06.2022
  • Released 03.06.2022
  • Expires For CME 03.06.2025

IDH-mutated diffuse astrocytomas

Introduction

Overview

This article discusses isocitrate dehydrogenase (IDH) mutated diffuse astrocytomas, their classification, natural history, and management options.

Key points

• IDH-mutated diffuse astrocytoma presents with a wide spectrum of neurologic manifestations.

• Median age at presentation is 46 years, with a slightly higher incidence in males.


• Magnetic resonance imaging with and without contrast is the standard approach for evaluating brain lesions.


• Tissue diagnosis by biopsy or surgery is essential.


• Radiation and chemotherapy prolong survival, but the exact timing is not well delineated.


• Progression-free survival, but not overall survival, is improved by early radiation.


• Procarbazine, CCNU (lomustine), and vincristine combination chemotherapy improves survival; temozolomide likely does as well.


• Observation may be a reasonable option for select cases, keeping in mind that regular imaging is needed in this setting.

Historical note and terminology

Brain tumors were managed historically with surgical resection and radiotherapy starting in the era of Harvey Cushing. In 1976, adjuvant chemotherapy began to be utilized when cyclohexyl chloroethyl nitrosourea (CCNU) was found to increase survival—albeit by only a few months (14). During this era, our understanding and classification of gliomas were based entirely on histology and the anatomical location of the tumors. This approach continued until 2016 when a new classification system was developed, guided by a new molecular understanding of gliomas. In particular, mutations in the genes encoding isocitrate dehydrogenase (IDH1 and IDH2), as well as chromosomal 1p19q co-deletion were found to be strongly associated with improved prognosis (31; 43; 35). The 2016 World Health Organization classification system defines the following subtypes of grade 2 and grade 3 gliomas:


• Grade 2 diffuse astrocytoma, IDH-wildtype


• Grade 2 diffuse astrocytoma, IDH-mutated


• Grade 2 oligodendroglioma, IDH-mutated and 1p19q co-deleted


• Grade 3 anaplastic astrocytoma, IDH-wildtype


• Grade 3 anaplastic astrocytoma, IDH-mutated


• Grade 3 anaplastic oligodendroglioma IDH-mutated and 1p19q co-deleted


(24)

The focus of this article is on grade 2 diffuse astrocytoma, IDH-mutated (IDH1 or IDH2). It is important to recognize that the revised 2021 WHO classification makes use of a simplified system, only denoting the following subtypes:


• Astrocytoma, IDH-mutated


• Oligodendroglioma, IDH-mutated and 1p/19q-codeleted


• Glioblastoma, IDH-wildtype


(25)

Notably, the 2021 WHO classification does not distinguish between diffuse and anaplastic astrocytoma as these histological properties were not found to be as helpful as molecular and cellular properties for prognostication.

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