Glioma Subclassifications and Their Clinical Significance

Abstract

The impact of targeted therapies in glioma has been modest. All the therapies that have demonstrated a significant survival benefit for gliomas in Phase III trials, including radiation, chemotherapy (temozolomide and PCV [procarbazine, lomustine, vincristine]), and tumor-treating fields, are based on nonspecific targeting of proliferating cells. Recent advances in the molecular understanding of gliomas suggest some potential reasons for the failure of more targeted therapies in gliomas. Specifically, the histologic-based glioma classification is composed of multiple different molecular subtypes with distinct biology, natural history, and prognosis. As a result of these insights, the diagnosis and classification of gliomas have recently been updated by the World Health Organization. However, these changes and other novel observations regarding glioma biomarkers and subtypes highlight several clinical challenges. First, the field is faced with the difficulty of reinterpreting the results of prior studies and retrospective data using the new classifications to clarify prognostic assessments and treatment recommendations for patients. Second, the new classifications and insights require rethinking the design and stratification of future clinical trials. Last, these observations provide the essential framework for the development and testing of new specific targeted therapies for particular glioma subtypes. This review aims to summarize the current literature regarding glioma subclassifications and their clinical relevance in this evolving field.

Keywords: 1p/19q co-deletion; 2HG; BRAF; EGFR; Ependymoma; Glioma; IDH mutation; MGMT methylation; MR spectroscopy; TERT promoter; Targeted therapy; Vaccine therapy.

Fig. 1

A simplified algorithm for classification of the diffuse gliomas based on histological and genetic features (see text and [10] for details). A caveat to this diagram is that the diagnostic “flow” does not necessarily always proceed from histology first to molecular genetic features next, as molecular signatures can sometimes outweigh histological characteristics in achieving an “integrated” diagnosis. A similar algorithm can be followed for anaplastic-level diffuse gliomas. *Characteristic but not required for diagnosis. Reprinted with permission from the World Health Organization [10]

Fig. 2

Differences between the 2007 and 2016 World Health Organization classifification systems. Reprinted with permission from Elsevier [5]

Fig. 3

Subgroups of ependymoma and their molecular characteristics by location in the neuroaxis. Reprinted with permission from [67]