H-G Wirsching1, T Weiss1, P Roth1, M Weller2. 1. Klinik für Neurologie, Universitätsspital Zürich und Universität Zürich, Frauenklinikstraße 26, 8091, Zürich, Schweiz. 2. Klinik für Neurologie, Universitätsspital Zürich und Universität Zürich, Frauenklinikstraße 26, 8091, Zürich, Schweiz. michael.weller@usz.ch.
Abstract
BACKGROUND: Traditionally, gliomas were classified based on histopathological features alone. The revised World Health Organization (WHO) classification of tumors of the central nervous system from 2016 integrated molecular features into the histopathological diagnosis. OBJECTIVE: To summarize key aspects of the WHO classification from 2016 and implications for the clinical management of glioma patients. An overview of novel treatment approaches is also provided. RESULTS: Oligodendrogliomas are defined independently of their histopathological appearance by the simultaneous presence of a mutation in the isocitrate dehydrogenase (IDH)-1 or IDH-2 gene and co-deletion of chromosome arms 1p and 19q. Astrocytomas are classified based on the presence or absence of mutations in IDH. Astrocytic tumors with wild-type IDH comprise approximately 90% of glioblastomas, the most common malignant primary brain tumor in adults. The extent of resection is a favorable prognostic factor in diffuse gliomas. Postoperatively, most patients are treated with a combination of radiotherapy and alkylating agent chemotherapy. In IDH wild-type astrocytic tumors, hypermethylation of the promoter of the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) gene is predictive for benefit from the alkylating agent temozolomide. Most novel treatment approaches that are currently being assessed in clinical trials aim at reprogramming the immune system to specifically eradicate tumor cells, but the efficacy of such approaches in gliomas remains to be demonstrated. DISCUSSION: To date the classical treatment modalities comprising surgery, radiotherapy and chemotherapy remain the mainstay of glioma treatment. The integration of molecular features into the classification of gliomas is a basis for personalized treatment approaches.
BACKGROUND: Traditionally, gliomas were classified based on histopathological features alone. The revised World Health Organization (WHO) classification of tumors of the central nervous system from 2016 integrated molecular features into the histopathological diagnosis. OBJECTIVE: To summarize key aspects of the WHO classification from 2016 and implications for the clinical management of gliomapatients. An overview of novel treatment approaches is also provided. RESULTS:Oligodendrogliomas are defined independently of their histopathological appearance by the simultaneous presence of a mutation in the isocitrate dehydrogenase (IDH)-1 or IDH-2 gene and co-deletion of chromosome arms 1p and 19q. Astrocytomas are classified based on the presence or absence of mutations in IDH. Astrocytic tumors with wild-type IDH comprise approximately 90% of glioblastomas, the most common malignant primary brain tumor in adults. The extent of resection is a favorable prognostic factor in diffuse gliomas. Postoperatively, most patients are treated with a combination of radiotherapy and alkylating agent chemotherapy. In IDH wild-type astrocytic tumors, hypermethylation of the promoter of the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) gene is predictive for benefit from the alkylating agent temozolomide. Most novel treatment approaches that are currently being assessed in clinical trials aim at reprogramming the immune system to specifically eradicate tumor cells, but the efficacy of such approaches in gliomas remains to be demonstrated. DISCUSSION: To date the classical treatment modalities comprising surgery, radiotherapy and chemotherapy remain the mainstay of glioma treatment. The integration of molecular features into the classification of gliomas is a basis for personalized treatment approaches.
Authors: Martin J van den Bent; Brigitta Baumert; Sara C Erridge; Michael A Vogelbaum; Anna K Nowak; Marc Sanson; Alba Ariela Brandes; Paul M Clement; Jean Francais Baurain; Warren P Mason; Helen Wheeler; Olivier L Chinot; Sanjeev Gill; Matthew Griffin; David G Brachman; Walter Taal; Roberta Rudà; Michael Weller; Catherine McBain; Jaap Reijneveld; Roelien H Enting; Damien C Weber; Thierry Lesimple; Susan Clenton; Anja Gijtenbeek; Sarah Pascoe; Ulrich Herrlinger; Peter Hau; Frederic Dhermain; Irene van Heuvel; Roger Stupp; Ken Aldape; Robert B Jenkins; Hendrikus Jan Dubbink; Winand N M Dinjens; Pieter Wesseling; Sarah Nuyens; Vassilis Golfinopoulos; Thierry Gorlia; Wolfgang Wick; Johan M Kros Journal: Lancet Date: 2017-08-08 Impact factor: 79.321
Authors: Michael Weller; Nicholas Butowski; David D Tran; Lawrence D Recht; Michael Lim; Hal Hirte; Lynn Ashby; Laszlo Mechtler; Samuel A Goldlust; Fabio Iwamoto; Jan Drappatz; Donald M O'Rourke; Mark Wong; Mark G Hamilton; Gaetano Finocchiaro; James Perry; Wolfgang Wick; Jennifer Green; Yi He; Christopher D Turner; Michael J Yellin; Tibor Keler; Thomas A Davis; Roger Stupp; John H Sampson Journal: Lancet Oncol Date: 2017-08-23 Impact factor: 41.316
Authors: David N Louis; Arie Perry; Guido Reifenberger; Andreas von Deimling; Dominique Figarella-Branger; Webster K Cavenee; Hiroko Ohgaki; Otmar D Wiestler; Paul Kleihues; David W Ellison Journal: Acta Neuropathol Date: 2016-05-09 Impact factor: 17.088
Authors: Michael Weller; Patrick Roth; Matthias Preusser; Wolfgang Wick; David A Reardon; Michael Platten; John H Sampson Journal: Nat Rev Neurol Date: 2017-05-12 Impact factor: 42.937
Authors: Mark R Gilbert; James J Dignam; Terri S Armstrong; Jeffrey S Wefel; Deborah T Blumenthal; Michael A Vogelbaum; Howard Colman; Arnab Chakravarti; Stephanie Pugh; Minhee Won; Robert Jeraj; Paul D Brown; Kurt A Jaeckle; David Schiff; Volker W Stieber; David G Brachman; Maria Werner-Wasik; Ivo W Tremont-Lukats; Erik P Sulman; Kenneth D Aldape; Walter J Curran; Minesh P Mehta Journal: N Engl J Med Date: 2014-02-20 Impact factor: 91.245
Authors: Roger Stupp; Sophie Taillibert; Andrew Kanner; William Read; David Steinberg; Benoit Lhermitte; Steven Toms; Ahmed Idbaih; Manmeet S. Ahluwalia; Karen Fink; Francesco Di Meco; Frank Lieberman; Jay-Jiguang Zhu; Giuseppe Stragliotto; David Tran; Steven Brem; Andreas Hottinger; Eilon D. Kirson; Gitit Lavy-Shahaf; Uri Weinberg; Chae-Yong Kim; Sun-Ha Paek; Garth Nicholas; Jordi Bruna; Hal Hirte; Michael Weller; Yoram Palti; Monika E. Hegi; Zvi Ram Journal: JAMA Date: 2017-12-19 Impact factor: 56.272
Authors: Teri N Kreisl; Lyndon Kim; Kraig Moore; Paul Duic; Cheryl Royce; Irene Stroud; Nancy Garren; Megan Mackey; John A Butman; Kevin Camphausen; John Park; Paul S Albert; Howard A Fine Journal: J Clin Oncol Date: 2008-12-29 Impact factor: 44.544
Authors: Timothy J Brown; Matthew C Brennan; Michael Li; Ephraim W Church; Nicholas J Brandmeir; Kevin L Rakszawski; Akshal S Patel; Elias B Rizk; Dima Suki; Raymond Sawaya; Michael Glantz Journal: JAMA Oncol Date: 2016-11-01 Impact factor: 31.777