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Grundlagen zur Diagnose und Therapie von Gliomen

Basic principles of diagnosis and treatment of gliomas

  • Grundlagenforschung für den Kliniker
  • Published:
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Zusammenfassung

Hintergrund

Traditionell wurden Gliome basierend auf ihren histopathologischen Eigenschaften klassifiziert. Mit Einführung der revidierten WHO(„World Health Organization“)-Klassifikation der Tumoren des Zentralnervensystems von 2016 wurden molekulare Eigenschaften in die Diagnose integriert.

Ziel der Arbeit

Kernaspekte der WHO-Klassifikation von 2016 und Implikationen für die klinische Versorgung von Gliompatienten werden zusammengefasst. Zudem wird ein Überblick über experimentelle Therapiekonzepte gegeben.

Ergebnisse

Oligodendrogliome werden seit 2016 durch das gleichzeitige Vorliegen einer Isozitratdehydrogenase(IDH)-1- oder -2-Mutation und einer Kodeletion der Chromosomenarme 1p und 19q definiert. Astrozytäre Tumoren werden in solche mit IDH-Wildtyp und mutierter IDH unterteilt. Astrozytome mit IDH-Wildtyp umfassen auch etwa 90 % der Glioblastome, die häufigsten und prognostisch ungünstigsten primären malignen Hirntumoren. Das Ausmaß der Resektion ist ein wichtiger prognostischer Faktor bei Patienten mit diffus wachsenden Gliomen. Postoperativ wird in der Regel kombiniert mit Strahlentherapie und alkylierender Chemotherapie behandelt. Die Hypermethylierung des Promoters des DNA-Reparaturgens O6-Methylguanin-DNA-Methyltransferase (MGMT) ist bei astrozytären Tumoren mit IDH-Wildtyp prädiktiv für das Ansprechen auf das Alkylans Temozolomid. Viele der sich aktuell in klinischer Testung befindlichen Therapieansätze zielen auf die Förderung einer gegen Tumorzellen gerichteten Immunantwort ab. Bislang existiert aber noch kein zugelassenes immuntherapeutisches Behandlungskonzept für Gliome.

Diskussion

Etablierte Therapien von Gliomen sind Chirurgie, Strahlen- und Chemotherapie. Die Integration molekularer Aspekte in die Klassifikation von Gliomen bildet die Grundlage für personalisierte Therapieansätze.

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.

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Authors and Affiliations

  1. Klinik für Neurologie, Universitätsspital Zürich und Universität Zürich, Frauenklinikstraße 26, 8091, Zürich, Schweiz

    H.-G. Wirsching, T. Weiss, P. Roth & M. Weller

Authors
  1. H.-G. Wirsching
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  2. T. Weiss
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  3. P. Roth
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  4. M. Weller
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Corresponding author

Correspondence to M. Weller.

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Interessenkonflikt

H.-G. Wirsching erhielt Honorare für die Teilnahme an Beratungsgremien von Roche. P. Roth erhielt Honorare für Vorträge und Teilnahmen an Beratungsgremien von BMS, Novartis, Novocure, MSD, Virometix, Roche und Covagen. M. Weller erhielt Forschungsgelder von Abbvie, Acceleron, Actelion, Bayer, Merck, Sharp & Dohme (MSD), Merck (EMD), Novocure, OGD2, Piqur, Roche und Tragara, und Honorare für Vorträge oder Teilnahme an Beratungsgremien von Abbvie, BMS, Celgene, Celldex, Merck, Sharp & Dohme (MSD), Merck (EMD), Novocure, Orbus, Pfizer, Progenics, Roche, Teva und Tocagen. T. Weiss gibt an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.

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Wirsching, HG., Weiss, T., Roth, P. et al. Grundlagen zur Diagnose und Therapie von Gliomen. Nervenarzt 89, 692–698 (2018). https://doi.org/10.1007/s00115-018-0519-z

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  • DOI: https://doi.org/10.1007/s00115-018-0519-z

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