Long-term survival with IDH wildtype glioblastoma: first results from the ETERNITY Brain Tumor Funders’ Collaborative Consortium (EORTC 1419)

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Caroline Hertler - , University of Zurich (Author)
  • Jörg Felsberg - , Heinrich Heine University Düsseldorf (Author)
  • Dorothee Gramatzki - , University of Zurich (Author)
  • Emilie Le Rhun - , University of Zurich, Université de Lille (Author)
  • Jennifer Clarke - , University of California at San Francisco (Author)
  • Riccardo Soffietti - , Azienda Ospedaliera - Universitaria Città della Salute e della Scienza di Torino (Author)
  • Wolfgang Wick - , Heidelberg University , German Cancer Research Center (DKFZ) (Author)
  • Olivier Chinot - , Aix-Marseille Université (Author)
  • François Ducray - , Hospices civils de Lyon, Universite Claude Bernard Lyon 1 (Author)
  • Patrick Roth - , University of Zurich (Author)
  • Kerrie McDonald - , University of New South Wales (Author)
  • Peter Hau - , University of Regensburg (Author)
  • Andreas F. Hottinger - , University of Lausanne (Author)
  • Jaap Reijneveld - , Vrije Universiteit Amsterdam (VU), Epilepsy Institutes of the Netherlands Foundation (Author)
  • Oliver Schnell - , University of Freiburg (Author)
  • Christine Marosi - , Medical University of Vienna (Author)
  • Michael Glantz - , Pennsylvania State University (Author)
  • Amélie Darlix - , University of Montpellier (Author)
  • Giuseppe Lombardi - , IRCCS Istituto Oncologico Veneto - Padova (Author)
  • Dietmar Krex - , Department of Neurosurgery, German Center for Neurodegenerative Diseases, Dresden site (Partner: DZNE of the Helmholtz Association), TUD Dresden University of Technology (Author)
  • Martin Glas - , University of Duisburg-Essen (Author)
  • David A. Reardon - , Dana-Farber Cancer Institute, Harvard University (Author)
  • Martin van den Bent - , Erasmus University Rotterdam (Author)
  • Florence Lefranc - , University Hospital Brussels (Author)
  • Ulrich Herrlinger - , University of Bonn (Author)
  • Evangelia Razis - , Hygeia Hospital (Author)
  • Antoine F. Carpentier - , Université Paris Cité (Author)
  • Samuel Phillips - , University of California at San Francisco (Author)
  • Roberta Rudà - , Azienda Ospedaliera - Universitaria Città della Salute e della Scienza di Torino (Author)
  • Antje Wick - , Heidelberg University  (Author)
  • Emeline Tabouret - , Aix-Marseille Université (Author)
  • David Meyronet - , Universite Claude Bernard Lyon 1, Hospices civils de Lyon (Author)
  • Claude Alain Maurage - , Université de Lille (Author)
  • Elisabeth Rushing - , University of Zurich (Author)
  • Robert Rapkins - , University of New South Wales (Author)
  • Elisabeth Bumes - , University of Regensburg (Author)
  • Monika Hegi - , University of Lausanne (Author)
  • Astrid Weyerbrock - , Epilepsy Institutes of the Netherlands Foundation (Author)
  • Dawit Aregawi - , Pennsylvania State University (Author)
  • Christian Gonzalez-Gomez - , University of California at San Francisco (Author)
  • Alessia Pellerino - , Azienda Ospedaliera - Universitaria Città della Salute e della Scienza di Torino (Author)
  • Martin Klein - , Vrije Universiteit Amsterdam (VU) (Author)
  • Matthias Preusser - , Medical University of Vienna (Author)
  • Martin Bendszus - , Heidelberg University  (Author)
  • Vassilis Golfinopoulos - , European Organisation for Research and Treatment of Cancer Data Center (Author)
  • Andreas von Deimling - , Heidelberg University , German Cancer Research Center (DKFZ) (Author)
  • Thierry Gorlia - , European Organisation for Research and Treatment of Cancer Data Center (Author)
  • Patrick Y. Wen - , Dana-Farber Cancer Institute, Harvard University (Author)
  • Guido Reifenberger - , Heinrich Heine University Düsseldorf, German Cancer Research Center (DKFZ) (Author)
  • Michael Weller - , University of Zurich (Author)

Abstract

Background: Median survival with glioblastoma remains in the range of 12 months on population levels. Only few patients survive for more than 5 years. Patient and disease features associated with long-term survival remain poorly defined. Methods: European Organization for Research and Treatment of Cancer (EORTC) 1419 (ETERNITY) is a registry study supported by the Brain Tumor Funders Collaborative in the US and the EORTC Brain Tumor Group. Patients with glioblastoma surviving at least 5 years from diagnosis were identified at 24 sites in Europe, US, and Australia. In patients with isocitrate dehydrogenase (IDH) wildtype tumours, prognostic factors were analysed using the Kaplan-Meier method and the Cox proportional hazards model. A population-based reference cohort was obtained from the Cantonal cancer registry Zurich. Results: At the database lock of July 2020, 280 patients with histologically centrally confirmed glioblastoma (189 IDH wildtype, 80 IDH mutant, 11 incompletely characterised) had been registered. In the IDH wildtype population, median age was 56 years (range 24–78 years), 96 patients (50.8%) were female, 139 patients (74.3%) had tumours with O6-methylguanine DNA methyltransferase (MGMT) promoter methylation. Median overall survival was 9.9 years (95% confidence interval [95% CI] 7.9–11.9). Patients without recurrence experienced longer median survival (not reached) than patients with one or more recurrences (8.92 years) (p < 0.001) and had a high rate (48.8%) of MGMT promoter-unmethylated tumours. Conclusions: Freedom from progression is a powerful predictor of overall survival in long-term survivors with glioblastoma. Patients without relapse often have MGMT promoter-unmethylated glioblastoma and may represent a distinct subtype of glioblastoma.

Details

Original languageEnglish
Article number112913
JournalEuropean journal of cancer
Volume189
Publication statusPublished - Aug 2023
Peer-reviewedYes

External IDs

PubMed 37277265

Keywords

Sustainable Development Goals

ASJC Scopus subject areas

Keywords

  • IDH, MGMT, Outcome, Prognosis, Registry, Wildtype, Humans, Middle Aged, Male, Neoplasm Recurrence, Local/genetics, Brain Neoplasms/genetics, Isocitrate Dehydrogenase/genetics, Glioblastoma/genetics, Young Adult, DNA Methylation, DNA Modification Methylases/genetics, Female, Adult, Aged, DNA Repair Enzymes/genetics, Retrospective Studies