Department of Neurology, University Hospital and University of Zurich, Zürich, Switzerland
Michael Weller , Joerg Felsberg , Dorothee Gramatzki , Emilie Le Rhun , Jennifer Leigh Clarke , Riccardo Soffietti , Wolfgang Wick , Olivier L. Chinot , Francois Ducray , Patrick Roth , Peter Hau , Martin Klein , Matthias Preusser , Martin Bendszus , Vassilis Golfinopoulos , Andreas von Deimling , Thierry Gorlia , Patrick Y. Wen , Guido Reifenberger , Caroline Hertler
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 by 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 tumors, prognostic factors were analyzed 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 cut-off of July 2020, 280 patients with histologically centrally confirmed glioblastoma (189 IDH wildtype, 80 IDH mutant, 11 not otherwise specified) 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 tumors with O6-methylguanine DNA methyltransferase (MGMT) promoter methylation. Median overall survival was 9.9 years (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 of MGMT promoter unmethylated tumors. Conclusions: Freedom from progression is a powerful predictor of overall survival in long-term survivors with glioblastoma. Never relapsing patients often have MGMT promoter-unmethylated glioblastoma and may represent a distinct subtype of glioblastoma. Clinical trial information: NCT03770468.
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