Long-term survival with IDH wildtype glioblastoma: first results from the ETERNITY Brain Tumor Funders’ Collaborative Consortium (EORTC 1419)
Caroline Hertler
(1, 2)
,
Jörg Felsberg
(3, 4)
,
Dorothee Gramatzki
(1, 2)
,
Emilie Le Rhun
(1, 2, 5, 6)
,
Jennifer Clarke
(7)
,
Riccardo Soffietti
(8)
,
Wolfgang Wick
(9, 10)
,
Olivier Chinot
(11, 12)
,
François Ducray
(13, 14, 15)
,
Patrick Roth
(1, 2)
,
Kerrie Mcdonald
(16)
,
Peter Hau
(17)
,
Andreas Hottinger
(18)
,
Jaap Reijneveld
(19, 20)
,
Oliver Schnell
(21)
,
Christine Marosi
(22)
,
Michael Glantz
(23, 24)
,
Amélie Darlix
(25, 26)
,
Giuseppe Lombardi
(27)
,
Dietmar Krex
(28, 29)
,
Martin Glas
(30, 29)
,
David A Reardon
(31, 32)
,
Martin van den Bent
(33)
,
Florence Lefranc
(34)
,
Ulrich Herrlinger
(35)
,
Evangelia Razis
(36)
,
Antoine F Carpentier
(37, 38)
,
Samuel Phillips
(7)
,
Roberta Rudà
(8)
,
Antje Wick
(10)
,
Emeline Tabouret
(11, 12)
,
David Meyronet
(13, 14, 15)
,
Claude-Alain Maurage
(39)
,
Elisabeth Rushing
(1)
,
Robert Rapkins
(16)
,
Elisabeth Bumes
(17)
,
Monika Hegi
(18)
,
Astrid Weyerbrock
(20)
,
Dawit Aregawi
(23, 24)
,
Christian Gonzalez-Gomez
(7)
,
Alessia Pellerino
(8)
,
Martin Klein
(19)
,
Matthias Preusser
(22)
,
Martin Bendszus
(40)
,
Vassilis Golfinopoulos
(41)
,
Andreas von Deimling
(40, 9)
,
Thierry Gorlia
(41)
,
Patrick Wen
(31, 32)
,
Guido Reifenberger
(3, 4)
,
Michael Weller
(1, 2)
1
University hospital of Zurich [Zurich]
2 UZH - Universität Zürich [Zürich] = University of Zurich
3 Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf]
4 University Hospital Düsseldorf
5 Département de Neurochirurgie[Lille]
6 PRISM - Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192
7 UC San Francisco - University of California [San Francisco]
8 Azienda Ospedalerio - Universitaria Città della Salute e della Scienza di Torino = University Hospital Città della Salute e della Scienza di Torino
9 DKFZ - German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg]
10 Universität Heidelberg [Heidelberg] = Heidelberg University
11 INP - Institut de neurophysiopathologie
12 Neuro-Oncologie [Hôpital de la Timone - APHM]
13 UCBL - Université Claude Bernard Lyon 1
14 HCL - Hospices Civils de Lyon
15 UNICANCER/CRCL - Centre de Recherche en Cancérologie de Lyon
16 UNSW - University of New South Wales [Sydney]
17 University Hospital Regensburg
18 CHUV - Centre Hospitalier Universitaire Vaudois = Lausanne University Hospital [Lausanne]
19 VUMC - Vrije Universiteit Medical Centre
20 SEIN - Stichting Epilepsie Instellingen Nederland
21 Uniklinik - Universitäts Klinikum Freiburg = University Medical Center Freiburg
22 Medizinische Universität Wien = Medical University of Vienna
23 Penn State College of Medicine
24 Penn State Health Milton S. Hershey Medical Center
25 IGF - Institut de Génomique Fonctionnelle
26 ICM - Institut régional de Cancérologie de Montpellier
27 Veneto Institute of Oncology IOV-IRCCS [Padua, Italy]
28 University Hospital Carl Gustav Carus [Dresden, Germany]
29 DKTK - German Cancer Consortium [Heidelberg]
30 University of Duisbourg-Essen
31 Dana-Farber Cancer Institute [Boston]
32 HMS - Harvard Medical School [Boston]
33 Erasmus MC - Erasmus University Medical Center [Rotterdam]
34 Hôpital Universitaire de Bruxelles
35 University Hospital Bonn
36 Hygeia Hospital
37 AP-HP - Hopital Saint-Louis [AP-HP]
38 UPCité - Université Paris Cité
39 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
40 Heidelberg University Hospital [Heidelberg]
41 EORTC - European Organisation for Research and Treatment of Cancer [Bruxelles]
2 UZH - Universität Zürich [Zürich] = University of Zurich
3 Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf]
4 University Hospital Düsseldorf
5 Département de Neurochirurgie[Lille]
6 PRISM - Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192
7 UC San Francisco - University of California [San Francisco]
8 Azienda Ospedalerio - Universitaria Città della Salute e della Scienza di Torino = University Hospital Città della Salute e della Scienza di Torino
9 DKFZ - German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg]
10 Universität Heidelberg [Heidelberg] = Heidelberg University
11 INP - Institut de neurophysiopathologie
12 Neuro-Oncologie [Hôpital de la Timone - APHM]
13 UCBL - Université Claude Bernard Lyon 1
14 HCL - Hospices Civils de Lyon
15 UNICANCER/CRCL - Centre de Recherche en Cancérologie de Lyon
16 UNSW - University of New South Wales [Sydney]
17 University Hospital Regensburg
18 CHUV - Centre Hospitalier Universitaire Vaudois = Lausanne University Hospital [Lausanne]
19 VUMC - Vrije Universiteit Medical Centre
20 SEIN - Stichting Epilepsie Instellingen Nederland
21 Uniklinik - Universitäts Klinikum Freiburg = University Medical Center Freiburg
22 Medizinische Universität Wien = Medical University of Vienna
23 Penn State College of Medicine
24 Penn State Health Milton S. Hershey Medical Center
25 IGF - Institut de Génomique Fonctionnelle
26 ICM - Institut régional de Cancérologie de Montpellier
27 Veneto Institute of Oncology IOV-IRCCS [Padua, Italy]
28 University Hospital Carl Gustav Carus [Dresden, Germany]
29 DKTK - German Cancer Consortium [Heidelberg]
30 University of Duisbourg-Essen
31 Dana-Farber Cancer Institute [Boston]
32 HMS - Harvard Medical School [Boston]
33 Erasmus MC - Erasmus University Medical Center [Rotterdam]
34 Hôpital Universitaire de Bruxelles
35 University Hospital Bonn
36 Hygeia Hospital
37 AP-HP - Hopital Saint-Louis [AP-HP]
38 UPCité - Université Paris Cité
39 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
40 Heidelberg University Hospital [Heidelberg]
41 EORTC - European Organisation for Research and Treatment of Cancer [Bruxelles]
Caroline Hertler
- Fonction : Auteur
- PersonId : 1224404
- ORCID : 0000-0001-6181-2895
Dorothee Gramatzki
- Fonction : Auteur
- PersonId : 1283968
- ORCID : 0000-0002-9054-5498
Jennifer Clarke
- Fonction : Auteur
- PersonId : 1283970
- ORCID : 0000-0002-8054-7342
Riccardo Soffietti
- Fonction : Auteur
- PersonId : 1283971
- ORCID : 0000-0002-9204-7038
Wolfgang Wick
- Fonction : Auteur
- PersonId : 766695
- ORCID : 0000-0002-6171-634X
Olivier Chinot
- Fonction : Auteur
- PersonId : 1158688
- ORCID : 0000-0001-6317-9691
François Ducray
- Fonction : Auteur
- PersonId : 760118
- ORCID : 0000-0002-8150-5785
Oliver Schnell
- Fonction : Auteur
- PersonId : 1283972
- ORCID : 0000-0002-1284-1427
Christine Marosi
- Fonction : Auteur
- PersonId : 899740
Amélie Darlix
- Fonction : Auteur
- PersonId : 1032139
- ORCID : 0000-0003-1384-1709
- IdRef : 170923215
Giuseppe Lombardi
- Fonction : Auteur
- PersonId : 1224354
- ORCID : 0000-0003-1316-2132
Martin van den Bent
- Fonction : Auteur
- PersonId : 760121
- ORCID : 0000-0001-5710-5127
Ulrich Herrlinger
- Fonction : Auteur
- PersonId : 1373700
- ORCID : 0000-0002-4011-9327
Antoine F Carpentier
- Fonction : Auteur
- PersonId : 1222842
- ORCID : 0000-0003-2926-0060
Emeline Tabouret
- Fonction : Auteur
- PersonId : 172013
- IdHAL : emeline-tabouret
- ORCID : 0000-0002-4031-2178
- IdRef : 184235065
David Meyronet
- Fonction : Auteur
- PersonId : 774596
- ORCID : 0000-0001-9943-4578
Elisabeth Rushing
- Fonction : Auteur
- PersonId : 1283973
- ORCID : 0000-0001-7616-6320
Robert Rapkins
- Fonction : Auteur
- PersonId : 1283974
- ORCID : 0000-0002-7831-3870
Elisabeth Bumes
- Fonction : Auteur
- PersonId : 1283975
- ORCID : 0000-0001-6915-3206
Monika Hegi
- Fonction : Auteur
- PersonId : 1284002
- ORCID : 0000-0003-0855-6495
Astrid Weyerbrock
- Fonction : Auteur
- PersonId : 1283976
- ORCID : 0000-0001-9060-4462
Alessia Pellerino
- Fonction : Auteur
- PersonId : 1283977
- ORCID : 0000-0003-3243-0059
Martin Klein
- Fonction : Auteur
- PersonId : 1283978
- ORCID : 0000-0001-5553-7911
Matthias Preusser
- Fonction : Auteur
- PersonId : 1224405
- ORCID : 0000-0003-3541-2315
Martin Bendszus
- Fonction : Auteur
- PersonId : 791101
- ORCID : 0000-0002-9094-6769
Vassilis Golfinopoulos
- Fonction : Auteur
- PersonId : 1224379
- ORCID : 0000-0002-8667-9477
Andreas von Deimling
- Fonction : Auteur
- PersonId : 1224376
- ORCID : 0000-0002-5863-540X
Patrick Wen
- Fonction : Auteur
- PersonId : 1360674
- ORCID : 0000-0002-0774-7700
Michael Weller
- Fonction : Auteur
- PersonId : 781346
- ORCID : 0000-0002-1748-174X
- IdRef : 194357112
Résumé
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
2 C. Hertler et al. / European Journal of Cancer 189 (2023) 112913 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 longterm survivors with glioblastoma. Patients without relapse often have MGMT promoterunmethylated glioblastoma and may represent a distinct subtype of glioblastoma
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