Local and systemic therapy of recurrent ependymoma in children and adolescents: short- and long-term results of the E-HIT-REZ 2005 study.


Journal

Neuro-oncology
ISSN: 1523-5866
Titre abrégé: Neuro Oncol
Pays: England
ID NLM: 100887420

Informations de publication

Date de publication:
01 06 2021
Historique:
pubmed: 18 12 2020
medline: 22 6 2021
entrez: 17 12 2020
Statut: ppublish

Résumé

Survival in recurrent ependymomas in children and adolescents mainly depends on the extent of resection. Studies on repeated radiotherapy and chemotherapy at relapse have shown conflicting results. Using data from the German multi-center E-HIT-REZ-2005 study, we examined the role of local therapy and the efficacy of chemotherapy with blockwise temozolomide (TMZ) in children and adolescents with recurrent ependymomas. Fifty-three patients with a median age of 6.9 years (1.25-25.4) at first recurrence and a median follow-up time of 36 months (2-115) were recruited. Gross- and near-total resection (GTR/NTR) were achieved in 34 (64.2%) patients and associated with a markedly improved 5-year overall survival (OS) of 48.7% vs. 5.3% in less than GTR/NTR. Radiotherapy showed no improvement in OS following complete resection (OS: 70 (CI: 19.9-120.1) vs. 95 (CI: 20.7-169.4) months), but an advantage was found in less than GTR/NTR (OS: 22 (CI: 12.7-31.3) vs. 7 (CI: 0-15.8) months). Following the application of TMZ, disease progression was observed in most evaluable cases (18/21). A subsequent change to oral etoposide and trofosfamide showed no improved response. PF-A EPN were most abundant in relapses (n = 27). RELA-positive EPN (n = 5) had a 5-year OS of 0%. The extent of resection is the most important predictor of survival at relapse. Focal re-irradiation is a useful approach if complete resection cannot be achieved, but no additional benefit was seen after GTR/NTR. Longer-term disease stabilization (>6 months) mediated by TMZ occurred in a small number of cases (14.3%).

Sections du résumé

BACKGROUND
Survival in recurrent ependymomas in children and adolescents mainly depends on the extent of resection. Studies on repeated radiotherapy and chemotherapy at relapse have shown conflicting results.
METHODS
Using data from the German multi-center E-HIT-REZ-2005 study, we examined the role of local therapy and the efficacy of chemotherapy with blockwise temozolomide (TMZ) in children and adolescents with recurrent ependymomas.
RESULTS
Fifty-three patients with a median age of 6.9 years (1.25-25.4) at first recurrence and a median follow-up time of 36 months (2-115) were recruited. Gross- and near-total resection (GTR/NTR) were achieved in 34 (64.2%) patients and associated with a markedly improved 5-year overall survival (OS) of 48.7% vs. 5.3% in less than GTR/NTR. Radiotherapy showed no improvement in OS following complete resection (OS: 70 (CI: 19.9-120.1) vs. 95 (CI: 20.7-169.4) months), but an advantage was found in less than GTR/NTR (OS: 22 (CI: 12.7-31.3) vs. 7 (CI: 0-15.8) months). Following the application of TMZ, disease progression was observed in most evaluable cases (18/21). A subsequent change to oral etoposide and trofosfamide showed no improved response. PF-A EPN were most abundant in relapses (n = 27). RELA-positive EPN (n = 5) had a 5-year OS of 0%.
CONCLUSION
The extent of resection is the most important predictor of survival at relapse. Focal re-irradiation is a useful approach if complete resection cannot be achieved, but no additional benefit was seen after GTR/NTR. Longer-term disease stabilization (>6 months) mediated by TMZ occurred in a small number of cases (14.3%).

Identifiants

pubmed: 33331885
pii: 6040794
doi: 10.1093/neuonc/noaa276
pmc: PMC8168820
doi:

Substances chimiques

Temozolomide YF1K15M17Y

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1012-1023

Commentaires et corrections

Type : CommentIn

Informations de copyright

© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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Auteurs

Jonas E Adolph (JE)

Department of Pediatrics III, University Hospital of Essen, Essen, Germany.

Gudrun Fleischhack (G)

Department of Pediatrics III, University Hospital of Essen, Essen, Germany.

Ruth Mikasch (R)

Department of Pediatrics III, University Hospital of Essen, Essen, Germany.

Julia Zeller (J)

Department of Pediatrics III, University Hospital of Essen, Essen, Germany.

Monika Warmuth-Metz (M)

Institute of Diagnostic and Interventional Neuroradiology and Neurosurgical Clinic, University Hospital Wuerzburg, Wuerzburg, Germany.

Brigitte Bison (B)

Institute of Diagnostic and Interventional Neuroradiology and Neurosurgical Clinic, University Hospital Wuerzburg, Wuerzburg, Germany.

Martin Mynarek (M)

Department of Pediatric Hematology and Oncology, Center for Obstetrics and Pediatrics and Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Stefan Rutkowski (S)

Department of Pediatric Hematology and Oncology, Center for Obstetrics and Pediatrics and Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Ulrich Schüller (U)

Department of Pediatric Hematology and Oncology, Center for Obstetrics and Pediatrics and Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Katja von Hoff (K)

Department of Pediatric Oncology and Hematology, Charité University Medicine Berlin, Berlin, Germany.

Denise Obrecht (D)

Department of Pediatric Hematology and Oncology, Center for Obstetrics and Pediatrics and Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Torsten Pietsch (T)

Institute of Neuropathology, DGNN Brain Tumor Reference Center and Department of Pediatric Hematology and Oncology, University Hospital of Bonn, Bonn, Germany.

Stefan M Pfister (SM)

Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Department of Pediatric Oncology and Hematology, University Hospital Heidelberg, Heidelberg, Germany.
Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.

Kristian W Pajtler (KW)

Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Department of Pediatric Oncology and Hematology, University Hospital Heidelberg, Heidelberg, Germany.
Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.

Olaf Witt (O)

Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Department of Pediatric Oncology and Hematology, University Hospital Heidelberg, Heidelberg, Germany.
Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.

Hendrik Witt (H)

Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Department of Pediatric Oncology and Hematology, University Hospital Heidelberg, Heidelberg, Germany.
Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.

Rolf-Dieter Kortmann (RD)

Department of Radio-Oncology, University Leipzig, Leipzig, Germany.

Beate Timmermann (B)

Department of Particle Therapy, University Hospital Essen, West German Proton Therapy Centre Essen, Essen, Germany.

Jürgen Krauß (J)

Institute of Diagnostic and Interventional Neuroradiology and Neurosurgical Clinic, University Hospital Wuerzburg, Wuerzburg, Germany.

Michael C Frühwald (MC)

University Children's Hospital Augsburg, Swabian Children's Cancer Center, Augsburg, Germany.

Andreas Faldum (A)

Institute of Biostatistics and Clinical Research, University of Muenster, Muenster, Germany.

Robert Kwiecien (R)

Institute of Biostatistics and Clinical Research, University of Muenster, Muenster, Germany.

Udo Bode (U)

Institute of Neuropathology, DGNN Brain Tumor Reference Center and Department of Pediatric Hematology and Oncology, University Hospital of Bonn, Bonn, Germany.

Stephan Tippelt (S)

Department of Pediatrics III, University Hospital of Essen, Essen, Germany.

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