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EPEN-04. SIOP EPENDYMOMA I: FINAL RESULTS, LONG TERM FOLLOW-UP AND MOLECULAR ANALYSIS OF THE TRIAL COHORT: A BIOMECA CONSORTIUM STUDY

INTRODUCTION: Surgery and radiotherapy are established childhood ependymoma treatments. The efficacy of chemotherapy has been debated. We report final results of the SIOP Ependymoma I trial, with 12-year follow-up, in the context of a post-hoc analysis of more recently described biomarkers. AIMS AND...

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Autores principales: A. Ritzmann, Timothy, Chapman, Rebecca J, Macarthur, Donald, Mallucci, Conor, Kilday, John-Paul, Thorp, Nicola, Modena, Piergiorgio, Giagnacovo, Marzia, Dineen, Rob, Jaspan, Timothy, Pajtler, Kristian W, Jacques, Thomas S, Paine, Simon M L, Ellison, David W, Bouffet, Eric, Grundy, Richard G
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168242/
http://dx.doi.org/10.1093/neuonc/noab090.054
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author A. Ritzmann, Timothy
Chapman, Rebecca J
Macarthur, Donald
Mallucci, Conor
Kilday, John-Paul
Thorp, Nicola
Modena, Piergiorgio
Giagnacovo, Marzia
Dineen, Rob
Jaspan, Timothy
Pajtler, Kristian W
Jacques, Thomas S
Paine, Simon M L
Ellison, David W
Bouffet, Eric
Grundy, Richard G
author_facet A. Ritzmann, Timothy
Chapman, Rebecca J
Macarthur, Donald
Mallucci, Conor
Kilday, John-Paul
Thorp, Nicola
Modena, Piergiorgio
Giagnacovo, Marzia
Dineen, Rob
Jaspan, Timothy
Pajtler, Kristian W
Jacques, Thomas S
Paine, Simon M L
Ellison, David W
Bouffet, Eric
Grundy, Richard G
author_sort A. Ritzmann, Timothy
collection PubMed
description INTRODUCTION: Surgery and radiotherapy are established childhood ependymoma treatments. The efficacy of chemotherapy has been debated. We report final results of the SIOP Ependymoma I trial, with 12-year follow-up, in the context of a post-hoc analysis of more recently described biomarkers. AIMS AND METHODS: The trial assessed event free (EFS) and overall survival (OS) of patients aged three to 21 years with non-metastatic intracranial ependymoma, treated with a staged management strategy targeting maximum local control. The study also assessed: the response rate (RR) of subtotally resected (STR) disease to vincristine, etoposide and cyclophosphamide (VEC); and surgical operability. Children with gross total resection (GTR) received radiotherapy of 54 Gy in 30 daily fractions over six weeks, whilst those with STR received VEC before radiotherapy. We retrospectively assessed methylation and 1q status alongside hTERT, RELA, Tenascin C, H3K27me3 and pAKT expression. RESULTS: Between 1999 and 2007, 89 participants were enrolled, 15 were excluded with metastatic (n=4) or non-ependymoma tumours (n=11) leaving a final cohort of 74. Five- and ten-year EFS was 49.5% and 46.7%, OS was 69.3% and 60.5%. 1q gain was associated with poorer EFS (p=0.002, HR=3.00, 95%CI 1.49–6.10). hTERT expression was associated with worse five-year EFS (20.0% Vs 83.3%, p=0.014, HR=5.8). GTR was achieved in 33/74 (44.6%) and associated with improved EFS (p=0.006, HR=2.81, 95% confidence interval 1.35–5.84). There was an improvement in GTR rates in the latter half of the trial (1999-2002 32.4% versus 2003-2007 56.8%). Despite the protocol, 12 participants with STR did not receive chemotherapy. However, chemotherapy RR was 65.5% (19/29, 95%CI 45.7–82.1). CONCLUSIONS: VEC exceeded the pre-specified RR of 45% in children over three years with STR intracranial ependymoma. However, cases of inaccurate stratification at treating centres highlights the need for rapid central review. We also confirmed associations between 1q gain, hTERT expression and outcome.
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spelling pubmed-81682422021-06-02 EPEN-04. SIOP EPENDYMOMA I: FINAL RESULTS, LONG TERM FOLLOW-UP AND MOLECULAR ANALYSIS OF THE TRIAL COHORT: A BIOMECA CONSORTIUM STUDY A. Ritzmann, Timothy Chapman, Rebecca J Macarthur, Donald Mallucci, Conor Kilday, John-Paul Thorp, Nicola Modena, Piergiorgio Giagnacovo, Marzia Dineen, Rob Jaspan, Timothy Pajtler, Kristian W Jacques, Thomas S Paine, Simon M L Ellison, David W Bouffet, Eric Grundy, Richard G Neuro Oncol Ependymoma INTRODUCTION: Surgery and radiotherapy are established childhood ependymoma treatments. The efficacy of chemotherapy has been debated. We report final results of the SIOP Ependymoma I trial, with 12-year follow-up, in the context of a post-hoc analysis of more recently described biomarkers. AIMS AND METHODS: The trial assessed event free (EFS) and overall survival (OS) of patients aged three to 21 years with non-metastatic intracranial ependymoma, treated with a staged management strategy targeting maximum local control. The study also assessed: the response rate (RR) of subtotally resected (STR) disease to vincristine, etoposide and cyclophosphamide (VEC); and surgical operability. Children with gross total resection (GTR) received radiotherapy of 54 Gy in 30 daily fractions over six weeks, whilst those with STR received VEC before radiotherapy. We retrospectively assessed methylation and 1q status alongside hTERT, RELA, Tenascin C, H3K27me3 and pAKT expression. RESULTS: Between 1999 and 2007, 89 participants were enrolled, 15 were excluded with metastatic (n=4) or non-ependymoma tumours (n=11) leaving a final cohort of 74. Five- and ten-year EFS was 49.5% and 46.7%, OS was 69.3% and 60.5%. 1q gain was associated with poorer EFS (p=0.002, HR=3.00, 95%CI 1.49–6.10). hTERT expression was associated with worse five-year EFS (20.0% Vs 83.3%, p=0.014, HR=5.8). GTR was achieved in 33/74 (44.6%) and associated with improved EFS (p=0.006, HR=2.81, 95% confidence interval 1.35–5.84). There was an improvement in GTR rates in the latter half of the trial (1999-2002 32.4% versus 2003-2007 56.8%). Despite the protocol, 12 participants with STR did not receive chemotherapy. However, chemotherapy RR was 65.5% (19/29, 95%CI 45.7–82.1). CONCLUSIONS: VEC exceeded the pre-specified RR of 45% in children over three years with STR intracranial ependymoma. However, cases of inaccurate stratification at treating centres highlights the need for rapid central review. We also confirmed associations between 1q gain, hTERT expression and outcome. Oxford University Press 2021-06-01 /pmc/articles/PMC8168242/ http://dx.doi.org/10.1093/neuonc/noab090.054 Text en © The Author(s) 2021. 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. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Ependymoma
A. Ritzmann, Timothy
Chapman, Rebecca J
Macarthur, Donald
Mallucci, Conor
Kilday, John-Paul
Thorp, Nicola
Modena, Piergiorgio
Giagnacovo, Marzia
Dineen, Rob
Jaspan, Timothy
Pajtler, Kristian W
Jacques, Thomas S
Paine, Simon M L
Ellison, David W
Bouffet, Eric
Grundy, Richard G
EPEN-04. SIOP EPENDYMOMA I: FINAL RESULTS, LONG TERM FOLLOW-UP AND MOLECULAR ANALYSIS OF THE TRIAL COHORT: A BIOMECA CONSORTIUM STUDY
title EPEN-04. SIOP EPENDYMOMA I: FINAL RESULTS, LONG TERM FOLLOW-UP AND MOLECULAR ANALYSIS OF THE TRIAL COHORT: A BIOMECA CONSORTIUM STUDY
title_full EPEN-04. SIOP EPENDYMOMA I: FINAL RESULTS, LONG TERM FOLLOW-UP AND MOLECULAR ANALYSIS OF THE TRIAL COHORT: A BIOMECA CONSORTIUM STUDY
title_fullStr EPEN-04. SIOP EPENDYMOMA I: FINAL RESULTS, LONG TERM FOLLOW-UP AND MOLECULAR ANALYSIS OF THE TRIAL COHORT: A BIOMECA CONSORTIUM STUDY
title_full_unstemmed EPEN-04. SIOP EPENDYMOMA I: FINAL RESULTS, LONG TERM FOLLOW-UP AND MOLECULAR ANALYSIS OF THE TRIAL COHORT: A BIOMECA CONSORTIUM STUDY
title_short EPEN-04. SIOP EPENDYMOMA I: FINAL RESULTS, LONG TERM FOLLOW-UP AND MOLECULAR ANALYSIS OF THE TRIAL COHORT: A BIOMECA CONSORTIUM STUDY
title_sort epen-04. siop ependymoma i: final results, long term follow-up and molecular analysis of the trial cohort: a biomeca consortium study
topic Ependymoma
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168242/
http://dx.doi.org/10.1093/neuonc/noab090.054
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