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Locally dose-escalated radiotherapy may improve intracranial local control and overall survival among patients with glioblastoma

BACKGROUND: The dismal overall survival (OS) prognosis of glioblastoma, even after trimodal therapy, can be attributed mainly to the frequent incidence of intracranial relapse (ICR), which tends to present as an in-field recurrence after a radiation dose of 60 Gray (Gy). In this study, molecular mar...

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Autores principales: Zschaeck, Sebastian, Wust, Peter, Graf, Reinhold, Misch, Martin, Onken, Julia, Ghadjar, Pirus, Badakhshi, Harun, Florange, Julian, Budach, Volker, Kaul, David
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6299982/
https://www.ncbi.nlm.nih.gov/pubmed/30567592
http://dx.doi.org/10.1186/s13014-018-1194-8
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author Zschaeck, Sebastian
Wust, Peter
Graf, Reinhold
Misch, Martin
Onken, Julia
Ghadjar, Pirus
Badakhshi, Harun
Florange, Julian
Budach, Volker
Kaul, David
author_facet Zschaeck, Sebastian
Wust, Peter
Graf, Reinhold
Misch, Martin
Onken, Julia
Ghadjar, Pirus
Badakhshi, Harun
Florange, Julian
Budach, Volker
Kaul, David
author_sort Zschaeck, Sebastian
collection PubMed
description BACKGROUND: The dismal overall survival (OS) prognosis of glioblastoma, even after trimodal therapy, can be attributed mainly to the frequent incidence of intracranial relapse (ICR), which tends to present as an in-field recurrence after a radiation dose of 60 Gray (Gy). In this study, molecular marker-based prognostic indices were used to compare the outcomes of radiation with a standard dose versus a moderate dose escalation. METHODS: This retrospective analysis included 156 patients treated between 2009 and 2016. All patients were medically fit for postoperative chemoradiotherapy. In the dose-escalation cohort a simultaneous integrated boost of up to 66 Gy (66 Gy RT) within small high-risk volumes was applied. All other patients received daily radiation to a total dose of 60 Gy or twice daily to a total dose of 59.2 Gy (60 Gy RT). RESULTS: A total of 133 patients received standard 60 Gy RT, while 23 received 66 Gy RT. Patients in the 66 Gy RT group were younger (p <  0.001), whereas concomitant temozolomide use was more frequent in the 60 Gy RT group (p <  0.001). Other intergroup differences in known prognostic factors were not observed. Notably, the median time to ICR was significantly prolonged in the 66 Gy RT arm versus the 60 Gy RT arm (12.2 versus 7.6 months, p = 0.011), and this translated to an improved OS (18.8 versus 15.3 months, p = 0.012). A multivariate analysis revealed a strong association of 66 Gy RT with a prolonged time to ICR (hazard ratio = 0.498, p = 0.01) and OS (hazard ratio = 0.451, p = 0.01). These differences remained significant after implementing molecular marker-based prognostic scores (ICR p = 0.008, OS p = 0.007) and propensity-scored matched pairing (ICR p = 0.099, OS p = 0.023). CONCLUSION: Radiation dose escalation was found to correlate with an improved time to ICR and OS in this cohort of glioblastoma patients. However, further prospective validation of these results is warranted. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13014-018-1194-8) contains supplementary material, which is available to authorized users.
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spelling pubmed-62999822018-12-20 Locally dose-escalated radiotherapy may improve intracranial local control and overall survival among patients with glioblastoma Zschaeck, Sebastian Wust, Peter Graf, Reinhold Misch, Martin Onken, Julia Ghadjar, Pirus Badakhshi, Harun Florange, Julian Budach, Volker Kaul, David Radiat Oncol Research BACKGROUND: The dismal overall survival (OS) prognosis of glioblastoma, even after trimodal therapy, can be attributed mainly to the frequent incidence of intracranial relapse (ICR), which tends to present as an in-field recurrence after a radiation dose of 60 Gray (Gy). In this study, molecular marker-based prognostic indices were used to compare the outcomes of radiation with a standard dose versus a moderate dose escalation. METHODS: This retrospective analysis included 156 patients treated between 2009 and 2016. All patients were medically fit for postoperative chemoradiotherapy. In the dose-escalation cohort a simultaneous integrated boost of up to 66 Gy (66 Gy RT) within small high-risk volumes was applied. All other patients received daily radiation to a total dose of 60 Gy or twice daily to a total dose of 59.2 Gy (60 Gy RT). RESULTS: A total of 133 patients received standard 60 Gy RT, while 23 received 66 Gy RT. Patients in the 66 Gy RT group were younger (p <  0.001), whereas concomitant temozolomide use was more frequent in the 60 Gy RT group (p <  0.001). Other intergroup differences in known prognostic factors were not observed. Notably, the median time to ICR was significantly prolonged in the 66 Gy RT arm versus the 60 Gy RT arm (12.2 versus 7.6 months, p = 0.011), and this translated to an improved OS (18.8 versus 15.3 months, p = 0.012). A multivariate analysis revealed a strong association of 66 Gy RT with a prolonged time to ICR (hazard ratio = 0.498, p = 0.01) and OS (hazard ratio = 0.451, p = 0.01). These differences remained significant after implementing molecular marker-based prognostic scores (ICR p = 0.008, OS p = 0.007) and propensity-scored matched pairing (ICR p = 0.099, OS p = 0.023). CONCLUSION: Radiation dose escalation was found to correlate with an improved time to ICR and OS in this cohort of glioblastoma patients. However, further prospective validation of these results is warranted. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13014-018-1194-8) contains supplementary material, which is available to authorized users. BioMed Central 2018-12-19 /pmc/articles/PMC6299982/ /pubmed/30567592 http://dx.doi.org/10.1186/s13014-018-1194-8 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Zschaeck, Sebastian
Wust, Peter
Graf, Reinhold
Misch, Martin
Onken, Julia
Ghadjar, Pirus
Badakhshi, Harun
Florange, Julian
Budach, Volker
Kaul, David
Locally dose-escalated radiotherapy may improve intracranial local control and overall survival among patients with glioblastoma
title Locally dose-escalated radiotherapy may improve intracranial local control and overall survival among patients with glioblastoma
title_full Locally dose-escalated radiotherapy may improve intracranial local control and overall survival among patients with glioblastoma
title_fullStr Locally dose-escalated radiotherapy may improve intracranial local control and overall survival among patients with glioblastoma
title_full_unstemmed Locally dose-escalated radiotherapy may improve intracranial local control and overall survival among patients with glioblastoma
title_short Locally dose-escalated radiotherapy may improve intracranial local control and overall survival among patients with glioblastoma
title_sort locally dose-escalated radiotherapy may improve intracranial local control and overall survival among patients with glioblastoma
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6299982/
https://www.ncbi.nlm.nih.gov/pubmed/30567592
http://dx.doi.org/10.1186/s13014-018-1194-8
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