A Meta-Analysis of Survival Outcomes Following Reoperation in Recurrent Glioblastoma: Time to Consider the Timing of Reoperation

Background: Glioblastoma multiforme (GBM) inevitably recurs, but no standard regimen has been established for recurrent patients. Reoperation at recurrence alleviates mass effects, and the survival benefit has been reported in many studies. However, in most studies, the effect of reoperation timing...

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Main Authors: Yu-Hang Zhao, Ze-Fen Wang, Zhi-Yong Pan, Dominik Péus, Juan Delgado-Fernandez, Johan Pallud, Zhi-Qiang Li
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-03-01
Series:Frontiers in Neurology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fneur.2019.00286/full
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spelling doaj-89a84425d63c44b8ab890e094efde67f2020-11-24T22:01:05ZengFrontiers Media S.A.Frontiers in Neurology1664-22952019-03-011010.3389/fneur.2019.00286444731A Meta-Analysis of Survival Outcomes Following Reoperation in Recurrent Glioblastoma: Time to Consider the Timing of ReoperationYu-Hang Zhao0Ze-Fen Wang1Zhi-Yong Pan2Dominik Péus3Juan Delgado-Fernandez4Johan Pallud5Johan Pallud6Zhi-Qiang Li7Department of Neurosurgery, Zhongnan Hospital, Wuhan University, Wuhan, ChinaDepartment of Physiology, School of Basic Medical Sciences, Wuhan University, Wuhan, ChinaDepartment of Neurosurgery, Zhongnan Hospital, Wuhan University, Wuhan, ChinaDepartment of Neurosurgery, University Hospital Zurich, Zurich, SwitzerlandDivision of Neurosurgery, University Hospital La Princesa, Madrid, SpainDepartment of Neurosurgery, Sainte-Anne Hospital, Paris, FranceParis Descartes University, Sorbonne Paris Cité, Paris, FranceDepartment of Neurosurgery, Zhongnan Hospital, Wuhan University, Wuhan, ChinaBackground: Glioblastoma multiforme (GBM) inevitably recurs, but no standard regimen has been established for recurrent patients. Reoperation at recurrence alleviates mass effects, and the survival benefit has been reported in many studies. However, in most studies, the effect of reoperation timing on survival benefit was ignored. The aim of this meta-analysis was to investigate whether reoperation provided similar survival benefits in recurrent GBM patients when it was analyzed as a fixed or time-dependent covariate.Methods: A systematic literature search of PubMed, EMBASE, and Cochrane databases was performed to identify original articles that evaluated the associations between reoperation and prognosis in recurrent GBM patients.Results: Twenty-one articles involving 8,630 patients were included. When reoperation was considered as a fixed covariate, it was associated with better overall survival (OS) and post-progression survival (PPS) (OS: HR = 0.66, 95% CI 0.61-0.71, p < 0.001, I2 = 0%; PPS: HR = 0.70, 95% CI 0.57–0.88, p < 0.01, I2 = 70.2%). However, such a survival benefit was not observed when reoperation was considered as a time-dependent covariate (OS: HR = 2.19, 95% CI 1.47–3.27, p < 0.001; PPS: HR = 0.95, 95% CI 0.82–1.10, p = 0.51, I2 = 0%). The estimate bias caused by ignoring the time-dependent nature of reoperation was further demonstrated by the re-analysis of survival data in three included studies.Conclusions: The timing of reoperation may have an impact on the survival outcome in recurrent GBM patients, and survival benefits of reoperation in recurrent GBM may be overestimated when analyzed as fixed covariates. Proper analysis methodology should be used in future work to confirm the clinical benefits of reoperation.https://www.frontiersin.org/article/10.3389/fneur.2019.00286/fullglioblastomarecurrencereoperationtime-dependent covariatesurvival
collection DOAJ
language English
format Article
sources DOAJ
author Yu-Hang Zhao
Ze-Fen Wang
Zhi-Yong Pan
Dominik Péus
Juan Delgado-Fernandez
Johan Pallud
Johan Pallud
Zhi-Qiang Li
spellingShingle Yu-Hang Zhao
Ze-Fen Wang
Zhi-Yong Pan
Dominik Péus
Juan Delgado-Fernandez
Johan Pallud
Johan Pallud
Zhi-Qiang Li
A Meta-Analysis of Survival Outcomes Following Reoperation in Recurrent Glioblastoma: Time to Consider the Timing of Reoperation
Frontiers in Neurology
glioblastoma
recurrence
reoperation
time-dependent covariate
survival
author_facet Yu-Hang Zhao
Ze-Fen Wang
Zhi-Yong Pan
Dominik Péus
Juan Delgado-Fernandez
Johan Pallud
Johan Pallud
Zhi-Qiang Li
author_sort Yu-Hang Zhao
title A Meta-Analysis of Survival Outcomes Following Reoperation in Recurrent Glioblastoma: Time to Consider the Timing of Reoperation
title_short A Meta-Analysis of Survival Outcomes Following Reoperation in Recurrent Glioblastoma: Time to Consider the Timing of Reoperation
title_full A Meta-Analysis of Survival Outcomes Following Reoperation in Recurrent Glioblastoma: Time to Consider the Timing of Reoperation
title_fullStr A Meta-Analysis of Survival Outcomes Following Reoperation in Recurrent Glioblastoma: Time to Consider the Timing of Reoperation
title_full_unstemmed A Meta-Analysis of Survival Outcomes Following Reoperation in Recurrent Glioblastoma: Time to Consider the Timing of Reoperation
title_sort meta-analysis of survival outcomes following reoperation in recurrent glioblastoma: time to consider the timing of reoperation
publisher Frontiers Media S.A.
series Frontiers in Neurology
issn 1664-2295
publishDate 2019-03-01
description Background: Glioblastoma multiforme (GBM) inevitably recurs, but no standard regimen has been established for recurrent patients. Reoperation at recurrence alleviates mass effects, and the survival benefit has been reported in many studies. However, in most studies, the effect of reoperation timing on survival benefit was ignored. The aim of this meta-analysis was to investigate whether reoperation provided similar survival benefits in recurrent GBM patients when it was analyzed as a fixed or time-dependent covariate.Methods: A systematic literature search of PubMed, EMBASE, and Cochrane databases was performed to identify original articles that evaluated the associations between reoperation and prognosis in recurrent GBM patients.Results: Twenty-one articles involving 8,630 patients were included. When reoperation was considered as a fixed covariate, it was associated with better overall survival (OS) and post-progression survival (PPS) (OS: HR = 0.66, 95% CI 0.61-0.71, p < 0.001, I2 = 0%; PPS: HR = 0.70, 95% CI 0.57–0.88, p < 0.01, I2 = 70.2%). However, such a survival benefit was not observed when reoperation was considered as a time-dependent covariate (OS: HR = 2.19, 95% CI 1.47–3.27, p < 0.001; PPS: HR = 0.95, 95% CI 0.82–1.10, p = 0.51, I2 = 0%). The estimate bias caused by ignoring the time-dependent nature of reoperation was further demonstrated by the re-analysis of survival data in three included studies.Conclusions: The timing of reoperation may have an impact on the survival outcome in recurrent GBM patients, and survival benefits of reoperation in recurrent GBM may be overestimated when analyzed as fixed covariates. Proper analysis methodology should be used in future work to confirm the clinical benefits of reoperation.
topic glioblastoma
recurrence
reoperation
time-dependent covariate
survival
url https://www.frontiersin.org/article/10.3389/fneur.2019.00286/full
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