Abstract
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.
Highlights
Glioblastoma multiforme (GBM) is the most common malignant brain tumor in adults, and the tumor recurs in most patients, with a median survival of 12–15 months from initial diagnosis [1]
The beneficial effect of repeat resection on survival has been reported in recurrent GBM patients in some studies [10,11,12,13,14,15,16,17,18], but a reverse effect of reoperation was shown in other studies [19,20,21,22,23,24,25,26,27]
The Mesh terms used for literature search included “Glioblastoma,” “Recurrenc,” and “Reoperation.” The following non-Mesh terms were used: [1] “Glioblastomas,” “Astrocytoma, Grade IV,” “Astrocytomas, Grade IV,” “Grade IV Astrocytoma,” “Grade IV Astrocytomas,” “Glioblastoma Multiforme,” “Giant Cell Glioblastoma,” “Giant Cell Glioblastomas,” “Glioblastoma, Giant Cell,” “Glioblastomas, Giant Cell”; [2] “Recurrences,” “Recrudescence,” “Recrudescences,” “Relapse,” “Relapses”; [3] “Surgical Revision,” “Surgery, Repeat,” “Revision, Surgical,” “Revision Surgery,” “Revision Surgeries,” “Surgery, Revision,” “Repeat Surgery,” “Revision, Joint,” “Joint Revision,” “Repeat operation,” “Repeat resection,” and “Second surgery,” Reviews as well as the references of the included studies were checked to avoid the omission of relevant publications
Summary
Glioblastoma multiforme (GBM) is the most common malignant brain tumor in adults, and the tumor recurs in most patients, with a median survival of 12–15 months from initial diagnosis [1]. Survival outcome in GBM patients is affected by many confounding factors, including age, Karnofsky performance status (KPS), tumor volume, tumor location, treatment schedule, resection extent, and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation as well as IDH1 mutation status. These confounding factors are incorporated into survival analyses as fixed covariates or time-dependent covariates. 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
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
