BACKGROUND Glioblastoma (GBM) is the most frequent intraaxial malignant brain tumour, in which recurrence management is a frequent and demanding issue. Recently, reintervention has emerged as a useful tool for treatment. However, some new evidence has shown that most of the articles published could have overestimated its effects. We aimed to analyse the effect on survival of reintervention considering it as a time-dependent variable and to compare it with classic statistical analysis. METHODS We performed a retrospective study with GBM patients between 2007 and 2017. We compared the overall survival (OS) between reintervention and non-reintervention groups with time-dependent statistical methods (Simon-Makuch and landmarking methods and time-dependent multivariable Cox analysis) and compared them with those obtained with non-dependent time variable analysis. RESULTS A total of 183 patients were included in the analysis and 44 of them were reoperated. The standard analysis with Kaplan-Meier and multivariable Cox regression of the cohort showed an OS of 22.2 months (95% CI 12.56-16.06) in the reintervention group and 11.8 months (95% CI 9.87-13.67) in the non-reintervention group (p < .001); and an HR 0.649 (95% CI 0.434-0.97 p = .035) for reintervention, demonstrating an increase in OS. However, time-dependent analysis with the Simon-Makuch test and the landmarking method showed that the relationship was not consistent, as this increase in OS was not significant. Moreover, time-dependent multivariable Cox analysis did not show that reintervention improved OS in our cohort (HR 0.997 95% CI 0.976-1.018 p = 0.75). CONCLUSIONS There has been a temporal bias in the literature that has led to an overestimation of the positive effect of reintervention in recurrent GBM. However, reintervention could still be useful in some selected patients, who should be individualized according to prognostic factors related to the patient, biology of the tumour, and characteristics of surgical procedure.

中文翻译：

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再次干预会改善复发性胶质母细胞瘤的存活率吗？面对文献中的时间偏差。

背景胶质母细胞瘤（GBM）是最常见的轴内恶性脑肿瘤，其中复发管理是一个常见且要求严格的问题。最近，再干预已经成为治疗的有用工具。但是，一些新证据表明，大多数已发表的文章可能高估了其影响。我们旨在分析重新干预对生存的影响，并将其作为时间依赖性变量，并将其与经典统计分析进行比较。方法我们对2007年至2017年间GBM患者进行了回顾性研究。我们使用时间依赖性统计方法（Simon-Makuch和标志性方法以及时间依赖性多变量Cox分析）比较了干预组和非干预组之间的总生存期（OS），并将其与非依赖性时间变量分析所获得的生存期进行了比较。结果分析共纳入183例患者，其中44例再次手术。使用Kaplan-Meier和队列的多变量Cox回归进行的标准分析显示，再干预组的OS为22.2个月（95％CI 12.56-16.06），而非再干预组的OS为11.8个月（95％CI 9.87-13.67）（ p <.001）；HR 0.649（95％CI 0.434-0.97 p = .035）进行再次干预，表明OS升高。然而，使用Simon-Makuch检验和地标方法进行的时间依赖性分析表明，这种关系不一致，因为OS的增加并不明显。此外，时间相关的多变量Cox分析未显示我们的队列中再次干预改善了OS（HR 0.997 95％CI 0.976-1.018 p = 0.75）。结论文献中存在时间偏差，导致对复发性GBM中再次干预的积极作用高估。但是，再次干预在某些选定的患者中仍然可能有用，应根据与患者，肿瘤的生物学以及手术过程的特征有关的预后因素对患者进行个体化。时间相关的多变量Cox分析未显示我们的队列中再次干预改善了OS（HR 0.997 95％CI 0.976-1.018 p = 0.75）。结论文献中存在时间偏差，导致对复发性GBM中再次干预的积极作用高估。但是，再次干预在某些选定的患者中仍然可能有用，应根据与患者，肿瘤的生物学以及手术过程的特征有关的预后因素对患者进行个体化。时间相关的多变量Cox分析未显示我们的队列中再次干预改善了OS（HR 0.997 95％CI 0.976-1.018 p = 0.75）。结论文献中存在时间偏差，导致对复发性GBM中再次干预的积极作用高估。但是，再次干预在某些选定的患者中仍然可能有用，应根据与患者，肿瘤的生物学以及手术过程的特征有关的预后因素对患者进行个体化。