BACKGROUND TERT gene alterations (TERT-alt) have been linked to increased risk of recurrence in meningiomas, whereas the association to mortality largely remain incompletely investigated. As incongruence between clinical course and WHO grade exists, reliable biomarkers have been sought. METHODS We applied the Preferred Reporting Items for Systematic Review and Meta-Analyses of individual participant data Statement. We compiled data from eight studies and allocated patients to TERT-alt (n=59) or TERT promoter wild-type (TERTp-wt; n=618). We compared the two groups stratified for WHO grades as: incidence rates, survival probabilities and cumulative recurrences. We estimated the effects of WHO grade, age at diagnosis and sex as HRs. RESULTS TERT-alt occurred in 4.7%, 7.9% and 15.4% of WHO-I/WHO-II/WHO-III meningiomas, respectively. The median recurrence-free survival was 14 months for all TERT-alt patients versus 101 months for all TERTp-wt patients. The HR for TERT-alt was 3.74 in reference to TERTp-wt. For all TERT-alt patients versus all TERTp-wt patients, the median overall survival was 58 months and 160 months, respectively. The HR for TERT-alt was 2.77 compared with TERTp-wt. TERT-alt affected prognosis independent of WHO grades. Particularly, the recurrence rate was 4.8 times higher in WHO-I/-II TERT-alt patients compared with WHO-III TERTp-wt patients. The mortality rate was 2.7 times higher in the WHO-I and WHO-II TERT-alt patients compared with WHO-III TERTp-wt patients. CONCLUSIONS TERT-alt is an important biomarker for significantly higher risk of recurrence and death in meningiomas. TERT-alt should be managed and surveilled aggressively. We propose that TERT-alt analysis should be implemented as a routine diagnostic test in meningioma and integrated into the WHO classification. TRIAL REGISTRATION NUMBER PROSPERO: CRD42018110566.

中文翻译：

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脑膜瘤中与TERT基因改变有关的不良预后与WHO分类无关：单独的患者数据荟萃分析。

背景技术TERT基因改变（TERT-alt）与脑膜瘤复发风险增加有关，而与死亡率的关联在很大程度上尚未得到充分研究。由于临床过程与WHO等级之间存在不一致，因此一直在寻找可靠的生物标志物。方法我们将首选报告项目应用于个体参与者数据陈述的系统评价和荟萃分析。我们汇总了八项研究的数据，并将患者分配为TERT-alt（n = 59）或TERT启动子野生型（TERTp-wt; n = 618）。我们将按WHO等级分层的两组进行了比较：发病率，生存率和累积复发。我们估计了WHO等级，诊断年龄和性别作为HR的影响。结果TERT-alt分别占WHO-I / WHO-II / WHO-III脑膜瘤的4.7％，7.9％和15.4％。所有TERT-alt患者的中位无复发生存期为14个月，而所有TERTp-wt患者为10​​1个月。相对于TERTp-wt，TERT-alt的HR为3.74。对于所有TERT-alt患者与所有TERTp-wt患者，中位总生存期分别为58个月和160个月。与TERTp-wt相比，TERT-alt的HR为2.77。TERT-alt影响的预后与WHO等级无关。特别是，与WHO-III TERTp-wt患者相比，WHO-I / -II TERT-alt患者的复发率高4.8倍。与WHO-III TERTp-wt患者相比，WHO-I和WHO-II TERT-alt患者的死亡率高2.7倍。结论TERT-alt是重要的生物标志物，可大大提高脑膜瘤的复发和死亡风险。应积极管理和监视TERT-alt。我们建议将TERT-alt分析作为脑膜瘤的常规诊断检测方法，并纳入WHO分类标准。试用注册号PROSPERO：CRD42018110566。