METHODS: A systematic search of seven electronic databases from inception to February 2020 was conducted following PRISMA guidelines. Articles were screened against pre-specified criteria to include lower-grade glioma (LGG, WHO Grade II/III) and glioblastoma (GBM, WHO Grade IV) separately. Progression free survival (PFS) and overall survival (OS) from Kaplan-Meier and multivariable analyses were outcomes of interest.
RESULTS: Nine institutional studies describing 2193 IDH-mutant gliomas satisfied criteria for evaluation, with 1756 (80%) LGG and 437 (20%) GBM. When reported, the proportion of CDKN2A homozygous deleted gliomas ranged from 9 to 43%, with a median incidence of 22%. For LGG, Kaplan-Meier analyses demonstrated shorter PFS in the presence of CDKN2A homozygous deletion in three studies (median values, 31 versus 91 months), and shorter OS in five studies (median values, 61 versus 154 months). For GBM, Kaplan-Meier analyses demonstrated shorter PFS in the presence of CDKN2A homozygous deletion in two studies (median values, 16 versus 30 months), and shorter OS in four studies (median values, 38 versus 86 months). By multivariable analyses, CDKN2A homozygous deletion was a predictor of significantly shorter PFS and OS in both LGG and GBM across all included studies.
CONCLUSIONS: The CDKN2A homozygous deletion is an important prognostic factor for survival outcomes of IDH-mutant glioma patients across multiple histologic WHO grades with specific molecular features likely dependent on IDH-mutant status. Greater understanding of how identifying this deletion can assist in the stratification of management for these tumors to optimize clinical course is required.
方法:根据PRISMA指南,从开始到2020年2月对七个电子数据库进行了系统搜索。根据预先指定的标准筛选文章,以包括低级别神经胶质瘤(LGG,世卫组织II/III级)和胶质母细胞瘤(GBM,世卫组织四级)单独。来自Kaplan-Meier和多变量分析的无进展生存期(PFS)和总生存期(OS)是感兴趣的结果。
结果:描述2193个IDH突变神经胶质瘤的九项机构研究满足评估标准,1756(80%)LGG和437(20%)GBM。报告时,CDKN2A纯合缺失胶质瘤的比例为9-43%,发病率中位数为22%。对于LGG,Kaplan-Meier分析表明,在三项研究中,CDKN2A纯合缺失的存在下PFS较短(中值,31个月对91个月),五项研究中的OS较短(中值,61个月对154个月)。对于GBM,Kaplan-Meier分析显示,在两项研究中存在CDKN2A纯合缺失的情况下,PFS较短(中值,16个月对30个月),四项研究中的OS较短(中值,38对86个月)。通过多变量分析,在所有纳入的研究中,CDKN2A纯合缺失是LGG和GBM中PFS和OS显著缩短的预测因子。
结论:CDKN2A纯合缺失是IDH突变型胶质瘤患者生存结局的重要预后因素,这些患者在多种组织学WHO分级中具有特定的分子特征,可能依赖于IDH突变型状态。需要更好地了解识别这种缺失如何有助于对这些肿瘤的管理进行分层以优化临床过程。