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多灶性和分子标志物对胶质母细胞瘤生存的影响

Impact of Multifocality and Molecular Markers on Survival of Glioblastoma.

作者信息

Ahmadipour Yahya, Jabbarli Ramazan, Gembruch Oliver, Pierscianek Daniela, Darkwah Oppong Marvin, Dammann Philipp, Wrede Karsten, Özkan Neriman, Müller Oliver, Sure Ulrich, El Hindy Nicolai

机构信息

Department of Neurosurgery, University Hospital, Essen, Germany.

Department of Neurosurgery, University Hospital, Essen, Germany.

出版信息

World Neurosurg. 2019 Feb;122:e461-e466. doi: 10.1016/j.wneu.2018.10.075. Epub 2018 Oct 19.

DOI:10.1016/j.wneu.2018.10.075
PMID:30347300
Abstract

OBJECTIVE

Several parameters like extent of resection and MGMT promotor methylation in glioblastoma (GBM) are known to influence survival. Other elements like multifocality and proliferation indices are not commonly used. The aim of the present study was to analyze routinely and not routinely assessed prognostic markers for survival of patients suffering from GBM in a single center.

METHODS

Adult cases with GBM operated at our institution were included in this survey. The association of age, Karnofsky performance status (KPS), MGMT promotor methylation, Ki67 proliferation index, IDH1/2 mutational status, and multifocality on overall survival (OS) was analyzed in univariate and multivariate cox regression models.

RESULTS

We analyzed 565 patients with a mean age of 62.2 (18-84) years. Median OS was 12.5 months. MGMT promoter methylation and IDH 1/2 mutation were associated with significant better OS (P < 0.01). In 48 cases (8.5%), the tumor was localized in both hemispheres, which was associated with a significant worse OS than tumor infiltration of 1 hemisphere (P = 0.039). Mean Ki67 proliferation index increased to 18% when both hemispheres were infiltrated. Multivariate analysis for OS revealed IDH 1/2 wildtype (adjusted odds ratio [aOR] 4.3), higher age (aOR 4.2), unmethylated MGMT promotor (aOR 3.5), preoperative KPS score <70 (aOR 1.9), and multifocality (aOR 2.1) as independent parameters for worse survival.

CONCLUSIONS

This study confirms well-known parameters like MGMT promoter methylation, IDH 1/2 mutational status, KPS, and age as independent prognostic factors for survival and reveals multifocality as further independent prognostic marker for survival. The dismal prognosis of multifocal involvement is associated with an increasing Ki67 proliferation index.

摘要

目的

已知胶质母细胞瘤(GBM)的几个参数,如切除范围和MGMT启动子甲基化会影响生存率。其他因素,如多灶性和增殖指数并不常用。本研究的目的是分析在单一中心GBM患者生存中常规和非常规评估的预后标志物。

方法

本调查纳入了在我们机构接受手术的成年GBM病例。在单变量和多变量Cox回归模型中分析年龄、卡诺夫斯基功能状态(KPS)、MGMT启动子甲基化、Ki67增殖指数、IDH1/2突变状态和多灶性与总生存期(OS)的关联。

结果

我们分析了565例患者,平均年龄为62.2岁(18 - 84岁)。中位总生存期为12.5个月。MGMT启动子甲基化和IDH 1/2突变与显著更好的总生存期相关(P < 0.01)。在48例(8.5%)病例中,肿瘤位于双侧半球,与肿瘤侵犯一个半球相比,总生存期显著更差(P = 0.039)。当双侧半球均受侵犯时,平均Ki67增殖指数增至18%。总生存期的多变量分析显示,IDH 1/2野生型(调整优势比[aOR] 4.3)、年龄较大(aOR 4.2)、MGMT启动子未甲基化(aOR 3.5)、术前KPS评分<70(aOR 1.9)和多灶性(aOR 2.1)是生存较差的独立参数。

结论

本研究证实了MGMT启动子甲基化、IDH 1/2突变状态、KPS和年龄等众所周知的参数是生存的独立预后因素,并揭示多灶性是生存的另一个独立预后标志物。多灶性受累的预后不佳与Ki67增殖指数增加有关。

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