胶质母细胞瘤：从体积分析到分子预测因子。

Glioblastoma: from volumetric analysis to molecular predictors.

机构信息

Unit of Neurosurgery, Department of Neuroscience, Santa Maria della Misericordia University Hospital, Udine, Italy -

Institute of Neurosurgery, Sacred Heart Catholic University, Rome, Italy.

出版信息

J Neurosurg Sci. 2022 Jun;66(3):173-186. doi: 10.23736/S0390-5616.20.04850-X. Epub 2020 Feb 4.

DOI:10.23736/S0390-5616.20.04850-X

PMID:32031360

Abstract

BACKGROUND

Decades of therapeutic and molecular refinements, the prognosis of patients with glioblastoma (GBM) still remains unfavorable. Integrative clinical studies allow a better understanding of the natural evolution of GBM. To assess independent predictors of overall survival (OS) and progression free survival (PFS) clinical, surgical, molecular and radiological variables were evaluated. A novel preoperative volumetric magnetic resonance imaging (MRI) Index for tumor prognosis in GBM patients was investigated.

METHODS

A cohort of 195 cases of patients operated for newly GBM were analyzed. Extent of tumoral resection (EOR), tumor growth pattern, expressed by preoperative volumetric ΔT1-T2 MRI Index, molecular markers such as O6-methylguanine-DNA methyltransferase (MGMT) methylation and isocitrate dehydrogenase 1/2 (IDH1/2) mutation, were analyzed. Analysis of survival was done using Cox-proportional hazard models.

RESULTS

The 1-, 2- years estimated OS and PFS rate for the whole population were 61% and 27%, 38% and 17%, respectively. A better survival rate, both in terms of survival and tumor progression, was observed in patient with higher EOR (P=0.000), younger age (P=0.000), MGMT methylation status (P=0.001) and lower preoperative ΔT1-T2 MRI Index (P=0.004). Regarding the tumor growth pattern a cut-off value of 0.75 was found to discriminate patient with different prognosis. Patients with a preoperative ΔT1-T2 MRI Index <0.75 had a 1-year estimated OS of 67%, otherwise patients with a preoperative ΔT1-T2 MRI Index >0.75 had a 1-year estimated OS of 34%.

CONCLUSIONS

In this investigation longer survival is associated with younger age, EOR, promoter methylation of MGMT and preoperative tumor volumetric features expressed by ΔT1-T2 MRI Index The preoperative ΔT1-T2 MRI Index could be a promising prognostic factor potentially useful in GBM management. Future investigations based on multiparametric MRI data and next generation sequences analysis, may better clarify this result.

摘要

背景

经过几十年的治疗和分子学上的改进，胶质母细胞瘤（GBM）患者的预后仍然不容乐观。综合临床研究可以更好地了解 GBM 的自然演变。为了评估总生存（OS）和无进展生存（PFS）的独立预测因素，评估了临床、手术、分子和影像学变量。研究了一种新的术前容积磁共振成像（MRI）指数，用于预测 GBM 患者的肿瘤预后。

方法

分析了 195 例新诊断为 GBM 患者的病例。评估了肿瘤切除程度（EOR）、肿瘤生长模式，通过术前容积ΔT1-T2 MRI 指数表示、O6-甲基鸟嘌呤-DNA 甲基转移酶（MGMT）甲基化和异柠檬酸脱氢酶 1/2（IDH1/2）突变等分子标志物。使用 Cox 比例风险模型进行生存分析。

结果

全人群的 1 年、2 年估计 OS 和 PFS 率分别为 61%和 27%、38%和 17%。在 EOR 更高（P=0.000）、年龄更小（P=0.000）、MGMT 甲基化状态（P=0.001）和术前ΔT1-T2 MRI 指数更低（P=0.004）的患者中，观察到更好的生存和肿瘤进展。关于肿瘤生长模式，发现 0.75 为截断值，可以区分预后不同的患者。术前ΔT1-T2 MRI 指数<0.75 的患者 1 年估计 OS 为 67%，而术前ΔT1-T2 MRI 指数>0.75 的患者 1 年估计 OS 为 34%。