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左乙拉西坦和拉科酰胺在替莫唑胺联合放疗辅助治疗期间对异柠檬酸脱氢酶野生型胶质母细胞瘤患者生存及癫痫控制的影响

Effects of Levetiracetam and Lacosamide on survival and seizure control in IDH-wild type glioblastoma during temozolomide plus radiation adjuvant therapy.

作者信息

Bianconi Andrea, Koumantakis Emanuele, Gatto Andrea, Zeppa Pietro, Saaid Ayoub, Nico Elsa, Bruno Francesco, Pellerino Alessia, Rizzo Francesca, Junemann Carola Vera, Melcarne Antonio, Garbossa Diego, Dalmasso Paola, Cofano Fabio

机构信息

Neurosurgery, Department of Neuroscience, University of Turin, Turin, Italy.

Department of Public Health and Pediatrics, University of Turin, Turin, Italy.

出版信息

Brain Spine. 2023 Dec 14;4:102732. doi: 10.1016/j.bas.2023.102732. eCollection 2024.

Abstract

INTRODUCTION

There are no clear indications for the best choice of anti-seizure medications to control brain tumor related epilepsy. In vitro studies have shown an antitumoral effect of Levetiracetam and Lacosamide on glioblastoma IDH-wild type.

RESEARCH QUESTION

This study investigates whether the use of levetiracetam and/or lacosamide impacts survival rates. The secondary aim was to evaluate the efficacy of both ASMs in controlling seizures.

MATERIALS AND METHODS

In this observational retrospective single-cohort study, patients underwent chemoradiation protocol after GBM surgery. They were grouped as follows: (1) use of levetiracetam, (2) use of lacosamide, (3) simultaneous use of levetiracetam and lacosamide, (4) no ASM usage. Survival curves were plotted using the Kaplan-Meier method coupled with a log-rank test for difference assesments. To evaluate the pharmacological efficacy of post-operative seizure control, a negative binomial regression was conducted.

RESULTS

The study included 272 patients, 174 of which underwent adjuvant chemoradiation treatment. Patients without ASM therapy had a non-significant longer median OS (compared to the other groups (log-rank = 0.37). The IRR of seizure relapse was 2.57 (p = 0.007) times higher in lacosamide users, and MGMT promoter methylation demonstrated a protective effect against postoperative seizure onset (p = 0.05), regardless of the aforementioned confounding factors.

DISCUSSION AND CONCLUSIONS

In patients diagnosed with GBM IDH-WT undergoing chemoradiation therapy, the use of levetiracetam or lacosamide for controlling BTRE does not seem to modify survival. Lacosamide users exhibited a higher IRR of postoperative seizures compared to levetiracetam users, and MGMT promoter methylation appears to be a protective factor.

摘要

引言

对于控制脑肿瘤相关癫痫的抗癫痫药物的最佳选择,目前尚无明确指征。体外研究表明,左乙拉西坦和拉科酰胺对异柠檬酸脱氢酶(IDH)野生型胶质母细胞瘤具有抗肿瘤作用。

研究问题

本研究调查使用左乙拉西坦和/或拉科酰胺是否会影响生存率。次要目的是评估这两种抗癫痫药物控制癫痫发作的疗效。

材料与方法

在这项观察性回顾性单队列研究中,患者在胶质母细胞瘤手术后接受放化疗方案。他们被分为以下几组:(1)使用左乙拉西坦;(2)使用拉科酰胺;(3)同时使用左乙拉西坦和拉科酰胺;(4)未使用抗癫痫药物。使用Kaplan-Meier方法绘制生存曲线,并结合对数秩检验进行差异评估。为评估术后癫痫控制的药理疗效,进行了负二项回归分析。

结果

该研究纳入了272例患者,其中174例接受了辅助放化疗。未使用抗癫痫药物治疗的患者中位总生存期较长,但差异无统计学意义(与其他组相比,对数秩=0.37)。拉科酰胺使用者癫痫复发的发病率比(IRR)高2.57倍(p=0.007),且无论上述混杂因素如何,O6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)启动子甲基化对术后癫痫发作具有保护作用(p=0.05)。

讨论与结论

在接受放化疗的异柠檬酸脱氢酶野生型胶质母细胞瘤患者中,使用左乙拉西坦或拉科酰胺控制脑肿瘤相关癫痫似乎不会改变生存率。与左乙拉西坦使用者相比,拉科酰胺使用者术后癫痫发作的发病率比更高,且MGMT启动子甲基化似乎是一个保护因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/709d/10951696/a320ac75c635/gr1.jpg

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