免疫检查点抑制剂在神经系统癌症中的毒性概况:利用美国食品和药物管理局不良事件报告系统进行的全面比例失调分析。

IF 3.2 4区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL
Rongrong Liu, Hui Zhao, Zenghong Lu, Lingshuai Zeng, Huaqiu Shi, Longqiu Wu, Jing Wang, Fangjun Zhong, Chuanjian Liu, Yu Zhang, Zhengang Qiu
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引用次数: 0

摘要

背景:免疫检查点抑制剂(ICIs)治疗期间总会发生免疫相关不良事件(irAEs)。神经系统癌症(NSC)患者可能会从 ICIs 中获得临床获益,但很少有人研究 NSC 患者的 irAEs。因此,我们的研究系统地总结了NSC的irAEs报告:我们从美国食品和药物管理局不良事件报告系统中获取了 2013 年第一季度(Q1)至 2022 年第四季度(Q4)的信息。我们研究了 NSC 患者使用 ICIs 和化疗联合疗法(ICI_Chemo)或仅使用化疗(ICI_Chemo)的情况。我们采用了多重不对称分析来评估irAEs。分析了基因表达总库(GEO)中的多组学数据,以探索与NSC患者irAEs相关的潜在分子机制:结果:去除重复数据后,在8357名NSC患者中发现了14种irAEs;前五种事件分别是癫痫发作、精神错乱、脑病、肌肉无力和步态障碍。老年患者比年轻患者更容易发生虹膜AE。从开始使用 ICIs_Chemo 到发生 irAEs,不同年龄组的患者发生 irAEs 的时间存在显著差异。irAEs 的发生机制可能涉及炎症反应、炎症介质的分泌和病理通路的异常激活:本研究有助于描述接受 ICIs 治疗的 NSC 患者的 irAEs 特征。我们结合 GEO 数据库分析,探索了 irAEs 的潜在分子机制。本研究的结果为改善 ICIs 在 NSC 患者中的毒性效应提供了依据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Toxicity profiles of immune checkpoint inhibitors in nervous system cancer: a comprehensive disproportionality analysis using FDA adverse event reporting system.

Toxicity profiles of immune checkpoint inhibitors in nervous system cancer: a comprehensive disproportionality analysis using FDA adverse event reporting system.

Background: Immune-related adverse events (irAEs) always occur during treatment with immune checkpoint inhibitors (ICIs). Patients with nervous system cancer (NSC) may gain clinical benefit from ICIs, but irAEs in NSC patients are rarely examined. Therefore, our study systematically summarized reports of irAEs in NSC.

Methods: We obtained information from the FDA adverse event reporting system from the first quarter (Q1) of 2013 to the fourth quarter (Q4) of 2022. We examined use of a combination of ICIs and chemotherapy (ICI_Chemo) or chemotherapy only (ICI_Chemo) for patients with NSC. Multiple disproportionality analyses were applied to assess irAEs. Multiomics data from the gene expression omnibus (GEO) database were analyzed to explore potential molecular mechanisms associated with irAEs in NSC patients.

Results: Fourteen irAEs were identified in 8,357 NSC patients after removing duplicates; the top five events were seizure, confused state, encephalopathy, muscular weakness and gait disturbance. Older patients were more likely to develop irAEs than were younger patients. From the start of ICIs_Chemo to irAE occurrence, there was a significant difference in the time to onset of irAEs between age groups. irAEs may occur via mechanisms involving the inflammatory response, secretion of inflammatory mediators, and aberrant activation of pathologic pathways.

Conclusions: This study helps to characterize irAEs in NSC patients treated with ICIs. We combined GEO database analysis to explore the potential molecular mechanisms of irAEs. The results of this study provide a basis for improving the toxic effects of ICIs in NSC patients.

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来源期刊
Clinical and Experimental Medicine
Clinical and Experimental Medicine 医学-医学:研究与实验
CiteScore
4.80
自引率
2.20%
发文量
159
审稿时长
2.5 months
期刊介绍: Clinical and Experimental Medicine (CEM) is a multidisciplinary journal that aims to be a forum of scientific excellence and information exchange in relation to the basic and clinical features of the following fields: hematology, onco-hematology, oncology, virology, immunology, and rheumatology. The journal publishes reviews and editorials, experimental and preclinical studies, translational research, prospectively designed clinical trials, and epidemiological studies. Papers containing new clinical or experimental data that are likely to contribute to changes in clinical practice or the way in which a disease is thought about will be given priority due to their immediate importance. Case reports will be accepted on an exceptional basis only, and their submission is discouraged. The major criteria for publication are clarity, scientific soundness, and advances in knowledge. In compliance with the overwhelmingly prevailing request by the international scientific community, and with respect for eco-compatibility issues, CEM is now published exclusively online.
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