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复发性脑膜瘤的功能精准医学检测:原理验证。病例说明。

Functional precision medicine assay for recurrent meningioma: a proof of principle. Illustrative case.

作者信息

Shelton William J, Santos Horta Erika, Stephen Nix James, Gokden Murat, Rodriguez Analiz

机构信息

Departments of Neurosurgery, University of Arkansas for Medical Sciences, College of Medicine, Little Rock, Arkansas.

Departments of Medical Oncology, University of Arkansas for Medical Sciences, College of Medicine, Little Rock, Arkansas.

出版信息

J Neurosurg Case Lessons. 2024 Jul 29;8(5). doi: 10.3171/CASE24242.

Abstract

BACKGROUND

Meningiomas are the most prevalent primary central nervous system tumors. Although low-grade meningiomas are considered benign tumors, a subset of these can behave aggressively, showing progression and recurrence. In such cases, functional assays could influence treatment decisions and improve patient outcomes.

OBSERVATIONS

A 78-year-old female presented with a long-standing history of a supratentorial meningioma that was initially resected and treated with Gamma Knife radiosurgery. Surveillance revealed progression. She began systemic therapy with everolimus and octreotide but was lost to follow-up and did not continue the treatment. She returned because of a rapid decline in her neurological status. Biopsy with advanced molecular characterization by next-generation sequencing revealed NF2 and CREBBP mutations, and a commercial functional assay was done. This assay successfully isolated cancer stem cells (CSCs) from biopsy cores and identified potential drugs based on cellular sensitivity profiles. This is the first reported case in which a commercial functional drug screen was used for a meningioma.

LESSONS

In cases in which meningiomas exhibit specific genetic alterations and characteristics of aggressiveness, functional assays can be a useful tool for isolating CSCs. The authors report success in obtaining drug-screen profiling for a World Health Organization grade 1 meningioma. Multimodal approaches utilizing multi-omics analyses with functional assays can improve patient outcomes. https://thejns.org/doi/10.3171/CASE24242.

摘要

背景

脑膜瘤是最常见的原发性中枢神经系统肿瘤。尽管低级别脑膜瘤被认为是良性肿瘤,但其中一部分可能具有侵袭性,会出现进展和复发。在这种情况下,功能分析可能会影响治疗决策并改善患者预后。

观察结果

一名78岁女性,有幕上脑膜瘤病史,最初接受了手术切除并进行了伽玛刀放射治疗。监测发现病情进展。她开始使用依维莫司和奥曲肽进行全身治疗,但失访且未继续治疗。因神经功能迅速恶化而复诊。通过下一代测序进行的具有先进分子特征的活检显示存在NF2和CREBBP突变,并进行了一项商业功能分析。该分析成功地从活检组织中分离出癌症干细胞(CSCs),并根据细胞敏感性谱鉴定出潜在药物。这是首次报道将商业功能药物筛选用于脑膜瘤的病例。

经验教训

在脑膜瘤表现出特定基因改变和侵袭性特征的病例中,功能分析可以成为分离癌症干细胞的有用工具。作者报告了成功获得世界卫生组织1级脑膜瘤药物筛选图谱的案例。利用多组学分析与功能分析的多模式方法可以改善患者预后。https://thejns.org/doi/10.3171/CASE24242。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c28/11301594/61401091e2d9/CASE24242_figure_1.jpg

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