Validation and next-generation update of a DNA methylation-based recurrence predictor for meningioma: a multicenter prospective study.

IF 16.4 1区 医学 Q1 CLINICAL NEUROLOGY Neuro-oncology Pub Date : 2024-11-06 DOI:10.1093/neuonc/noae236
Alexander P Landry, Justin Z Wang, Vikas Patil, Chloe Gui, Mamatjan Yasin, Zeel Patel, Rebecca Yakubov, Ramneet Kaloti, Parnian Habibi, Mark Wilson, Andrew Ajisebutu, Yosef Ellenbogen, Qingxia Wei, Olivia Singh, Julio Sosa, Sheila Mansouri, Christopher Wilson, Aaron A Cohen-Gadol, Piiamaria Virtanen, Noah Burket, Matthew Blackwell, Jenna Koenig, Anthony Alfonso, Joseph Davis, Mohamed A Zaazoue, Ghazaleh Tabatabai, Marcos Tatagiba, Felix Behling, Jill S Barnholtz-Sloan, Andrew E Sloan, Silky Chotai, Lola B Chambless, Alireza Mansouri, Felix Ehret, David Capper, Derek S Tsang, Kenneth Aldape, Andrew Gao, Farshad Nassiri, Gelareh Zadeh
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Abstract

Background: We previously developed a DNA methylation-based risk predictor for meningioma, which has been used locally in a prospective fashion since its original publication. As a follow-up, we validate this model using a large prospective cohort and introduce a streamlined next-generation predictor compatible with newer methylation arrays.

Methods: Genome-wide methylation profiles were generated with the Illumina EPICArray. The performance of our next-generation predictor was compared with our original model and standard-of-care 2021 WHO grade using time-dependent receiver operating characteristic curves. An nomogram was generated by incorporating our methylation predictor with WHO grade and extent of resection.

Results: A total of 1347 meningioma cases were utilized in the study, including 469 prospective cases from 3 institutions and an external cohort of 100 WHO grade 2 cases for model validation. Both the original and next-generation models significantly outperform 2021 WHO grade in predicting early postoperative recurrence. Dichotomizing patients into grade-specific risk subgroups was predictive of outcome within both WHO grades 1 and 2 tumours (p<0.05), while all WHO grade 3 tumours were considered high-risk. Multivariable Cox regression demonstrated benefit of adjuvant radiotherapy in high-risk cases specifically, reinforcing its informative role in clinical decision making. Finally, our next-generation predictor contains nearly 10-fold fewer features than the original model, allowing for targeted arrays.

Conclusions: This next-generation DNA methylation-based meningioma outcome predictor significantly outperforms 2021 WHO grading in predicting time to recurrence. We make this available as a point-and-click tool which will improve prognostication, inform patient selection for RT, and allow for molecularly-stratified clinical trials.

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基于DNA甲基化的脑膜瘤复发预测指标的验证和下一代更新:一项多中心前瞻性研究。
背景:我们之前开发了一种基于 DNA 甲基化的脑膜瘤风险预测模型,该模型自首次发表以来一直在当地以前瞻性的方式使用。作为后续研究,我们利用一个大型前瞻性队列验证了这一模型,并推出了一种与较新甲基化阵列兼容的简化下一代预测方法:方法:利用 Illumina EPICArray 生成全基因组甲基化图谱。方法:利用 Illumina EPICArray 生成了全基因组甲基化图谱,并利用时间依赖性接收器操作特征曲线将下一代预测因子的性能与我们的原始模型和 2021 WHO 分级标准进行了比较。通过将我们的甲基化预测因子与 WHO 分级和切除范围相结合,生成了一个提名图:研究共使用了 1347 例脑膜瘤病例,包括来自 3 家机构的 469 例前瞻性病例和用于模型验证的 100 例 WHO 2 级病例的外部队列。在预测术后早期复发方面,原始模型和新一代模型都明显优于2021 WHO分级。将患者二分为特定等级的风险亚组对WHO 1级和2级肿瘤的预后都有预测作用(p结论:这种基于DNA甲基化的新一代脑膜瘤预后预测方法在预测复发时间方面明显优于2021年的WHO分级。我们将其作为点选式工具提供,这将改善预后,为患者选择 RT 提供依据,并有助于进行分子分层临床试验。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Neuro-oncology
Neuro-oncology 医学-临床神经学
CiteScore
27.20
自引率
6.30%
发文量
1434
审稿时长
3-8 weeks
期刊介绍: Neuro-Oncology, the official journal of the Society for Neuro-Oncology, has been published monthly since January 2010. Affiliated with the Japan Society for Neuro-Oncology and the European Association of Neuro-Oncology, it is a global leader in the field. The journal is committed to swiftly disseminating high-quality information across all areas of neuro-oncology. It features peer-reviewed articles, reviews, symposia on various topics, abstracts from annual meetings, and updates from neuro-oncology societies worldwide.
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