Background Meningiomas are the most common primary intracranial tumor in adults. Clinical care is currently guided by the World Health Organization (WHO) grade assigned to meningiomas, a 3-tiered grading system based on histopathology features, as well as extent of surgical resection. Clinical behavior, however, often fails to conform to the WHO grade. Additional prognostic information is needed to optimize patient management. Methods We evaluated whether chromosomal copy-number data improved prediction of time-to-recurrence for patients with meningioma who were treated with surgery, relative to the WHO schema. The models were developed using Cox proportional hazards, random survival forest, and gradient boosting in a discovery cohort of 527 meningioma patients and validated in 2 independent cohorts of 172 meningioma patients characterized by orthogonal genomic platforms. Results We developed a 3-tiered grading scheme (Integrated Grades 1-3), which incorporated mitotic count and loss of chromosome 1p, 3p, 4, 6, 10, 14q, 18, 19, or CDKN2A. 32% of meningiomas reclassified to either a lower-risk or higher-risk Integrated Grade compared to their assigned WHO grade. The Integrated Grade more accurately identified meningioma patients at risk for recurrence, relative to the WHO grade, as determined by time-dependent area under the curve, average precision, and the Brier score. Conclusion We propose a molecularly integrated grading scheme for meningiomas that significantly improves upon the current WHO grading system in prediction of progression-free survival. This framework can be broadly adopted by clinicians with relative ease using widely available genomic technologies and presents an advance in the care of meningioma patients.

中文翻译：

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脑膜瘤的分子整合等级

背景 脑膜瘤是成人中最常见的原发性颅内肿瘤。目前，临床护理由分配给脑膜瘤的世界卫生组织 (WHO) 分级指导，这是一种基于组织病理学特征以及手术切除范围的 3 级分级系统。然而，临床行为通常不符合 WHO 等级。需要额外的预后信息来优化患者管理。方法 我们评估了相对于 WHO 模式，染色体拷贝数数据是否改善了对接受手术治疗的脑膜瘤患者的复发时间的预测。这些模型是使用 Cox 比例风险、随机生存森林、和梯度提升在 527 名脑膜瘤患者的发现队列中进行，并在 2 个独立的 172 名脑膜瘤患者队列中进行了验证，这些队列具有正交基因组平台特征。结果 我们开发了一个 3 级分级方案（综合等级 1-3），其中包括有丝分裂计数和染色体 1p、3p、4、6、10、14q、18、19 或 CDKN2A 的丢失。与指定的 WHO 等级相比，32% 的脑膜瘤被重新分类为风险较低或风险较高的综合等级。相对于 WHO 等级，综合等级更准确地识别出有复发风险的脑膜瘤患者，这是由时间依赖性曲线下面积、平均精度和 Brier 评分确定的。结论 我们提出了一种脑膜瘤分子综合分级方案，该方案显着改进了当前 WHO 分级系统预测无进展生存期的能力。使用广泛可用的基因组技术，临床医生可以相对轻松地广泛采用该框架，并在脑膜瘤患者的护理方面取得进步。