Treatment of the tumor and dural margin with surgery and sometimes radiation are cornerstones of therapy for meningioma. Molecular classifications have provided insights into the biology of disease; however, response to treatment remains heterogeneous. In this study, we used retrospective data on 2,824 meningiomas, including molecular data on 1,686 tumors and 100 prospective meningiomas, from the RTOG-0539 phase 2 trial to define molecular biomarkers of treatment response. Using propensity score matching, we found that gross tumor resection was associated with longer progression-free survival (PFS) across all molecular groups and longer overall survival in proliferative meningiomas. Dural margin treatment (Simpson grade 1/2) prolonged PFS compared to no treatment (Simpson grade 3). Molecular group classification predicted response to radiotherapy, including in the RTOG-0539 cohort. We subsequently developed a molecular model to predict response to radiotherapy that discriminates outcome better than standard-of-care classification. This study highlights the potential for molecular profiling to refine surgical and radiotherapy decision-making.

通过手术和有时放疗治疗肿瘤和硬脑膜边缘是脑膜瘤治疗的基础。分子分类为疾病生物学提供了见解;然而，对治疗的反应仍然存在异质性。在这项研究中，我们使用了来自 RTOG-0539 2 期试验的 2,824 例脑膜瘤的回顾性数据，包括 1,686 例肿瘤和 100 例前瞻性脑膜瘤的分子数据，以确定治疗反应的分子生物标志物。使用倾向评分匹配，我们发现大体肿瘤切除与所有分子组的较长无进展生存期 （PFS） 和增殖性脑膜瘤的总生存期较长相关。与不治疗（Simpson 3 级）相比，硬脑膜切缘治疗（Simpson 1/2 级）延长了 PFS。分子组分类预测了对放疗的反应，包括 RTOG-0539 队列。我们随后开发了一个分子模型来预测对放疗的反应，该模型比标准护理分类更能区分结果。这项研究强调了分子分析在改进手术和放疗决策方面的潜力。