Department of Neurosurgery, Huashan Hospital, Fudan University, 12# Mid Wulumuqi Road, Shanghai, China.
Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, 6# Tiantanxili, Beijing, China.
J Neurooncol. 2018 Dec;140(3):591-603. doi: 10.1007/s11060-018-2985-3. Epub 2018 Sep 11.
Maximal surgical resection is associated with survival benefit in the majority of studies in adult diffuse glioma. This study aims to characterize the prognostic value of surgical resection in molecular subgroups of diffuse glioma.
1178 patients with diffuse glioma from our centers and 422 from TCGA dataset were collected. The Kaplan-Meier analysis and multivariable Cox regression models were conducted to identify the prognostic value of surgical resection through different histological and molecular stratifications.
Firstly, we confirmed progression-free survival (PFS) benefit associated with gross total resection (GTR) over sub-total resection (STR) in lower-grade glioma (HR 1.49; 95% CI 1.17-1.90; P = 0.001). Intriguingly however, we were unable to detect a significant PFS or overall survival (OS) benefit in oligodendroglioma (N = 397; HR 1.36; 95% CI 0.86-2.14; P = 0.19 and HR 1.05; 95% CI 0.55-1.99; P = 0.89, respectively). Secondly, when analyzed in molecular subgroups, we were similarly unable to detect a significant PFS or OS benefit in IDH MT/codel subgroup (N = 269; HR 1.47; 95% CI 0.92-2.34; P = 0.11 and HR 1.54; 95% CI 0.78-3.05; P = 0.21, respectively), oligodendroglioma with IDH MT/codel subgroup (N = 233; HR 1.33; 95% CI 0.79-2.21; P = 0.28 and HR 1.16; 95% CI 0.53-2.54; P = 0.70, respectively) or other relevant subgroups. TCGA validation also showed a significant survival benefit in astrocytoma rather than oligodendroglioma. Exploratory RNAseq analysis displayed that fewer cell proliferation-related gene expression features were specific to oligodendroglioma.
These results suggest that the benefit of maximal surgery may be attenuated in patients within oligodendroglioma relevant subgroups because of the chemosensitive and indolent nature. The aggressive surgery accompanying with risk of neurologic morbidity may be unnecessary for these patients given the lack of survival benefit with gross total resection.
最大程度的手术切除与大多数成人弥漫性神经胶质瘤的研究中的生存获益相关。本研究旨在研究手术切除在弥漫性神经胶质瘤的分子亚群中的预后价值。
收集了来自我们中心的 1178 名弥漫性神经胶质瘤患者和来自 TCGA 数据集的 422 名患者。通过不同的组织学和分子分层,使用 Kaplan-Meier 分析和多变量 Cox 回归模型来确定手术切除的预后价值。
首先,我们证实低级别神经胶质瘤中全切除(GTR)与次全切除(STR)相比无进展生存期(PFS)获益(HR 1.49;95%CI 1.17-1.90;P=0.001)。然而,令人好奇的是,我们未能在少突胶质细胞瘤(N=397;HR 1.36;95%CI 0.86-2.14;P=0.19 和 HR 1.05;95%CI 0.55-1.99;P=0.89)中检测到明显的 PFS 或总生存期(OS)获益。其次,当在分子亚组中进行分析时,我们同样未能在 IDH MT/共缺失亚组(N=269;HR 1.47;95%CI 0.92-2.34;P=0.11 和 HR 1.54;95%CI 0.78-3.05;P=0.21)、具有 IDH MT/共缺失亚组的少突胶质细胞瘤(N=233;HR 1.33;95%CI 0.79-2.21;P=0.28 和 HR 1.16;95%CI 0.53-2.54;P=0.70)或其他相关亚组中检测到明显的 PFS 或 OS 获益。TCGA 验证也显示在星形细胞瘤中而不是少突胶质细胞瘤中存在显著的生存获益。探索性 RNAseq 分析显示,与少突胶质细胞瘤相关的基因表达特征中,更少的细胞增殖相关基因表达特征是特异性的。
这些结果表明,由于化疗敏感性和惰性,在少突胶质细胞瘤相关亚组中的患者中,最大限度手术的获益可能会减弱。由于缺乏全切除的生存获益,对于这些患者来说,伴随神经功能障碍风险的积极手术可能是不必要的。