BACKGROUND In the molecular era, the relevance of tumor grade for prognostication of IDH1/2-wildtype (WT) gliomas has been debated. It has been suggested that histologic grade II and III astrocytomas with molecular features of glioblastoma, IDH1/2-WT have a similar prognosis to glioblastoma and should be considered for the same clinical trials. METHODS We integrated prospective clinical sequencing from 564 patients with IDH1/2-WT gliomas (26 grade II, 71 grade III and 467 grade IV) with clinical and radiographic data to assess associations between molecular features, grade and outcome. RESULTS Compared to histologic grade IV IDH1/2-WT astrocytomas, histologic grade II astrocytomas harbor fewer chromosome 7/10 alterations (P = 0.04), EGFR amplifications (P = 0.022) and alterations in cell-cycle effectors (P = 1.9e-11), but a similar frequency of TERT promoter mutations. In contrast, there is no difference in the frequency of these canonical molecular features in histologic grade III vs. IV IDH1/2-WT disease. Progression-free (PFS) and overall survival (OS) for histologic grade II tumors were significantly longer than grade III tumors (P = 0.02 and P = 0.008, respectively), whereas there was no difference in PFS and OS for histologic grade III compared to grade IV tumors. Median PFS for histologic grade II, III and IV tumors was 19, 11 and 9 months, respectively. Median OS for the same tumors was 44, 23 and 23 months, respectively. In histologic grade II and III IDH1/2 WT tumors, gliomatosis is associated with the absence of cell-cycle alterations (P = 0.008) and enriched in grade II features (P = 0.1) and alterations in the PI3K-AKT pathway (P = 0.09). CONCLUSIONS Grade II histology has genotypic and phenotypic associations with prognostic implications in IDH1/2-WT astrocytomas.

中文翻译：

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IDH1 / 2野生型星形细胞瘤的前瞻性收集分子概况队列的预后和影像学相关性。

背景技术在分子时代，关于肿瘤分级与IDH1 / 2野生型（WT）神经胶质瘤的预后相关性存在争议。有人提出，具有胶质母细胞瘤分子特征的组织学II级和III级星形细胞瘤IDH1 / 2-WT的预后与胶质母细胞瘤相似，应考虑用于相同的临床试验。方法我们将564例IDH1 / 2-WT胶质瘤患者（26例II级，71例III级和467例IV级）的前瞻性临床测序与临床和影像学数据相结合，以评估分子特征，级别和结果之间的关联。结果与组织学IV级IDH1 / 2-WT星形细胞瘤相比，组织学II级星形细胞瘤具有较少的染色体7/10改变（P = 0.04），EGFR扩增（P = 0.022）和细胞周期效应子改变（P = 1.9e- 11），但TERT启动子突变的频率相似。相反，在组织学III级和IV级IDH1 / 2-WT疾病中，这些规范分子特征的频率没有差异。组织学II级肿瘤的无进展（PFS）和总生存期（OS）明显长于III级肿瘤（分别为P = 0.02和P = 0.008），而组织学III级肿瘤的PFS和OS没有差异达到IV级肿瘤。组织学II，III和IV级肿瘤的中位PFS分别为19、11和9个月。相同肿瘤的中位OS分别为44、23和23个月。在组织学II级和III级IDH1 / 2 WT肿瘤中，胶质瘤病与缺乏细胞周期改变（P = 0.008）和II级特征（P = 0.1）以及PI3K-AKT途径的改变（P = 0.09）。