PURPOSE Integrated histomolecular diagnostics of gliomas according to the World Health Organization (WHO) classification of 2016 has refined diagnostic accuracy and prediction of prognosis. This study aimed at exploring the prognostic value of dynamic O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) PET in newly diagnosed, histomolecularly classified astrocytic gliomas of WHO grades III or IV. METHODS Before initiation of treatment, dynamic FET PET imaging was performed in patients with newly diagnosed glioblastoma (GBM) and anaplastic astrocytoma (AA). Static FET PET parameters such as maximum and mean tumour/brain ratios (TBRmax/mean), the metabolic tumour volume (MTV) as well as the dynamic FET PET parameters time-to-peak (TTP) and slope, were obtained. The predictive ability of FET PET parameters was evaluated concerning the progression-free and overall survival (PFS, OS). Using ROC analyses, threshold values for FET PET parameters were obtained. Subsequently, univariate Kaplan-Meier and multivariate Cox regression survival analyses were performed to assess the predictive power of these parameters for survival. RESULTS Sixty patients (45 GBM and 15 AA patients) of two university centres were retrospectively identified. Patients with isocitrate dehydrogenase (IDH)-mutant or O6-methylguanine-DNA-methyltransferase (MGMT) promoter-methylated tumours had a significantly longer PFS and OS (both P < 0.001). Furthermore, ROC analysis of IDH-wildtype glioma patients (n = 45) revealed that a TTP > 25 min (AUC, 0.90; sensitivity, 90%; specificity, 87%; P < 0.001) was highly prognostic for longer PFS (13 vs. 7 months; P = 0.005) and OS (29 vs. 12 months; P < 0.001). In contrast, at a lower level of significance, TBRmax, TBRmean, and MTV were only prognostic for longer OS (P = 0.004, P = 0.038, and P = 0.048, respectively). Besides complete resection and a methylated MGMT promoter, TTP remained significant in multivariate survival analysis (all P ≤ 0.02), indicating an independent predictor for OS. CONCLUSIONS Our data suggest that dynamic FET PET allows the identification of patients with longer OS among patients with newly diagnosed IDH-wildtype GBM and AA.

中文翻译：

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使用动态O-（2- [18F]-氟乙基）-L-酪氨酸PET预测IDH野生型星形细胞胶质瘤患者的生存。

目的根据2016年世界卫生组织（WHO）分类对神经胶质瘤进行组织分子诊断，具有更高的诊断准确性和预后预测。这项研究旨在探讨动态O-（2- [18F]-氟乙基）-L-酪氨酸（FET）PET在WHOⅢ级或Ⅳ级新诊断，组织分类的星形胶质瘤中的预后价值。方法在开始治疗之前，对新诊断为胶质母细胞瘤（GBM）和间变性星形细胞瘤（AA）的患者进行动态FET PET成像。获得了静态FET PET参数，例如最大和平均肿瘤/脑比（TBRmax /平均值），代谢肿瘤体积（MTV）以及动态FET PET参数峰时（TTP）和斜率。评估了FET PET参数关于无进展生存期和总体生存期（PFS，OS）的预测能力。使用ROC分析，获得FET PET参数的阈值。随后，进行了单变量Kaplan-Meier和多元Cox回归生存分析，以评估这些参数对生存的预测能力。结果回顾性鉴定了两个大学中心的60例患者（45 GBM和15例AA患者）。患有异柠檬酸脱氢酶（IDH）突变或O6-甲基鸟嘌呤-DNA-甲基转移酶（MGMT）启动子-甲基化的患者的PFS和OS明显更长（均P <0.001）。此外，对IDH野生型神经胶质瘤患者（n = 45）的ROC分析显示，TTP> 25分钟（AUC，0.90;敏感性，90％;特异性，87％; P <0。001）对更长的PFS（13 vs. 7个月； P = 0.005）和OS（29 vs. 12个月； P <0.001）有较高的预后。相反，在较低的显着性水平下，TBRmax，TBRmean和MTV仅对较长的OS有预后性（分别为P = 0.004，P = 0.038和P = 0.048）。除了完全切除和甲基化的MGMT启动子外，TTP在多变量生存分析中仍然很重要（所有P≤0.02），表明OS的独立预测因子。结论我们的数据表明，动态FET PET可以识别新诊断为IDH野生型GBM和AA的患者中OS较长的患者。除了完全切除和甲基化的MGMT启动子外，TTP在多变量生存分析中仍然很重要（所有P≤0.02），表明OS的独立预测因子。结论我们的数据表明，动态FET PET可以识别新诊断为IDH野生型GBM和AA的患者中OS较长的患者。除了完全切除和甲基化的MGMT启动子外，TTP在多变量生存分析中仍然很重要（所有P≤0.02），表明OS的独立预测因子。结论我们的数据表明，动态FET PET可以识别新诊断为IDH野生型GBM和AA的患者中OS较长的患者。