Department of Neurosurgery, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany.
Department of Nuclear Medicine, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany.
Eur J Nucl Med Mol Imaging. 2023 Feb;50(3):859-869. doi: 10.1007/s00259-022-06006-1. Epub 2022 Nov 4.
Glioma patients, especially recurrent glioma, suffer from a poor prognosis. While advances to classify glioma on a molecular level improved prognostication at initial diagnosis, markers to prognosticate survival in the recurrent situation are still needed. As 18 kDa translocator protein (TSPO) was previously reported to be associated with aggressive histopathological glioma features, we correlated the TSPO positron emission tomography (PET) signal using [F]GE180 in a large cohort of recurrent glioma patients with their clinical outcome.
In patients with [F]GE180 PET at glioma recurrence, [F]GE180 PET parameters (e.g., SUV) as well as other imaging features (e.g., MRI volume, [F]FET PET parameters when available) were evaluated together with patient characteristics (age, sex, Karnofsky-Performance score) and neuropathological features (e.g. WHO 2021 grade, IDH-mutation status). Uni- and multivariate Cox regression and Kaplan-Meier survival analyses were performed to identify prognostic factors for post-recurrence survival (PRS) and time to treatment failure (TTF).
Eighty-eight consecutive patients were evaluated. TSPO tracer uptake correlated with tumor grade at recurrence (p < 0.05), with no significant differences in IDH-wild-type versus IDH-mutant tumors. Within the subgroup of IDH-mutant glioma (n = 46), patients with low SUV (median split, ≤ 1.60) had a significantly longer PRS (median 41.6 vs. 25.3 months, p = 0.031) and TTF (32.2 vs 8.7 months, p = 0.001). Also among IDH-wild-type glioblastoma (n = 42), patients with low SUV (≤ 1.89) had a significantly longer PRS (median not reached vs 8.2 months, p = 0.002). SUV remained an independent prognostic factor for PRS in the multivariate analysis including CNS WHO 2021 grade, IDH status, and age. Tumor volume defined by [F]FET PET or contrast-enhanced MRI correlated weakly with TSPO tracer uptake. Treatment regimen did not differ among the median split subgroups.
Our data suggest that TSPO PET using [F]GE180 can help to prognosticate recurrent glioma patients even among homogeneous molecular subgroups and may therefore serve as valuable non-invasive biomarker for individualized patient management.
胶质瘤患者，尤其是复发性胶质瘤患者，预后较差。尽管在分子水平上对胶质瘤进行分类的进展提高了初始诊断的预后，但仍需要预测复发性情况下生存的标志物。由于 18 kDa 转位蛋白（TSPO）先前被报道与侵袭性组织病理学胶质瘤特征相关，我们在大量复发性胶质瘤患者中使用 [F]GE180 进行正电子发射断层扫描（PET）研究，将 TSPO 的 PET 信号与他们的临床结果相关联。
在有 [F]GE180 PET 检测的复发性胶质瘤患者中，评估 [F]GE180 PET 参数（如 SUV）以及其他成像特征（如 MRI 体积，有 [F]FET PET 参数时），并与患者特征（年龄、性别、卡诺夫斯基-佩尔菲姆评分）和神经病理学特征（如 2021 年世界卫生组织 [WHO] 分级、异柠檬酸脱氢酶 [IDH] 突变状态）相关联。使用单变量和多变量 Cox 回归以及 Kaplan-Meier 生存分析来确定与复发性后生存（PRS）和治疗失败时间（TTF）相关的预后因素。
对 88 例连续患者进行了评估。TSPO 示踪剂摄取与复发时的肿瘤分级相关（p<0.05），IDH 野生型与 IDH 突变型肿瘤之间无显著差异。在 IDH 突变型胶质瘤亚组（n=46）中，SUV 较低（中位数分割，≤1.60）的患者具有显著更长的 PRS（中位数 41.6 与 25.3 个月，p=0.031）和 TTF（32.2 与 8.7 个月，p=0.001）。在 IDH 野生型胶质母细胞瘤（n=42）中，SUV 较低（≤1.89）的患者也具有显著更长的 PRS（中位数未达到与 8.2 个月，p=0.002）。SUV 在包括中枢神经系统 [CNS] WHO 2021 分级、IDH 状态和年龄在内的多变量分析中仍然是 PRS 的独立预后因素。[F]FET PET 或对比增强 MRI 定义的肿瘤体积与 TSPO 示踪剂摄取弱相关。治疗方案在中位数分割亚组之间没有差异。
我们的数据表明，使用 [F]GE180 的 TSPO PET 甚至可以帮助预测同质分子亚组中的复发性胶质瘤患者，因此可能成为个体化患者管理的有价值的非侵入性生物标志物。
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