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F-FET-PET 作为化疗后非增强性脑胶质瘤治疗反应的生物标志物。

F-FET-PET as a biomarker for therapy response in non-contrast enhancing glioma following chemotherapy.

机构信息

Department of Neurosurgery, Ludwig-Maximilians University, University Hospital Munich, Marchioninistr. 15, 81377, Munich, Germany.

German Cancer Consortium (DKTK), Partner Site Munich, German Cancer Research Center (DKFZ), Heidelberg, Germany.

出版信息

J Neurooncol. 2018 Sep;139(3):721-730. doi: 10.1007/s11060-018-2919-0. Epub 2018 Jun 8.

Abstract

BACKGROUND

Monitoring treatment response after chemotherapy of gadolinium-(Gd)-negative gliomas is challenging as conventional MRI often indicates no radiological changes. We hypothesize that F-FET-PET can be used as a biomarker for response assessment in Gd-negative gliomas undergoing chemotherapy.

METHODS

Sixty-one patients harboring Gd-negative WHO grade II or III glioma receiving alkylating agents (temozolomide or CCNU/procarbacine) were included. All patients underwent MRI and F-FET-PET before chemotherapy and 6 months later. We calculated T-volume, F-FET-PET based biological tumour volume (BTV) and maximal tumour-to-brain ratio (TBR). Moreover, dynamic PET acquisition was performed using time-activity-curves (TACs) analysis. For MRI-based response assessment, RANO criteria for low-grade glioma were used. For F-FET-PET, following classification scheme was tested: responsive disease (RD) when a decrease in either BTV ≥ 25% and/or TBR ≥ 10% occurred, an increase in BTV ≥ 25% and/or TBR increase > 10% characterized progressive disease (PD), minor changes ± 25% for BTV and ± 10% for TBR were regarded as stable disease (SD). Post-chemotherapy survival (PCS) and time-to-treatment failure (TTF) were calculated using the Kaplan-Meier method.

RESULTS

F-FET-PET based response has shown patients with RD to have the longest TTF time (78.5 vs 24.6 vs 24.1 months, p = 0.001), while there was no significant difference between patients with a SD and PD. A comparable pattern was observed for PCS (p < 0.001). T-volume based assessment was not associated with outcome.

CONCLUSION

F-FET-PET is a promising biomarker for early response assessment in Gd-negative gliomas undergoing chemotherapy. It might be helpful for a timely adjustment of potentially ineffective treatment concepts and overcomes limitations of conventional structural imaging.

摘要

背景

在接受化疗的钆(Gd)阴性胶质瘤患者中,监测治疗反应具有挑战性,因为常规 MRI 通常显示没有影像学变化。我们假设 F-FET-PET 可以用作化疗后 Gd 阴性胶质瘤反应评估的生物标志物。

方法

纳入 61 例 Gd 阴性 WHO 2 级或 3 级胶质瘤患者,接受烷化剂(替莫唑胺或卡莫司汀/洛莫司汀)治疗。所有患者在化疗前和 6 个月后均接受 MRI 和 F-FET-PET 检查。我们计算了 T 体积、基于 F-FET-PET 的肿瘤生物学体积(BTV)和最大肿瘤与脑比(TBR)。此外,还通过时间-活性曲线(TAC)分析进行了动态 PET 采集。对于 MRI 基于的反应评估,使用低级别胶质瘤的 RANO 标准。对于 F-FET-PET,测试了以下分类方案:当 BTV 减少≥25%和/或 TBR 增加≥10%时,称为反应性疾病(RD);当 BTV 增加≥25%和/或 TBR 增加>10%时,称为进行性疾病(PD);BTV 和 TBR 的变化分别为±25%和±10%,则认为是稳定疾病(SD)。使用 Kaplan-Meier 方法计算化疗后生存(PCS)和治疗失败时间(TTF)。

结果

F-FET-PET 基于的反应表明,RD 患者的 TTF 时间最长(78.5 个月 vs 24.6 个月 vs 24.1 个月,p=0.001),而 SD 和 PD 患者之间无显着差异。PCS 也观察到类似的模式(p<0.001)。基于 T 体积的评估与结果无关。

结论

F-FET-PET 是 Gd 阴性胶质瘤化疗后早期反应评估的有前途的生物标志物。它可能有助于及时调整潜在无效的治疗概念,并克服常规结构成像的局限性。

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