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在接受贝伐单抗联合洛莫司汀治疗的胶质母细胞瘤患者首次进展时,使用 FET PET 与 MRI 进行早期治疗反应评估。

Early treatment response evaluation using FET PET compared to MRI in glioblastoma patients at first progression treated with bevacizumab plus lomustine.

机构信息

Department of Neurology, University Hospital Cologne, Josef-Stelzmann St. 9, 50937, Cologne, Germany.

Institute of Neuroscience and Medicine (INM-3, -4), Forschungszentrum Juelich, Leo-Brandt-St. 5, 52425, Juelich, Germany.

出版信息

Eur J Nucl Med Mol Imaging. 2018 Dec;45(13):2377-2386. doi: 10.1007/s00259-018-4082-4. Epub 2018 Jul 7.

Abstract

BACKGROUND

The goal of this prospective study was to compare the value of both conventional MRI and O-(2-F-fluoroethyl)-L-tyrosine (FET) PET for response evaluation in glioblastoma patients treated with bevacizumab plus lomustine (BEV/LOM) at first progression.

METHODS

After chemoradiation with concomitant and adjuvant temozolomide, 21 IDH wild-type glioblastoma patients at first progression (age range, 33-75 years; MGMT promoter unmethylated, 81%) were treated with BEV/LOM. Contrast-enhanced MRI and FET-PET scans were performed at baseline and after 8-10 weeks. We obtained FET metabolic tumor volumes (MTV) and tumor/brain ratios. Threshold values of FET-PET parameters for treatment response were established by ROC analyses using the post-progression overall survival (OS) ≤/>9 months as the reference. MRI response assessment was based on RANO criteria. The predictive ability of FET-PET thresholds and MRI changes on early response assessment was evaluated subsequently concerning OS using uni- and multivariate survival estimates.

RESULTS

Early treatment response as assessed by RANO criteria was not predictive for an OS>9 months (P = 0.203), whereas relative reductions of all FET-PET parameters significantly predicted an OS>9 months (P < 0.05). The absolute MTV at follow-up enabled the most significant OS prediction (sensitivity, 85%; specificity, 88%; P = 0.001). Patients with an absolute MTV below 5 ml at follow-up survived significantly longer (12 vs. 6 months, P < 0.001), whereas early responders defined by RANO criteria lived only insignificantly longer (9 vs. 6 months; P = 0.072). The absolute MTV at follow-up remained significant in the multivariate survival analysis (P = 0.006).

CONCLUSIONS

FET-PET appears to be useful for identifying responders to BEV/LOM early after treatment initiation.

摘要

背景

本前瞻性研究旨在比较常规 MRI 和 O-(2-氟乙基)-L-酪氨酸(FET)PET 在贝伐珠单抗联合洛莫司汀(BEV/LOM)治疗首次进展的胶质母细胞瘤患者中的应用价值。

方法

在接受同步和辅助替莫唑胺放化疗后,21 例 IDH 野生型胶质母细胞瘤患者(年龄 33-75 岁;MGMT 启动子未甲基化,81%)在首次进展时接受 BEV/LOM 治疗。在基线和 8-10 周后进行对比增强 MRI 和 FET-PET 扫描。我们获得 FET 代谢肿瘤体积(MTV)和肿瘤/脑比值。通过使用无进展生存期(OS)>9 个月和≤9 个月作为参考的 ROC 分析,确定 FET-PET 参数的治疗反应阈值。MRI 反应评估基于 RANO 标准。随后,使用单变量和多变量生存估计,根据 OS 评估 FET-PET 阈值和 MRI 变化对早期反应评估的预测能力。

结果

根据 RANO 标准评估的早期治疗反应与 OS>9 个月无关(P=0.203),而所有 FET-PET 参数的相对减少均显著预测 OS>9 个月(P<0.05)。随访时的绝对 MTV 能最显著地预测 OS(敏感性为 85%,特异性为 88%,P=0.001)。随访时 MTV 绝对值<5ml 的患者的生存时间明显更长(12 个月 vs. 6 个月,P<0.001),而根据 RANO 标准定义的早期反应者的生存时间仅稍长(9 个月 vs. 6 个月,P=0.072)。在多变量生存分析中,随访时的 MTV 绝对值仍具有显著性(P=0.006)。

结论

FET-PET 似乎可用于在 BEV/LOM 治疗开始后早期识别对治疗有反应的患者。

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