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.
Eur J Nucl Med Mol Imaging. 2018 Dec;45(13):2377-2386. doi: 10.1007/s00259-018-4082-4. Epub 2018 Jul 7.
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.
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.
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).
FET-PET appears to be useful for identifying responders to BEV/LOM early after treatment initiation.
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。
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。
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)。
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。