Response assessment of bevacizumab in patients with recurrent malignant glioma using [18F]Fluoroethyl-l-tyrosine PET in comparison to MRI
Response assessment of bevacizumab in patients with recurrent malignant glioma using [18F]Fluoroethyl-l-tyrosine PET in comparison to MRI
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DOI：
10.1007/s00259-012-2251-4
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发表时间：
2013-01-01
影响因子：
9.1
通讯作者：
Langen, Karl-Josef
中科院分区：
文献类型：
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作者：
Galldiks, Norbert;Rapp, Marion;Langen, Karl-Josef
为了前瞻性研究O-（2-[F-18]fluoroethyl）-l-tyrosine（F-18-FET）PET与MRI相比在评估复发性高级别胶质瘤（rHGG）患者对抗血管生成治疗的反应中的潜力，10例rHGG患者每两周接受贝伐单抗/伊立替康（BEV/IR）治疗。在基线和治疗开始后随访时（中位数4.9周）获得MR图像和动态F-18-FET PET扫描。使用MRI，根据RANO（神经肿瘤学缓解评估）标准评价治疗缓解。对于F-18-FET PET评价，代谢活性肿瘤体积减少> 45%被认为是治疗反应，代谢活性肿瘤定义为肿瘤与脑的比率（TBR）为千分之一日元1.6。治疗评估结果与无进展生存期（PFS）和总生存期（OS）相关。为了进一步评价PET数据，在基线和随访时使用感兴趣区域分析计算最大和平均TBR。此外，在基线和随访时对所有患者进行F-18-FET摄取动力学研究。生成时间-活性曲线并计算峰值摄取时间（TTP）（从动态采集开始到最大摄取的分钟数）。在随访时，MRI显示10例患者中有1例（10%）完全缓解，5例（50%）部分缓解，4例（40%）疾病稳定。因此，MRI未检测到肿瘤进展。相比之下，F-18-FET PET显示6例代谢应答者（60%）和4例无应答者（40%）。在单变量生存分析中，F-18-FET PET检测到的缓解预测PFS（中位PFS，9个月vs. 3个月; P = 0.001）和OS（中位OS 23.0个月vs. 3.5个月; P = 0.001）显著延长。此外，在4例患者（40%）中，根据RANO标准和F-18-FET PET的诊断不一致。在这些患者中，PET能够比MRI更早地检测到肿瘤进展（中位时间获益10.5周;范围6-12周）。在基线和随访时，无应答者的TTP显著短于应答者（基线TTP 10 +/- 8 min vs. 35 +/- 9 min; P = 0.002;随访TTP 23 +/- 9 min vs. 39 +/- 8 min; P = 0.02）。此外，本发明还在基线时，在无应答者中更常见的动力学模式是F-18-FET摄取的早期峰值，随后持续下降（P = 0.018）。从（18）F-FET PET得到的标准和动力学成像参数似乎都能预测BEV/IR治疗失败，因此在MRI反应获得的信息之外，为临床管理提供了重要的额外信息根据RANO标准进行评估。
To investigate prospectively the potential of O-(2-[F-18]fluoroethyl)-l-tyrosine (F-18-FET) PET in comparison to MRI for the assessment of the response of patients with recurrent high-grade glioma (rHGG) to antiangiogenic treatment.Ten patients with rHGG were treated biweekly with bevacizumab/irinotecan (BEV/IR). MR images and dynamic F-18-FET PET scans were obtained at baseline and at follow-up after the start of treatment (median 4.9 weeks). Using MRI treatment response was evaluated according to RANO (Response Assessment in Neuro-Oncology) criteria. For F-18-FET PET evaluation, a reduction > 45 % of the metabolically active tumour volume was considered as a treatment response, with the metabolically active tumour being defined as a tumour-to-brain ratio (TBR) of a parts per thousand yen1.6. The results of the treatment assessments were related to progression-free survival (PFS) and overall survival (OS). For further evaluation of PET data, maximum and mean TBR were calculated using region-of-interest analysis at baseline and at follow-up. Additionally, F-18-FET uptake kinetic studies were performed at baseline and at follow-up in all patients. Time-activity curves were generated and the times to peak (TTP) uptake (in minutes from the beginning of the dynamic acquisition to the maximum uptake) were calculated.At follow-up, MRI showed a complete response according to RANO criteria in one of the ten patients (10 %), a partial response in five patients (50 %), and stable disease in four patients (40 %). Thus, MRI did not detect tumour progression. In contrast, F-18-FET PET revealed six metabolic responders (60 %) and four nonresponders (40 %). In the univariate survival analyses, a response detected by F-18-FET PET predicted a significantly longer PFS (median PFS, 9 vs. 3 months; P = 0.001) and OS (median OS 23.0 months vs. 3.5 months; P = 0.001). Furthermore, in four patients (40 %), diagnosis according to RANO criteria and by F-18-FET PET was discordant. In these patients, PET was able to detect tumour progression earlier than MRI (median time benefit 10.5 weeks; range 6-12 weeks). At baseline and at follow-up, in nonresponders TTP was significantly shorter than in responders (baseline TTP 10 +/- 8 min vs. 35 +/- 9 min; P = 0.002; follow-up TTP 23 +/- 9 min vs. 39 +/- 8 min; P = 0.02). Additionally, at baseline a kinetic pattern characterized by an early peak of F-18-FET uptake followed by a constant descent was more frequently observed in the nonresponders (P = 0.018).Both standard and kinetic imaging parameters derived from(18)F-FET PET seem to predict BEV/IR treatment failure and thus contribute important additional information for clinical management over and above the information obtained by MRI response assessment based on RANO criteria.