Department for Nuclear Medicine, University Hospital of Cologne, Cologne, Germany.
J Nucl Med. 2011 Dec;52(12):1871-7. doi: 10.2967/jnumed.111.094458. Epub 2011 Nov 7.
The purpose of this study was to evaluate the relevance for the prediction of clinical benefit of first-line treatment with erlotinib using different quantitative parameters for PET with both (18)F-FDG and 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) in patients with advanced non-small cell lung cancer.
Data were used from a prospective trial involving patients with untreated stage IV non-small cell lung cancer. (18)F-FDG PET and (18)F-FLT PET were performed before and 1 (early) and 6 (late) weeks after erlotinib treatment. Several quantitative standardized uptake values (SUVs) using different definitions of volumes of interest with varying isocontours (maximum SUV [SUV(max)], 2-dimensional peak SUV [SUV(2Dpeak)], 3-dimensional [3D] peak SUV [SUV(3Dpeak)], 3D isocontour at 50% of the maximum pixel value [SUV(50)], 3D isocontour at 50% adapted for background [SUV(A50)], 3D isocontour at 41% of the maximum pixel value adapted for background [SUV(A41)], 3D isocontour at 70% of the maximum pixel value [SUV(70)], 3D isocontour at 70% adapted for background [SUV(A70)], and relative SUV threshold level [SUV(RTL)]) and metabolically active volume measurements were obtained in the hottest single tumor lesion and in the sum of up to 5 lesions per scan in 30 patients. Metabolic response was defined as a minimum reduction of 30% in each of the different SUVs and as a minimum reduction of 45% in metabolically active volume. Progression-free survival (PFS) was compared between patients with and without metabolic response measured with each of the different parameters, using Kaplan-Meier statistics and a log-rank test.
Patients with a metabolic response on early (18)F-FDG PET and (18)F-FLT PET in the hottest single tumor lesion as well as in the sum of up to 5 lesions per scan had a significantly longer PFS, regardless of the method used to calculate SUV. However, the highest significance was obtained for SUV(max), SUV(50), SUV(A50), and SUV(A41.) Patients with a metabolic response measured by SUV(max) and SUV(3Dpeak) on late (18)F-FDG PET in the hottest single tumor lesion had a significantly longer PFS. Furthermore, Kaplan-Meier analyses showed a strong association between PFS and response seen by metabolically active volume, measured either in early (18)F-FLT or in late (18)F-FDG.
Early (18)F-FDG PET and (18)F-FLT PET can predict PFS regardless of the method used for SUV calculation. However, SUV(max), SUV(50), SUV(A50), and SUV(A41) measured with (18)F-FDG might be the best robust SUV to use for early response prediction. Metabolically active volume measurement in early (18)F-FLT PET and late (18)F-FDG PET may have an additional predictive value in monitoring response in patients with advanced non-small cell lung cancer treated with erlotinib.
本研究旨在评估使用（18）F-FDG 和 3'-脱氧-3'-(18)F-氟胸苷（（18）F-FLT）正电子发射断层扫描（PET）不同定量参数对预测一线厄洛替尼治疗晚期非小细胞肺癌（NSCLC）患者的临床获益的相关性。
数据来自一项前瞻性试验，涉及未经治疗的 IV 期非小细胞肺癌患者。在厄洛替尼治疗前、1 周（早期）和 6 周（晚期）进行（18）F-FDG PET 和（18）F-FLT PET。使用不同感兴趣区（ROI）定义和不同等距线获得几种标准化摄取值（SUVs），包括最大 SUV（SUV(max)）、二维峰值 SUV（SUV(2Dpeak)）、三维峰值 SUV（SUV(3Dpeak)）、最大像素值的 50%等距线 SUV（SUV(50)）、适应背景的 50%最大像素值等距线 SUV（SUV(A50)）、适应背景的 41%最大像素值等距线 SUV（SUV(A41)）、最大像素值的 70%等距线 SUV（SUV(70)）、适应背景的 70%最大像素值等距线 SUV（SUV(A70)）和相对 SUV 阈值水平（SUV(RTL)））和代谢活跃体积测量值，在 30 名患者的单个肿瘤热区和最多 5 个肿瘤的总和中获得。代谢反应定义为每个不同 SUV 的最小减少 30%，以及代谢活跃体积的最小减少 45%。使用 Kaplan-Meier 统计学和对数秩检验比较有代谢反应和无代谢反应患者的无进展生存期（PFS）。
在单个肿瘤热区以及最多 5 个肿瘤的总和中，早期（18）F-FDG 和（18）F-FLT PET 上有代谢反应的患者无论使用哪种 SUV 计算方法，PFS 均显著延长。然而，SUV(max)、SUV(50)、SUV(A50)和 SUV(A41)的结果具有最高的统计学意义。在单个肿瘤热区中，晚期（18）F-FDG PET 上 SUV(max)和 SUV(3Dpeak)测量的代谢反应患者的 PFS 显著延长。此外，Kaplan-Meier 分析表明，代谢活跃体积的测量值（早期（18）F-FLT 或晚期（18）F-FDG）与 PFS 和代谢反应之间存在很强的相关性。
早期（18）F-FDG PET 和（18）F-FLT PET 可以预测 PFS，无论 SUV 计算方法如何。然而，SUV(max)、SUV(50)、SUV(A50)和 SUV(A41)可能是用于早期反应预测的最佳稳健 SUV。晚期（18）F-FDG PET 和早期（18）F-FLT PET 代谢活跃体积测量可能对监测接受厄洛替尼治疗的晚期非小细胞肺癌患者的反应具有额外的预测价值。
