Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Clin Cancer Res. 2011 Oct 15;17(20):6553-62. doi: 10.1158/1078-0432.CCR-10-3290. Epub 2011 Aug 25.
The primary objective of this study was to investigate whether changes in 3'-deoxy-3'-[¹⁸F]fluorothymidine (¹⁸F-FLT) kinetic parameters, taken early after the start of therapy, could predict overall survival (OS) and progression-free survival (PFS) in patients with recurrent malignant glioma undergoing treatment with bevacizumab and irinotecan.
High-grade recurrent brain tumors were investigated in 18 patients (8 male and 10 female), ages 26 to 76 years. Each had 3 dynamic positron emission tomography (PET) studies as follows: at baseline and after 2 and 6 weeks from the start of treatment, ¹⁸F-FLT (2.0 MBq/kg) was injected intravenously, and dynamic PET images were acquired for 1 hour. Factor analysis generated factor images from which blood and tumor uptake curves were derived. A three-compartment, two-tissue model was applied to estimate tumor ¹⁸F-FLT kinetic rate constants using a metabolite- and partial volume-corrected input function. Different combinations of predictor variables were exhaustively searched in a discriminant function to accurately classify patients into their known OS and PFS groups. A leave-one-out cross-validation technique was used to assess the generalizability of the model predictions.
In this study population, changes in single parameters such as standardized uptake value or influx rate constant did not accurately classify patients into their respective OS groups (<1 and ≥ 1 year; hit ratios ≤ 78%). However, changes in a set of ¹⁸F-FLT kinetic parameters could perfectly separate these two groups of patients (hit ratio = 100%) and were also able to correctly classify patients into their respective PFS groups (<100 and ≥ 100 days; hit ratio = 88%).
Discriminant analysis using changes in ¹⁸F-FLT kinetic parameters early during treatment seems to be a powerful method for evaluating the efficacy of therapeutic regimens.
本研究的主要目的是探究在接受贝伐单抗和伊立替康治疗的复发性恶性胶质瘤患者中，治疗开始后早期 3'-去氧-3'-[¹⁸F]氟代胸苷（¹⁸F-FLT）动力学参数的变化是否可以预测总生存期（OS）和无进展生存期（PFS）。
对 18 名患者（8 名男性和 10 名女性）的高级别复发性脑肿瘤进行了研究，年龄为 26 至 76 岁。每位患者均进行了 3 次动态正电子发射断层扫描（PET）研究，如下所示：在基线以及治疗开始后 2 周和 6 周时，静脉注射 2.0 MBq/kg 的¹⁸F-FLT，并采集 1 小时的动态 PET 图像。因子分析从因子图像中生成了血池和肿瘤摄取曲线。应用三房室两组织模型，使用经代谢物和部分容积校正的输入函数来估计肿瘤¹⁸F-FLT 动力学速率常数。在判别函数中，对不同的预测变量组合进行了穷尽搜索，以准确地将患者分为已知的 OS 和 PFS 组。采用留一法交叉验证技术评估模型预测的泛化能力。
在本研究人群中，单个参数（如标准化摄取值或摄取速率常数）的变化并不能准确地将患者分为各自的 OS 组（<1 年和≥1 年；命中率≤78%）。然而，一组 ¹⁸F-FLT 动力学参数的变化可以完美地区分这两组患者（命中率=100%），并且还可以正确地将患者分为各自的 PFS 组（<100 天和≥100 天；命中率=88%）。
使用治疗开始后早期¹⁸F-FLT 动力学参数的变化进行判别分析，似乎是评估治疗方案疗效的有力方法。
