Reproducibility and changes in the apparent diffusion coefficients of solid tumours treated with combretastatin A4 phosphate and bevacizumab in a two-centre phase I clinical trial
Reproducibility and changes in the apparent diffusion coefficients of solid tumours treated with combretastatin A4 phosphate and bevacizumab in a two-centre phase I clinical trial
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DOI：
10.1007/s00330-009-1469-4
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发表时间：
2009-11-01
影响因子：
5.9
通讯作者：
Nathan, Paul
中科院分区：
文献类型：
--
作者：
Koh, Dow-Mu;Blackledge, Matthew;Nathan, Paul
其目的是确定在两个中心的I期临床试验中表观扩散系数（ADC）测量的重现性;并跟踪血管破坏剂考布他汀A4磷酸盐（CA 4P）和抗血管生成药物贝伐单抗顺序给药后ADC的变化。16例实体瘤患者接受了CA 4P和贝伐单抗治疗。使用6个B值（B = 0-750 s/mm（2））进行回波平面扩散加权MRI（x2），并在第一剂CA 4 P后3和72 h进行。在第二剂CA 4P后4小时给予贝伐单抗，并在CA 4P后3小时和贝伐单抗治疗后72小时进行成像。通过Bland-Altman分析计算总ADC值（所有B值）、高ADC值（B = 100-750）和低ADC值（B = 0-100）的重复性系数（r）。总ADC和高ADC显示出良好的测量再现性（r% = 13.3，14.1）。灌注敏感性ADC值低（r% = 62.5），重复性差。在CA 4P的第二剂量后3小时，中位ADC总量和ADC高值发生显著增加（p < 0.05）。ADC测量在双中心临床试验环境中具有高度可重复性，并且似乎有希望用于评估靶向肿瘤血管系统的药物的作用。
The purpose was to determine the reproducibility of apparent diffusion coefficient (ADC) measurements in a two-centre phase I clinical trial; and to track ADC changes in response to the sequential administration of the vascular disrupting agent, combretastatin A4 phosphate (CA4P), and the anti-angiogenic drug, bevacizumab. Sixteen patients with solid tumours received CA4P and bevacizumab treatment. Echo-planar diffusion-weighted MRI was performed using six b values (b = 0-750 s/mm(2)) before (x2), and at 3 and 72 h after a first dose of CA4P. Bevacizumab was given 4 h after a second dose of CA4P, and imaging performed 3 h post CA4P and 72 h after bevacizumab treatment. The coefficient of repeatability (r) of ADC total (all b values), ADC high (b = 100-750) and ADC low (b = 0-100) was calculated by Bland-Altman analysis. The ADC total and ADC high showed good measurement reproducibility (r% = 13.3, 14.1). There was poor reproducibility of the perfusion-sensitive ADC low (r% = 62.5). Significant increases in the median ADC total and ADC high occurred at 3 h after the second dose of CA4P (p < 0.05). ADC measurements were highly reproducible in a two-centre clinical trial setting and appear promising for evaluating the effects of drugs that target tumour vasculature.