Choudhury Kingshuk Roy, Keir Stephen T, Ashcraft Kathleen A, Boss Mary-Keara, Dewhirst Mark W
Department of Biostatistics and Bioinformatics, Duke University Medical Center, NC, USA.
Preston Robert Tisch Brain Tumor Research Center, Duke University Medical Center, NC, USA.
Oncotarget. 2015 Jun 10;6(16):14656-68. doi: 10.18632/oncotarget.4141.
We present a method for estimating the empirical dynamic treatment effect (DTE) curves from tumor growth delay (TGD) studies. This improves on current common methods of TGD analysis, such as T/C ratio and doubling times, by providing a more detailed treatment effect and overcomes their lack of reproducibility. The methodology doesn't presuppose any prior form for the treatment effect dynamics and is shown to give consistent estimates with missing data. The method is illustrated by application to real data from TGD studies involving three types of therapy. Firstly, we demonstrate that radiotherapy induces a sharp peak in inhibition in a FaDu model. The height, duration and timing of the peak increase linearly with radiation dose. Second, we demonstrate that a combination of temozolomide and an experimental therapy in a glioma PDX model yields an effect, similar to an additive version of the DTE curves for the mono-therapies, except that there is a 30 day delay in peak inhibition. In the third study, we consider the DTE of anti-angiogenic therapy in glioma. We show that resulting DTE curves are flat. We discuss how features of the DTE curves should be interpreted and potentially used to improve therapy.
我们提出了一种从肿瘤生长延迟（TGD）研究中估计经验性动态治疗效果（DTE）曲线的方法。通过提供更详细的治疗效果，该方法改进了当前常用的TGD分析方法，如T/C比值和倍增时间，并克服了它们缺乏可重复性的问题。该方法不预先假定治疗效果动态的任何先验形式，并且在存在缺失数据的情况下也能给出一致的估计。通过应用于涉及三种治疗类型的TGD研究的真实数据来说明该方法。首先，我们证明放疗在FaDu模型中诱导出抑制的尖锐峰值。峰值的高度、持续时间和时间随辐射剂量线性增加。其次，我们证明在胶质瘤PDX模型中替莫唑胺与一种实验性治疗的联合产生的效果，类似于单药治疗DTE曲线的相加版本，只是峰值抑制延迟了30天。在第三个研究中，我们考虑抗血管生成治疗在胶质瘤中的DTE。我们表明所得的DTE曲线是平坦的。我们讨论了DTE曲线的特征应如何解释以及潜在地用于改善治疗。
