Departement d'Oncologie Medicale, Hopital Europeen Georges Pompidou, AP-HP, 20, rue Leblanc, 75015, Paris, France.
Contemp Clin Trials. 2012 Jan;33(1):178-83. doi: 10.1016/j.cct.2011.09.010. Epub 2011 Oct 1.
Analysis of preclinical studies using human tumors xenografted into rodents is commonly performed with Tumor Growth Index (TGI) and Tumor Growth Delay index (TGDi). To circumvent the limitations of these parameters, two new parameters, Time To Relapse (TTR) and Tumor Growth Speed (TGS), were developed using a mathematical modeling approach based on an exponential tumor growth. TTR is similar to progression free survival used in human clinical trials and TGS characterizes the pattern of tumor cell proliferation. Parameters were estimated for each rodent by the maximum likelihood method and statistical analyses were performed using ANOVA. These criteria can be used when tumor growths are assessed by repeated measures of their volume. As an example, we used data from a previously published study, which aimed to evaluate the relationship between histology, genetic parameters, and response to alkylating agents in a series of twelve gliomas. The group treated with temozolomide was reanalyzed using our criteria. This group presented a significantly longer TTR than the control group. TTR was also different according to tumor type: oligodendrogliomas relapsed later than glioblastomas. The TGS was different according to the tumor type. Loss of heterozygosity (LOH) 1p ± 19q, LOH 10p ± 10q, telomerase activity, PTEN mutation, and EGFR amplification were related to temozolomide efficacy. Our criteria provide additional information to those given by TGI and TGDi. Due to statistical properties of TTR and TGS, some relations between the parameters such as tumor type or genetic alterations can be studied with TTR and TGS and not with TGI or TGDi.
使用异种移植入啮齿动物的人类肿瘤进行临床前研究的分析通常使用肿瘤生长指数（TGI）和肿瘤生长延迟指数（TGDi）进行。为了规避这些参数的局限性，我们采用基于指数肿瘤生长的数学建模方法开发了两个新的参数，即复发时间（TTR）和肿瘤生长速度（TGS）。TTR 类似于人类临床试验中使用的无进展生存期，而 TGS 则描述了肿瘤细胞增殖的模式。通过最大似然法估计每个啮齿动物的参数，并通过方差分析进行统计分析。当通过重复测量肿瘤体积来评估肿瘤生长时，可以使用这些标准。例如，我们使用先前发表的一项研究的数据，该研究旨在评估一系列 12 个神经胶质瘤中组织学、遗传参数与烷化剂反应之间的关系。使用我们的标准重新分析了接受替莫唑胺治疗的组。该组的 TTR 明显长于对照组。根据肿瘤类型，TTR 也有所不同：少突胶质细胞瘤比胶质母细胞瘤复发时间晚。TGS 根据肿瘤类型而不同。杂合性缺失（LOH）1p±19q、LOH 10p±10q、端粒酶活性、PTEN 突变和 EGFR 扩增与替莫唑胺疗效相关。我们的标准提供了 TGI 和 TGDi 给出的信息之外的更多信息。由于 TTR 和 TGS 的统计特性，TTR 和 TGS 可用于研究某些参数之间的关系，例如肿瘤类型或遗传改变，而 TGI 或 TGDi 则不行。
