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Classical Mathematical Models for Description and Prediction of Experimental Tumor Growth

机译:描述和预测实验性肿瘤生长的经典数学模型

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摘要

Despite internal complexity, tumor growth kinetics follow relatively simple laws that can be expressed as mathematical models. To explore this further, quantitative analysis of the most classical of these were performed. The models were assessed against data from two in vivo experimental systems: an ectopic syngeneic tumor (Lewis lung carcinoma) and an orthotopically xenografted human breast carcinoma. The goals were threefold: 1) to determine a statistical model for description of the measurement error, 2) to establish the descriptive power of each model, using several goodness-of-fit metrics and a study of parametric identifiability, and 3) to assess the models' ability to forecast future tumor growth. The models included in the study comprised the exponential, exponential-linear, power law, Gompertz, logistic, generalized logistic, von Bertalanffy and a model with dynamic carrying capacity. For the breast data, the dynamics were best captured by the Gompertz and exponential-linear models. The latter also exhibited the highest predictive power, with excellent prediction scores (≥80%) extending out as far as 12 days in the future. For the lung data, the Gompertz and power law models provided the most parsimonious and parametrically identifiable description. However, not one of the models was able to achieve a substantial prediction rate (≥70%) beyond the next day data point. In this context, adjunction of a priori information on the parameter distribution led to considerable improvement. For instance, forecast success rates went from 14.9% to 62.7% when using the power law model to predict the full future tumor growth curves, using just three data points. These results not only have important implications for biological theories of tumor growth and the use of mathematical modeling in preclinical anti-cancer drug investigations, but also may assist in defining how mathematical models could serve as potential prognostic tools in the clinic.
机译:尽管内部复杂,但肿瘤生长动力学遵循相对简单的定律,可以将其表示为数学模型。为了进一步探讨这一点,对其中最经典的进行了定量分析。针对来自两个体内实验系统的数据评估了模型:异位同基因肿瘤(刘易斯肺癌)和原位异种移植的人乳腺癌。目标有三方面:1)确定用于描述测量误差的统计模型,2)使用几个拟合优度指标和参数可识别性研究,建立每个模型的描述能力,以及3)评估模型预测未来肿瘤生长的能力。研究中包括的模型包括指数模型,指数线性模型,幂律模型,Gompertz模型,逻辑模型,广义逻辑模型,冯·贝塔兰菲模型和动态承载能力模型。对于乳房数据,动力学最好通过Gompertz模型和指数线性模型来捕获。后者也表现出最高的预测能力,未来的最佳预测分数(≥80%)可延伸到未来的12天。对于肺部数据,Gompertz和幂定律模型提供了最简约和参数可识别的描述。但是,没有一个模型能够在第二天的数据点之后获得可观的预测率(≥70%)。在这种情况下,关于参数分布的先验信息的附加导致相当大的改进。例如,当使用幂律模型仅使用三个数据点来预测完整的未来肿瘤生长曲线时,预测成功率从14.9%增至62.7%。这些结果不仅对肿瘤生长的生物学理论以及数学模型在临床前抗癌药物研究中的应用具有重要意义,而且可能有助于定义数学模型如何在临床中用作潜在的预后工具。

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