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Classical mathematical laws for description and prediction of experimental tumor growth

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Despite internal complexity, tumor growth kinetics follow relatively simple laws that can be expressed as mathematical models. To explore this further, we will present a quantitative analysis of the most classical of these. 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 twofold : 1) to establish the descriptive power of each model, using several goodness-of-fit metrics and a study of parametric identifiability, and 2) 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.

Surprisingly, for both experimental systems, the logistic model was not able to capture the tumor growth dynamics and was in this detectably distinct from other sigmoid models such as the Gompertz. 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 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.

- References

  • Sébastien Benzekry, Clare Lamont, Afshin Beheshti, Amanda Tracz, John M. L. Ebos, Lynn Hlatky & Philip Hahnfeldt, Classical mathematical models for description and prediction of experimental tumor growth, PloS Computational Biology, 10 (8), e1003800, 2014 Online

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