Mathematical Models for Tumor Growth and the Reduction of Overtreatment

Author:

Heesterman Berdine1,Bokhorst John-Melle1,de Pont Lisa1,Verbist Berit2,Bayley Jean-Pierre3,van der Mey Andel1,Corssmit Eleonora4,Hes Frederik5,van Benthem Peter1,Jansen Jeroen1

Affiliation:

1. Department of Otorhinolaryngology, Leiden University Medical Center, Leiden, The Netherlands

2. Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands

3. Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands

4. Department of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands

5. Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands

Abstract

Background To improve our understanding of the natural course of head and neck paragangliomas (HNPGL) and ultimately differentiate between cases that benefit from early treatment and those that are best left untreated, we studied the growth dynamics of 77 HNPGL managed with primary observation. Methods Using digitally available magnetic resonance images, tumor volume was estimated at three time points. Subsequently, nonlinear least squares regression was used to fit seven mathematical models to the observed growth data. Goodness of fit was assessed with the coefficient of determination (R 2) and root-mean-squared error. The models were compared with Kruskal–Wallis one-way analysis of variance and subsequent post-hoc tests. In addition, the credibility of predictions (age at onset of neoplastic growth and estimated volume at age 90) was evaluated. Results Equations generating sigmoidal-shaped growth curves (Gompertz, logistic, Spratt and Bertalanffy) provided a good fit (median R 2: 0.996–1.00) and better described the observed data compared with the linear, exponential, and Mendelsohn equations (p < 0.001). Although there was no statistically significant difference between the sigmoidal-shaped growth curves regarding the goodness of fit, a realistic age at onset and estimated volume at age 90 were most often predicted by the Bertalanffy model. Conclusions Growth of HNPGL is best described by decelerating tumor growth laws, with a preference for the Bertalanffy model. To the best of our knowledge, this is the first time that this often-neglected model has been successfully fitted to clinically obtained growth data.

Publisher

Georg Thieme Verlag KG

Subject

Neurology (clinical)

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