Personalized Tumor Growth Prediction with Multiscale Tumor Modeling

Abstract

AbstractBackgroundCancer is one of the most complex phenomena in biology and medicine. Extensive attempts have been made to work around this complexity. In this study, we try to take a selective approach; not modeling each particular facet in detail but rather only the pertinent and essential parts of the tumor system are simulated and followed by optimization, revealing specific traits. This leads us to a pellucid personalized model which is noteworthy as it closely approximates existing experimental results.MethodFor years, research has focused on modeling tumor growth but not many studies have put forward a framework for the personalization of models. In the present study, a hybrid modeling approach which consists of cellular automata for discrete cell state representation and diffusion equations to calculate distribution of relevant substances in the tumor micro-environment is favored. Moreover, naive Bayesian decision making with weighted stochastic equations and a Bayesian network to model the temporal order of mutations is presented. The model is personalized according to the evidence using Markov Chain Monte Carlo. Ultimately, this way of thinking about tumor modeling leads us to a vascular multi-scale model of tumor growth.ResultsTo validate the tumor model, a data set belonging to the A549 cell line is used. The data represents the growth of a tumor for 30 days. We optimize the coefficients of the stochastic decision making equations using first half of the timeline. Then we predict next 15 days of growth without any other supervision. Results are promising with their low error margin and simulated growth data is in line with laboratory results.ConclusionThere are many subsystems which have an effect in the growth of a tumor. A detailed model which includes all of them is currently virtually impossible to implement. We have therefore focused on a system that only includes fundamental components in this study, and have evaluated its predictions. We propose novel probability functions to obtain a personalized model and estimate the individual importance (weights) of each with parameter optimization. Our approach of using simulated annealing for parameter estimation and the subsequent validation of the prediction with in-vitro tumor growth data are, to our knowledge, unique in the literature.