Can the Kuznetsov Model Replicate and Predict Cancer Growth in Humans?

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Mohammad El Wajeh - , RWTH Aachen University (Author)
  • Falco Jung - , RWTH Aachen University (Author)
  • Dominik Bongartz - , RWTH Aachen University (Author)
  • Chrysoula Dimitra Kappatou - , Imperial College London (Author)
  • Narmin Ghaffari Laleh - , RWTH Aachen University (Author)
  • Alexander Mitsos - , RWTH Aachen University, JARA-CSD, Jülich Research Centre (Author)
  • Jakob Nikolas Kather - , RWTH Aachen University, Heidelberg University  (Author)

Abstract

Several mathematical models to predict tumor growth over time have been developed in the last decades. A central aspect of such models is the interaction of tumor cells with immune effector cells. The Kuznetsov model (Kuznetsov et al. in Bull Math Biol 56(2):295–321, 1994) is the most prominent of these models and has been used as a basis for many other related models and theoretical studies. However, none of these models have been validated with large-scale real-world data of human patients treated with cancer immunotherapy. In addition, parameter estimation of these models remains a major bottleneck on the way to model-based and data-driven medical treatment. In this study, we quantitatively fit Kuznetsov’s model to a large dataset of 1472 patients, of which 210 patients have more than six data points, by estimating the model parameters of each patient individually. We also conduct a global practical identifiability analysis for the estimated parameters. We thus demonstrate that several combinations of parameter values could lead to accurate data fitting. This opens the potential for global parameter estimation of the model, in which the values of all or some parameters are fixed for all patients. Furthermore, by omitting the last two or three data points, we show that the model can be extrapolated and predict future tumor dynamics. This paves the way for a more clinically relevant application of mathematical tumor modeling, in which the treatment strategy could be adjusted in advance according to the model’s future predictions.

Details

Original languageEnglish
Article number130
JournalBulletin of mathematical biology
Volume84
Issue number11
Publication statusPublished - Nov 2022
Peer-reviewedYes
Externally publishedYes

External IDs

PubMed 36175705

Keywords

Sustainable Development Goals

Keywords

  • Mathematical oncology, Parameter estimation, Parameter identifiability analysis, Tumor growth modeling, Tumor growth prediction