A mathematical model of dynamics of cell populations in squamous epithelium after irradiation
- 17 July 2020
- journal article
- research article
- Published by Taylor & Francis Ltd in International Journal of Radiation Biology
- Vol. 96 (9), 1165-1172
- https://doi.org/10.1080/09553002.2020.1787540
Abstract
Purpose: To develop multi-compartment mechanistic models of dynamics of stem and functional cell populations in epithelium after irradiation. Methods and materials: We present two models, with three (3C) and four (4C) compartments respectively. We use delay differential equations, and include accelerated proliferation, loss of division asymmetry, progressive death of abortive stem cells, and turnover of functional cells. The models are used to fit experimental data on the variations of the number of cells in mice mucosa after irradiation with 13 Gy and 20 Gy. Akaike information criteria (AIC) was used to evaluate the performance of each model. Results: Both 3C and 4C models provide good fits to experimental data for 13 Gy. Fits for 20 Gy are slightly poorer and may be affected by larger uncertainties and fluctuations of experimental data. Best fits are obtained by imposing constraints on the fitting parameters, so to have values that are within experimental ranges. There is some degeneration in the fits, as different sets of parameters provide similarly good fits. Conclusions: The models provide good fits to experimental data. Mechanistic approaches like this can facilitate the development of mucositis response models to non-standard schedules/treatment combinations not covered by datasets to which phenomenological models have been fitted. Studying the dynamics of cell populations in multifraction treatments, and finding links with induced toxicity, is the next step of this work.Keywords
Funding Information
- Instituto de Salud Carlos III (PI17/01428, DTS17/00123)
- ISCIII (CPII17/00028)
- FEDER and Xunta de Galicia (GRC2013-014)
- Spanish Ministry of Science, Innovation and Universities (MTM2017-86459-R)
This publication has 34 references indexed in Scilit:
- Normal Tissue Complication Probability (NTCP) Modelling of Severe Acute Mucositis using a Novel Oral Mucosal Surface Organ at RiskClinical Oncology, 2017
- Functional Data Analysis Applied to Modeling of Severe Acute Mucositis and Dysphagia Resulting From Head and Neck Radiation TherapyInternational Journal of Radiation Oncology*Biology*Physics, 2016
- Optimal treatment and stochastic modeling of heterogeneous tumorsBiology Direct, 2016
- Normal tissue complication probability (NTCP) modelling using spatial dose metrics and machine learning methods for severe acute oral mucositis resulting from head and neck radiotherapyRadiotherapy and Oncology, 2016
- The nucleo-shuttling of the ATM protein as a basis for a novel theory of radiation response: resolution of the linear-quadratic model*International Journal of Radiation Biology, 2016
- Dose–response analysis of acute oral mucositis and pharyngeal dysphagia in patients receiving induction chemotherapy followed by concomitant chemo-IMRT for head and neck cancerRadiotherapy and Oncology, 2012
- The Linear-Quadratic Model Is an Appropriate Methodology for Determining Isoeffective Doses at Large Doses Per FractionSeminars in Radiation Oncology, 2008
- A mathematical model for cell density and proliferation in squamous epithelium after single-dose irradiationInternational Journal of Radiation Biology, 2001
- Three A's of repopulation during fractionated irradiation of squamous epithelia: Asymmetry loss, Acceleration of stem-cell divisions and Abortive divisionsInternational Journal of Radiation Biology, 1997
- A new look at the statistical model identificationIEEE Transactions on Automatic Control, 1974