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Multi-Species Models of Tumor Growth
Multi-Species Models of Tumor Growth
General Assumptions
The model is composed of the following volume fractions: proliferative (φP ), hypoxic (φH )
and necrotic (φN ) tumor cells, and the nutrients (φσ ). The total tumor (φT ) volume fraction is
giving by
φT = φP + φH + φN . (1)
The models defined below uses the Heaviside function (H ) as a switch. This value of this
function is one for positive arguments and zero otherwise.
1
2 The Phase-Field Model
Assuming that the velocities of the constituents are negligible, the following system of mass
balance equation is obtained:
∂φT 2 2 2 2 2 2
= ∇ · MP φP (1 − φP ) + MH φH (1 − φH ) + MN φN (1 − φN ) ∇µ + ST ,
∂t 2
2
µ = 2ĒφT 1 − 3φT + 2φT − T ∆φT ,
∂φH 2 2
= ∇ · MH φH (1 − φH ) ∇µ + SH , (6)
∂t
∂φN
= ∇ · MN φ2N (1 − φN )2 ∇µ + SN ,
∂t
∂φσ
= ∇ · Mσ ∇φσ + Sσ ,
∂t
where SH , SN and Sσ are defined as in (3) and ST is defined below.
The source terms in our model take the form
1
ST = λP φσ φP (1 − φT ) + H (t − Ttreat ) (λd − 1)(λdk,H φH + λdk,P φP ), (7)
1 + λr (t − Ttreat ) k,N
θ 2 = {Ē, T } ∪ θ 1 , (8)
4 Michaelis-Menten type
λPc φP + λH
c φH
Sσ = − M
φσ + λs ktrans (10)
φσ + φσ
5 Other hypothesis
6 Papers
• Wise et al. [1]: same source terms but tumor = viable + necrotic;
• Liu and Yang [2]: logistic + treatment effects (exponential) just during treatment interval;
• Barazzuol et al. [3]: ODE model + linear-quadratic (LQ) treatment model (survival);
• Bodgi et al. [4]: good historical synopsis, several cell survival/radiation models (Fig 2);
2
• Borasi and Nahum [5]: reaction-diffusion (RD) model with exponential growth + LQ
model;
• Enderling and AJ Chaplain [8]: ODEs for growth rate (exponential, logistic, Gompertz)
and dynamically carrying capacity;
• Byrne and Chaplain [9]: radially symmetric tumor growth with necrosis;
• Galochkina et al. [11]: RD model with logistic growth (normal and damaged tumor cells),
using also the LQ model (optimization);
• Benzekry et al. [12]: Model selection with AIC, ODE with logistic and Gompertz models,
dynamic carrying capacity, Von Bertalanffy and power law (for volume);
• Xu et al. [13]: Phase-field model which incorporate hypoxic and necrotic through the
chemical potential;
• Liu and Yang [15]: same model as Liu and Yang [2] but added chemotherapy;
• Marušić [17]: model selection using BIC for several ODE modeling tumor volume;
• Altrock et al. [21]: good review (examples): ODE, PDE, hybrid models, game theory and
metastasis;
References
[1] S. M. Wise, J. S. Lowengrub, H. B. Frieboes, V. Cristini, Three-dimensional multispecies
nonlinear tumor growthi: model and numerical method, Journal of theoretical biology 253
(2008) 524–543.
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[5] G. Borasi, A. Nahum, Modelling the radiotherapy effect in the reaction-diffusion equation,
Physica Medica 32 (2016) 1175–1179.
[9] H. M. Byrne, M. Chaplain, Growth of necrotic tumors in the presence and absence of
inhibitors, Mathematical biosciences 135 (1996) 187–216.
[10] J. F. Fowler, The linear-quadratic formula and progress in fractionated radiotherapy, The
British journal of radiology 62 (1989) 679–694.
[13] J. Xu, G. Vilanova, H. Gomez, A mathematical model coupling tumor growth and angio-
genesis, PloS one 11 (2016) e0149422.
[14] N. Kirkby, N. Burnet, D. Faraday, Mathematical modelling of the response of tumour cells
to radiotherapy, Nuclear Instruments and Methods in Physics Research Section B: Beam
Interactions with Materials and Atoms 188 (2002) 210–215.
[16] C. Lo, Stochastic gompertz model of tumour cell growth, Journal of Theoretical Biology
248 (2007) 317–321.
[20] C. Park, L. Papiez, S. Zhang, M. Story, R. D. Timmerman, Universal survival curve and
single fraction equivalent dose: useful tools in understanding potency of ablative radiother-
apy, International Journal of Radiation Oncology* Biology* Physics 70 (2008) 847–852.
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[22] J. A. Adam, A simplified mathematical model of tumor growth, Mathematical biosciences
81 (1986) 229–244.