1 Mathematical Modelling in Radiotherapy

In this chapter we discuss the significance of radiotherapy as a cancer treatment and focus
on mathematical modeling to understand the dynamics of healthy and cancer cells under
radiation therapy based on a paper by Zijian Liu and Chenxue Yang [?]. The paper references
previous studies on mathematical models related to cancer treatment, particularly those
considering the effects of radiation on both healthy and cancer cells. We outline our approach
in sections, including presenting their model, establishing conditions for coexistence, and
providing sufficient conditions for the existence and stability of periodic solutions.

1.1 Model of therapy

Zijian Liu and Chenxue Yang simplify the model by assuming that cancer and healthy
cell concentrations coexist in the same region within the organism [?]. It further posits that
radiation administration removes a significant portion of cancer cells and a minor fraction
of healthy cells from the system. The terms "large" and "small" are contextually defined
in relation to the cell populations at specific locations in the organism. The concept of
radiotherapy is presented as a control mechanism, influencing the rates of change in cancer
and healthy cell concentrations by selectively harvesting them.
To describe the model, first we should introduce some notations.

• Let x1 (t) be the healthy cell concentration, and let x2 (t) be the concentration of cancer
cells at time t. The term "concentration of cells" refers to the number of cells per unit
volume in a given sample.

• ẋ = dx/dt and D(t) is the strategy of the radiotherapy. The differential equation rep-
resents the rate of change of these concentrations with respect to time. The function
D(t) is introduced to represent the radiotherapy strategy, that could include informa-
tion about dosage, timing, targeting and duration.

• αi > 0 (i = 1, 2) are the respective proliferation coefficients. The proliferation co-

efficient, also known as the growth fraction or proliferation index, is a measure that
quantifies the proportion of actively dividing (proliferating) cells within a population
of cells. In the context of cancer, the proliferation coefficient is often used to assess the
rate at which cancer cells are actively dividing and growing.

• Ki (i = 1, 2) are the respective carrying capacities. The concept of carrying capacity

in the context of cancer is related to the ability of a tissue or organism to support the
growth and expansion of cancer cells.

1
While the proliferation coefficient focuses on the rate of cell division within a tumor, carrying
capacity considers broader environmental constraints that influence tumor growth.

• βi (i = 1, 2) are the respective competition coefficients;

• The proportion of the radiation is εD(t), where ε > 0. ε = 0 is the ideal, but impossible
to achieve in a practical scenario.

The model takes the following form:

 
x1
ẋ1 = α1 x1 1 − − β1 x1 x2 − εD(t)x1
K1
  (1)
x2
ẋ2 = α2 x2 1 − − β2 x1 x2 − D(t)x2
K2
It is assumed that

γ > 0, when t ∈ [nω, nω + L) (treatment stage)
D(t) ≡
0, when t ∈ [nω + L, (n + 1)ω) (no treatment stage)

for all n = 0, 1, 2, . . ., where ω is the period of treatment and 0 < L < ω is the radiation
treatment time. In biological context, we only consider the nonnegative solutions. Hence,
we suppose that x1 (0) ⩾ 0 and x2 (0) ⩾ 0.

1.2 The cells coexistence

In this section, we will explore the coexistence of healthy and cancer cells. It will be
observed that by selecting the radiation dosage γ from a specified range, the cancer cells
exhibit neither uncontrolled growth nor complete elimination [?].
To make our model more comprehensible, let us express the system (1) in a different
form:  
x1
ẋ1 = α1 x1 1 − − β1 x1 x2 − εγx1
K1
 
x2
ẋ2 = α2 x2 1 − − β2 x1 x2 − γx2 ,
K2
t ∈ [nω, nω + L)( treatment stage ),
(2)
 
x1
ẋ1 = α1 x1 1 − − β1 x1 x2
K1
 
x2
ẋ2 = α2 x2 1 − − β 2 x1 x2 ,
K2
t ∈ [nω + L, (n + 1)ω)( no treatment stage ),
n = 0, 1, 2 . . .

2
We should investigate the positive equilibrium of system (1) to determine whether the sys-
tem’s variables reach a stable configuration with positive values. In this step, we rewrite the
model given by equation (2) as the competitive Lotka-Volterra model:

u̇(t) = u(t) [b1 − a11 u(t) − a12 v(t)]

(3)
v̇(t) = v(t) [b2 − a21 u(t) − a22 v(t)]

where bi > 0, aij > 0, i, j = 1, 2. From (2) and (3), so we will get that
 
α1
ẋ1 (t) ⩾ x1 (t) α1 − εγ − x1 (t) − β1 x2 (t)
K1
  (4)
α2
ẋ2 (t) ⩾ x2 (t) α2 − γ − β2 x1 (t) − x2 (t)
K2

for all t ⩾ 0. By using the comparison theorem, (see [?] and [?]) with x1 (t) ⩾ u(t) and
x2 (t) ⩾ v(t) for all t ⩾ 0, where (u(t), v(t)) is the solution of the following auxiliary system:
 
α1
u̇(t) = u(t) α1 − εγ − u(t) − β1 v(t)
K1
  (5)
α2
v̇(t) = v(t) α2 − γ − β2 u(t) − v(t)
K2

with the initial values u(0) = x1 (0) and v(0) = x2 (0). Hence, we can transfer the beneficial
properties of system (3) to system (5). Let us perform this operation for the lemma at hand.
Lemma 1. System (3) has a unique positive equilibrium point (u∗ , v ∗ ) if inequality

a11 b1 a12
> > (6)
a21 b2 a22
or

a12 b1 a11
> > (7)
a22 b2 a21
is satisfied. Moreover, if inequality (6) is satisfied, then the equilibrium point (u∗ , v ∗ )
of system (3) is globally asymptotically stable and if inequality (7) is satisfied, (u∗ , v ∗ ) is
unstable.
On the other hand, by applying this lemma to system (5), we will get the theorem:
Theorem 2. Assume that the following conditions
α1 α1 − εγ K 2 β1
α2 − γ > 0, > > (8)
K 1 β2 α2 − γ α2
hold. Then the healthy cells and cancer cells coexist.
Remark 3. Under conditions of Theorem 1, system (1) has a positive ω-periodic solution.

3
1.3 Periodic solution for Cancer eradication
The assurance of the existence of a positive ω-periodic solution is affirmed by Remark 3.
Subsequently, we will outline specific criteria for the presence of a periodic solution indicating
cancer eradication in the context of system (2) [?].
Initially, we delve into the examination of the system’s periodic solution associated with
cancer eradication. We consider a subsystem of system (2) where x2 (t) is constantly zero.
 
ẋ1 = α1 x1 1 − Kx11 − εγx1 , t ∈ [nω, nω + L),
 
ẋ1 = α1 x1 1 − Kx11 , t ∈ [nω + L, (n + 1)ω), (9)
n = 0, 1, 2 . . .
When t ∈ [0, L), we have

α1
x1 (t) =
K1 (α1 − εγ)
  −1 (10)
1 α1
+ − exp {− (α1 − εγ) t} ,
x1 (0) K1 (α1 − εγ)
from the continuity of x1 (t),

α1
x1 (L) =
K1 (α1 − εγ)
  −1 (11)
1 α1
+ − exp {− (α1 − εγ) L} .
x1 (0) K1 (α1 − εγ)
Then when t ∈ [L, ω), we have
   −1
1 1 1
x1 (t) = + − exp {−α1 (t − L)} ; (12)
K1 x1 (L) K1
hence,
   −1
1 1 1
x1 (ω) = + − exp {−α1 (ω − L)}
K1 x1 (L) K1
 
1 α1 1
= + −
K1 K1 (α1 − εγ) K1

1 α1
 (13)
+ −
x1 (0) K1 (α1 − εγ)
× exp {− (α1 − εγ) L}]
× exp {−α1 (ω − L)}}−1 .
If system (9) has a positive ω-periodic solution, then we need x1 (ω) = x1 (0), which leads
to

4
 x1 (0) = (1 − exp {εγL − α1 ω})
 
1 α1 1
×( + − exp {−α1 (ω − L)}
K1 K1 (α1 − εγ) K1 (14)
−1
α1
− exp {εγL − α1 ω} .
K1 (α1 − εγ)
From expression (14) we can calculate that x1 (0) > 0 is equivalent to εγL < α1 ω. Then
we get the following result.
Theorem 4. System (1) has a periodic solution for cancer eradication (x∗1 (t), 0) if the
inequality εγL < α1 ω is satisfied [?].
The presence of a periodic solution indicating cancer victory in system (1) can be similarly
examined. In this context, we will present only the outcome.
Theorem 5. System (1) has a cancer win periodic solution (0, x∗2 (t)) if the inequality
γL < α2 ω is satisfied [?].

1.4 Conclusion
In conclusion, the main findings of this paper provide periodic solutions for the proposed
system (1). Theorems 4 and 5 rigorously outline the conditions under which periodic solution
for cancer eradication and cancer victory, respectively, manifest. Specifically, Theorem 4
asserts the existence of a cancer eradication periodic solution when the inequality εγL < α1 ω
is satisfied. Similarly, Theorem 5 establishes the presence of a cancer win periodic solution
when γL < α2 ω. Additionally, Theorem 2 provides conditions for the coexistence of healthy
and cancer cells. These results contribute valuable knowledge to the understanding of the
system’s behavior under various circumstances, shedding light on the complex dynamics of
cancer and potential therapeutic strategies.