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Tumor Growth Model         Method of Characteristics   Solutions for various growth rates   Future Work




                       Dynamic Tumor Growth Modelling

                                Prof. Thomas Witelski,
                     Matthew Tanzy, Ben Owens, Oleksiy Varfolomiyev


                                            NJIT, June 2011
Tumor Growth Model     Method of Characteristics   Solutions for various growth rates   Future Work




Cancer background
      Current medical understanding of some types of cancer




         1   Disease starts from a primary tumor which grows in one
             location
         2   The primary tumor may shed cancer cells which get carried to
             other parts of the body by the circulatory system
Tumor Growth Model       Method of Characteristics        Solutions for various growth rates   Future Work




      Colony size distribution of metastatic tumors with cell number x at
      time t is governed by von Foerster Equation
                                    ∂ρ   ∂
                                       +    (g (x) ρ) = 0                                      (1)
                                    ∂t   ∂x
      g (x) is tumor growth rate determined by
                                               dx
                                                  = g (x)                                      (2)
                                               dt
      Initially no metastatic tumor exists

                                               ρ(x, 0) = 0                                     (3)

      Intitial tumor birth rate
                                               ∞
                     g (1)ρ(1, t) =                β(x)ρ(x, t)dx + β(xp (t)),                  (4)
                                           1

      β(x) tumor birth rate
Tumor Growth Model   Method of Characteristics     Solutions for various growth rates   Future Work




Linear Growth Function: g (x) = k − Ex


      Assuming that in the beginning the main contribution to the tumor
      growth is given by primary tumor (i.e. neglecting the integral term
      in the BC) we have

                         ∂ρ(x, t) ∂ (g (x)ρ(x, t))
                                 +                 =0                                   (5)
                           ∂t            ∂x
                                          ρ(x, 0) = 0                                   (6)
                     g (1)ρ(1, t) = β(xp ),          β(x) = mx α                        (7)
                                  dx
                                     = k − Ex = g (x)                                   (8)
                                  dt
Tumor Growth Model   Method of Characteristics    Solutions for various growth rates    Future Work




Solution by the Method of Characteristics


                                    dρ
                                        = Eρ                                            (9)
                                    dt
      along the characteristics given by
                                        dx
                                           = k − Ex                                    (10)
                                        dt
      Therefore
                                ρ(x, t) = ρ0 (x(0)) e Et                               (11)
      along the characteristics
                                                 K
                       x(t) = x(0)e −Et +          1 − e −Et                           (12)
                                                 E
Tumor Growth Model    Method of Characteristics     Solutions for various growth rates   Future Work




Solution by the Method of Characteristics


      First we use the BC to solve for ρ0 (x(0)), i.e.
                                                                                                α
                             K                                                 K
      (K − E ) ρ0 e Et +       1 − e Et           e Et = m e −Et +               1 − e −Et
                             E                                                 E

      Finally, the colony size distribution of metastatic tumors with cell
      number x at time t is
                                                                          α
                                         mE −α         e −Et (E −k)2
                        ρ (x, t) =       k−Ex     k+      Ex−k
Tumor Growth Model      Method of Characteristics   Solutions for various growth rates   Future Work




Growth function: g (x) = Ex




                     Figure: ρ(x) at t = 10 with all parameters at 1
Tumor Growth Model      Method of Characteristics   Solutions for various growth rates   Future Work




Growth function: g (x) = k − Ex




               Figure: ρ(x) at t = 10 with E = 0.2, k = 0.3, and m = 0.1
Tumor Growth Model    Method of Characteristics   Solutions for various growth rates   Future Work




Single primary tumor size growth (no drug is active)
      Growth function: g (x) = (k − E (t)e −rt )x
      Here no drug is active (i.e. g (x) = kx)




      Figure: ρ(x) at t = 3650 with k = 0.006, α = 0.663, and m = 5.3 × 10−8
Tumor Growth Model     Method of Characteristics   Solutions for various growth rates   Future Work




Single primary tumor size growth (drug effect)
      At time t1 drug is activated
                                                   −r (t−t1 )
      In a region of constant E : x (t) = Ae kt+Ee            /r




      Figure: ρ(x) at t = 3650 with k = 0.006, α = 0.663, E = 0.0083,
      r = 1 × 10−5 and m = 5.3 × 10−8
Tumor Growth Model        Method of Characteristics       Solutions for various growth rates           Future Work




Linear Separable Growth Rate Solution



      Now we have Linear Separable Growth Rate
                                         dx
                                            = [k − E (t)] x
                                         dt
      Colony size distribution

                                                      m                m            t
                               m              −α−1− k−E (t)       α+ k−E (t)   (        k−E (s)ds )t
              ρ(x, t) =      k−E (t)      x                   e                    0
Tumor Growth Model   Method of Characteristics          Solutions for various growth rates   Future Work




Logistic Tumor Growth Rate Solution



      Now we have Tumor Growth Rate given by Logistic Equation
                                     dx
                                        = (k − Ex) x
                                     dt
      Resulting colony size distribution

                                                        e −kt
                               ρ(x, t) =                            2
                                                 (E x0 (e kt −1)+k )
Tumor Growth Model      Method of Characteristics   Solutions for various growth rates   Future Work




Future Work



             Fitting data to models, parameter estimation for multiple
             tumor and multiple patient data
             Incorporating limitations on measurable clinical data
             Comparing PDE, discrete population and polymerization
             models
             Solution of inverse problems for the birth rate
             Probability and statistics of different forms of clinical data

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Dynamic Tumor Growth Modelling

  • 1. Tumor Growth Model Method of Characteristics Solutions for various growth rates Future Work Dynamic Tumor Growth Modelling Prof. Thomas Witelski, Matthew Tanzy, Ben Owens, Oleksiy Varfolomiyev NJIT, June 2011
  • 2. Tumor Growth Model Method of Characteristics Solutions for various growth rates Future Work Cancer background Current medical understanding of some types of cancer 1 Disease starts from a primary tumor which grows in one location 2 The primary tumor may shed cancer cells which get carried to other parts of the body by the circulatory system
  • 3. Tumor Growth Model Method of Characteristics Solutions for various growth rates Future Work Colony size distribution of metastatic tumors with cell number x at time t is governed by von Foerster Equation ∂ρ ∂ + (g (x) ρ) = 0 (1) ∂t ∂x g (x) is tumor growth rate determined by dx = g (x) (2) dt Initially no metastatic tumor exists ρ(x, 0) = 0 (3) Intitial tumor birth rate ∞ g (1)ρ(1, t) = β(x)ρ(x, t)dx + β(xp (t)), (4) 1 β(x) tumor birth rate
  • 4. Tumor Growth Model Method of Characteristics Solutions for various growth rates Future Work Linear Growth Function: g (x) = k − Ex Assuming that in the beginning the main contribution to the tumor growth is given by primary tumor (i.e. neglecting the integral term in the BC) we have ∂ρ(x, t) ∂ (g (x)ρ(x, t)) + =0 (5) ∂t ∂x ρ(x, 0) = 0 (6) g (1)ρ(1, t) = β(xp ), β(x) = mx α (7) dx = k − Ex = g (x) (8) dt
  • 5. Tumor Growth Model Method of Characteristics Solutions for various growth rates Future Work Solution by the Method of Characteristics dρ = Eρ (9) dt along the characteristics given by dx = k − Ex (10) dt Therefore ρ(x, t) = ρ0 (x(0)) e Et (11) along the characteristics K x(t) = x(0)e −Et + 1 − e −Et (12) E
  • 6. Tumor Growth Model Method of Characteristics Solutions for various growth rates Future Work Solution by the Method of Characteristics First we use the BC to solve for ρ0 (x(0)), i.e. α K K (K − E ) ρ0 e Et + 1 − e Et e Et = m e −Et + 1 − e −Et E E Finally, the colony size distribution of metastatic tumors with cell number x at time t is α mE −α e −Et (E −k)2 ρ (x, t) = k−Ex k+ Ex−k
  • 7. Tumor Growth Model Method of Characteristics Solutions for various growth rates Future Work Growth function: g (x) = Ex Figure: ρ(x) at t = 10 with all parameters at 1
  • 8. Tumor Growth Model Method of Characteristics Solutions for various growth rates Future Work Growth function: g (x) = k − Ex Figure: ρ(x) at t = 10 with E = 0.2, k = 0.3, and m = 0.1
  • 9. Tumor Growth Model Method of Characteristics Solutions for various growth rates Future Work Single primary tumor size growth (no drug is active) Growth function: g (x) = (k − E (t)e −rt )x Here no drug is active (i.e. g (x) = kx) Figure: ρ(x) at t = 3650 with k = 0.006, α = 0.663, and m = 5.3 × 10−8
  • 10. Tumor Growth Model Method of Characteristics Solutions for various growth rates Future Work Single primary tumor size growth (drug effect) At time t1 drug is activated −r (t−t1 ) In a region of constant E : x (t) = Ae kt+Ee /r Figure: ρ(x) at t = 3650 with k = 0.006, α = 0.663, E = 0.0083, r = 1 × 10−5 and m = 5.3 × 10−8
  • 11. Tumor Growth Model Method of Characteristics Solutions for various growth rates Future Work Linear Separable Growth Rate Solution Now we have Linear Separable Growth Rate dx = [k − E (t)] x dt Colony size distribution m m t m −α−1− k−E (t) α+ k−E (t) ( k−E (s)ds )t ρ(x, t) = k−E (t) x e 0
  • 12. Tumor Growth Model Method of Characteristics Solutions for various growth rates Future Work Logistic Tumor Growth Rate Solution Now we have Tumor Growth Rate given by Logistic Equation dx = (k − Ex) x dt Resulting colony size distribution e −kt ρ(x, t) = 2 (E x0 (e kt −1)+k )
  • 13. Tumor Growth Model Method of Characteristics Solutions for various growth rates Future Work Future Work Fitting data to models, parameter estimation for multiple tumor and multiple patient data Incorporating limitations on measurable clinical data Comparing PDE, discrete population and polymerization models Solution of inverse problems for the birth rate Probability and statistics of different forms of clinical data