cancer tumor kinetics gretchen a. koch goucher college peer utk 2011

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Cancer Tumor Kinetics Gretchen A. Koch Goucher College PEER UTK 2011

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Page 1: Cancer Tumor Kinetics Gretchen A. Koch Goucher College PEER UTK 2011

Cancer Tumor Kinetics

Gretchen A. KochGoucher CollegePEER UTK 2011

Page 2: Cancer Tumor Kinetics Gretchen A. Koch Goucher College PEER UTK 2011

Special Thanks To:Dr. Claudia Neuhauser

University of Minnesota – Rochester Author and creator of modules

Page 3: Cancer Tumor Kinetics Gretchen A. Koch Goucher College PEER UTK 2011

Learning ObjectivesAfter completion of this module, the student will be able

to:

1. Build a data‐driven phenomenological model of tumor growth with a minimal number of parameters

2. Make predictions about the kinetic behavior of a tumor based on a mathematical model

3. Define growth rate and exponential growth

4. Develop a differential equations describing tumor growth

5. Use WolframAlpha to solve algebraic equations and take limits

Page 4: Cancer Tumor Kinetics Gretchen A. Koch Goucher College PEER UTK 2011

Prerequisites1. Volume of a sphere

2. Straight lines

3. Natural logarithm and exponential functions

4. Graphing in Excel

5. Logarithmic transformation

6. Fitting a straight line to data points in Excel and displaying the equation

Page 5: Cancer Tumor Kinetics Gretchen A. Koch Goucher College PEER UTK 2011

Knowledge Gained1. Continuous time population models

2. Fitting a straight line to data

3. Doubling time of an exponentially growing population

4. Growth rate and exponential growth

Page 6: Cancer Tumor Kinetics Gretchen A. Koch Goucher College PEER UTK 2011

Concept Map

Page 7: Cancer Tumor Kinetics Gretchen A. Koch Goucher College PEER UTK 2011

New Cases of Cancer 2010

Map from American Cancer Society. Cancer Facts & Figures 2010. Atlanta: American Cancer Society; 2010.

Page 8: Cancer Tumor Kinetics Gretchen A. Koch Goucher College PEER UTK 2011

Cancer Tumor KineticsThe growth and spread of the cancer tumor

Tumor metastasis and survival rates

Table from American Cancer Society. Cancer Facts & Figures 2010. Atlanta: American Cancer Society; 2010.

Page 9: Cancer Tumor Kinetics Gretchen A. Koch Goucher College PEER UTK 2011

Why model cancer tumor kinetics?

Page 10: Cancer Tumor Kinetics Gretchen A. Koch Goucher College PEER UTK 2011

Case StudyPatient with breast cancer tumor and growth of

(untreated) tumor over time

Diameter (mm)

Measurement Date D1 D2 D3

1 06/26/69 4 4 4

2 11/27/69 5 4 6

3 11/24/70 7 8 9

4 07/06/71 11 12 14

5 08/17/73 29 33 31

6 09/18/73 32 36 34

D. v. Fournier, E. Weber, W. Hoeffken, M. Bauer, F. Kubli, and V. Barth. 1980. Growth rate of 147 mammary carcinoma. Cancer 8: 2198‐2207.

Page 11: Cancer Tumor Kinetics Gretchen A. Koch Goucher College PEER UTK 2011

Questions to AnswerWhen will the patient die?

Lethal burden of tumor

When did the cancer start?Depends on growth rate (doubling time)

Page 12: Cancer Tumor Kinetics Gretchen A. Koch Goucher College PEER UTK 2011

Model Assumptions1. The shape of a tumor is a sphere

2. A tumor is a solid mass of tumor cells

3. An individual tumor cell is a sphere with diameter

4. 1 gram of tumor cells corresponds to 109 cells

Page 13: Cancer Tumor Kinetics Gretchen A. Koch Goucher College PEER UTK 2011

Create the Model: Background Information

Volume of a sphere with radius, r:

Relationship between diameter, d, and radius, r:

Page 14: Cancer Tumor Kinetics Gretchen A. Koch Goucher College PEER UTK 2011

Create the ModelVolume of a cancer tumor, VT, with diameter, D:

Volume of individual cancer tumor cell, VC, with diameter, d:

Page 15: Cancer Tumor Kinetics Gretchen A. Koch Goucher College PEER UTK 2011

Think, Pair, Share:Create the Model

Given the two volumes, find the number of tumor cells in any given cancer tumor.

Time to Share!

Page 16: Cancer Tumor Kinetics Gretchen A. Koch Goucher College PEER UTK 2011

Create the ModelThe number of cells in any tumor is

Page 17: Cancer Tumor Kinetics Gretchen A. Koch Goucher College PEER UTK 2011

Create the ModelThe number of cells in any tumor is

Page 18: Cancer Tumor Kinetics Gretchen A. Koch Goucher College PEER UTK 2011

Create the ModelSince 109 tumor cells weigh 1 gram, the weight

of the tumor is

Page 19: Cancer Tumor Kinetics Gretchen A. Koch Goucher College PEER UTK 2011

Think, Pair, Share:Create the Model

1. Download the cancer data set from the Schedule webpage.

2. Under the Patient 1 tab, calculate each of the following

a. Column G: Average diameter for the tumor of the patient

b. Column H: Volume of the tumor based on the average diameter

c. Column I: Number of cells in the tumor

d. Column J: Weight of the tumor

Time to Share!

Page 20: Cancer Tumor Kinetics Gretchen A. Koch Goucher College PEER UTK 2011

Create the ModelExcel Time!

Page 21: Cancer Tumor Kinetics Gretchen A. Koch Goucher College PEER UTK 2011

Think, Pair, Share:Kinetics Model

1. Under the Patient 1 tab, calculate each of the following

a. Column C – Days between observations: Excel can calculate the number of days between observations by using simple subtraction. Set the date of the first observation to be day 0, and calculate the days between subsequent observations.

b. Plot the Number of Tumor Cells (Column I) as a function of time (Column C).

c. Determine if transforming either or both axes logarithmically gives a straight line fit.

d. What type of function should we use to fit our data?

Time to Share!

Page 22: Cancer Tumor Kinetics Gretchen A. Koch Goucher College PEER UTK 2011

Kinetics ModelExcel Time!

Page 23: Cancer Tumor Kinetics Gretchen A. Koch Goucher College PEER UTK 2011

Think, Pair, Share:Kinetics Model

1. Use the Trendline option to fit an exponential function to the data and on the graph, display the equation of the form

2. Determine and record the values of a and c.

Time to Share!

Page 24: Cancer Tumor Kinetics Gretchen A. Koch Goucher College PEER UTK 2011

Kinetics ModelExcel Time!

Page 25: Cancer Tumor Kinetics Gretchen A. Koch Goucher College PEER UTK 2011

Think, Pair, Share:Kinetics Model

1. A number of studies have shown that a primary tumor starts from a single cell. Use the model equation to predict the date when the tumor started.

2. Tumors can be detected by palpitation when their size is about 107 to 109 cells. Tumors become lethal when their size is about 1012 to 1013 cells. This size is called the lethal burden. Based on the model equation, determine when the tumor was detectable and when the tumor reached the lethal burden?

Time to Share!

Page 26: Cancer Tumor Kinetics Gretchen A. Koch Goucher College PEER UTK 2011

Kinetics ModelExcel Time!

Page 27: Cancer Tumor Kinetics Gretchen A. Koch Goucher College PEER UTK 2011

Doubling Time

Page 28: Cancer Tumor Kinetics Gretchen A. Koch Goucher College PEER UTK 2011

Doubling Time

Page 29: Cancer Tumor Kinetics Gretchen A. Koch Goucher College PEER UTK 2011

Doubling Time

Page 30: Cancer Tumor Kinetics Gretchen A. Koch Goucher College PEER UTK 2011

Doubling Time

Page 31: Cancer Tumor Kinetics Gretchen A. Koch Goucher College PEER UTK 2011

Doubling Time

Page 32: Cancer Tumor Kinetics Gretchen A. Koch Goucher College PEER UTK 2011

Doubling Time

Page 33: Cancer Tumor Kinetics Gretchen A. Koch Goucher College PEER UTK 2011

Doubling Time

Page 34: Cancer Tumor Kinetics Gretchen A. Koch Goucher College PEER UTK 2011

Doubling TimeThen, the doubling time does not depend on the

number of cells present.

Page 35: Cancer Tumor Kinetics Gretchen A. Koch Goucher College PEER UTK 2011

Doubling TimeI forget how to do this!

WolframAlpha

Page 36: Cancer Tumor Kinetics Gretchen A. Koch Goucher College PEER UTK 2011

Think, Pair, Share:Doubling Time

1. Use Excel to find the doubling time for our tumor kinetics model.

Time to Share!

Page 37: Cancer Tumor Kinetics Gretchen A. Koch Goucher College PEER UTK 2011

Think, Pair, Share:Doubling Time

1. Excel time!

Page 38: Cancer Tumor Kinetics Gretchen A. Koch Goucher College PEER UTK 2011

Learning ObjectivesAfter completion of this module, the student will be able

to:

1. Build a data‐driven phenomenological model of tumor growth with a minimal number of parameters

2. Make predictions about the kinetic behavior of a tumor based on a mathematical model

3. Define growth rate and exponential growth

4. Develop a differential equations describing tumor growth

5. Use WolframAlpha to solve algebraic equations and take limits

Page 39: Cancer Tumor Kinetics Gretchen A. Koch Goucher College PEER UTK 2011

Putting it all together Complete the group project on page 7 of the Cancer Tumor

Kinetics pdf to find the time to lethal burden and detection time for:

Primary Cancer Doubling Time (days)

Number of Cases

Malignant Melanoma

48 10

Colon 109 10

116 25

Kidney 66 5

132 8

Thyroid, anaplastic

29 7

Data Source: Table III from Friberg, S. and S. Mattson. 1997. On the growth rates of human malignant tumors: Implications for medical decision making. Journal of Surgical Oncology 65: 284‐297