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Cancer Tumor Kinetics Gretchen A. Koch-Noble Goucher College PEER UTK 2012

Cancer Tumor Kinetics

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Cancer Tumor Kinetics. Gretchen A. Koch-Noble Goucher College PEER UTK 2012. Special Thanks To:. Dr. Claudia Neuhauser University of Minnesota – Rochester Author and creator of modules. Learning Objectives. After completion of this module, the student will be able to: - PowerPoint PPT Presentation

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Page 1: Cancer Tumor Kinetics

Cancer Tumor Kinetics

Gretchen A. Koch-NobleGoucher CollegePEER UTK 2012

Page 2: Cancer Tumor Kinetics

Special Thanks To:Dr. Claudia Neuhauser

University of Minnesota – Rochester Author and creator of modules

Page 3: Cancer Tumor Kinetics

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 parameters2. Make predictions about the kinetic behavior of a tumor

based on a mathematical model3. Define growth rate and exponential growth4. Develop a differential equations describing tumor

growth5. Use WolframAlpha to solve algebraic equations and take

limits

Page 4: Cancer Tumor Kinetics

Prerequisites1. Volume of a sphere2. Straight lines3. Natural logarithm and exponential functions4. Graphing in Excel5. Logarithmic transformation6. Fitting a straight line to data points in Excel and

displaying the equation

Page 5: Cancer Tumor Kinetics

Knowledge Gained1. Continuous time population models2. Fitting a straight line to data3. Doubling time of an exponentially growing

population4. Growth rate and exponential growth

Page 6: Cancer Tumor Kinetics

Concept Map

Page 7: Cancer Tumor Kinetics

New Cases of Cancer 2011

Map from American Cancer Society. Cancer Facts & Figures 2011. Atlanta: American Cancer Society; 2011.

Page 8: Cancer Tumor Kinetics

Cancer Tumor KineticsThe growth and spread of the cancer tumorTumor metastasis and survival rates

Table from American Cancer Society. Cancer Facts & Figures 2011. Atlanta: American Cancer Society; 2011.

Page 9: Cancer Tumor Kinetics

Why model cancer tumor kinetics?

Page 10: Cancer Tumor Kinetics

Case StudyPatient with breast cancer tumor and growth of

(untreated) tumor over timeDiameter (mm)

Measurement Date D1 D2 D31 06/26/69 4 4 42 11/27/69 5 4 63 11/24/70 7 8 94 07/06/71 11 12 145 08/17/73 29 33 316 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

Questions to AnswerWhen will the patient die?

Lethal burden of tumorWhen did the cancer start?

Depends on growth rate (doubling time)

Page 12: Cancer Tumor Kinetics

Model Assumptions1. The shape of a tumor is a sphere2. A tumor is a solid mass of tumor cells3. An individual tumor cell is a sphere with

diameter

4. 1 gram of tumor cells corresponds to 109 cells

Page 13: Cancer Tumor Kinetics

Create the Model: Background Information

Volume of a sphere with radius, r:

Page 14: Cancer Tumor Kinetics

Create the Model: Background Information

Volume of a sphere with radius, r:

Page 15: Cancer Tumor Kinetics

Create the Model: Background Information

Volume of a sphere with radius, r:

Relationship between diameter, d, and radius, r:

Page 16: Cancer Tumor Kinetics

Create the Model: Background Information

Volume of a sphere with radius, r:

Relationship between diameter, d, and radius, r:

Page 17: Cancer Tumor Kinetics

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

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

Page 18: Cancer Tumor Kinetics

Think, Pair, Share:Create the Model

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

5:00

Page 19: Cancer Tumor Kinetics

Think, Pair, Share:Create the Model

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

4:00

Page 20: Cancer Tumor Kinetics

Think, Pair, Share:Create the Model

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

3:00

Page 21: Cancer Tumor Kinetics

Think, Pair, Share:Create the Model

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

2:00

Page 22: Cancer Tumor Kinetics

Think, Pair, Share:Create the Model

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

1:00

Page 23: Cancer Tumor Kinetics

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 24: Cancer Tumor Kinetics

Create the ModelThe number of cells in any tumor is

Page 25: Cancer Tumor Kinetics

Create the ModelThe number of cells in any tumor is

Page 26: Cancer Tumor Kinetics

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

of the tumor is

Page 27: Cancer Tumor Kinetics

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 tumord. Column J: Weight of the tumor

10:00

Page 28: Cancer Tumor Kinetics

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 tumord. Column J: Weight of the tumor

9:00

Page 29: Cancer Tumor Kinetics

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 tumord. Column J: Weight of the tumor

8:00

Page 30: Cancer Tumor Kinetics

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 tumord. Column J: Weight of the tumor

7:00

Page 31: Cancer Tumor Kinetics

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 tumord. Column J: Weight of the tumor

6:00

Page 32: Cancer Tumor Kinetics

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 tumord. Column J: Weight of the tumor

5:00

Page 33: Cancer Tumor Kinetics

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 tumord. Column J: Weight of the tumor

4:00

Page 34: Cancer Tumor Kinetics

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 tumord. Column J: Weight of the tumor

3:00

Page 35: Cancer Tumor Kinetics

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 tumord. Column J: Weight of the tumor

2:00

Page 36: Cancer Tumor Kinetics

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 tumord. Column J: Weight of the tumor

1:00

Page 37: Cancer Tumor Kinetics

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 tumord. Column J: Weight of the tumor

Time to Share!

Page 38: Cancer Tumor Kinetics

Create the ModelExcel Time!

Page 39: Cancer Tumor Kinetics

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?

5:00

Page 40: Cancer Tumor Kinetics

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?

4:00

Page 41: Cancer Tumor Kinetics

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?

3:00

Page 42: Cancer Tumor Kinetics

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?

2:00

Page 43: Cancer Tumor Kinetics

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?

1:00

Page 44: Cancer Tumor Kinetics

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 45: Cancer Tumor Kinetics

Kinetics ModelExcel Time!

Page 46: Cancer Tumor Kinetics

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.

5:00

Page 47: Cancer Tumor Kinetics

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.

4:00

Page 48: Cancer Tumor Kinetics

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.

3:00

Page 49: Cancer Tumor Kinetics

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.

2:00

Page 50: Cancer Tumor Kinetics

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.

1:00

Page 51: Cancer Tumor Kinetics

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 52: Cancer Tumor Kinetics

Kinetics ModelExcel Time!

Page 53: Cancer Tumor Kinetics

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?

10:00

Page 54: Cancer Tumor Kinetics

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?

9:00

Page 55: Cancer Tumor Kinetics

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?

8:00

Page 56: Cancer Tumor Kinetics

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?

7:00

Page 57: Cancer Tumor Kinetics

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?

6:00

Page 58: Cancer Tumor Kinetics

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?

5:00

Page 59: Cancer Tumor Kinetics

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?

4:00

Page 60: Cancer Tumor Kinetics

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?

3:00

Page 61: Cancer Tumor Kinetics

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?

2:00

Page 62: Cancer Tumor Kinetics

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?

1:00

Page 63: Cancer Tumor Kinetics

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 64: Cancer Tumor Kinetics

Kinetics ModelExcel Time!

Page 65: Cancer Tumor Kinetics

Doubling Time

Page 66: Cancer Tumor Kinetics

Doubling Time

Page 67: Cancer Tumor Kinetics

Doubling Time

Page 68: Cancer Tumor Kinetics

Doubling Time

Page 69: Cancer Tumor Kinetics

Doubling Time

Page 70: Cancer Tumor Kinetics

Doubling Time

Page 71: Cancer Tumor Kinetics

Doubling Time

Page 72: Cancer Tumor Kinetics

Doubling TimeThen, the doubling time does not depend on the

number of cells present.

Page 73: Cancer Tumor Kinetics

Doubling TimeI forget how to do this!

WolframAlpha

Page 74: Cancer Tumor Kinetics

Think, Pair, Share:Doubling Time

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

3:00

Page 75: Cancer Tumor Kinetics

Think, Pair, Share:Doubling Time

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

2:00

Page 76: Cancer Tumor Kinetics

Think, Pair, Share:Doubling Time

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

1:00

Page 77: Cancer Tumor Kinetics

Think, Pair, Share:Doubling Time

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

Time to Share!

Page 78: Cancer Tumor Kinetics

Think, Pair, Share:Doubling Time

1. Excel time!

Page 79: Cancer Tumor Kinetics

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 parameters2. Make predictions about the kinetic behavior of a tumor

based on a mathematical model3. Define growth rate and exponential growth4. Develop a differential equations describing tumor growth5. Use WolframAlpha to solve algebraic equations and take

limits

Page 80: Cancer Tumor Kinetics

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 10116 25

Kidney 66 5132 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