Patient Guide to Colon Cancer Surgery and Treatment GHI30033_1011 Key Points: This slide deck provides basic information on the diagnosis and treatment of colon cancer. The materials provided encourage patients to learn as much as they can about colon cancer. The slides also assist patients by providing the right questions to ask and to discuss all options with their physician.

Table of Contents Colon anatomy About colon cancer Characterizing your cancer Your treatment decision Oncotype DX® Your treatment profile My Colon Cancer Coach Resources [Review information on slide] 2

Where to Begin Learn all you can about colon cancer Find the best care that gives you confidence Feel comfortable talking with your healthcare team Understand your diagnosis and treatment plan Keep track of how you are feeling Stay involved in all treatment decisions [Review information on slide] 3

Anatomy of the Colon Transverse Colon Descending Colon Ascending Colon Blood Vessels Lymph Nodes Sigmoid Colon Cecum Rectum Key Points: The cecum is connected to the ileum and is the first part of the colon The ascending colon travels up the right side of the body from the cecum The transverse colon runs across the abdomen, just below the stomach The descending colon runs down the left side of the body The sigmoid colon is a short, S-shaped section of the colon just before the rectum The rectum is the last section of the colon The anus is an opening at the end of the digestive tract through which wastes are expelled from the body Blood vessels supply oxygen and nutrients to tissues of the colon Lymph nodes are part of the lymphatic system. The lymphatic system drains and filters fluids from cells and is an important part of the immune system Anus 4

What is Colon Cancer? Colon cancer develops over a number of years and usually begins with the growth of a polyp (a benign tumor). Some types of polyps can become malignant tumors and grow into the wall of the colon and spread further into tissues of the colon, blood vessels and nearby lymph nodes. There are different types of colon cancer. Most are a type called adenocarcinoma. Others such as carcinoid tumors and gastrointestinal stromal tumors (GISTs) are less common. Colon Ascending Colon Tumor [Review information on slide] Polyps Cecum 5

What Causes Colon Cancer Several known risk factors are associated with colon cancer. Colon cancers results from changes in DNA (deoxyribonucleic acid) within the cells. Changes (mutations) can be inherited or acquired during a person’s lifetime. The majority of patients acquire mutations in their colon cells that results in malignant tumors over time. A small percentage of colon cancer patients have inherited a susceptibility to colon cancer. [Review information on slide] 6

How Colon Cancer Is Diagnosed Physical exam Review of medical history Review of family history Symptoms Blood in the stool Increased stomach discomfort Changes in bowel habits Unexplained weight loss Constant or unexplained fatigue and weakness Medical Consultation Diagnostic Tests Key Points: During your medical consultation, your physician will collect information such as symptoms and information from a physical review as well as review your medical history and your family’s medical history You will also undergo a series of diagnostic tests, including a biopsy , which is required for a definitive diagnosis of colon cancer Colonoscopy Sigmoidoscopy Imaging Blood 7

Diagnostic Tests Procedures Imaging Blood Tests Colonoscopy: A method used to view the entire colon (looking for polyps and suspicious growth). Sigmoidoscopy: A method used to view the sigmoid portion of the colon (looking for polyps and suspicious growth). Imaging Chest X-ray, CT (computed tomography) scan, MRI (magnetic resonance imaging), and PET (positron emission tomography) will provide accurate details of the colon and other organs. Key Points: There are a number of diagnostic tests (procedures, imaging, and blood tests) that can assist a physician in detecting if colon cancer is present. Colonoscopy: During this test, a lighting instrument called a colonoscope examines the entire colon. Precancerous and cancerous growths throughout the colon can be found and either removed or biopsied, including growths on the upper part of the colon which would be missed by a sigmoidoscopy Sigmoidoscopy: During this test, a lighted instrument called a sigmoidoscope examines the rectum and lower colon. Precancerous and cancerous growths can be found and either removed or biopsied Imaging tests are used to provide accurate details about the colon and other organs. Another important part of a patient’s evaluation is blood work. Blood tests are used to see if an indication of colon cancer is present; they are also used throughout treatment to monitor the patient’s overall health and organ function. Blood Tests CEA (carcinoembryonic antigen) indicates the presence of colon cancer. CBC (complete blood count) rules out anemia due to blood loss from a bleeding tumor. Metabolic panel assesses organ function (such as kidneys or liver function). 8

Biopsy During a colonoscopy or surgical procedure, tissue samples are collected and sent to a pathologist for review. The pathologist examines the biopsy samples under a microscope and may also perform genetic testing on them. A biopsy is performed on all polyps removed during a colonoscopy as well as on tissue removed during a surgical procedure. A biopsy is required for a colon cancer diagnosis. [Review information on slide] 9

The Pathology Report Tumor cell type: The kind of cells that form your tumor. Tumor grade: Describes how different cells in the tumor appear, compared to normal cells in the colon. The higher the grade, the more the cells differ from normal. For example, low-grade tumor cells look like normal cells, while high-grade tumor cells look different from normal cells. Tumor depth: How far the tumor has grown or spread into surrounding tissues. Tumor size: Usually reported in millimeters or centimeters (1 cm = 10 mm = 0.4 inches). Key Points: The pathology report provides detailed information about your colon cancer. This information is obtained from tests performed on the biopsy sample or surgical sample taken from your tumor. It is important to discuss the pathology report with your physician as soon as the results are available. The information on your pathology report along with other factors, including your age, general health, and medical and family history help you and your doctor make treatment decisions. Tumor cell type is also known as histologic subtype, this is how a pathologist classifies the type of tumor a patient has. Terms such as adenocarcinoma, mucinous, small cell, squamous are a few terms used to describe tumor cells. Colon cancer grading “Grade” is a term used to describe how closely the cells in your tumor resemble normal tissue cells under a microscope. The higher the grade, the more the cells differ from normal. For example, low grade tumor cells look like normal cells, while high grade tumor cells look different from normal cells. The tumor grade is more important for some types of tumors than others Tumor depth measures how far the tumor has grown or spread into the surrounding tissues, terms such as tumor extension, invasion and margins are all used to describe the depth of the tumor Tumor size is measured in millimeters or centimeters and can easily be remembered by comparing coins, fruit and other objects that are approximate representations of tumor sizes Pea, peanut, walnut, and lime show tumor sizes. 10 ©Terese Winslow U.S. Govt has certain rights

The Pathology Report (cont’d) Surgical margins • Negative margins – cancer was entirely removed during surgery. • Positive margins – residual cancer cells may remain following surgery. Lymphovascular involvement: Whether the blood vessels and lymphatic drainage system have been invaded by cancer cells. Lymph node status: Whether or not cancer is detected in lymph nodes removed during surgery. Mismatch repair (MMR) status: Tests for mismatch repair deficiency (MMR-D), an acquired or inherited biological feature associated with some types of colon cancers. Knowing your MMR status may help you and your doctor in making treatment decisions. Studies have shown that stage II colon cancer patients with MMR-deficient (MMR-D) tumors have a lower risk of recurrence compared to patients with MMR-proficient (MMR-P) tumors. Key Points: Surgical margin is used in the pathology report to describe how much cancer was removed and the amount of normal tissue that is a part of the sample Lymphovascular involvement defines if blood vessels and lymphatic drainage systems have been invaded by cancer cells Lymph node (LN) status is used to describe whether cancer has invaded the lymph nodes removed during surgery; LN status also assists physicians with tumor staging Mismatch repair testing is helpful in making treatment decisions. Studies have shown that stage II colon cancer patients with MMR-deficient (MMR-D) tumors have a lower risk of recurrence compared to patients with MMR-proficient (MMR-P) tumors. 11

Pathology Report Example Key Points: The pathology report is the key to a patient’s diagnosis and treatment Not all pathology reports look the same and some of the information can be difficult to understand It is important to discuss the pathology report with your physician as soon as the results are available. It will be helpful to have a copy of your pathology report on hand when looking into educational resources within the online community 12 College of American Pathologists. http://www.cap.org/apps/cap.portal Accessed September 28th, 2011. Based on AJCC/UICC TNM, 7th edition. October 2009.

Colon Cancer Staging The TNM System T (Tumor): Tumor size and location Key Points: Staging is a method of organizing information about your colon cancer that helps your doctor to describe your tumor and how far it has spread. It gives physicians a common language and is useful for deciding on treatment options following surgery. Staging is usually done after the tumor is removed and the lymph nodes have been examined. Staging is based on three criteria: T (Tumor) – the tumor size and location N (Nodes) – whether any lymph nodes are involved M (Metastasis) – whether the cancer has spread beyond the lymph nodes. Numbers or letters are added after T, N and M to provide additional information. For example: TX means primary tumor cannot be assessed and the numbers associated with T0-T4 refer to the extent of tumor invasion N1 means metastasis in 1–3 lymph nodes M0 means no distant metastasis. The TNM System T (Tumor): Tumor size and location N (Nodes): Whether any lymph nodes are involved M (Metastasis): Tumor has spread to other organs 13

Treatment Approaches Treatment Decisions Surgery: Removal of cancerous part of colon (colectomy) Chemotherapy: Drugs that kill cancer cells Targeted therapy: Drugs that disrupt cancer cell growth Radiation: Uses high energy X-rays to destroy cancer cells Treatment Decisions Additional tumor testing, such as the Oncotype DX® colon cancer test, can further guide treatment decisions, including whether to undergo chemotherapy following surgery. Oncotype DX can help people with certain types of colon cancer learn more about the biological features of their specific tumor and how likely it is that their cancer might return in the future. Key Points: There are several conventional approaches to the treatment of colon cancer Before making any treatment decisions, be sure to discuss your options and their potential effects with your physician Surgery: For early stage cancers, a local excision may be performed where the doctor may remove the cancer without cutting the abdominal wall. If the cancer is larger, the doctor will perform a partial colectomy (removing the cancer and a small amount of healthy tissue around it). The doctor may then perform an anastomosis to sew the healthy parts of the colon together Chemotherapy: Cancer treatments that use drugs to stop the growth of cancer cells by either killing the cells or stopping them from dividing and growing Targeted Therapy: A type of treatment that uses drugs or other substances to identify and attack specific cancer cells without harming normal cells. Monoclonal antibodies are a type of targeted therapy used in the treatment of colon cancer Radiation: A cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or stop them from growing 14

Treatment by Stage I II III IV Recur Local Surgery (removal of polyps or larger tumors) Surgery followed by observation I Surgery followed by chemotherapy or observation II Surgery followed by chemotherapy III Surgery, chemotherapy, radiation, targeted therapy IV Surgery if recurrence is local; chemotherapy, targeted therapy, radiation as required Recur Key Points: When developing a colon cancer treatment plan, it is important to consider the stage of your cancer Depending on the stage, more than one treatment approach may be used 15

Understanding Your Risk of Recurrence After Surgery One of the challenges in treating patients with colon cancer is determining the risk that the disease will return after surgery and determining the need for post-surgical chemotherapy. For patients with stage II colon cancer, the Oncotype DX® colon cancer test provides additional insight into an individual’s risk of recurrence based on the patient’s unique tumor biology, independent of T-stage, node involvement, and MMR status. The Oncotype DX Colon Cancer test looks at the activity of 12 genes in a sample taken from your colon cancer tumor sample in order to provide a Recurrence Score® result. The Recurrence Score has been shown to be valuable in patients with early-stage (stage II), lymph node-negative colon cancer. Key Points: If you have stage II colon cancer, the Oncotype DX® test is a gene-based diagnostic test that will help you learn more about your specific tumor and the likelihood of cancer recurrence. The decision to use the Oncotype DX test depends on a number of factors and should be discussed with your doctor. 16

Oncotype DX® Colon Cancer Test Results Your Colon Cancer Recurrence Score® Your Risk of recurrence at 3 years Key Points: A common challenge in treating patients with colon cancer is determining the risk that the disease will return after surgery and determining the need for post-surgical chemotherapy For patients with stage II colon cancer, the Oncotype DX® Colon Cancer Test provides additional insight into an individual’s risk of recurrence based on the patients unique tumor biology, independent of TNM staging and MMR status A detailed Oncotype DX Colon Cancer Test Patient Report is generated for each patient, with test results provided as a Recurrence Score® result on a scale from 0-100. The report also includes information to aid in interpreting the result Page 1 of the report provides the RS both numerically and graphically. Page 1 also provides the patient’s risk of recurrence at 3 years 17

Oncotype DX® Colon Cancer Test Results (cont’d) Key Points: On page 2 of the report (shown on this slide) shows the patient’s individual RS result displayed in context of tumor staging and MMR status recurrence risks. The three curves represent the RS functions for three groups: T4, MMR-Proficient patients; T3, MMR-Proficient patients; and T3, MMR-Deficient patients. 18

Informing Treatment Decisions The Recurrence Score® result The Oncotype DX® colon cancer test looks at the activity of 12 genes in a sample taken from your colon cancer tumor sample in order to provide a Recurrence Score. The Recurrence Score result has been shown to be valuable in patients with early-stage (stage II), lymph node–negative colon cancer. How is the test performed? The Oncotype DX test is performed on tissue removed during your initial surgery (resection). Results are typically provided 7 to 10 calendar days from the date laboratory processing begins. Results will be sent to the doctor treating you and the pathologist who submitted the sample. As with any laboratory test, an authorized healthcare provider, such as your surgeon or oncologist, must order and deliver the Oncotype DX test results. [Review information on slide] 19

Steps to Consider in Treatment Planning 1 3 5 SCREENING Colonoscopy Sigmoidoscopy SURGERY Resection Anastomosis Oncotype DX® TESTING 2 4 6 DIAGNOSIS Biopsy Imaging DEFINITIVE DIAGNOSIS Resection Pathology evaluation MMR ADJUVANT TREATMENT DECISION Chemotherapy No treatment Recurrence and MMR status: Knowing your MMR status may help you and your doctor in making treatment decisions. Studies have shown that stage II colon cancer patients with MMR-deficient (MMR-D) tumors have a lower risk of recurrence compared to patients with MMR-proficient (MMR-P) tumors. 20

Am I eligible for the test? You may be a candidate for the Oncotype DX test if: You have recently been diagnosed with stage II colon cancer, and you and your doctor are making treatment decisions regarding chemotherapy. The decision whether or not to order the Oncotype DX test is one that you and your doctor should make together. [Review information on slide] 21

Does my insurance cover the Oncotype DX® test? Genomic Health offers the Genomic Access Program (GAP), a comprehensive program designed to help you with the coverage process and provide financial assistance when necessary, based on eligibility. Expanding payor coverage by both public and private payors. Please call 866-ONCOTYPE (866-662-6897) for more information on insurance and financial aid questions. [Review information on slide] 22

What will I learn from the Oncotype DX® colon cancer test? Your doctor will receive a report with the results of your Oncotype DX colon cancer test. The report contains your Recurrence Score® result, which is a number between 0 and 100. It provides a specific estimate of your risk of colon cancer recurrence within 3 years of surgery. Individuals with a lower Recurrence Score have a lower risk of their colon cancer recurring. Individuals with a higher Recurrence Score have a higher risk of their colon cancer recurring. A Recurrence Score result, along with other information, can help you and your physician make a more informed, individualized treatment decision. It is important to understand that having a lower Recurrence Score result does not mean that there is no chance that your colon cancer will return. Likewise, having a higher Recurrence Score does not mean that your colon cancer will definitely return. [Review information on slide] 23

Patient Ambassador: Dan Clementi, Oncotype DX® Colon Cancer Patient Click here to watch Dan’s story. http://www.oncotypedx.com/en-US/Colon/PatientCaregiver/PatientStories.aspx [Video plays without click] 24

Personalized Treatment Options Questions to Ask Your Doctor My Colon Cancer Coach www.mycoloncancercoach.org Colon Cancer 101 Personalized Treatment Options Questions to Ask Your Doctor Key Points: In addition to learning more about your personal treatment options based on your specific diagnosis, MyColonCancerCoach.org also provides general information about colon cancer Colon Cancer 101: An overview of the disease, from warning signs to different stages and methods for detection Questions for your Doctor: Questions to ask your health care providers to guide discussions and help you take an active role in your health care decisions Guidance: Dr. Richard Goldberg, Distinguished Professor of Gastrointestinal Cancer and Research and Associate Director for Clinical Research at the University of North Carolina’s Lineberger Comprehensive Cancer Center, explains each step of My Colon Cancer Coach as you progress through the site Tools for Sharing: With the click of a button, you can email or share resources online and tell others about My Colon Cancer Coach

Free online tool designed specifically for patients MyColonCancerCoach.org Free online tool designed specifically for patients Answer a few short questions to receive your personalized treatment options report [Review information on slide] To answer the questions, you’ll need the following information: The stage of your cancer Your tumor’s MMR/MSI status (for stage II) Whether or not your tumor contains a mutated KRAS gene (for stage IV) Whether or not your cancer has metastasized (spread to areas beyond your colon)) 26

A Report to Make Sense of Your Diagnosis [Review information on slide] E-mail Summary Printed Report 27

What to Ask Your Doctor How do I obtain a copy of my pathology report and testing information? How large and at what stage is my tumor? Is there a way to tell how quickly my cancer is growing or if it is invasive? How likely is my cancer to spread? Am I a candidate for the Oncotype DX®1,2 test, or other tumor specific tests? Am I going to need radiation or chemotherapy and if so, what can I expect during that period of time? Has my cancer metastasized? How quickly can I expect to recover? What is my risk of having the cancer come back (recurrence)? What can I do to help prevent the return of my cancer? How often do you recommend I be screened for recurrent cancer? Do you have any recommendations for support groups? [Review information on slide] 28

Resources Patient Key Points: www.cancercare.org www.cancer.org www.fightcolorectalcancer.org Patient http://cancersupportcommunity.org/ www.cancer.gov Key Points: The world wide web has several patient-focused resources available. Many of the listed organizations provide information on colon cancer prevention, treatment, staying healthy, research and community activities. The websites provided are an excellent resource for educational materials, including information on colon cancer, clinical trials, ongoing research and patient support. The American Cancer Society (cancer.org) The Cancer Support Community (cancersupportcommunity.org) The Colon Cancer Alliance (ccalliance.org) Fight Colorectal Cancer (fightcolorectalcancer.org) The National Cancer Institute (cancer.gov) Cancer Care (cancercare.org) My Colon Cancer Coach is the first patient-focused, interactive online tool where newly diagnosed colon cancer patients can learn more about their disease. The site includes a questionnaire that takes less than 10 minutes to complete and provides patients with information unique to their diagnosis, including personalized treatment options to discuss with their physician. (mycoloncancercoach.org) www.mycoloncancercoach.org www.ccalliance.org 29

Oncotype DX® Colon Cancer Assay Make it part of the conversation, and make the informed, more individualized treatment decision. 30

BACK UP SLIDES 31

Colon Cancer Staging T (Tumor): Tumor size and location Key Points: Staging is a method of organizing information about your colon cancer that helps your doctor to describe your tumor and how far it has spread. It gives physicians a common language and is useful for deciding on treatment options following surgery. Staging is usually done after the tumor is removed and the lymph nodes have been examined. Staging is based on three criteria: T (Tumor) – the tumor size and location N (Nodes) – whether any lymph nodes are involved M (Metastasis) – whether the cancer has spread beyond the lymph nodes. Numbers or letters are added after T, N and M to provide additional information. For example: TX means primary tumor cannot be assessed and the numbers associated with T0-T4 refer to the extent of tumor invasion N1 means metastasis in 1–3 lymph nodes M0 means no distant metastasis. The TNM System T (Tumor): Tumor size and location N (Nodes): Whether any lymph nodes are involved M (Metastasis): Tumor has spread to other organs 32 Image adapted from The National Cancer Institute