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IntroductionColorectal cancer (CRC) refers to malignant neoplasms that develop in the epithelium of the colon or rectum. Usually, CRC develops from adenomatous polyps.1 They are very common, and there are several types and subtypes. However, a very small percentage of adenomatous polyps become malignant.1,2

*Based on 5-year relative survival rates

Incidence It is estimated there will be approximately 135,000 new cases of CRC in the U.S. this year5

CRC is the:

• 3rd most commonly diagnosed cancer worldwide5

• 3rd leading cause of cancer-related deaths in the U.S.6

As with other types of cancer, the risk of developing CRC increases with age.5

CRC is slightly more common in men than women6

Common Metastatic Sites Approximately 20% of patients have metastatic CRC at diagnosis.7

Most common metastatic site:7,8

• Liver

n CRC will metastasize to the liver in about 50% of patients

nThis is believed to be caused by the colon and rectum’s venous drainage

Other common sites:7

• Lung

• Bone

• Central nervous system (specifically the brain)

Stages of CancerCRC staging is based on the TNM system developed by the American Joint Committee on Cancer3:

• T = Tumor • N = Node • M = Metastasis

Stage is a significant factor in determining a patient’s treatment plan and prognosis. Early diagnosis is important, as survival rates for each stage decrease.4

Stage3 Description3Overall Survival Rates*4

Colon Cancer Rectal Cancer

0Cancer has not spread beyond the mucosa (inner lining) of the colon or rectum.

N/A N/A

The tumor:

• Has grown through mucosa into submucosa and possibly into muscularis propria

• Has not spread to lymph nodes or to distant sites

92% 87%

The tumor:

• Has grown beyond the muscularis propria into pericolorectal tissues

• May have grown to the surface of visceral peritoneum or invaded other organs or structures

• Has not spread to lymph nodes or distant sites

63%-87% 49%-80%

The tumor:

• Has invaded submucosa, muscularis propria, and regional lymph nodes

• Has not spread to distant lymph nodes or distant sites

53%-89% 58%-84%

IVThe tumor has spread to at least one distant organ or distant set of lymph nodes. It may be located in any layer of the colon or rectum.

11% 12%

References 1. Levin B, Lieberman DA, McFarland B, et al. Screening and surveillance for the early detection of colorectal cancer and adenomatous polyps,

2008: a joint guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology. CA Cancer J Clin. 2008;58:130-160. doi:10.3322/CA.2007.0018.

2. American Cancer Society. Understanding your pathology report: Colon polyps (sessile or traditional serrated adenomas). www.cancer.org/treatment/understanding-your-diagnosis/tests/understanding-your-pathology-report/colon-pathology/colon-polyps-sessile-or-traditional-serrated-adenomas.html. Updated February 27, 2017. Accessed October 9, 2017.

3. American Cancer Society. Colorectal cancer stages. www.cancer.org/cancer/colon-rectal-cancer/detection-diagnosis-staging/staged.html. Revised March 2, 2017. Accessed October 6, 2017.

4. American Cancer Society. What are the survival rates for colorectal cancer, by stage? www.cancer.org/cancer/colon-rectal-cancer/detection-diagnosis-staging/survival-rates.html. Revised March 2, 2017. Accessed October 3, 2017.

5. National Cancer Institute. Rectal cancer treatment (PDQ®)–Health professional version. www.cancer.gov/types/colorectal/hp/rectal-treatment-pdq. Revised April 27, 2017. Accessed September 30, 2017.

6. Marley A, Nan H. Epidemiology of colorectal cancer. Int J Mol Epidemiol Genet. 2016;7(3):105-114.

7. Qiu M, Hu J, Yang D, Cosgrove DP, Xu R. Pattern of distant metastases in colorectal cancer: a SEER based study. Oncotarget 2015;6(36):38568-38666.

8. Vatandoust S, Price TJ, Karapetis CS. Colorectal cancer: metastases to a single organ. World J Gastroenterol. 2015;21(41):11767-11776. Published November 7, 2015. doi:10.3748/wjg.v21.i41.11767.

9. Summers RM. Polyp size measurement at CT colonography: what do we know and what do we need to know? Radiology. 2010;255(3):707-720. Published June 2015. doi:10.1148/radiol.10090877.

10. Sandmeier D, Seelentag W, Bouzourene H. Serrated polyps of the colorectum: is sessile serrated adenoma distinguishable from hyperplastic polyp in a daily practice? Virchows Arch. 2007;450:613-618. Published April 21, 2007. doi:10.1007/s00428-007-0413-8.

11. Yang JF, Tang S-J, Lash, RH; Wu R, Yang Q. Anatomic distribution of sessile serrated adenoma/polyp with and without cytologic dysplasia. Arch Pathol Lab Med. 2015;139:388-393. doi:10.5858/arpa.2013-0523-OA.

12. Bujanda L, Cosme A, Gil I, Arenas-Mirave, JI. Malignant colorectal polyps. World J Gastroenterol. 2010;16(25):3103-3111. doi:10.3748/wjg.v16.i25.3103.

13. Rittershaus AC, Appelman HD. Benign gastrointestinal mesenchymal BUMPS: a brief review of some spindle cell polyps with published names. Arch Pathol Lab Med. 2011;135:1311-1319. doi:10.5858/arpa.2011-0038-RA.

14. Kalimuthu SN, Chelliah A, Chetty R. From traditional serrated adenoma to tubulovillous adenoma and beyond. World J Gastrointest Oncol. 2016;8(12):805-809. doi:10.4251/wjgo.v8.i12.805.

15. National Cancer Institute. Genetics of colorectal cancer (PDQ®)–Health professional version. www.cancer.gov/types/colorectal/hp/colorectal-genetics-pdq. Revised August 14, 2017. Accessed October 1, 2017.

16. National Comprehensive Cancer Network. Clinical practice guidelines in oncology (NCCN Guidelines®): Rectal cancer. Version 3.2017. Published March 13, 2017. www.nccn.org/professionals/physician_gls/pdf/rectal.pdf. Accessed October 3, 2017.

17. Sorich MJ, Wiese MD, Rowland A, et al. Extended RAS mutations and anti-EGFR monoclonal antibody survival benefit in metastatic colorectal cancer: a meta-analysis of randomized, controlled trials. Ann Oncol. 2015;26:13-21. doi:10.1093/annonc/mdu378.

18. Al-Shamsi HO, Alhazzani W, Wolff RA. Extended RAS testing in metastatic colorectal cancer—refining the predictive molecular biomarkers. J Gastrointest Oncol. 2015;6(3):314-321. doi:10.3978/j.issn.2078-6891.2015.016.

19. Yaeger R, Saltz L. BRAF mutations in colorectal cancer: clinical relevance and role in targeted therapy. J Natl Compr Canc Netw. 2012;10(11):1456-1458.

20. Hampel H. Genetic testing for hereditary colorectal cancer. Surg Oncol Clin N Am. 2009;18(4):687. doi:10.1016/j.soc.2009.08.001.

21. National Institutes of Health. Familial adenomatous polyposis. https://ghr.nlm.nih.gov/condition/familial-adenomatous-polyposis. Published September 26, 2017. Accessed October 2, 2017.

22. National Institutes of Health. Lynch syndrome. https://ghr.nlm.nih.gov/condition/lynch-syndrome. Published September 26, 2017. Accessed October 2, 2017.

23. Stigliano V, Sanchez-Mete L, Martayan A, et al. Early-onset colorectal cancer: a sporadic or inherited disease? World J Gastroenterol. 2014;20(35):12420-12430. doi:10.3748/wjg.v20.i35.12420.

24. Jang E, Chung DC. Hereditary colon cancer: lynch syndrome. Gut and Liver. 2010:4(2):151-160. doi:10.5009/gnl.2010.4.2.151.

25. National Comprehensive Cancer Network. Clinical practice guidelines in oncology (NCCN Guidelines®): Colorectal cancer screening. Version 1.2017. Published May 22, 2017. www.nccn.org/professionals/physician_gls/PDF/colorectal_screening.pdf. Accessed October 3, 2017.

26. National Cancer Institute. Colon cancer treatment (PDQ®)–Health professional version. www.cancer.gov/types/colorectal/hp/colon-treatment-pdq#section/_1. Accessed September 29, 2017.

27. National Comprehensive Cancer Network. Clinical practice guidelines in oncology (NCCN Guidelines®): Colon cancer. Version 2.2017. Published March 13, 2017. www.nccn.org/professionals/physician_gls/pdf/colon.pdf. Accessed October 3, 2017.

28. National Cancer Institute. Dictionary of cancer terms: Embolization. www.cancer.gov/publications/dictionaries/cancer-terms?cdrid=46436. Accessed October 3, 2017.

29. American Cancer Society. Targeted therapy drugs for colorectal cancer. www.cancer.org/cancer/colon-rectal-cancer/treating/targeted-therapy.html. Accessed October 23, 2017.

30. American Cancer Society. Immunotherapy for colorectal cancer. www.cancer.org/cancer/colon-rectal-cancer/treating/immunotherapy.html. Accessed October 23, 2017.

AVC/102017/0022a 2017 © One World DMG

Colorectal CancerLungs

Mucosa

Tumors

SubmucosaMuscularis propriaPericorectal tissues

Lymph node

II III

Nervous system

GI Tract

Understanding

CRC is the:

• Liver

• Lung

• Bone

N/A N/A

The tumor:

92% 87%

The tumor:

63%-87% 49%-80%

The tumor:

53%-89% 58%-84%

11% 12%

Mucosa

Tumors

Lymph node

II III

Nervous system

GI Tract

Understanding

CRC is the:

• Liver

• Lung

• Bone

N/A N/A

The tumor:

92% 87%

The tumor:

63%-87% 49%-80%

The tumor:

53%-89% 58%-84%

11% 12%

Mucosa

Tumors

Lymph node

II III

Nervous system

GI Tract

Understanding

Types of Polyps

Precursor LesionsAdenomatous polyps are the most common type of polyp to develop into CRC. They develop from glandular tissue in the epithelium and are called adenocarcinoma when they become cancerous.1,2

Genetics

There are 3 categories of CRC based on genetic risk15: • Sporadic: no hereditary

component; caused by somatic variants

• Familial: family history that may be caused by common nongenetic risk factors and/or genetic risk factors; may be somatic or germline

• Hereditary: a germline variant (mutation) is present

Polyposis

Adenomatous polyposis syndromes21:

• Familial adenomatous polyposis (FAP) and attenuated FAP (AFAP)

- Involves the APC gene

• MUTYH-associated polyposis (MAP)

- Involves the MUTYH gene

Hamartomatous polyposis syndromes20:

• Juvenile Polyposis syndrome (JPS)

• Peutz-Jeghers syndrome (PJS)

• Hyperplastic Polyposis syndrome (HPS)

• PTEN Hamartomatous Tumor syndrome

Genetic Testing in mCRCGenetic testing typically looks for:

Mutations in the following genes, both of which are resistant to anti-EGFR therapy16,17:

• KRAS and NRAS (referred to as extended RAS analysis): associated with about 50-55% of mCRC16-18

• BRAF: associated with 5%-10% of mCRC19

Microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) mCRC, about 5% of mCRC16

Nonpolyposis

Lynch syndrome

• Most common hereditary CRC20

• Requires more complicated testing than that required for polyposis20

• Involves genes MLH1, MLH2, MSH6, PMS2, and EPCAM22

• Has an early age of onset23

• Often involves proximal colon24

There are 2 forms of hereditary CRC20:

Serrated polyps have a saw-tooth appearance under the microscope and are typically benign.2

Generally9

Higher risk of becoming cancerous:

Larger polyps (> 1 cm)

Lower risk of becoming cancerous:

Smaller polyps (< 1 cm)

Malignant lesionsA polyp is malignant when it has invaded the submucosa.12

Benign LesionsSome types of lesions are typically benign10,13:

• Hyperplastic polyps • Lymphoid aggregates

• Hamartomas • Inflammatory polyps

Tubular polyps—small tube-shaped polyps2

Villous adenoma—villous growth pattern; more likely to become cancerous2 Sessile serrated

adenomas—most commonly found in the proximal colon10,11

Traditional serrated adenoma—the least common type of serrated polyp14

Hyperplastic polyps—the most common type of serrated polyp. These are often found in the distal part of the colon and rectum. They are usually smaller than 5 mm and rarely become cancerous.9,10

Screening

Average-risk patients ≥ 50 years old25

Every year (followed by a colonoscopy if test results are positive):

• Fecal immunochemical test (FIT)

• Guaiac-based fecal occult blood test (gFOBT)

Every 3 years (followed by a colonoscopy if test results are positive): FIT-DNA test (also referred to as the stool DNA test)

Every 5 years (followed by a colonoscopy if test results are positive):

• CT colonography (virtual colonoscopy)

• Flexible sigmoidoscopy

• Double-contrast barium enema (DCBE)

Every 10 years: Colonoscopy

The frequency and types of recommended screening tests depend on the patient’s history.

Patients at increased risk for CRC include those with5:

• Personal history of polyps

• Personal history of CRC

• Family history of CRC

Patients at high risk for CRC include those with16:

• Genetic predisposition (FAP, Lynch syndrome)

• Personal history of inflammatory bowel disease (chronic ulcerative colitis or Crohn’s disease)

Increased- or high-risk patients

Tubulovillous adenomas polyps—polyps that have features of both subtypes2

Surgery5,26

Surgery is the most common treatment for CRC and may include:

• Polypectomy: removal of the polyp

• Local tumor excision or mesorectal excision

• Colon or rectal resection

• Colectomy: removal of a section of the colon

nNearby lymph nodes are also removed

n Remaining sections of the colon/rectum are anastomosed

Some procedures may be open, transanal, or laparoscopic.

Chemotherapy5 Chemotherapy may be administered systemically or regionally (e.g., as a hepatic artery infusion). It is used as adjuvant treatment (after surgery) or neoadjuvant treatment (before surgery).

Radiation therapy16

Radiation therapy may be used with chemotherapy and is more commonly used to treat rectal cancer than colon cancer. Common types are:

• Intraoperative radiation therapy (IORT)

• External-beam

• Internal (brachytherapy)

• Radioembolization

Ablation or embolization Ablation is a minimally invasive technique that destroys cancer cells directly. It is typically used to treat liver metastases, but it can be used to treat other metastatic sites. Three primary types are5,26,27:

• Radiofrequency ablation (RFA)

• Ethanol ablation, also known as percutaneous ethanol injection (PEI)

• Cryosurgery, also known as cryotherapy

Embolization is a minimally invasive technique designed to block blood flow to the liver. Three primary types are16,27,28:

• Arterial embolization (trans-arterial embolization [TAE])

• Chemoembolization (trans-arterial chemoembolization [TACE])

Targeted therapy29 Targeted therapies, such as monoclonal antibodies, can be used alone or with chemotherapy.

• Some prevent formation of new blood vessels (e.g., vascular endothelial growth factor [VEGF] receptors)

• Others target specific proteins on the surface of cancer cells (e.g., epidermal growth factor receptor [EGFR] inhibitors, kinase inhibitors)

Immunotherapy30 Immunotherapy is a type of targeted therapy that helps the body’s own immune system fight the cancer. Immunotherapy drugs bind to specific proteins to boost an immune response.

Treating CRC

Treatment depends on the cancer’s stage, location and the patient’s health and medical history.5,6

Treatment TypesFamilial – 25% (5-6% of which is hereditary)

Sporadic – 75%

Types of Polyps

Genetics

Polyposis

Nonpolyposis

Lynch syndrome

Generally9

Screening

Surgery5,26

Radiation therapy16

• External-beam

Treating CRC

Sporadic – 75%

Types of Polyps

Genetics

Polyposis

Nonpolyposis

Lynch syndrome

Generally9

Screening

Surgery5,26

Radiation therapy16

• External-beam

Treating CRC

Sporadic – 75%

CRC is the:

• Liver

• Lung

• Bone

N/A N/A

The tumor:

92% 87%

The tumor:

63%-87% 49%-80%

The tumor:

53%-89% 58%-84%

11% 12%

Mucosa

Tumors

Lymph node

II III

Nervous system

GI Tract

Understanding

AboutColorectal CancerWhat Is Cancer?Normally, cells get old and die. Then healthy new cells take their place. But cancer cells don’t die. Instead, they divide into more cancer cells and form an abnormal growth (tumor). These cells can also grow into nearby tissues.

Cancer can start anywhere in the body. Colorectal cancer is the name for cancer that starts in the lining of either the colon or the rectum.

Stages of CancerStages tell how much the cancer has grown, if it has spread, and how far. If it has spread to other parts of the body, it is called metastatic cancer. Knowing the stage helps doctors know how to treat the cancer.

Stage 0:

Cancer has not spread. It is only in the inner lining of the colon or rectum

Talk to your healthcare provider if you have any questions about colorectal cancer.

Stage 1:

Cancer has grown deeper into the wall of the colon or rectum. It is in the inner and middle layers of tissue

Stage 2:

Cancer has grown through all layers of the colon or rectum. It may have spread to nearby tissues, but not to lymph nodes or to far away organs (called distant sites)

Stage 3:

Cancer has spread near or into nearby lymph nodes. It may have spread into nearby tissues, but not to distant sites

Stage 4:

Cancer has spread to 1 or more distant sites (metastatic cancer)

Transverse colon

Ascending colon

Descending colon

Rectum

Lymph node

Cancer growth I

II III

For Patient Use

Risk Factors for Colorectal CancerIf you have colorectal cancer, you’re not alone. In fact, experts estimate that about 135,000 people in the U.S. will be diagnosed with colorectal cancer this year.

Risk factors for colorectal cancer:

• Being age 50 or above • Personal history • Genetic factors (mutations)

• Having certain types of • Family history • Lifestyle factors polyps in the colon or rectum

Diagnosing Colorectal CancerMany tests are used to diagnose colorectal cancer, including:

• Medical history

• Physical exam, which may include a digital rectal exam (DRE)

• Chest X-ray

• Ultrasound

• Computed tomography (CT)

• Magnetic resonance imaging (MRI)

• Positron emission tomography (PET)

• Angiography

• Biopsy, which may include molecular gene tests

• Blood tests

• Colonoscopy

Common symptoms of colorectal cancer include: abnormal bowel habits lasting more than a few days (e.g. diarrhea, constipation, narrow stools), blood in the stool (bright red or dark), abdominal discomfort (pain, bloating, fullness, cramps), unexplained weight loss and fatigue.

Treatments for Colorectal Cancer

There are many types of treatments for colorectal cancer. Which treatment is used depends on where the cancer is and how healthy the person is. Talk to your doctor about what is best for you.

• Surgery: most common treatment for colorectal cancer. It may be open or laparoscopic. In laparoscopic surgery a device is inserted through the abdominal wall to examine the inside of the abdomen.

• Chemotherapy: uses drugs to kill cancer cells or stop them from dividing into more cancer cells

• Radiation therapy (radiotherapy): uses high-energy rays to kill cancer cells or keep them from growing. It can also help shrink tumors.

• Ablation: procedure to kill tumors without removing them

• Chemoembolization: blocks the flow of blood to the liver to treat cancer that has spread there

• Targeted therapy: uses drugs or other substances (i.e. proteins) to identify and attack specific types of cancer cells with less harm to normal cells. Some types of targeted therapies help the immune system kill cancer cells.

Microscopic image of tumor tissue taken from a biopsy.

For Patient Use

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