Downloadable slides highlighting key concepts in colorectal cancer screening and appropriate therapy selection and application in the adjuvant setting and beyond.
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Workshop with the Experts: Colorectal Cancer Series
1. Workshop With the Experts:
Colorectal Cancer Series
This program is supported by educational grants from
Originally posted 3/27/2012 at clinicaloptions.com/ss/CRCVA12
2. Workshop With the Experts: Colorectal Cancer Series
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3. Workshop With the Experts: Colorectal Cancer Series
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Faculty
Program Director Edward Chu, MD
Herbert Hurwitz, MD Chief
Division of Hematology/Oncology
Associate Professor of Medicine
University of Pittsburgh School of
Department of Hematology/Oncology
Medicine
Duke Cancer Institute
Deputy Director
Durham, North Carolina
University of Pittsburgh Cancer
Faculty Institute
Pittsburgh, Pennsylvania
Al B. Benson III, MD, FACP
Professor, Division of
Hematology/Oncology
George A. Fisher, MD, PhD
Feinberg School of Medicine at Associate Professor of Medicine
Northwestern University Department of Medicine/Oncology
Associate Director for Clinical Stanford Cancer Center
Investigations Palo Alto, California
Robert H. Lurie Comprehensive
Cancer Center
Chicago, Illinois
4. Workshop With the Experts: Colorectal Cancer Series
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Faculty
Scott Kopetz, MD, PhD, FACP Muhammad Wasif Saif, MD
Assistant Professor Professor of Clinical Medicine
Department of Gastrointestinal Medical Department of Medicine
Oncology Director, GI Oncology Section
University of Texas M. D. Anderson Cancer Herbert Irving Comprehensive Cancer
Center Center
Houston, Texas Columbia University College of Physicians
and Surgeons
Mark Kozloff, MD New York, New York
Clinical Associate Professor of Medicine
Department of Medicine
The University of Chicago Medical Center
Chicago, Illinois Weijing Sun, MD
Associate Professor of Medicine
Caio Max S. Rocha-Lima, MD Director, GI Medical Oncology Program
Professor of Medicine Abramson Cancer Center
Colorectal/Pancreatohepatobiliary Programs University of Pennsylvania
Co-Leader, Phase I Unit Philadelphia, Pennsylvania
Co-Director, Sylvester Cancer Center
University of Miami Sylvester Comprehensive
Cancer Center
Miami, Florida
5. Workshop With the Experts: Colorectal Cancer Series
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Faculty Disclosures
Al B. Benson III, MD, FACP, has disclosed that he has received
research support on behalf of Northwestern University from Amgen,
Bayer, Genentech, and Gilead and consulting fees from Abbott, Bayer,
Genentech, Genomic Health, Precision Therapeutics, and sanofi-aventis.
Edward Chu, MD, has disclosed that he has received consulting fees
from Roche.
Herbert Hurwitz, MD, has disclosed that he has received research
support from Bristol-Myers Squibb, GlaxoSmithKline, Pfizer, and Roche/
Genentech and consulting fees from Roche/Genentech.
George A. Fisher, MD, PhD, has disclosed that he has received
research support from Amgen, Bristol-Myers Squibb, Exelixis, and
Genentech.
6. Workshop With the Experts: Colorectal Cancer Series
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Faculty Disclosures
Scott Kopetz, MD, PhD, FACP, has disclosed that he has received
research support from AstraZeneca and Roche and consulting fees from
AstraZeneca, Bayer, MedImmune, Roche, and sanofi-aventis.
Mark Kozloff, MD, has disclosed that he has received consulting fees
from Genentech and fees for non-CME services from Eli Lilly,
Genentech, and Roche.
Caio Max S. Rocha-Lima, MD, has no significant financial relationships
to disclose.
Muhammad Wasif Saif, MD, has disclosed that he has received fees for
non-CME services from Amgen, Bristol-Myers Squibb, Eli Lilly, and
Genentech.
Weijing Sun, MD, has no significant financial relationships to disclose.
7. Workshop With the Experts: Colorectal Cancer Series
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Outline
Epidemiology of CRC
Current Screening Modalities and Guidelines
Early-Stage CRC
– CRC Staging
– Adjuvant Therapy Options
– Guidelines and Risk Assessment for Stage II CRC Patients
Metastatic CRC
– Initial and Salvage Therapy Options
– Therapy and Adverse Effect Management
– Continuum of Care
8. Workshop With the Experts: Colorectal Cancer Series
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CRC: Epidemiology in 2012
Third most common cancer Third leading cause of cancer
diagnosis in US[1] deaths in 2011 (estimated
49,380 deaths)[1]
– Estimated 143,460 new cases in
2012; 1:1 male:female ratio[2] Race/Ethnicity Death Rates in 2008,
per 100,000[3]
At diagnosis, 39% localized All races 16.4
(stage 0-II), 37% regional (stage
White 15.8
III), 20% metastatic (stage IV)[3]
African American 23.0
Steady decrease in age- Asian/Pacific Islander 11.5
adjusted incidence rates of distal American Indian/ 19.1
colon, proximal colon, and rectal Alaska Native
cancers in 1976-2005[4] Hispanic 12.1
1. American Cancer Society. Colorectal cancer facts & figures. 2011-2013. 2. Siegel R, et al. CA Cancer
J Clin. 2012;62:10-29. 3. SEER. Stat fact sheets: colon and rectum. 4. Cheng L, et al. Am Clin Oncol.
2011;34:573-580.
10. Workshop With the Experts: Colorectal Cancer Series
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Major Risk Factors for CRC
Factors That Increase Risk Relative Risk*
Heredity and Medical History
Family history
• 1 first-degree relative 2.2
• More than 1 relative 4.0
• Relative with diagnosis before 45 yrs of age 3.9
Inflammatory bowel disease
• Crohn’s disease 2.6
• Ulcerative colitis (colon) 2.8
Diabetes 1.2
Smoking 1.2
* Relative risk compares risk of disease in people with “exposure” to risk of people without exposure.
Factors that decrease risk are physical activity (in colon cancer),
calcium, and consumption of milk
American Cancer Society. Colorectal cancer facts & figures. 2011-2013.
11. Workshop With the Experts: Colorectal Cancer Series
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Impact of Personal and Family History
in CRC
≈ 20% of patients with CRC have close relative with CRC
≈ 5% of CRC cases are associated with genetic syndrome
– Lynch syndrome (HNPCC) most common, accounting for 2% to
4% of all cases
– Higher risk of other cancers (eg, endometrial, ovarian, pancreatic)
– Familial adenomatous polyposis, second most common and
associated with nearly 100% lifetime risk of CRC without
intervention
– BRCA associated with increased risk of CRC
Previous history of localized CRC associated with increased
risk of new CRC tumors
American Cancer Society. Colorectal cancer facts & figures. 2011-2013.
12. Workshop With the Experts: Colorectal Cancer Series
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CRC Screening Alternatives
Tests That Are Likely to Detect Both Adenomatous Polyps and Cancer
Test Some Benefits Some Limitations
Rapid, few complications, minimal bowel Views only 1/3 of colon, no removal of large
Flexible sigmoidoscopy
prep, no sedation polyps, low risk of infection/tear
Permits examination of entire colon and Full bowel prep, sedation, high expense, higher
Colonoscopy
removal of polyps risk of bowel tears or infection vs other tests
Can miss small polyps and cancers, full bowel
Can usually view entire colon, few
Double-contrast barium enema prep, unable to remove polyps, exposure to
complications, no sedation required
low-dose radiation
Noninvasive, permits examination of entire Can miss some polyps and cancers, full bowel
CT colonography
colon, few complications, no sedation prep, unable to remove polyps, exposure to
(virtual colonoscopy)
needed low-dose radiation
Tests That Are Primarily Effective for Detection of Cancer
Test Some Benefits Some Limitations
Will miss most polyps and some cancers, may
No bowel prep, sampling done at home,
Fecal occult blood test require multiple samples, higher false-positive
noninvasive
rate than other tests
Will miss most polyps and some cancers,
No bowel prep, sampling done at home,
Stool DNA test new technology with uncertain test intervals,
noninvasive
high cost vs other stool tests
American Cancer Society. Colorectal cancer facts & figures. 2011-2013. Levin B, et al. CA Cancer J Clin.
2008;58:130-160.
13. Workshop With the Experts: Colorectal Cancer Series
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CRC Screening Guidelines
Begin at 50 yrs of age
– Earlier in higher-risk groups (family history, IBD, African American
patients, etc)
Frequency
– Colonoscopy: 10 yrs
– Flexible sigmoidoscopy: 5 yrs
– CT colonography and FOBT variable recommendations
ACG recommends “split dosing” for bowel preparation (at least
one half of the preparation is taken on the day of the test)
Rex DK, et al. Am J Gastroenterol. 2009;104:739-750. NCCN. Clinical practice guidelines in oncology:
colorectal cancer screening. v.2.2011. US Preventive Services Task Force. Ann Intern Med. 2008;149:
627-637.
15. Workshop With the Experts: Colorectal Cancer Series
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CRC Staging
Stage Description
0 Intraepithelial; lamina propria invasion
I Submucosa (T1) or muscularis propria (T2) invasion
A: pericolorectal tissue invasion (T3)
II B: penetration to visceral peritoneum surface (T4a)
C: invasion/adherence to other organs/structures (T4b)
A: T1-T2 + 1-3 regional LN; T1 + 4-6 regional LN
B: T3-T4a + 1-3 regional LN; T2-T3 + 4-6 regional LN; T1-T2 + ≥ 7
III regional LN
C: T4a + 4-6 regional LN; T3-T4a + ≥ 7 regional LN; T4b + any
regional LN
A: metastasis to 1 organ/site
IV
B: metastases to multiple organs/sites or peritoneum
Edge SB, et al. AJCC cancer staging manual, 7th ed. New York, NY: Springer; 2010.
16. Workshop With the Experts: Colorectal Cancer Series
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5-Yr Survival Rates by Colon Cancer
Stage
Stage Observed 5-Yr Survival,%
I 74.3-78.7
IIA 66.7
IIB 60.6
IIC 45.7
IIIA 64.7-73.7
IIIB 42.1-58.2
IIIC 12.9-32.5
IV 19.2*
*2001-2003 SEER data.
Gunderson LL, et al. J Clin Oncol. 2010;28:264-271. Kopetz S, et al. J Clin Oncol. 2009;27:3677-3683.
17. Workshop With the Experts: Colorectal Cancer Series
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For the rest of this presentation…
Epidemiology of CRC
Current Screening Modalities and Guidelines
Early-Stage CRC
– CRC Staging
– Adjuvant Therapy Options
– Guidelines and Risk Assessment for Stage II CRC Patients
Metastatic CRC
– Initial and Salvage Therapy Options
– Therapy and Adverse Effect Management
– Continuum of Care
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Editor's Notes
This slide lists the faculty who were involved in the production of these slides.
This slide lists the faculty who were involved in the production of these slides.
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This slide lists the disclosure information of the faculty involved in the development of these slides.
CRC, colorectal cancer.
CRC, colorectal cancer. Colorectal cancer is the third most common cancer diagnosed in the United States and the third leading cause of death According to an annual National Cancer Institute Surveillance Epidemiology and End Results (SEER) Registries Review, 71,850 men and 69,360 women were expected to receive a new diagnosis of colon or rectal cancer in 2011, at a median age of 70 years. At diagnosis, about 39% of CRCs are localized; 37% are regional; and 20% are metastatic. In a study of CRC incidence trends based upon 9 SEER registry data, between 1976 and 2005, the age-adjusted incidence of proximal and distal colon, and rectal cancers steadily decreased. The greatest decline was in the incidence of distal colon cancers, and the least change in incidence rates was among proximal colon cancers. A steady increase in proximal CRC subsites occurred in both men and women beginning at age 50. Women experienced a greater increase than men.
CRC, colorectal cancer. Individuals with a first-degree relative (parent, sibling, or offspring) who was diagnosed with CRC have a 2 to 3 times the risk of developing the disease than do people without the same family history. The relative risk of acquiring CRC increases when more than one relative has been diagnosed, and when a relative is diagnosed before age 45. Other factors that increase risk of CRC are forms of Inflammatory bowel disease, diabetes, smoking, and no prior screening. Factors that are associated with a decrease in the risk of CRC include physical activity for both men and women (in colon cancer), intake of calcium, and consumption of milk.
CRC, colorectal cancer; FAP, familial adenomatous polyposis. Approximately 20% of colorectal cancer patients have a close relative with the disease, and about 5% of colorectal cancers are linked to a known genetic syndrome. Lynch syndrome—or hereditary nonpolyposis colorectal cancer– is the most common genetic form of the disease, accounting for from 2 to 4 percent of all cases. The second most common known genetic form of colorectal cancer is familial adenomatous polyposis, or FAP. Without identification and intervention, persons with this form of the disease have an almost 100% lifetime risk of colorectal cancer. Individuals with BRCA mutations also appear to be at an increased risk for colon cancer.
CRC, colorectal cancer. In 2008, the American Cancer Society collaborated with the American College of Radiology and U.S. Multi-Society Task Force on Colorectal Cancer (a consortium that included the American College of Gastroenterology, American Society of Gastrointestinal Endoscopy, the American Gastroenterological Association, and the American College of Physicians). The goal was to develop consensus guidelines for CRC screening. The resulting guidelines drew a distinction between screening tests that primarily detect cancer—that is, stool tests—and those tests that can detect both cancer and precancerous growths. Recommendations, which did not point to one preferred test, instead emphasized that cancer prevention should be the primary goal of screening and that screening tests should be selected on the basis of their ability to both detect and prevent CRC.
ACG, American College of Gastroenterology ; CRC, colorectal cancer; CT, computed tomography; FOBT, fecal occult blood test; IBD, inflammatory bowel disease. The American College of Gastroenterology recommends colonoscopy screening every 10 years beginning at age 50. African Americans, because of a higher risk for CRC, should begin regular screening earlier, at the suggested age of 45. Note that the increased risk in this population may reflect lower access to care and screening rather than a genetic predisposition. Barium enema is not recommended, but the ACG indicates that CT colonography every 5 years is an alternative to colonoscopy. The ACG also recommends that the pre-test preparation include a split dosing strategy, with at least one-half of the bowel prep solution being taken on the same day as the CRC screening test. The most recent guidelines for colorectal cancer (CRC) screening from the NCCN include a recommendation for colonoscopy every 10 year; flexible sigmoidoscopy every 5 years; or CT colonography every 5 years. For people of average risk for CRC, an annual immunohistochemical (IHC)-based stool testing, with or without flexible sigmoidscopy, is a primary screening option. No current consensus has been developed for use of CT colonography—known as “virtual colonoscopy.” Expert consensus is currently evolved on frequency of screening and the minimal polyp size for referral to colonoscopy. The U.S. Preventive Services Task Force (USPSTF) recommends CRC screening using fecal occult blood testing, sigmoidoscopy, or colonoscopy, beginning at age 50 and continuing at suggested intervals until age 75. Higher-risk individuals (ie, those with a family history of CRC) should be screened beginning at an earlier age. The USPSTF recommends consulting a physician for advice on CRC screening after age 75.
CRC, colorectal cancer; LN, lymph node
Notably 5-year survival for patients with stage IIC CRC is poorer than for those with SIIIA indicating more concerning with locally aggressive disease compared to involvement of a few nodes.