Colorectal Cancer 101- Research Advocacy Training Webinar

Colorectal Cancer 101Research Advocacy Training and Support Program

Our webinar will begin shortly.

WELCOME!

• Speaker(s): Dennis Ahnen, MD

• Archived Webinars: FightColorectalCancer.org/Webinars

• AFTER THE WEBINAR: Expect an email with links to the material & a survey. If you fill it out, we’ll send you a Blue Star pin.

• Ask a question in the panel on the RIGHT SIDE of your screen

• Follow along via Twitter – use the hashtag #CRCWebinar

Today’s Webinar:

What is a RESEARCH ADVOCATE? A research advocate brings a patient viewpoint to the research process and communicates a collective patient perspective

Fight CRC’s Research Advocacy Training and Support (RATS) Program: • Goal is to improve the ability of research advocates to

effectively participate in the research process. • In person meetings, online trainings, and webinars. • Continued education and ongoing training and support

Brought to you by RATS:

Resources:

Disclaimer:

The information and services provided by Fight Colorectal Cancer are for general informational purposes only. The information and services are not intended to be substitutes for professional medical advice, diagnoses or treatment.

If you are ill, or suspect that you are ill, see a doctor immediately. In an emergency, call 911 or go to the nearest emergency room.

Fight Colorectal Cancer never recommends or endorses any specific physicians, products or treatments for any condition.

Speaker:Dennis Ahnen, MD is an active clinician and investigator. He is the Co-Director of the University of Colorado Hereditary Cancer Clinic and Director of the Genetics Clinic at Gastroenterology of the Rockies; he provides consultative service to GI cancer families along with a genetic councilor in both clinics. Dr. Ahnen’s clinical and research interests are in understanding the process of colorectal cancer and its prevention. After over 30 years, Dr. Ahnen retired from his Staff Physician position at the Department of Veterans Affairs in Oct of 2014. He maintains an appointment as Professor of Medicine at the University of Colorado School of Medicine and has a part time appointment at Gastroenterology of the Rockies. Disclosures- Dr. Ahnen is on the Scientific Advisory boards of EXACT Sciences and Cancer Prevention Pharmaceuticals

Colorectal Cancer 101

Dennis J. Ahnen MDDirector, Genetics Clinic

Gastroenterology of the RockiesProfessor of Medicine,

University of Colorado School of Medicine

• What is colorectal cancer (CRC)?• Clinically• Biologically/Molecularly

• Who is at risk for CRC and what is the risk?• How can CRC be prevented?

• Lifestyle, nutritional, and chemoprevention• Screening

• Staging and Treatment of CRC


What is Colorectal Cancer?

Normalepithelium

Abnormalepithelium

Smalladenoma

Largeadenoma

Coloncarcinoma

10-15 Years

The Adenoma Carcinoma Sequence

Molecular Pathways to CRC

NormalEpithelium

Colon Carcinoma

Chromosomal Instability- Mutations, LOH, Aneuploidy- 70%

Microsatellite Instability- Lynch Syndrome- <5%

CIMP Pathway- Serrated/Epigenetic- 25%

Lung

CRC

49,700

Breast Prostate

Lung

CRC

132,700

Other Other

Prostate

Breast

Pancreas

New Cases- 1,658,370 Deaths- 577,190

Who is at Risk for CRC?CRC Incidence and Mortality- U.S. 2015

Cancer Mortality Time TrendsMen Women

The Good News

Incidence

Men

WomenMortality

WomenMen

CRC MortalityWomen Men

CRC Incidence and Mortality (Women)

Incidence Mortality

Who is at CRC risk?• Identifiable Risk Factors

• Demographic• Family History• Lifestyle• Diet

• Those who don’t get screened

Risk Factors Demographic

• Country of origin• Age• Sex• Race/Ethnicity• SES• Family History

Lifestyle• Obesity• Low Physical Activity• Smoking• Alcohol

Diet• High Red/Processed Meat• Low Fiber Containing foods

•Fruits and Vegetables

CRC Mortality

globocan.iarc.fr/factsheets/cancers/colorectal.asp

Colorectal Cancer Incidence and Mortality Men Women

Men > Women

CRC Incidence-Age and Sex

Lifetime risk5-6%

5-6%

Cumulative CRC Mortality by Race





•Fruits and Vegetables

Familial Colorectal Cancer

Adapted from Burt RW et al. Prevention and Early Detection of CRC, 1996

Sporadic (≈ 70%)

Familial (≈ 25%)

Lynch Syndrome (≈ 3%) (HNPCC)

Familial Adenomatous Polyposis (<1%)

Rare CRC Syndromes

Familial Adenomatous Polyposis

• Rare• Autosomal Dominant• High CRC risk ≈100%• Early Onset• Easily recognized• Genetic testing or

screening at around age 12

• Surveillance annually

Lynch Syndrome• Autosomal Dominant – 3% of CRCs• High CRC risk- up to 50%• Early onset- 44 yrs• Proximal location- 65%• Other cancers• Under-recognized• Screening works

• Annual colonoscopy• Start at age 25 or 10 years younger than

earliest Lynch cancer in the family

Familial Colorectal Cancer

Adapted from Burt RW et al. Prevention and Early Detection of CRC, 1996

Sporadic (≈ 70%)

Familial (≈ 25%)

Lynch Syndrome (2-3%) (HNPCC)

Familial Adenomatous Polyposis (<1%)

Rare CRC Syndromes

Family History of CRC Increases RiskFo

ld R

isk

Lifetime Risk 5%

Screening Intensity

Family History of CRC Increases Risk

Fuchs et al NEJM 1994





• Low Fruit and Vegetable

Protective Factors• Screened• Aspirin for selected groups

Normalepithelium

Abnormalepithelium

Smalladenoma

Largeadenoma

Coloncarcinoma

40% 20% 30% 40% Adenoma

IncidenceMetachronous

Adenoma Incidence

CRC Mortality 35%CRC Incidence

CRC Survival 20%

ASA and the Ad-Carc Sequence

Lynch CRCs50%

Normalepithelium

Abnormalepithelium

Smalladenoma

Largeadenoma

Coloncarcinoma

ASA PreventsWhy not use it in everyone?

Benefit is smallLifetime CRC risk- 5% 3%Lifetime CRC Mortality- 2.5% 1.6%Additive with surveillance?

Risks of ASA2-6 X GI BleedIntracraneal Hemorrhage

Aspirin Chemoprevention

ASA Chemoprevention Should Be Considered In….

• High CRC risk• History of CRC or

Advanced Adenoma• Lynch Syndrome• Strong FH

• High CVD Risk• Established CAD• Metabolic syndrome• CVD risk >10-15%

• Low GI Bleeding Risk• No PUD/GI Bleed• No ASA Intolerance• No H. pylori/on PPI

• Low IC Bleed Risk• No Uncontrolled

Hypertension

An adjunct to high quality CRC screening

Screening Rate (%

)Incidence

Mortality

Overall Screening

Lower Endoscopy

1975197619771978197919801981198219831984198519861987198819891990199119921993199419951996199719981999200020012002200320042005200620072008200920102015202020252030

0

50

100

150

200

250 CRC Time Trends- US

17

75-

60-

45-

30--

15-

0-

CR

C p

er 1

00,0

00

Normalepithelium

Abnormalepithelium

Smalladenoma

Largeadenoma

Coloncarcinoma

The Adenoma Carcinoma Sequence

Prevention- Risk Factors Endoscopic Polypectomy

Early DetectionStool Tests

Screening Test USPSTF MSTF

High Sens FOBT annual

Yes Yes

Flex Sig q 5 yr +/- interval FOBT

Yes Yes

Colonoscopy q 10 yr

Yes Yes

CT Colonography q 10 yr

No Yes

Stool DNA No Yes

CRC Screening Tests

Fecal Occult Blood Test (FOBT)

High Sensitivity Fecal Occult Blood Test (FOBT)

EndoscopyFlexible Sigmoidoscopy Colonoscopy

EndoscopyFlexible Sigmoidoscopy Colonoscopy

HO FIT FS+FIT Colon HO FIT FS+FIT Colon

Incidence Mortality

Zauber et al Ann Int Med 2009

Perc

ent R

educ

tion

Effectiveness of CRC Screening

Screening Test USPSTF MSTF

High Sens FOBT annual

Yes Yes

Flex Sig q 5 yr +/- interval FOBT

Yes Yes

Colonoscopy q 10 yr

Yes Yes

CT Colonography q 10 yr

No Yes

Stool DNA No Yes

CRC Screening Tests

New Screening TechnologiesStool DNA

CT Colonography

Colon Capsule

Multi-target Stool DNA/FIT vs FIT Trial

Multi-target sDNA Performance FIT Performance P-Value

Cancer 92.3%(83.0-97.5)

73.8%(61.5-84.0)

0.0018

Advanced Adenoma

42.4%(38.9-46.0)

23.8%(20.8-27.0)

< 0.0001

Specificity 86.6%(85.9-87.2)

94.9%(94.4-95.3) < 0.0001

Specificity 89.8%(88.9-90.7)

96.4%(95.8-96.9) < 0.0001

Imperiale TF et al. N Engl J Med. 2014;370(14):1287-1297

CRC Screening- Risk Groups• Average risk

• No personal or FH of colonic neoplasia or IBD • Start CRC screening at age 50, stop at age 75-85• Options for screening (FIT, Endoscopy)

• Increased risk- FDRs of patients with CRC• Start at age 40 or earlier depending on # and age of

CRCs in family, colonoscopy is preferred • Hereditary Syndromes

• Start much earlier (12-25), annual colonoscopy

CRC Screening- Risk Groups• Increased risk- FDRs of patients with CRC

• 1 FDR > 60 years old- 10% population• Start screening at age 40• Use any standard screening approach

• 1 FDR <60 years or >1 FDR- 3% population• Start screening at age 40 or 10 yrs younger

than earliest CRC in family• Use colonoscopy every 5 years

Colonoscopy Rates Are Improving In FDRs But…..

2005 20100

20

40

60

80

FDRs ≥50 Colonoscopy within 10 years

Perc

ent

Non-FDRs ≥50

Tsai et al. Prev Chronic Dis 2015;12:140533

Colonoscopy Rates Are Improving In FDRs But…..

2005 20100

20

40

60

80

Perc

ent

Non-FDRs ≥50FDRs ≥50

FDRs 40-49

Tsai et al. Prev Chronic Dis 2015;12:140533

Colonoscopy within 10 years

CRC Staging

5 year survival

Stage and Survival

Stage 5 Year Survival

Stage I (T1 N0 M0) >90%

Stage II (T2/3 N0 M0) 70-85%

Stage III (Tx N1 M0) 35-65%

Stage IV (Tx Nx M1) 5%

CRC- Treatment

Advances in Treatment of Metastatic CRC

• What is colorectal cancer (CRC)?• Common, lethal, preventable, molecularly diverse

• Who is at risk for CRC and what is the risk?• Age >50, family history, genetically predisposed

• How can CRC be prevented?• Screening most effective; lifestyle changes prudent• Aspirin chemoprevention in selected patients

• Staging and Treatment of CRC• Surgery, adjuvant Rx, palliative chemotherapy• Molecularly tailored therapy


Question & Answer:

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Colorectal Cancer 101- Research Advocacy Training Webinar