Fight CRC has funded Dr. Christine Molmenti from Northwell Health and Dr. Heather Hampel from The Ohio State University Comprehensive Cancer Center to research the feasibility of determining advanced adenoma(s) history among first degree relatives of early onset colorectal cancer patients. In this month's webinar, Dr. Molmenti and Andrea (Andi) Dwyer from Fight CRC and University of Colorado, will explain why the research is important, how Fight CRC is involved, and how the results could have clinical implications.

1. Research Update:
advanced adenomas & EAO CRC

2. TODAY’S WEBINAR
 SPEAKER(S)
 Dr. Christine Molmenti; Andrea Dwyer
 QUESTIONS
 Ask a question in the panel on the RIGHT SIDE of your
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 WEBINAR ARCHIVE
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WEBINAR TECH

4. RESOURCES
TABOO-TY PODCAST MINI MAGAZINES YOUR GUIDE IN THE FIGHT

5. FIGHTCOLORECTALCANCERDISCLAIMER
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.

6. AndreaDwyer
Andrea (Andi) Dwyer is a public health practitioner from the University of
Colorado Cancer Center and Colorado School of Public Health. She joined Fight
Colorectal Cancer in 2014 to enhance patient educations and research
initiatives that provides relevant and timely information to survivors,
caregivers and families.
Andi joins the team bringing nearly ten years experience in cancer prevention
and survivorship, with a special concentration in colorectal cancer. As one of
her biggest accomplishments, as the co-director of the Colorado Colorectal
Screening Program, she is a leader in patient navigation and established one of
the largest screening patient navigation programs in the country. Colorectal
cancer is personal to Andi, her mother was diagnosed with the disease in her
early 40s.

7. Dr.ChristineMolmenti
Christine L. Sardo Molmenti, PhD, MPH is an Assistant Professor and
Cancer Epidemiologist, Department of Occupational Medicine,
Epidemiology, and Prevention, Donald and Barbara Zucker School of
Medicine at Hofstra/Northwell and in the Center for Health
Innovations and Outcomes Research.
Since 2003, Dr. Molmenti been integrally involved in the design and
conduct of cancer chemoprevention clinical trials and epidemiologic
pooling studies specifically focused on colorectal cancer, colorectal
adenomas, and risk factors related to the occurrence and recurrence
of colorectal cancer.
Dr. Molmenti holds a variety of leadership and advisory positions.

8. ABOUT FIGHT CRC
• National nonprofit advocacy org
founded in 2005
• Focus on 4 areas:
• Advocacy/policy
• Research
• Awareness
• Patient Education

9. EARLY AGE ONSET
• 2014: researchers at MD Anderson looked at
Surveillance, Epidemiology, and End
Results SEER program - made predictions
that by 2030:
• 1 in 10 colon cancers will be diagnosed in people
under 50
• 1 in 4 rectal cancers will be diagnosed in people
under 50
• 2017: The American Cancer Society (ACS)
published in the Journal of the National
Cancer Institute that CRC incidence rates are:
• continuing to rise in young + middle-aged adults
• rectal cancer rates are increasing fast – 3 in 10
diagnoses are in patients < age 55.

10. Early Onset CRC Epidemiology

11. One of the Most Profound Findings
CRC Incidence Among U.S. Adults Aged 45 & 50 years old
Age specific incidence is about the same for a 45 year old in 2015 as it
was for a 50 year old in 1993, about 30 per 100,000.

12. FIGHT CRC’S ROLE
SO FAR AND NEXT
STEPS
Collaboration with the ACS, Memorial Sloan
Kettering , and Erasmus University
(Netherlands)
• “Colorectal Cancer Screening Initiation
before the age of 50 years: A Microsimulation
Analysis.”
• What’s next???
• Funding of the Research
• Informing Policy
• Convening Researchers

13. A feasibility study to determine history of ADVANCED
COLORECTAL POLYPS among relatives of early onset colorectal
cancer patients
Christine Molmenti, PhD, MPH
Assistant Professor
Feinstein Institute for Medical Research
Donald and Barbara Zucker School of Medicine at Hofstra/Northwell
Department of Occupational Medicine, Epidemiology, and Prevention
Center for Health Innovations and Outcomes Research
Northwell Health
November 12, 2018

15. Overview
1. Introduction and rationale
• What are advanced polyps, why are they significant?
• Definitions – young onset, first degree relatives
• Research question
2. Study methods
• Plans for reaching patients and relatives
• Outcome measures
3. Future research & next steps

16. Introduction & rationale

17. Colonoscopy
• To decrease new cases and deaths from
colorectal cancer
1. Detect early stage (curable) cancer
2. Detect precancerous lesions (polyps)
Murphy CC, Am J Gastroenterol, 110: 633-641, 2014
Rex et al, 2017
Detection and removal of precancerous lesions (polyps)
prevents colorectal cancer

18.  Colorectal Polyps
• Two Main Types:
• Serrated lesions
o Hyperplastic polyps (frequent)
o Sessile serrated polyps (<10%)
o Traditional serrated adenoma (rare)
• Conventional adenomas
o 30-40% of the population will develop an adenoma by age 60
o 20%-50% of adenomas recur within 3-5 years
o Histological characteristics
 Dysplasia (high / low grade)
 Villousity (tublar, tubulovillous, villous)
Rex DK et al, Am J Gastroenterol 2017; 112:1016–1030

19. Fearon and Vogelstein, Cell, 61, 759-767, 1990
Terzic et al, Gastroenterology 138(6), 2101-2114 2010
Normal
Epithelium
Metastatic
Cancer
Dysplastic
lesion
Early
Adenoma
Late
Adenoma
Cancer
Cytokines, DNA repair genes, K-ras, P53, COX-2 overexpression
Target for prevention

20. Strum WB, NEJM 374(11); 2016
Larger size = more advanced
≤ 5mm adenomas
• 45-71% of
adenomas
• 7-16% advanced
features
• 0.05% malignant
(4mm)
6-9 mm adenomas
• 21-23% of
adenomas
• 10-34% advanced
features
• 0.2% malignant
(8mm) (20 mm)
≥ 10 mm adenomas
• 8-22% of adenomas
• All advanced based
on size
• 37-54% advanced
features
• 3.2-11% malignant

21. Advanced polyps
1. Tubular adenomas ≥1 cm in size, or any adenoma with
villous elements or with high grade dysplasia
2. Sessile serrated polyps ≥1 cm in size, or any serrated
lesion with cytologic dysplasia
3. Traditional sessile adenomas, regardless of size
Strum WB, NEJM 374(11); 2016

22. Young onset colorectal cancer
• Generally individuals diagnosed <50 years of age
• Adolescents and young adults defined as 19-39 years of age

23. Trends in young adults by 10-year age group
40-49
1.9% annually
since 1994
30-39
2.2% annually
since 1988
20-29
3.8% annually
since 1987
0
5
10
15
20
25
30
Incidencerateper100,000people
0
0.5
1
1.5
2
2.5
20-29 years
Source: SEER 9 delay-adjusted rates, 1975-2012; 3-year moving average
Siegel R, 2016

24. APC Change-based predicted incidence rates of colon
cancer by age compared with incidence rate in 2010
Bailey RB, JAMA 2015

25. First Degree Relatives (FDRs)
=Parents, siblings, children

26. Increased CRC risk among FDRs of
patients with advanced polyps
 FDRs of patients with ≥1 advanced polyp carry:
 4-6-fold increased risk of being diagnosed with an advanced
polyp
 2-4 fold increased risk of developing CRC
Regardless of the age at diagnosis of the affected relatives.
FDR = First Degree Relative (Parent, Sibling, Child)

27. Guidelines
1. United States Multi-
Society Task Force
(USMSTF)
Advanced adenoma in 2
FDRs (any age) or AA in 1
FDR < 60 y
Colonoscopy every 5 years
beginning 10 years before
the age at diagnosis or age
40 y, whichever is earlier.
Advanced adenoma in 1
FDR at age ≥60 y
Begin screening at 40.
Options for screening are
the same as those for
average-risk persons.
2. National
Comprehensive Cancer
Network (NCCN)
Advanced adenoma(s) in
an FDR regardless of age
Colonoscopy beginning at
age 40 y or at age of onset
of adenoma in relative,
whichever is first

28. •Research question
 What is the prevalence of advanced
adenomas among early onset colorectal
cancer EOCRC cases?
• Feasibility first

29. Methods

30. Unique cohort – EOCRC patients
• Patients enrolled Ohio Colorectal Cancer Prevention Initiative (OCCPI)
2013-2016
• Hampel, H (PI): Universal Screening for Lynch Syndrome (USLS)
• Paskett, E (PI): Adherence to Colorectal Cancer Screening (ACCS)

31. Unknown what percentage of EAO CRC is due
to family history of advanced adenoma
• Ohio Colorectal
Cancer Prevention
Initiative (OCCPI):
Universal Screening
for Lynch Syndrome
(USLS) Arm
• N=709
EAO CRC
56%
Sporadic
16%
Hereditary
14%
Family history
CRC
≥14%??
Family
History of
AA

32. Unknown what percentage of EAO CRC is due
to family history of advanced adenoma
• Ohio Colorectal
Cancer Prevention
Initiative (OCCPI):
Universal Screening
for Lynch Syndrome
(USLS) Arm
• N=709
EAO CRC
50%
Sporadic
16%
Hereditary
14%
Family history
CRC
20%
Family
History of
AA

33. Unknown what percentage of EAO CRC is due
to family history of advanced adenoma
• Ohio Colorectal
Cancer Prevention
Initiative (OCCPI):
Universal Screening
for Lynch Syndrome
(USLS) Arm
• N=709
56%
Sporadic
14%
Family history
of CRC
XX%
Family
History of
AA
40%
Sporadic
16%
Hereditary
14%
Family history
CRC
30%
Family
History of
AA

34. EAO CRC cases, n=492
Feasibility study, n=50
• EAO cases recruited between 2013 and 2016
 Diagnosed with a primary invasive colorectal
adenocarcinoma (all stages) <50 years of age
 Not identified as having a cancer susceptibility gene or
having a family history of colorectal cancer
• Anticipate 4 first degree relatives per EAO case
 N=~200 FDRs to contact and obtain medical records

35. Phase 1 – Contact Probands
Phase 2 – Contact First degree relatives
Phase 3 – Collect colonoscopy records
Phase 4 – Analysis

36. Collaboration

37. Collaboration

38. Phase 1
Probands contacted and
consented (n=50)
Letter/email
Data collected: FDR
contact information
Phase 2
FDRS contacted and
consented (n=~250)
Letter/email
Data collected:
Colonoscopy
information
Phase 3:
Consent and medical
release form signed
Colonoscopy facilities
contacted
Data collected:
colonoscopy records
Study flow
*FDRs who have not undergone colonoscopy will be
encouraged to do so as soon as possible. For those who
decline, other screening options will be offered

39. Feasibility outcomes
Recruitment rate of probands: The number enrolled in the study
(numerator) divided by the number of probands approached for the
study (denominator)
Recruitment rate of FDRs: The number of FDRs enrolled in the study
(numerator) divided by the number of FDRs approached for the study
(denominator)
Rate of medical record verification: The number of colonoscopy records
ascertained (numerator) divided by the number of endoscopy clinics
provided by the FDRs (denominator).

40. Additional estimates
Average length of time to obtain EMR records. If the average length of time
needed to obtain colonoscopy and pathology records is 1 month vs 1 year,
this will be important data for planning a large scale study.
Accuracy of self-reported colonoscopy results. This will be calculated as the
proportion of those who correctly reported their findings on colonoscopy.
Reasons probands and FDRs refuse participation. Understanding barriers
and facilitators to participation will allow us to find and employ strategies to
improve response rates in a large-scale study.

41. Future study / next steps

42. Future studies
A larger, future study, are needed to accurately estimate the prevalence of advanced
polyps among first degree relatives in the larger early age onset cohort
 Research initiatives are also needed to fully explore:
How to reach family members of individuals diagnosed with
advanced adenomas

43. Future outcomes
1) Prevalence of advanced polyps among
FDRs of early onset CRC patients who do
not have a hereditary syndrome or a first
degree relative with colorectal cancer.
2) Proportion (%) of early onset patients who would have been
recommended to start colonoscopy PRIOR to the age at
which they developed colorectal cancer based on the FDR
with an advanced adenoma.
3) Proportion (%) of patients that were diagnosed with a EAO
CRC that could have been realistically prevented or detected
early.

44. Impact
This research has the potential to yield important clinical
implications by raising awareness among gastroenterologists and
primary care physicians
And, improving communication of polyp findings, specifically
advanced polyp results, to patients and family members in order
to promote and ensure uptake of adequate screening guidelines.

45. Take home
1. Know your family history of CRC and colorectal polyps, particularly
advanced polyps
2. Talk to you your close family members so that they understand your
colonoscopy findings and you understand their findings as well. Talk to
your gastroenterologist to determine if early and more frequent
screening is recommended for you.

46. •Thank you
• Questions
• cmolmenti@northwell.edu

47. Q
&
A
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