The Second Annual Early Age Onset Colorectal Cancer Summit

YOUNG ADULT CRC:
A GLOBAL CHALLENGE
• Rebecca Siegel MPH American Cancer Society
• Deborah Alsina Bowel Cancer UK
• T. Peter Kingham MD FACS Memorial Sloan
Kettering Cancer Center
• Aung Ko Win MBS MPH PhD Melbourne
School of Population and Global Health

Increasing colorectal cancer incidence in
young adults in the US
Rebecca Siegel, MPH
Early-onset CRC Summit
March 19, 2016

Among <50 years: 14,200 cases and 3,300 deaths
Estimated numbers of new cases & deaths in 2016

Top 5 cancers, ages 20-49 years
Lung (16%)
Colorectum (13%)
Brain (9%)
Leukemia (7%)
Pancreas (6%)
Breast (27%)
Lung (13%)
Colorectum (9%)
Cervix uteri (7%)
Ovary (5%)
Colorectum (11%)
Testis (9%)
Melanoma (8%)
Prostate (7%)
NHL (7%)
Incidence Mortality
Breast (36%)
Thyroid (14%)
Melanoma (7%)
Colorectum (6%)
Cervix uteri (5%)
Men Women Men Women

Anatomy of the colorectum
(right-side)
(left-side)

Subsite distribution by sex and age
25%
25%
43%
7%
Male, < 50 yrs
proximal
distal
rectum
other
38%
25%
31%
6%
Male, 50+ yrs
24%
29%
38%
9%
Female, < 50 yrs
48%
21%
25%
7%
Female, 50+ yrs

Racial/ethnic distribution by age
66%
15%
12%
5%
2%
77%
12%
7%
3%
1%
0%
10%
20%
30%
40%
50%
60%
70%
80%
Non-Hispanic
White
Non-Hispanic
Black
Hispanic Asian or Pacific
Islander
Other
< 50 years 50+ years

0
50
100
150
200
250
300
350
400
Rateper100,000
Age at diagnosis
Men
Women
Source: SEER 18 delay-adjusted rates, 2008-2012.
Age-specific incidence rates by sex
89% of cases
0
5
10
15
20
25
30
35
40
20-24 25-29 30-34 35-39 40-44 45-49

0
10
20
30
40
50
60
70
1975 1980 1985 1990 1995 2000 2005 2010
Rateper100,000
Colorectum, -3% per year
Colon, -3% per year
Rectum, -2% per year
Incidence trends overall, 1975-2012
Source: SEER 9 delay-adjusted rates, 1975-2012.
Declines during 2003-2012:

The American Surgeon, Oct 2003
SEER 9, 5,383 patients 20-39
1973-1999
Cancer Epidemiol, Biomarkers, &
Prevention, June 2009
SEER 13, 20,646 patients 20-49
1992-2005
The American Surgeon, Sept 1998
LSU Medical Ctr, 37 patients < 40
1976-1997
Delayed awareness of the increasing trend

Incidence trends by age: 50+ versus 20-49
Source: SEER 9 delay-adjusted rates, 1975-2012; 2-yr moving average.
0
2
4
6
8
10
12
14
Men
Women
51% since 1994
0
50
100
150
200
250
300
Incidencerateper100,000
Men
Women
Ages 50+ Ages 20-49

Increase is confined to the left side
0
0.5
1
1.5
2
2.5
3
3.5
4
4.5
5
1975-77 1980-82 1985-87 1990-92 1995-97 2000-02 2005-07 2010-12
2.6 in 1991
4.8 in 2012
Distal colon
2.1% annually since 1994
Rectum
Proximal colon

Proportion of CRC diagnoses in young adults
7%
6%
8%
64%
11%
9%
14%
55%
0% 10% 20% 30% 40% 50% 60% 70%
CRC
Colon
Rectum
Population
1990 2012
Source: 1990 – SEER 9; 2012 – NAACCR.

Trends in young adults by stage at diagnosis
Source: SEER 9 delay-adjusted rates, 1975-2012; 3-year moving average.
0
0.5
1
1.5
2
2.5
3
Colon
Localized
Regional
Distant
0
0.5
1
1.5
2
2.5
3
Rectum
Localized
Regional
Distant
3.6% annually,
2003-2012
3.0% annually,
2003-2012

Trends in young adults by race/ethnicity
0
2
4
6
8
10
12
14
Non-Hispanic
white
Colorectum
Colon
Rectum
0
2
4
6
8
10
12
14
Non-Hispanic
black
0
2
4
6
8
10
12
14
Asian/Pacific
Islander
0
2
4
6
8
10
12
14
Hispanic
Colorectal Colon Rectum
NHW 2.4 1.8 3.3
Hispani
c
2.2 1.9 2.6
API stable 0.6 stable
NHB stable stable 1.7
Annual % change from 1992-2012
0
2
4
6
1992-94 2010-12
Rectal cancer incidence rate
NHW Hispanic API NHB

Trends in young adults by 10-year age group
40-49
30-39
20-29
0
5
10
15
20
25
Incidencerateper100,000people
0
0.5
1
1.5
2
2.5
20-29 years
20-29 years
6%
30-39 years
20%
40-49
years
74%

Timing and magnitude of increase by 10-year age group
1975 1980 1985 1990 1995 2000 2005 2010
Colon
Rectum
Colon
Rectum
Colon
Rectum
20-29
40-49
30-39
3.4% per year
3.4% per year
2.0% per year
2.9% per year
1.6% per year
2.6% per year

Age-specific trends in CRC from 20-64 years
0.1
1
10
100
1975-77 1980-82 1985-87 1990-92 1995-97 2000-02 2005-07 2010-12
Incidenceper100,000
60-64
55-59
50-54
45-49
40-44
35-39
30-34
25-29
20-24

Opposing trends within ages 50-59 years
0
5
10
15
20
25
30
35
40
Rectum
0
10
20
30
40
50
60
70
80
Colon
50-54
55-59
50-54
-0.8% annually,
2003-2012
+2.4% annually,
2003-2012
55-59
+0.7% annually,
2003-2012
-2.7% annually,
2003-2012

Increasing risk in successive generations since mid-century
1988 vs 1943 birth cohort:
colon, 3X higher risk
rectum, 4X higher risk

CRC testing prevalence by age
Source: National Health Interview Survey.
12
16
33
45
52 53
15
20
43
60
67
65
12
19
44
56
64
67
0
10
20
30
40
50
60
70
80
40-44 45-49 50-54 55-59 60-64 65+
Percent
Age
2005 2010 2013

State variation in incidence rates by age
50+ years20-49 years

Stage distribution: early vs. later onset
33%
38%
26%
3%
40%
35%
20%
5%
0%
5%
10%
15%
20%
25%
30%
35%
40%
45%
Localized Regional Distant Unknown
< 49 years
50+ years
Source: SEER 18 registries, 2005-2011.

Five-year relative survival
Data Sources: Trends, SEER 9 registries, 1975-2011; Stage-specific, SEER 18 registries, 2005-2011.
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
56%
68%
94%
77%
20%
90%
70%
12%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Localized Regional Distant
< 49 years
50+ years
By stageOver time

CRC mortality trends
0
0.5
1
1.5
2
2.5
3
3.5
4
4.5
5
1975 1980 1985 1990 1995 2000 2005 2010
Deathsper100,000
20-49 years
Source: National Center for Health Statistics, National Vital Statistics System.
0
20
40
60
80
100
120 50+

Strategies for reducing colorectal cancer risk
 Maintain a healthy weight
 Be physically active
 Consume a healthy diet
 Limit alcohol consumption
 Consume recommended levels of calcium
 Avoid tobacco products
 Screening at 50, OR earlier with a family history of
adenomas or CRC

Who should begin screening before 50?
High risk Age to begin
Familial adenomatous polyposis (FAP) 10-12 years
Lynch syndrome 20-25 years*
Inflammatory bowel disease
(ulcerative colitis or Crohn disease)
Varies depending on
age at onset
*Or 10 years before youngest case in immediate family

Who else should begin screening before 50?
Increased risk Age to begin
Cancer/adenomas in a first-degree
relative
40 years OR
10 years before
youngest case
Cancer in > 2 second-degree relatives 40 years

Conclusion
CRC incidence rates continue to increase in young adults
ACTION ITEMS
 Early screening when appropriate
 Increase awareness among clinicians and young adults to facilitate earlier
detection
 Know the symptoms
1. Rectal bleeding
2. Abdominal pain
3. Change in bowel habits
 Etiologic research – known risk factors don’t explain

Screening test use in ages 40-49 years
0
2
4
6
8
10
12
14
2000 2003 2005 2008 2010 2013
Percent
Ever routine endoscopy
0
2
4
6
8
10
12
14
2000 2003 2005 2008 2010 2013
Ever diagnostic endoscopy
Source: NHIS

Why doesn’t screening begin earlier?
• Increase unknown during previous evidence review (mid 2000s)
• Now in beginning stages of guideline review; independent, systematic
review of the literature, including harms & benefits of screening
• Screening before 50 recommended for many people; current evidence
will inform guideline update
• Benefits must outweigh harms at the population level
 rare before 50 (absolute risk 0.3% vs 5% for those 50+)
 serious adverse events (perforation, adverse reaction to sedation, etc)
 cost

Harms & limitations of colonoscopy screening
• 33% of patients report at least 1 GI symptom following the
procedure
• Serious adverse event rate: 2.8 per 1,000
• Adverse reaction to the sedative
• Bleeding if a polyp or tissue sample is taken
• Perforation of the colon wall
• Screening won’t detect all cancers

ACS screening guidelines – average risk
Men and women, ages 50+ Frequency
Fecal occult blood test (FOBT)
with at least 50% test
sensitivity for cancer, or fecal
immunochemical test (FIT)
with at least 50% test
sensitivity for cancer
Annual
Stool DNA test Every 3 years
Flexible sigmoidoscopy Every 5 years
Double contrast barium
enema
Every 5 years
Colonoscopy Every 10 years
CT colonography Every 5 years

35-39
30-34
25-29
20-24
0
2
4
6
8
10
12
1978
1981
1984
1987
1990
1993
1996
1999
2002
2005
20-49
Canada
UK
0
20
40
60
80
100
120
140
160
180
200
1978
1981
1984
1987
1990
1993
1996
1999
2002
2005
50+
Canada
UK
Early-onset CRC incidence trends elsewhere

65 64 65
55
73
77
66
65
45
72
58 58 58
50
66
68
59
56
42
68
6 6 7
5
7
9
7
9
4 4
0
10
20
30
40
50
60
70
80
overall (50-
75)
men women 50-59 60-69 70-79 white black < HS college grad
CRC Screening in 2010, BRFSS vs NHIS
BRFSS NHIS Difference
Data sources for screening

Factors that influence population cancer trends
Detection/imaging
practices
Risk factors
Screening behaviors MortalityIncidence
Treatment

Colorectal cancer risk factors: medical and family history
Relative risk
Family history
1 first-degree relative 2.2
More than 1 relative 4.0
Relative with diagnosis
before age 45
3.9
Medical history
Crohn disease 2.6
Ulcerative colitis
Colon 2.8
Rectum 1.9
Diabetes 1.2

Increase risk: Relative risk Trend
Alcohol consumption (heavy vs.
nondrinkers)
1.6
Obesity 1.2
Red meat consumption 1.2
Processed meat consumption 1.2 ?
Smoking (current vs. never) 1.2
Colorectal cancer risk factors: behavioral
Decrease risk: Relative risk Trend
Physical activity (colon) 0.7
Milk/total dairy consumption 0.8
Fruit consumption 0.9 ?
Vegetable consumption 0.9 ?
Total dietary fiber (10 g/day) 0.9 ?

Deborah Alsina
Executive Director
Bowel Cancer UK

Charity of the Year
2013/2014
Young Adult CRC: A Global Challenge
Deborah Alsina
Chief Executive
Bowel Cancer UK
2ND ANNUAL EARLY AGE ONSET CRC SUMMIT

Charity of the Year
2013/2014
What I am going to talk about:
 Introduction to colorectal cancer in the
UK
 Overview of early onset CRC in the UK
 Never Too Young UK priorities,
achievements and work still to do

Charity of the Year
2013/2014
Who we are..
Bowel Cancer UK is determined to
save lives and improve the quality
of life of all those affected by
bowel (colorectal/colon) cancer

Charity of the Year
2013/2014
What we do
• We support research
• We educate
• We campaign
• We are determined and ambitious

Charity of the Year
2013/2014
Colorectal cancer in the UK
The UK’s 2nd biggest cancer killer
Over 41,000 diagnosed
and over 16,000 deaths every year
290,000 people living in the UK today
have been diagnosed with colorectal cancer
and this is set to nearly double by 2030

Routes to diagnosis for under 50s
Screen
Detecte
d
GP
Referra
l
Urgent
GP
Referral
Non-
urgent
Other
Out-
patient
Inpatien
t
Elective
Emergency
Presentatio
n
Unknow
n
0% 19% 27% 9% 5%
34% 4%

Gender delays
• 54% of men were sent to a specialist after only 1 or 2 GP
visits compared with only 35% of women.
• 15% of men went to the GP 5 or more times, or were
diagnosed as an emergency before the GP could refer,
compared with 37% of women.

Solutions: Awareness & education
As of March 2015
Broadcast – 32 million people
Print – 11 million people
Social media – 125,000
Webpage views – 185,000
Celebrity campaign (Ricky Gervais, Stephen
Fry, Sir Chris Hoy etc) – 17 million

Solutions: clinical change
• GPs as gatekeepers – who to refer?
• NICE (England and Wales) and SIGN (Scotland) referral
guidance updated to include under 50 patients for the
first time.
• Risk Assessment Tool for use in primary care being
developed with Universities of Exeter and Durham led by
Professor William Hamilton

Risk Assessment Tool for Colorectal Cancers

High Risk groups
Genetic conditions – e.g. Lynch syndrome, FAP
Campaign led to Royal College of Pathology guidance –
all under 50s should be reflex tested
50% of centres do not offer genetic testing

Finding solutions
Partnership between all key
professional bodies
Met Tuesday 15th March to
discuss how to improve the
identification and
management of people at high
risk
Possible national genetics
registry for
surveillance screening??

Solutions: a guide & films for people
diagnosed under 50

Charity of the Year
2013/2014
I can’t wait to….
... wake up and not have cancer as my first thought
... be able to dye my hair!
... get all dressed up and dance all night
... feel like 'me' again
… have the energy to be a better Mummy
… be able to wash my hair and not see loads of it in
the bath tub
… watch my beautiful little girl grow up
... experience my healthy and exciting future
Charlotte (32)

Charity of the Year
2013/2014
Thank you
Deborah Alsina
Deborah.alsina@bowelcanceruk.org.uk
00 44 207 940 1768
@deborahalsina

Colorectal cancer in Nigeria
T. Peter Kingham MD FACS
Director, Global Cancer Disparity Initiatives
Memorial Sloan Kettering Cancer Center

• Cancer in low- and middle-income countries
(LMIC)
• African Research Group for Oncology (ARGO)
• Young patients with colorectal cancer (CRC)

Cancer is a growing problem in LMIC
• By 2050 70% of the predicted 24 million
people with cancer will reside in LMIC
– Lifestyle changes, life expectancy higher, infectious
disease treatments improved
• How do we improve outcomes of these
patients?
– Guidelines
– Training
– Surgery
Kingham, Lancet Oncology, 2013

Cancer case fatality is high in LMIC
– Ratio of incidence of cancer: mortality rate
annually = 75% in LMIC
(More deaths than AIDS, malaria, and TB combined)
Kerr et al. NEJM. 2010. 363(9): 801-803
Farmer et al. Lancet. 2010. 376(9747):1187-93

Tertiary care hospital in Malawi
Gyorki, Archives of Surgery, 2012

CRC in Nigeria
• Characteristics of CRC among Nigerians
– early age of onset
– aggressive disease pattern
– bulky tumors
– late presentation and diagnosis
• Investigating the outcomes and biology of
CRC in Nigeria is worthwhile

Increasing Incidence of CRC
Ilorin, Nigeria
• By 2030, 20 million cancer deaths
worldwide with 2/3 in LMIC
• CRC is the 2nd most common cancer in
women and 3rd in men
• In West Africa, CRC rates appear to be
increasing
NumberofCases
Yea
0
10
20
30
40
50
60
70
80
90
100
1979-83 1984-88 1989-93 1994-98 1999-2003 2004-08
Ibrahim, Nigerian J of Clin Practice, 2011

Comparison of Nigerian and American patients
Saluja, Surgery, 2013

Stage-matched Survival
North America Stage III
West Africa Stage III
North America Stage IV
West Africa Stage IV
0 2 4 6 8 10
Years after Dx
ProportionSurviving
p < 0.01
p < 0.01
1.0
0.8
0.6
0.4
0.2

Who gets CRC in West Africa?
Prospective data collection
• A multicenter study involving 4 tertiary health facilities in
South west of Nigeria and MSKCC, New York.
– OAUTHC Ile-Ife
– UITH Ilorin
– LAUTECH Osogbo
– FMC Owo
– University of Ibadan
• Each hospital has a team comprised of Surgeons,
Pathologists, Radiologists
– No medical oncologists
• Consortium created in Oct 2013

Nigerian patients present at young age
• Median ages
– Nigeria: 53 years
– USA: 68 years
• % younger than 50
years:
– Nigeria: 41%
– USA: 17%
#ofpatients
Kingham, unpublished data

Rectal cancer is most common in
Nigeria
• 65% elective, 35% emergency
Location # Percentage
Left colon 4 2%
Transverse colon 11 6%
Sigmoid colon 23 14%
Right colon 38 23%
Rectum 93 57%

Patients present late in Nigeria
Presenting stage % Nigeria
(n=145)
% USA
(SEER)
I 0% 39%
II 9% 36%
IIIa 27% -
IV 64% 20%

Metastatic pattern is different
Site Nigeria MSKCC
Peritoneal 63% 5%
Liver 60% 48%

Mortality rates in Nigeria are high
• No evidence of disease: 36 (21%)
• Alive with disease: 61 (36%)
• Dead of disease: 63 (37%)
• Dead of other causes: 11 (6%)
1 year overall survival = 46%
(USA 5-year survival stage IV = 13%)

No difference in presentation in young
patients
<50 years
N=72
>50 years
N=106
Rectal bleeding 33 (46%) 75 (71%)
Right colon 15 (21%) 25 (24%)
Rectum 35 (49%) 57 (54%)
Stage
II 3 (4%) 8 (8%)
III 18 (25%) 23 (22%)
IV 36 (50%) 56 (53%)
DOD 21 (29%) 35 (33%)
NED 12 (17%) 22 (21%)

Gene mutations found in Nigerian
(Blue) and MSKCC (Red) patients

How do we identify earlier stage
patients?

Symptoms of patients with rectal
bleeding
Symptoms N=100
-change in stool caliber 48%
-pellet like stool 24%
-None 52%
Weight loss over 6 months 45%
Hemorrhoids 71%
Polyps 21%
CRC present 20%
---Stage 2 45%
---Stage 3 35%
---Stage 4 20%

Pts with cancer
N=20
Pts without cancer
N=80
P value
Saw MD for bleeding 16 (80%) 67 (83.8%)
Duration of rectal
bleeding (median months)
6 (2-24) 6 (0.25-360)
Change in stool caliber <0.01
-pellet like stool 10 (50%) 14 (17.5%)
-none 4 (20%) 48 (60%)
Weight loss over 6 months 19 (95%) 26 (32.5%) <0.0001
Hemorrhoids 10 (50%) 61 (76.3%) 0.023

Summary of colonoscopy study
• 20/100 with CRC= 20%
• 16/100 with stage 2,3 Polyps= 21.0%
• Weight loss and pellet like stool more common in
patients with CRC
• Expanded to 3 cities and 300 patients

Knowledge regarding rectal bleeding is
mixed
• 82 pts with questionnaire regarding beliefs on
rectal bleeding:
– Hereditary: 37%
– Cancer: 39%
– Increased sugar intake: 78%
– Hemorrhoids: 90%
Kingham, unpublished data

Colorectal cancer incidence is rising
• Patients with CRC present at young age in
Nigeria, and most LMIC
• Screening is absent
– Screening guidelines are not applicable
• Novel screening and treatment strategies are
needed

Early-Onset Colorectal Cancer in
Australia and Asia
Presented at :
Early Age Onset Colorectal Cancer Summit 2016, New York
March 19, 2016.
Aung Ko Win MBBS MPH PhD
Senior Research Fellow
National Health and Medical Research Council Early Career Fellow
Centre for Epidemiology and Biostatistics
Faculty of Medicine, Dentistry and Health Sciences
Melbourne School of Population and Global Health
The University of Melbourne
Australia

Colorectal Cancer (CRC) in Australia
• CRC – 13.5% if all new cancers in both sexes
17,070 new CRC cases in 2015 (55% males)
• CRC – 8.8% of all deaths from cancer
4,120 deaths from CRC (53% males)
• CRC lifetime risk by age 85 years
1 in 12 (1 in 10 males and 1 in 15 females)
• Average age at CRC diagnosis = 69 years
Source: Australian Institute of Health and Welfare

Age-specific CRC incidence, 2015
90%10%
2-3%

CRC incidence and mortality, 1968 to 2012

• CRC is increasing in young adults aged <50 years in USA
• CRC screening for early-onset CRC is not justified at a
population level unless strong family history, predisposing
mutation or IBD
• CRC is 3rd leading cause of cancer deaths in young adults
aged 20-39 years behind leukaemia and cancers of the CNS
Young, Win, Rosty, et al. J Gastroenterol Hepatol. 2015;30(1):6-
Early-Onset CRC

Bowel Cancer in Young Adults in Australia

Reports from Australia/NZ
• New Zealand reports no rise in early-onset CRC (Shah et
al 2012)
– Stable or decreased 25-64 (no subset analysis)
• Victoria also reports no rise in early-onset CRC (Sia et al,
2014)
– Stable numbers under 50 (no subset analysis)
• Western Australia reported a rise in incidence in young
females over 1982 – 2000 (Haggar et al 2012)
• Queensland public hospital studied early-onset CRC as
there was a perception among local surgeons that they
were increasing in frequency (Turkiewicz et al 2001) and
that there were no contemporary Australian statistics
Reports on Early-Onset CRC in Australia

0
20
40
60
80
100
120
140
1990 1995 2000 2005 2010
40-44
45-49
50-54
55-59
0
1
2
3
4
5
6
7
8
9
10
1990 1995 2000 2005 2010
20-24
25-29
30-34
35-39
Early-Onset CRC Incidence in AUSTRALIA
20-39 Years 40-59 Years
Mandatory Reporting of all Cancers except NMSC
Age-specificincidenceper100000

Early-Onset CRC Incidence in South AUSTRALIA
20-39 Years 40-59 Years
0
1
2
3
4
5
6
7
8
9
10
1990 2000 2010
20-24
25-29
30-34
35-39
0
20
40
60
80
100
120
140
1990 2000 2010
40-44
45-49
50-54
55-59
Age-specificincidenceper100000

CRC incidence in ASIA (1955-1999)
Sung et al. Lancet Oncol. 2005;6(11):871-6.

RC incidence in ASIA (1993-1997)
Sung et al. Lancet Oncol. 2005;6(11):871-6.

CRC incidence in ASIA (1983-2002)
Center M, Jemal A, Ward E. Cancer Epidemiol Biomarkers Prev. 2009;18(6):1688-94.

Early-Onset CRC Incidence in JAPAN (1976-1994)
Takada et al. Dis Colon Rectum. 2002;45(9):1249-54.

Early-Onset CRC Incidence in JAPAN (1978-2004)
@ Confidential Unpublished data

Early-Onset CRC Incidence in KOREA (1999-2009)
Shin et al. Cancer research and treatment. 2012;44(4):219-26.

CRC Incidence in KOREA vs JAPAN (1999-2012)
Yoon et al. Epidemiology and health. 2015;37:e2015038.

Seydaoglu et al. Turkish Journal of Gastroenterology. 2013;24(6):521-31.
Early-Onset CRC Incidence in TURKEY (1993-2008)

Early-Onset CRC in ASIAN COUNTRIES

Men 30-49 years Women 30-49 years
Colorectal cancer mortality in HONG KONG,
JAPAN, SOUTH KOREA, AND SINGAPORE.
Shin A, Jung KW, Won YJ. World J Gastroenterol. 2013;19(7):979-83.

AUSTRALIA
•Highest incidence rate of CRC in the world
•Incidence of CRC in people aged >50 has been stabilized or
declining
•Incidence of CRC in young adults aged <40 has been increasing
after 2000
ASIA
•Incidence of CRC has been rapidly increasing over decades esp
Japan, Singapore, Korea, Hong Kong
•Incidence of CRC trends in young adults – inconsistent findings
– Before 2000, early-onset CRC incidence might not increase
– After 2000, early-onset CRC incidence increasing trend might be seen
if analyzed by stratifying age groups (esp age <40 years)
Summary: Early-Onset CRC in Australia and Asia

What is Known about CRC in Young Adults
• Rectal and Distal Colon Predominance
• High Grade Mucinous and Signet Ring Histologies
(traditionally aggressive features)
• More frequent late stage presentations
• Most cases symptomatic (because not included in the
screening population)
• Better or Equivalent Survival when matched for stage
with older patients
• High rate of radio- and chemotherapy

Problems about CRC in Young Adults
• Reports of outcome vary between studies
• Age boundary for definition of early-onset CRC
• Risk stratification in the young adult population
• Retrospective studies
• Single-center studies
• No large and prospective studies on ‘modern’ risk factors
• Majority of cases not explained by family history
• Most screening guidelines not capture young adults

Australian Bowel Cancer Screening Guidelines

National Bowel Cancer Screening Program

Factors in Diagnostic Delay
• Patient-associated factors
– CRC not considered to be cause of symptoms
– Some groups less likely to interact with the healthcare
system (social, cultural)
– Health-seeking vs unconcerned behaviors
• Primary healthcare provider factors
– CRC not considered to be cause of symptoms
– Often thought to have hemorrhoids
– Does not encourage clinical pattern recognition

How to address
• Increasing awareness in physicians and patients
• Potential risk modification/reduction approaches
• Identification of individuals at high-risk
• Primary health care screening tools for young adults
• Improved screening modalities with high acceptability

QUALITY OF LIFE SYMPOSIUM:
”TOOLS YOU CAN USE”
Martha Raymond MA CPN Michael’s Mission
Susan Peterson PhD MPH University of Texas MD
Anderson Cancer Center
Debra J. Wolf ESQ New York Legal Assistance Group
Carolyn Fulton LSCW Memorial Sloan Kettering
Cancer Center
Joanne Kelvin RN MSN AOCN Memorial Sloan
Kettering Cancer Center
Cynthia Gail Leichman MD New York University
School of Medicine

Martha Raymond, MA CPN
Early Age Onset Colorectal Cancer Summit
March 19, 2016
New York, New York
Patient Voices:
The Current State of
Young Adult Colorectal Cancer

Total of 125 Patients, Survivors & Caregivers
participated in the focus groups:
48 Male (38%)
77 Female (62%)
Sample groups from across the country.
Focus Group Findings

3%
9%
35%
31%
14%
7%
Under 25
25 to 29
30 to 34
35 to 39
40 to 44
45 to 49
Age at Diagnosis

0% 3%
49%
48%
Stage 1
Stage 2
Stage 3
Stage 4
Initial Stage at Diagnosis

46%
23%
11%
20%
Emergency Room
Primary Care
OB / GYN
Gastroenterologist
How were you diagnosed?

3%2%
3%
10%
34%
35%
13%
No Symptoms
0 to 3 months
3 to 6 months
6 to 12 months
12 to 18 months
18 to 24 months
24+ months
Time from symptoms to diagnosis

Yes: 7 (6%) No: 118 (94%)
Do you feel there were any obstacles in
the diagnostic process?
“Yes – young & otherwise healthy so physician and I
didn’t even consider screening for colon cancer”
 “Yes – my age, lack of insurance to cover screening”
 “Yes – older physician set in his ways – lack of knowledge
about young adult colorectal cancer”
 “Yes – checked for everything except colon cancer”
Do you feel you received a timely
diagnosis?

What additional areas of support would
have been helpful?
 Therapist/Social Worker/Navigator support
 Caregiver/Family support
 Side-effect management (ostomy, neuropathy, skin/rash care)
 Relationship/Sexual intimacy counseling
 Financial/Insurance information
 Treatment options – both medical and holistic
When diagnosed did you have
an adequate support system?
Yes: 24 (19%) No: 101 (81%)

 Living a life of purpose – living in the present
 Spirituality – reflection – devotion
 Giving back – helping others - advocacy
 Spending time with family and loved ones
 Letting go of negative people & situations
 Simple pleasures – nature – friends – pets
 Being productive – service to others
 Ability to be independent – healthy days
 Taking time to ‘just be in the moment’ – gratitude
What does a meaningful quality
of life look like to you now?

“I am stronger than I ever thought possible”
“I wish I had made my health a priority”
“Don’t take ‘no’ for an answer - advocate”
“If something doesn’t feel right, speak up”
“Not everyone will be there when you need them”
“Tell the people you love how you feel – today”
“I now know the symptoms of colorectal cancer”
“How my diagnosis would affect all aspects of my
life – family, parenting, relationships, intimacy,
physical activity, work, finances – my future”
What do you know now that you
wish you’d known prior to
diagnosis?

How to identify individuals under age 50 who most likely
would benefit from screening
Why is there such a large increase in the incidence rates
for young adults
Family history and genetic mutations in the young adult
population
Relationship between certain foods and environmental
factors
Improving treatment options and reducing long term side
effects
What should the top EAO-CRC
research priorities be?

Be more thorough when explaining diagnosis and
treatment options
Understand that cancer affects the entire family –
not just the patient – encourage counseling
Accept that all patients are not the same – one
treatment does not fit all
Encourage 2nd opinions
Educate the family and caregivers about the disease
and what to expect
Caregiver Insight: What is your
top recommendation to
healthcare providers?

The needs are clear:
 What can we do to better educate and raise
awareness about young adult colorectal cancer?
 What can we do to support and empower young
adult colorectal patients from diagnosis through
survivorship?
 What can we do to help caregivers, family and
loved ones of those affected by this disease?
Call To Action

• Focus Group Participants
• Dr. Tom Weber
• Mrs. Cindy Borassi and CCCF Team
• Ms. Caitlyn ‘Caity’ Grand and MM Team
• Colon Cancer Challenge Foundation Board of Directors
• Michael’s Mission Board of Directors
• Memorial Sloan Kettering – Research & Advisory Groups
• The Raymond Foundation – ‘Global Colon Cancer Survivor
Day’ focus group hosts/sponsors
• Online groups: ‘Colon Cancer Survivors & Warriors’ and
‘Know More: A Young Onset CRC Discussion Group’
Thank you!

Optimizing Psychosocial
Support for Young Adult
Colorectal Cancer Survivors
Susan K. Peterson, PhD, MPH
Professor, Behavioral Science
2nd Early Age Onset Colorectal Cancer
Summit
New York, NY
March 19, 2016

Cancer Survivorship
• Cancer survivorship = the state or process of
living after a diagnosis of cancer
• Encompasses not only the physical but also the
social, psychological, and spiritual/existential
impact of cancer on one’s life and for the
remainder of one’s life.

• Low social support → diminished ability to cope
& manage illness, worse health outcomes
• Emotional distress → impaired adherence,
cognition, motivation, less effective coping
• Chronic stress → depression, physiological
changes
• Effects on families and communities → reduced
financial/material resources, caregiver burden
Consequences of unmet psychosocial
needs

Psychosocial health care is integral to
cancer care and survivorship
Institute of Medicine (2008)
• Need for psychological and social
services and interventions as part of
cancer care
• Enable patients, their families, and
health care providers to optimize
biomedical health care
• Manage the psychological,
behavioral, and social aspects of
cancer and its consequences so as to
promote better health
Health and Medicine Division (HMD), formerly IOM, National
Academies of Science, Engineering and Medicine, 2008

Standard to improve psychosocial care for
cancer survivors

Psychosocial needs of cancer survivors &
services to address them

• Care standards and clinical practice guidelines
for psychosocial aspect of oncology care
– Distress screening, referral and management
• National Comprehensive Cancer Network (NCCN)
• Am College of Surgeons Commission on Cancer standards for
patient-centered care
– Valid, reliable self-report tools
• Distress thermometer, problem list (NCCN)
• Patient self-reported distress vs. oncologist rated
– 69% vs. 6% received referrals
– 28% vs. 4% accepted referral
Improving the provision of psychosocial care
for cancer survivors
Jacobsen , 2015; Bauwens
2014

• Was patient’s emotional well-being assessed
within 1 month of first oncology visit?
• If a problem was identified, was an action taken
to address that problem?
• Providing feedback on quality of care may lead
to improvements in care
– Assessment: 64% → 73%** (over one year)
– Taking action: 74% → 76%
Measuring quality of psychosocial health
care
** p<0.001
Jacobson, Neuss, et al. 2011
Am Society Psychosocial Oncology

• Quality of life concerns
– Managing distress & emotions related to cancer,
treatment, and fear of recurrence
“Not sick nor healthy”
– Social functioning and isolation
• Disclosure and communication
– Maintain/re-establish normalcy
– Intimacy, sexuality, fertility
– Loss: job/school, appearance change, relationship
changes
***Positive attitudes, beliefs, feelings emerge from
cancer experience
Psychosocial Health Services for Young
Cancer Survivors

• Survivorship care program
• Fertility and reproductive medicine program
• Psychosocial program
– Psychological assessment and counseling
• Psychotherapy, neurocognitive testing
– Career/vocational guidance & educational consultation
– Young adult life services
– Arts in Medicine
– Cancer 180 (peer support for survivors age 20s and 30s)
• Specialty services
– Pain Service, Palliative Care
– Integrative Medicine
– Body Image Therapy Program
– Energy Balance (exercise and diet)
– Tobacco Treatment Program
Adolescent and Young Adult Center
MD Anderson Cancer Center

“Addressing psychosocial needs should be an
integral part of quality cancer care. All components
of the health care system that are involved in
cancer care should explicitly incorporate attention
to psychosocial needs into their policies, practices,
and standards addressing clinical medical practice.
These policies, practices, and standards should be
aimed at ensuring the provision of psychosocial
health services to all patients who need them.”

GETTING YOUR AFFAIRS IN ORDER:
A Legal Perspective
• March 19, 2016

LegalHealth
• Since 2001, LegalHealth has partnered with medical
professionals to address the non-medical needs of low-
income people with serious health problems.
• LegalHealth complements health care with legal care,
providing free legal services at 25 medical facilities and
training healthcare professionals to understand the
legal issues their patients face.
• Since its inception, LegalHealth has emphasized serving
patients with cancer.
• LegalHealth extends its mission nationally by providing
technical assistance to medical legal partnerships.
149

Objectives
• Provide overview of common concerns for
young adults with cancer:
–Employment Rights and Responsibilities
–Disability Income
–Advanced Directives and Wills
–Debt
150

Employment:
Common Questions
Are there laws that protect me in the workplace if I
want to continue working?
Do I have to disclose my cancer diagnosis to my
employer?
151

152
Americans With Disabilities Act
• Applies to all employers with 15 or more employees
• Employer cannot discriminate against an employee or prospective
employee because of a disability or perceived disability
• Employer must provide reasonable accommodation so that an
employee can perform the essential functions of the job as long as
the accommodation does not impose an undue hardship
• Examples of reasonable accommodation: restructuring the
job; modifying the employee’s schedule; physical changes in
the work environment; working from home
• Time off for treatment can be an accommodation
• State laws may offer broader protections
• Disclosure rules

153
What if I have to stop working?
Family and Medical Leave Act (FMLA)
• FMLA protects the job of an employee who needs to take time off
from work to care for themselves or a qualified family member
• Applies to employers with 50 or more employees
• Employee must have worked at least 12 months and for 1250 hours
during the last year
• Unpaid leave with job protection for up to twelve weeks
• Can be used for intermittent leave
• Health insurance/benefits must continue during FMLA time
• If not eligible for FMLA, can request time off as a reasonable
accommodation

154
How will I support myself if
I have to stop working?
• Short term disability – Seven states (CA, HI, NY,
NJ,RI, & PR) require employers to offer a
minimum level of short-term disability protection.
• Many employers offer private STD Plans.
• If unable to work for at least 12 months, can
apply for Social Security Disability
• If insufficient work history, can apply for SSI

Advanced Planning
• What legal documents should I have prepared to
protect me and help my family assist me if
needed?
155

Health Care Proxy
• Health Care Proxy allows an agent to make
health care decisions for you if you become
incapacitated.
• Rules vary by state but generally no attorney
required to complete
• Provide your agent with clear guidelines about
your preferences regarding your health care
treatment
• Discuss your views and values with your
physician, your family and your agent
• Your agent is obligated to advocate for your
wishes, not decide what he/she thinks is “best”
for you! 156

Living Will
• A statement of one’s wishes with respect to one
or a number of potential end of life medical care
decisions.
• Laws vary by state:
– Only valid for the medical situations it addresses
– No lawyer generally needed to fill out form
– Generally has to be witnessed by two adults or notarized
– Will assist your family in making tough decisions and allow
them to follow your wishes
157

Power of Attorney
• Power of Attorney - a form that allows an
individual to name an agent to handle the
person’s personal (non health) affairs during
their lifetime, including banking, and other
financial matters.
– The authority designated in a Durable Power of Attorney
continues after a person becomes disabled or
incompetent, but not after the person dies
– The form needs to be notarized
• If executed while someone is competent, a
Power of Attorney can often avoid the need to
have a guardian appointed if that person
becomes disabled.
158

Wills
• A document in which a person specifies how her
property will be distributed upon her death.
• Must be competent to execute and free of undue
influence
• If no will, state chooses administrator and
property passes by law
• Wills must comply with state requirements to be
valid
• Not all states recognize hand written wills
159

Property That Does Not
Pass Under a Will
• Pensions and retirement plans with designated
beneficiaries
• Life insurance if beneficiary named
• Joint ownerships with rights of survivorship
• Certain bank accounts; joint, in trust for, payable
on death
• If no beneficiary named, estate becomes
beneficiary upon death
160

What about digital assets (the cloud) and
social media access permission?
• Will or POA can address digital property
• Make a list of passwords, store in secure place and
make sure family or agent knows where it is
• If you store digital property in the cloud, back up on
a regular basis and share access with agent/family
• Different sites require forms of identification and
proof of death to delete a profile (examples next
slide)
• Alternatively, you can give log-in information to
someone you trust, or write it down and save it
where someone will find it
161

Access to Social Media Upon Death
– Facebook: Special request for deceased person’s
account:
https://www.facebook.com/help/contact/22881325
7197480
• Request to turn page into memorial:
https://www.facebook.com/help/contact/160521327
9719667
– Twitter: Twitter starts deleting accounts after six
months of inactivity
• To remove deceased’s account:
https://support.twitter.com/articles/87894?lang=en
162

What happens to my debt if I am no longer
able to pay?
• Laws vary state by state
• Family is generally not personally responsible
unless co-signed debt or loan
• Student loan discharge for total and permanent
disability
• Certain parent loans may be discharged upon
death of student
163

164
Where can I go for legal help?
Resources:
National Cancer Legal Resource Network:
http://www.nclsn.org/
If reside in NYC
NYLAG cancer intake line:
(212) 946-0357
For more information visit our website
www.legalhealth.org

Unique Complexities Facing Young
Adult Patients and their Families
March 19th, 2016
Carolyn Fulton, LCSW-R
Clinical Social Worker, Palliative Medicine Service
Social Work Coordinator, MSKCC FamilyTherapy Clinic

Content for today’s Discussion
• Defining theYoung Adult
‒ PrioritiesTypical for theYoung Adult
‒ theYoungAdult facing Cancer
• Defining theYoung Adult in the Context of their Family
– Normative Developmental Patterns for this age group
– Looking at theYoung Adult Couple more closely
• Cancer and the Family
• Important Considerations when treating aYoung Adult Patients and their Families
– Who do they identify as primary caregivers
– Including their voice in the treatment plan
Resources Available for this Patient Population
Use light gray boxes to emphasize content

Defining theYoung Adult
• Young adulthood is 18-35 (Erickson, 1959)
• Developmental priorities typical at this stage (D’Agostino,
Penney, and Zebrack, 2011)
– Working to establish autonomy from their parents
– Developing a personal set of values and identity
– Looking to find strong peer relationships, including intimate and sexual relationships
– Obtaining adequate preparation to join the workforce

TheYoung Adult Facing Cancer
InTheirWords:
• “special set of psychological and social challenges”
• “youth and health are supposed to be synonymous”
• “the in-betweenness of young adulthood”
• “no choice but to grow up fast”
• “daunting questions… have become my urgent, everyday concerns”
29, 2012NYTimes - By SULEIKA JAOUA Marc
NYTimes, Suleika Jaquad March, 2012

Needs of theYoung Adult Patient
– Body of literature on the young adult cancer experience (distinct from
pediatric, adult & geriatric)
– Organizational interest to better serving this population (treatment &
post-treatment services)
– LIVESTRONG’s strategic plan in 2002; recommendations (care
standards)

TheYoung Adult within their Family
• The SingleYoung Adult
- Are they living on their own, with roommates, interested in dating or having
children in the future even if not currently dating?
-How do they define their relationship to their parents? Do they wish to
consider them part of the treatment plan, do they identify someone else as
their primary caregiver?
• TheYoung Adult in a Relationship
- Dating vs. Married
- Fertility Considerations
-Role of parents as caregivers
• Where do their Siblings Fit?

Young Adult Cancer Experience – Couples
Individual Challenges
• Isolation
• Interruption in Developmental
Milestones
• EstablishingAutonomy from
Parents
• Solidifying Peer Relationships
• Developing a Personal Set of
Values and Identity
Challenges to the Couple
• Isolation
• Interruption in Developmental
Milestones
• EstablishingAutonomy from
Parents
• Solidifying Peer Relationships
• Developing a Shared Set of
Values and Identity

Cancer and the Family
• Rolland (2005): “illness, disability, and death are universal experiences in
families”. Health care providers need an organized way of thinking about
the complexity of cancer in a family unit. Cancer is a family illness
• King & Quill (2006): many medical staff view working with families as one
of the most difficult aspects of palliative care ; they argue that family
concerns should be understood and addressed
• Zaider and Kissane (2009) discuss the importance of management and
assessment of distress in families at the end of life; how family
relationships can predict individual distress at the end of life.

Brief Overview of FamilyTherapy
• Attends to the form or structure of interactions; family maps and patterns
of relating
• Thinks systemically; individual’s challenges occur in context
• Looks at communications between family members in the here and now
• Notes circular interactions; behavior is both response and stimulus that
forms the family’s “rules”

Systemic Interventions to Consider
• Value and Explore Multiple Perspectives
– Family members think differently about their current situation.
– No perspective is inherently “better” than any other.
• Balance the “Both – And”
– Helping the family hold simultaneously different ways of
thinking
– Finding balance holding both this and that perspective
• Explore Family Narratives (current and potential new ones)

EngagingYoung Adults andTheir Families
• Who is present during clinic and treatment visits?
• If multiple friends or family members are present, focus on the young
adult patient specifically:
-ask them if it is ok to talk with everyone present
-if multiple family members have questions, particularly parents,
allow for multiple perspectives but ensure the young adult patient’s
voice and decisions are heard
-notice communication patterns between family members
• Allow for time alone with young adult patients, gauging what they may
share when loved ones aren’t around; specifically important when facing
more advanced illness

Important Considerations
• Body Image
• Sexual Functioning
• Quality of Life Goals may differ from older patients
• Fertility
• Social Isolation

Collaboration between Oncologist and
Mental Health Provider Key
• Patients may open up to their social workers/psychologists/psychiatrists
in more depth about their challenges during treatments
• Sharing some information may help in treatments goals and decisions
going forward
• May highlight the importance of inter-disciplinary communications
between team members
• Will aid in patients feeling well supported overall

Case Example
Brittany is a 28 year old female, recently engaged, diagnosed with Stage IV
colorectal cancer. She lived with her cancer, through multiple surgeries,
chemo, and radiation treatments for over 4 years. Prior to her diagnosis, she
was planning a “big white wedding”, as she referred to it. She also wanted
children and eventually to move out of NYC and return to the south with her
husband, buying a home and settling into a life together. She also had goals
to continue working in marketing.Towards the end of her cancer experience,
she was on four different systemic chemo treatments with goals to keep her
cancer contained, keeping her living as long as possible through her
treatment experience

Working with Brittany and her Family
Beginning Phase ofTreatment:
- She held back from life goals, with the hopes that she would resume these
plans once treatment ended
- Given the new relationship with her husband, she looked to her mother as her
primary caregiver
Middle Phase ofTreatment:
- She entered FamilyTherapy; goals were to assist Brittany with balancing her
new relationship, exploring ways she could complete life goals while receiving
treatment, and trusting her husband more with caregiving responsibilities
- We also explored her want to have a child, she and her husband together
chose embryo fertilization and hopes to have a surrogate mother carry their
child
- it was realized that not returning to work was her new reality, given treatment
side effects

Working with Brittany and her Family (Cont.)
End Phase ofTreatment
-in Brittany’s case, it was realized that her cancer was continuing to
progress, despite the various treatment options tried/offered
-Collaboration between social worker and oncologist became key in forming
shared quality of life goals for this couple and family
-Despite many milestones this couple lost, oncologist and social worker together
explored which milestones could still be accomplished in Brittany’s current
reality
-Brittany’s oncologist supported her decision to move to the south, buy a home
and a dog (so she could experience some aspect of maternal interest), and got
her connected to a local oncologist resuming the same chemo treatments she
was receiving at MSKCC

What this Case Example Illustrates
• Despite so much loss, young adults can continue to make milestones as
individuals and in relationships
• Treatment plans should include quality of life goals
• Supporting their interests to explore having children despite challenges
associated with that decision, even if the end result is that this option is
no longer possible
• Seeing the value of interdisciplinary resources, connecting this young
adult and her family for counseling

KnowingYour Resources
• Explore Support Programs offered by your institutions by Psychiatry and
SocialWork Departments
• Know Resources related to Fertility Preservation for both young adult
male and female patients, explore this potential interest with your
patients prior to beginning treatment
• Utilize your social workers for assistance with community resources,
particularly if your institutions don’t offer young adult support programs
• Know Resources related to Sexual Health and educate patients about
these programs as well

Program Development
Support Group Implementation:
Young Adult Couples
YoungAdult Patients
Young Adult Caregivers
Young Adult Partner’s Bereavement

Contact Information
Carolyn Fulton, LCSW-R
fultonc@mskcc.org
646-888-3532

Fertility Preservation
Before Cancer Treatment:
Developing a Program to Improve
Practice

Treatment of cancer may affect fertility
Surgery
Resection of reproductive structures
Radiation
Fibrosis of reproductive structures –
Risk based on % organ exposed and
cumulative dose
Chemotherapy
Gonadal toxicity - Risk based on
drugs used and cumulative dose

Fertility effects of treatment for colorectal
cancer include…
Males
• Loss of spermatogonial
stem cells → impaired
sperm production
• Erectile or ejaculatory
dysfunction
Females
• Loss of ovarian follicles →
infertility and premature
menopause
• Uterine fibrosis → inability
to carry a pregnancy

Fertility preservation options for patients with
colorectal cancer include…
Males
• Sperm banking
• Electroejaculation
• Testicular sperm
extraction
• Testicular shielding (RT)
Females
• Egg freezing
• Embryo freezing
• Ovarian transposition (RT)

Professional guidelines highlight the need for
clinicians to address fertility

Barriers for clinicians in discussing fertility
• Lack of knowledge
• Lack of resources
• Don’t know where to refer
• Concern about cost
• Lack of time
Forman, Anders, & Behera 2010; Kohler et al 2011; Kotronoulas,
Papadopoulou, & Patiraki 2009; Quinn et al 2009; Schover et al 2002

A systematic approach can help in developing a
program to help clinicians address fertility
Plan
Develop an
Infrastructure
Implement Evaluate

Plan
Establish a multidisciplinary advisory group
– Collaborate with clinicians from other services caring
for a high volume of young adult patients
– Invite select patients to participate
Assess current practice patterns and needs
– Patient survey – satisfaction w/ information received
– Clinician survey – knowledge, practices, perceived barriers
– Identify gaps in care and barriers to address

Plan
Consider designating one person as fertility specialist/navigator
– To provide services to patients
• Education, counseling, referrals, coordination of care
– To provide services to the organization
• Develop resources, educate staff

Develop an infrastructure
Develop resources for patient education
– Create your own
– Have created by partnering reproductive specialists
– Use established materials
• ASCO: Cancer.net
• Oncofertility Consortium: MyOncofertility, SaveMyFertility
• American Cancer Society
• LiveStrong Foundation

Develop resources for clinicians
– A clearly defined process for informing patients of their
fertility risks and options prior to initiation of treatment
• Encourage clinicians to define roles based on their
usual practice patterns, deciding how and when to
integrate this discussion into practice

– Develop electronic prompts or reminders
• Reports of young patients scheduled for consultation
• Patient intake forms with defined fields
• Clinician documentation forms with defined fields
• Consent forms
• Chemotherapy order alerts

– Identify local reproductive specialists for referral
if there are none within your organization
• American Society of Reproductive Medicine
• Society forAssisted ReproductiveTechnology
• Alliance for Fertility Preservation – Fertility Scout

– Select reproductive specialists to partner with based on
their ability to provide desired services
• Point person for scheduling
• Timely appointments (within 24-48 hours)
• Knowledgeable about relevant medical and
psychosocial issues in patients with cancer
• Willingness to provide discounted rates

– A clearly defined process for referring interested patients
to reproductive specialist
• Internal versus external provider
• Electronic, email, phone
• Alliance for Fertility Preservation – Fertility Scout

– Create a library of references
• Treatment-related risks & fertility preservation options
• Talking points
• Institutional policies, procedures, and processes
– Ensure availability of the information when needed in the
clinical setting (e.g., intranet site, paper toolkit)

Educate clinicians
– Invite reproductive specialists to present
– Use a variety of methods
• Didactic presentations (e.g., grand rounds, disease-
team presentations, fellow and nursing orientations)
• Interactive presentations (e.g. , journal clubs, case
presentations)

If implementing a fertility specialist/navigator role…
– Select appropriate provider
• NP/PA: medical assessment, diagnosis, management
• CNS: clinical care and organizational leadership
(develop resources, educate staff, monitor practice)
• RN: patient education, referral
• Other

Implement
Disseminate information about the program and go live!
– Consider implementing in one practice or service
at a time
– Focus on practices where there is interest
– Identify champions in the clinical setting

Implement
Consider the challenges in ensuring the program is
institutionalized (that all patients receive information)
– Variation in clinician practice
– Lack of knowledge among some clinicians
– Inconsistency in defining “appropriateness”
– Difficulty integrating into work flow
– Inconsistency in documentation

Implement
Consider the challenges in ensuring the program is sustainable
– How to maintain the improved practice of current
clinicians over time
– How to ensure new clinicians incorporate this into their
practice

Evaluate
Compare with baseline assessment
– Patient survey – satisfaction w/ information received
– Clinician survey – knowledge, practices, perceived barriers
Assess practice through monitoring of documentation based on
ASCO’s QOPI criteria
– Infertility risks discussed
– Fertility preservation options discussed

A final word for patients…
ASK QUESTIONS
• How will my planned treatment affect my ability to have
children in the future?
• What are my options to preserve fertility before beginning
treatment?
• Is there a reproductive specialist you can refer me to so
I can learn more about my options?
• What should I know about my family building options once
my treatment is completed?

Early Age Onset Colorectal Cancer:
Chemotherapy During Pregnancy
Cynthia Gail Leichman, MD
March 19, 2016

Scope of the Problem
• CRC is increasing in the younger population
• Cancer during pregnancy is increasing
• Expected further increase with trend to delay
pregnancy to later age

ISSUES:
• Clinical suspicion for diagnosis
– Overlapping pregnancy symptoms may yield later diagnosis
• Stage and type of cancer and goals of therapy
– Adjuvant, Disseminated
• Stage of pregnancy
– Trimester specific toxicity
– Effect of pregnancy on maternal prognosis
• Specific toxicities
– Choice of therapy
• Chemical, Biologic, ?Immunotherapy
• Combinations of different drug classes
– Ancillary medications
• Support
– Siblings, spouse

RISKS OF CHEMOTHERAPY DURING PREGNANCY
• Fetal risks – First Trimester:
– Spontaneous abortion, fetal death, major
malformations
– 10-25% risk major malformation; higher with
combination than single agent therapy
• Fetal risks – Second and Third Trimester
– Intrauterine growth retardation (IUGR), low birth
weight, and premature delivery
– Estimates: 7% IUGR, 5% premature delivery, 6% fetal
or neonatal death (N=376)

Maternal Risk:
• Impaired survival secondary to treatment
delay
• Enhanced physical stress of pregnancy and
chemotherapy toxicity
• Enhanced psychosocial stress
Maternal and Fetal Risk:
• Myelosuppression at delivery

GENERALLY ACCEPTED PRINCIPLES
• Health of the mother should come first
• Chemotherapy should be avoided in first
trimester to avoid congenital malformation
• Non-obstetrical surgery may be performed
during pregnancy without increased adverse
outcome
• In most cancers, pregnancy doesn’t adversely
affect maternal prognosis compared to matched
non-pregnant cancer patients

WHAT DATA DO WE HAVE TO GUIDE DECISIONS?
• Likely few cases for any single oncologist
– 0.02% to 0.1% of all pregnancies
– 1 cancer per 1000 pregnant women
• Can mammalian animal data help?
– Available preclinically for all new drugs
– Human dosing likely lower
Pereg, et al ; Cancer Treatment Reviews 2008

WHAT DATA DO WE HAVE TO GUIDE DECISIONS?
• Case reports and retrospective studies
– Summary by chemotherapy agents; Summary by
cancer type
• Numbers range between 3-150 pregnancies
– Impacted by publication bias
• Adverse outcome more likely reported
• Favorable outcome less likely published
– Lack long term follow-up
• Incomplete understanding of long-term cognitive, cardiac,
psychologic development; risk of subsequent malignancies
• Registries and Databases
– Few

November 5,2015

Study Overview
• Fetal exposure to maternal cancer during pregnancy with or without
treatment did not have an adverse effect on cognitive, cardiac, or
general development in early childhood.

Study Design and Recruitment.
Amant F et al. N Engl J Med 2015;373:1824-1834
3 CRC

Characteristics of the Children at Baseline.
Birth weight below
10th percentile
(small for
gestational age):
• 28/127 (22.0%) in
prenatal
exposure group
• 19/125 (15.2%) in
control group
• P=0.16

Cancer Treatment during Pregnancy for All Children and Those Categorized as Small for
Gestational Age.

Cognitive Outcome.
Bayley Scales of Infant
Development:
• Motor and Verbal
Skills
• Scores range 50-150
• Higher score = more
development
• Mean=100+/-15;
<85= developmental
delay
• Gestational age
relates to cognitive
score in both
groups (2A)
• Average cognitive
score increases 2.9
points for each
additional week in
gestational age at
birth

Echocardiographic Data and Other Measurements of Cardiac Function at 36 Months.

Conclusions
• Prenatal exposure to maternal cancer with or without treatment did not
impair the cognitive, cardiac, or general development of children in early
childhood.
• Prematurity was correlated with a worse cognitive outcome, but this effect
was independent of cancer treatment.

IN CONCLUSION:
• Given according to the best available data,
appropriate treatment for maternal cancer appears to
be safe in 2nd and 3rd trimesters for both mother and
fetus.
• The ultimate decision is individual to the patient –
based on informed discussion with her family and her
multidisciplinary care team
• We need to continue to improve upon the best
available data to provide to our patients to aid in
these decisions
• Continued development of registries into which ALL
data is entered is essential to accomplishing this goal

References
1. Cardonick E, Iacobucci A. Use of chemotherapy during human pregnancy.
The Lancet Oncology, 5: 283-91; 2004. USA
2. Pereg D, Koren G, Lishner M. Cancer in pregnancy: gaps, challenges, and
solutions. Cancer Treatment Reviews, 34: 302-12; 2 EUR
3. Amant F, Vandenbroucke M, Verheecke M, et.al. for the International
Network on Cancer, Infertility and Pregnancy (INCIP). Pediatric outcome
after maternal cancer diagnosed during pregnancy. N Engl J Med
373:1824-34; 2015. EUR
4. Koren G, Carey N, Gagnon, et. al. for the Society of Obstetricians and
Gynaecologists of Canada (SOGC). Cancer Chemotherapy and Pregnancy.
JOGC, 288: 263-78; 2013. CAN
5. Perspective on a modified developmental and reproductive toxicity
testing strategy for cancer immunotherapy. Int J Toxicol 2016 [epub]
6. CCOPE Database www.motherisk.org

EPIDEMIOLOGY:
WHAT IS DRIVING THE INCREASING
INCIDENCE OF YA CRC?
Christine Sardo-Molmenti PhD MPH mailman School of
Public Health, Columbia University
Elizabeth Kantor PhD MPH Memorial Sloan Kettering Cancer
Center
Barbara Cohn PhD Public Health Institute University of
California at Berkley
Aung Ko Win MBBS MPH PhD Melbourne School of
Population and Global Health
Stephen J.D. O’Keefe MD University of Pittsburgh School of
Medicine
Jordan Karlitz MD Tulane University School of Medicine

EAO CRC Risk Factors:
Literature Review
Christine L. Sardo Molmenti, MPH, PhD
Postdoctoral Research Scientist
NIH/NCI R25T Cancer Epidemiology Training Program
Columbia University
Mailman School of Public Health
Herbert Irving Comprehensive Cancer Center
Columbia University Medical Center
March 19, 2016

APC Change-based predictedincidence rates of colon cancer
by agecompared with incidence rate in 2010
Bailey RB, JAMA 2015

Colorectal cancer
Factors that increase risk Factors that decrease risk
Heredity and Medical History RR
Family history
• 1 FDR
• >1 relative
• Relative with cancer <45 years
2.2
4.0
3.9
• Crohn’s disease
• Ulcerative colitis
 Colon
 Rectum
2.6
2.8
1.9
Diabetes 1.2
Behavioral Factors RR
Alcohol consumption
Obesity
Red meat
Processed meat
Smoking
1.6
1.2
1.2
1.2
1.2
Garcia-Rodriguez LA, Huerta-Alvarez C, Epidemiology, 12(1):88-93, 2001
American Cancer Society Colorectal Cancer Facts and Figures, 2014-2016
Lifestyle factors RR
Physical activity (colon) 0.7
Dairy consumption 0.8
Fruit consumption 0.9
Vegetable consumption 0.9
Total dietary fiber (10g/day) 0.9
Aspirin use 0.5

Adenoma-to-carcinoma sequence
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
APC, K-ras, P53, COX-2 over-experession

Risk factors for EAO CRC
• Are they environmental?
• Are they lifestyle/behavioral?
• What is the timing of exposure?
• Where is the optimal place to intervene?
• Are the risk factors modifiable?
• Are the same determinants for >50?

Aims
1. Characterize modifiable risk factors relevant to early age
onset colorectal neoplasia
2. Summarize the potential biological links with early age
onset colorectal neoplasia
1. Further characterize clinically significant characteristics for
early age onset CRC in persons <50
Goal: Identify groups suitable for early screening/detection

Literature Review
141 articles identified
1939 to 2016
107 retrieved (34 requested)
“Young”
onset
• <50
• ≤45
• ≤40
• ≤30
MeSH terms: colorectal neoplasm
Key words: young onset, epidemiology, etiology, mortality, prevention and control
Inclusion
• Colorectal neoplasm
• Young, early-age onset
Exclusion
• Family history, inherited conditions (FAP, HNPCC)
Country
US
Australia
France
India
Sweden
Taiwan
Canada
Pakistan
UK
Israel
Denmark
Egypt
Hong Kong
Italy and Switzerland
Great Britain and Ireland
Saudi Arabia and New Zealand
Sri Lanka
Japan
New Zealand
Singapore
Study Design
• Retrospective chart review
• Cohort
• Case report and case series
• Cross sectional
• Case control
• Reviews
• Commentary
Year of publication
• 2011-2015 (40%)
• 2000-2010 (14%)
• 1990-1999 (16%)
• 1980-1989 (16%)
• 1939-1979 (11%)

What is the state of the EAO risk factor research?
Descriptive
Experimental
Clinical trials,
intervention
studies
Observational
Cohort, case-control,
cross sectional,
ecological
Distribution of disease
Analysis of disease
patterns according to
characteristics of person,
place, and time
Analytic
Hypothesis testingHypothesis generating
EPIDEMIOLOGIC STUDY DESIGNS

Risk factor related studies
18 observational studies
• 8 cohort
• 10 case control
Areas of study
• Obesity
• Diabetes
• Occupational exposures
• Physical activity
• Dietary exposures

12 studies related to obesity and EAO CRC

Cohort studies
Year
First
Author
Age Study population Outcome
1992
Lee and
Paffenbarger
< 55 and ≥ 55 17,595 Harvard Alumni Positive association
1992 Must 13-84
508 male adolescents in
Massachussetts
Positive association among men
only
2004 Jeffreys 2-54
2,347 children in England and
Scotland
Position association for smoking
related cancers
2008 Bjorge 14-61 226,678 Norwegian adolescents
Positive association for colorectal
cancer mortality
2011 Levi 17-59 1.1 million Israeli men
Positive association for colon
cancer but not rectal cancer
2014 Han 45-64
13,901 individuals from four US
states
Dose-response positive
association; independent of adult
body weight
2015 Zhang 42-99
109,771 individuals, (2,100
cases)
Positive association; independent
of adult body weight
7 Cohort studies - all positive

Case-control
Year
First
Author
Age Study population Outcome
1992 Le Marchand 49-63 52,539 male Hawaiian residents Positive association
2006 Hou 30-74
931 cases,1,552 controls in
Shanghai, China
Positive association
2007 Campbell 20-74
2696 cases, 2668 controls in
Ontario and Newfoundland,
Positive association
2010 Campbell 21-90
1,794 cases, 2,684 controls in
Canada, U.S., Australia,
Dose-response positive
association
2013 Rosato 19-45
329 cases, 1361 controls,
Switzerland and Italy
Negative association
5 Case-control studies - majority positive

Link between obesity and colorectal cancer
• Distribution of fat is a major determinant of
health
• Epidemiologic evidence supports excess body
fat as a major risk factor for colorectal cancer
• Gender differences
• Meta-analysis of 6 observational studies found
visceral adiposity was linearly associated with
odds of colorectal adenomas
• 25cm2 increase in visceral adiposity area elevates
the odds of colorectal adenomas by 13%
Biswas A et al. Annals of Internal Medicine, 162(2), 2015
Cong Y et al. British Journal of Cancer 110, 817-826, 2014
Keum N et al. Annals of Oncology 00:1-9, 2015

Diabetes, physical activity, dietary
factors, occupational exposures
1 cohort study
5 case control studies

Chen et al, 2012
Age-and sex-specific risks of colorectal cancers in
diabetic patients
Year First
author
Objective Age Study
population
Risk factor outcomes
2012 Chen To examine
age-and sex-
specific risks of
CRC in a
diabetic
population
≥ 45 Taiwan
National health
insurance database
Diabetic patients
(n=615,532)
Age and sex may significantly
modify the relationship
Males with diabetes aged 45-64 had
highest RR

Chen et al, 2012
Age-and sex-specific risks of colorectal cancers in
diabetic patients
Year First
author
Objective Age Study
population
Risk factor outcomes
2012 Chen To examine
age-and sex-
specific risks of
CRC in a
diabetic
population
≥ 45 Taiwan
National health
insurance database
Diabetic patients
(n=615,532)
Age and sex may significantly
modify the relationship
Males with diabetes aged 45-64 had
highest RR
• Diabetic patients and age- and sex-matched controls were followed up from 2000-2006
• Rates of admission due to colon and rectal cancers were estimated
• Overall significantly high risk of developing malignant colon neoplasm HR(95%CI)= 1.30
(1.21, 1.39) in men and 1.21 (1.13, 1.29) in women
• Patients <45 with diabetes not significantly associated with diabetes HR = 1.37 (0.88, 2.12)
• Patients 45-65 significantly associated with diabetes HR 1.45 (1.29, 1.63)

5 Case control studies
Year First
author
Title Age Study population Risk factor
outcomes
2013 Rosato Risk factors for young
onset CRC
≤ 45 3 Italian and Swiss
case-control studies
329 cases, 1361
controls
Alcohol, processed
meat, vegetables, fruit,
fish intake
2011 Cox School milk and risk of
CRC: A national case-
control study
30-69 New Zealand Cancer
Registry
562 cases and 571
controls
School milk
consumption
2008 Imperiale Risk factors for advanced
sporadic neoplasia in
persons <50
35-49 6 local hospitals in
Indianapolis
Cancer registry,
medical records,
endoscopy and
pathology reports
20 cases, 54 controls
Living with a
spouse/significant
other, pelvic
irradiation, FDR with
CRC, having had prior
sigmoid or
colonoscopy
1994 LaVecchia A case-control study of
diabetes mellitus and
cancer risk
<75 Integrated series of
case-control studies in
Northern Italy
Diabetes mellitus
1992 Peters A case-control study of
occupational and dietary
factors in colorectal cancer
in young men by subsite
25-44 Los Angeles Cancer
Surveillance Program
Physical activity;
dietary factors;
dust/fumes [strongest
for wood and metal
dusts]

1. Rosato et al, 2013
Risk factors for young-onset CRC
Year First
author
outcomes
onset CRC
≤ 45 3 Italian and Swiss case-
control studies
Alcohol, processed
fish intake
Study objective: To investigate risk factors for colorectal cancer in early-onset
cancers, to provide quantitative estimates for major selected risk factors.

Rosato et al, 2013
Year First
author
outcomes
onset CRC
control studies
Alcohol, processed
fish intake
Risk factors associated with increased risk OR (95% CI)
Family history of CRC in first-degree relative 4.50 (2.64, 7.68)
With affected siblings 11.68 (2.97,45.9)
With affected parents 3.75 (2.11, 6.66)
≥ 14 drinks/week of alcohol 1.56 (1.12, 2.16)
Highest tertile of processed meat 1.56 (1.11, 2.20)

Year First
author
outcomes
onset CRC
control studies
Alcohol, processed
fish intake
Risk factors associated with decreased risk OR (95% CI)
Highest tertile of vegetables 0.40 (0.28, 0.56)
Highest tertile of citrus fruit 0.61 (0.45-0.84)
Fish intake 0.78 (0.60, 1.00)
Β-carotene 0.52 (0.37, 0.72)
Vitamin C 0.68 (0.49, 0.94)
Vitamin E 0.38 (0.26, 0.58)
Folate 0.59 (0.40, 0.86)
Rosato et al, 2013

Year First
author
outcomes
onset CRC
control studies
Alcohol, processed
fish intake
No significant associations with physical activity, overweight,
and diabetes and young onset colorectal cancer.
Rosato et al, 2013

2. Cox et al, 2011
School milk and risk of colorectal cancer: A
national case-control study
Year First
author
outcomes
control study
Registry
562 cases and 571
controls
School milk
consumption
Study objective: To determine whether school milk
consumption in childhood decreased the risk of adult colorectal
cancer

Cox et al, 2011
School milk and risk of colorectal cancer: A
national case-control study
Year First
author
outcomes
control study
Registry
562 cases and 571
controls
School milk
consumption
Participation in school milk programs was associated with a reduced odds ratio
for colorectal cancer overall. OR (95% CI)=0.70 (0.51, 0.96)
*Not significant in the 30-49 year age group. OR (95% CI)=0.84 (0.33, 2.10)
Participation in school milk programs in New Zealand was associated with a
2.1% reduction in the odds ratio for colorectal cancer for every 100 half-point
bottles drunk (1 half-pint bottle=284 ml)

3. Imperiale et al, 2008
Risk factors for advanced sporadic colorectal
neoplasia in persons <50
Study objectives:
• Identify risk factors for advanced sporadic colorectal neoplasia
• Survey included: height, weight, self-measured waist and hip
circumference, occupation, hormone use, diabetes, aspirin,
NSAIDs, multivitamin use, alcohol, physical activity, tobacco
Year First
author
outcomes
2008 Imperiale Risk factors for advanced
sporadic neoplasia in
persons <50
35-49 6 local hospitals in
Indianapolis
Cancer registry,
medical records,
endoscopy and
pathology reports
Living with a
spouse/significant
other, pelvic
irradiation, FDR with
CRC, having had prior
sigmoid or
colonoscopy

Imperiale et al, 2008
Risk factors for advanced sporadic colorectal
neoplasia in persons <50
Factors that differed between cases and
controls
%
Living with a spouse/significant other 55 vs 80% (p=0.034)
Pelvic irradiation 20% vs 2% (p=0.019)
Having a first degree relative with CRC 25% vs 7% (p=0.05)
Having had a prior colonoscopy, sigmoidoscopy, or
barium enema
1.56 (1.12, 2.16)
Low recruitment rate of this study precludes it use for a larger, more
definitive study.

4. La Vecchia et al, 1994
A case-control study of diabetes mellitus and
cancer risk
Year First
author
outcomes
1994 LaVecchia A case-control study of
cancer risk
Northern Italy
Network of teaching
and general hospitals in
greater Milan
Diabetes mellitus
Study objective: To provide further quantitative information on the impact of
diabetes on the risk of cancers of several sites.

La Vecchia et al, 1994
A case-control study of diabetes mellitus and
cancer risk
Year First
author
outcomes
1994 La
Vecchia
A case-control study of
cancer risk
Northern Italy
Network of teaching
and general hospitals in
greater Milan
Diabetes mellitus
Significantly elevated relative risks for colorectal cancer among diabetes
were reported for cancers of the liver, pancreas, and enodmetrium.
No association between diabetes and colorectal cancer risk in diabetic
patients aged <40 years

5. Peters et al, 1989
A case-control study of occupational and
dietary factors in CRC in young men by subsite
Year First
author
Title Age Study
population
Risk factor
outcomes
1992 Peters A case-control study of
occupational and dietary
factors in colorectal
cancer in young men by
subsite
25-44
(74% between
35-44)
Los Angeles
Cancer
Surveillance
Program
147 cases, 147
controls
Physical activity; dietary
factors; dust/fumes
[strongest for wood and
metal dusts]
Study objective: Evaluate risk factors related to the rectum and three
subdivisions of the colon (right, transverse/descending, and sigmoid)

Potential biological links to EAO CRC
• Early postnatal period is a period of physiologic change
• Direct evidence that epigenetic regulatory mechanisms in the
gastrointestinal tract continue to develop in the postnatal
period

Hypothesized mechanisms
Adapted from Lynch et al, Cancer Epidemiol Biomarkers Prev, 2010
Sedentary
behavior
Diet,
sedentary
behavior,
physical
activity
Adiposity
Sex hormones
Androgens, estrogens
Metabolic Dysfunction
Insulin resistance, glucose
Inflammation
TNF-α IL-6 CRP
Vitamin D
Colorectal
Cancer
Development
and
Progression
Established association
Likely association
Possible association
Gut microbiome?

Points of prevention
Birth Colorectal neoplasia
Initiation Promotion Progression
Colorectal cancer
Mechanisms of tumor-suppressing agents
• Alteration in gene expression
• Inhibition of inflammation, cell proliferation
• Induction of apoptosis
• Inhibition of angiogenesis
Mechanisms of tumor-blocking agents
• Scavenging free radicals
• Antioxidant activity
• Induction of phase I and II drug-
metabolizing enzymes
• Induction of DNA repair
• Blockage of carcinogen uptake

Precursor to colorectal cancer
• >95% of sporadic colorectal cancers arise from the
adenomatous polyp
• 30% to 40% of the population will develop an
adenoma by age 60
• Evidence that prevalence in similar in patients 40-49
versus 50-59
• 20%-50% of adenomas recur within 3-5 years
o Villous architecture
o Size
o Number
o Location
o Advanced/no- advanced
ACS Colorectal Cancer Facts and Figures 2014-2016
Levine JS et al, New Engl J Med, 355; 24:2551-2557, 2006
Rundle et al, Gastroenterology, 2008

Jung et al, 2015
Risk factorsfor colorectalneoplasiain personsaged 30 to 39
years and 40-49 years
• To investigate risk factors in persons aged 30-39 years and 40-49
years and compare to those >50-59 years
• Korean adults who underwent colonoscopy as part of routine
preventive health care
In the 30-39 year age group
• Male sex, smoking, fatty liver, metabolic syndrome, obesity,
elevated fasting blood glucose levels, and elevated triglyceride
levels were associated with overall and neoplasia
• Corroborates previous studies on smoking and adenoma <40
• Current smokers twice as likely to develop colorectal adneomas vs non
smokers

Characteristicsofcolorectaladenoma recurrenceamong
individuals under 50 compared to those 50 yearsof ageor
older
Sardo Molmenti CL, Thomson CA, Yang JY, Hibler EA, Lance P,
Alberts DS, Neugut AI, Jacobs ET.
Manuscript in preparation

Aim
Investigate various demographic, lifestyle, and tumor
characteristics and odds of colorectal adenoma recurrence in
individuals under 50 years of age compared to those ≥ 50 years
of age.
Data pooled from two Phase III, randomized, placebo controlled
chemoprevention clinical trials
N=1730
Young onset colorectal adenoma
recurrence
Sardo Molmenti et al, manuscript in preparation

Preliminary Results
Less likely among <50 More likely among <50
• Non-Hispanic whites
• Previous polyps
• Aspirin use
• Sedentary behavior
• Consumption of total dietary fat
• Consumption of mono and poly unsaturated fatty
acids
• Hours of sleep
• Supplemental calcium
• Consumption of
saturated fatty acids
• Currently smoking
• Consumption of red meat
• Pro-inflammatory diet as
measured by the dietary
inflammatory index
A statistically significant difference was found for the following baseline
characteristics of participants <50 compared to those ≥50 years of age

Age (years)
Age< 50 years Age ≥ 50 years
OR (95% CI)* P value OR (95% CI) P value
Female ref. - ref. -
Male 1.687 (0.360, 7.895) 0.507 1.128 (0.824, 1.543) 0.453
Previous polyps
5.481 (1.190,
25.233)
0.029 1.339 (1.068, 1.678) 0.011
Current smoking
5.404 (1.248,
23.399)
0.024 1.427 (1.024, 1.989) 0.036
Preliminary Results
*Adjusted for age, gender, race/ethnicity, history of previous polyps, smoking, aspirin use, sedentary,
light-activity, MVPA, energy intake, total fat, saturated fat, fiber, calcium, alcohol

Implications for young-onset CRC
• History of previous polyps appears to be a stronger risk factor
for recurrence among those <50 compared to those ≥50 years
of age
• Unidentified risk factors that contribute to the formation of
adenomas in younger individuals
• Efforts to further investigate specific risk factors and the
biologic/molecular basis for the increasing incidence and
mortality of young-onset colorectal cancer are warranted

EAO CRC Risk factors summary
• Suggested link between early obesity and young onset colorectal cancer
• Evidence of an association with diabetes is unclear
• May imply a positive relationship between the duration of diabetes and the risk of CRC
– however needs further investigation
• Numerous dietary factors protective; dairy inconclusive
• Occupational exposures increase risk
• Require additional study of current exposures
• Metabolic syndrome, obesity, metabolic dysregulation, smoking,
associated with increased risk of colorectal neoplasia
• Suggestion that deleterious lifestyle factors more likely in the <50 age group

Next steps
1. Etiology of early onset CRC requires further investigation
o Case control studies
o Cohort studies
o Randomized clinical trials
2. Identify biomarkers and explore potential mechanisms of
action
3. Explore adding environmental and behavioral risk factors to
risk assessment models (metabolic syndrome)

ADOLESCENT BODY MASS INDEX AND
INFLAMMATION IN RELATION TO
COLORECTAL CANCER RISK
Elizabeth D. Kantor, PhD MPH
Department of Epidemiology and Biostatistics
Memorial Sloan Kettering Cancer Center
March 19, 2016
Early Onset Colorectal Cancer Summit
kantore@mskcc.org

Rationale
 Colorectal cancer (CRC) is the third most
common cancer among men and women in
the US
Siegel et al, CA Cancer J Clin,

Rationale
 Epidemiologic research has largely focused on
the role of adult exposures in the development
of CRC
 Know relatively little about how early-life
exposures may affect risk of cancer later in life

Body Mass Index & CRC
 Convincing evidence that adult body mass
index is positively associated with CRC risk
BMI CR
C

Body Mass Index & CRC
 Convincing evidence that adult body mass
index is positively associated with CRC risk
BMI CR
C
Steroid
Hormones
Lepti
n
Insuli
n
Inflammatio
n

Inflammation & CRC
 Chronic inflammation implicated in CRC
etiology
 Various lines of evidence point to the
involvement of inflammation early in colorectal
carcinogenesis

Early-life?
 Relatively little known about how early-life BMI
relates to risk of CRC
 No prior studies have evaluated the
association between inflammation measured
in early-life and CRC risk among healthy
individuals

Aims
 To evaluate the associations between late-
adolescent BMI and inflammation, as
measured by erythrocyte sedimentation rate,
and risk of CRC in a cohort of Swedish men

Significance
 Finding evidence of association between
early-life exposure and CRC could help us
better understand etiology of this disease and
shed light on potential points of intervention

Study Population
 Study population drawn from a cohort of men
conscribed in Swedish military between 1969
and 1976
 Conscription mandatory for all male Swedish
citizens
 Only men with severe disability or chronic disease
exempt
 Conscribed in late adolescence
 239,464 men ages 16-20 at conscription
 Excluded those with history of ulcerative
colitis/Crohn’s disease

Details on Conscription
Men completed extensive examinations
Recorded in the Swedish Military Conscription
Register

Exposure Assessment: BMI
 At conscription, height and weight measured
by trained personnel
 BMI categories:
 Underweight (<18.5 kg/m2)
 Normal weight (18.5- <25 kg/m2)
 Class I overweight (25- <27.5 kg/m2)
 Class II overweight (27.5- <30 kg/m2)
 Obese (30+ kg/m2)

Exposure Assessment: BMI
 At conscription, height and weight measured
by trained personnel
 BMI categories:
 Underweight (<18.5 kg/m2)
 Normal weight (18.5- <25 kg/m2)
 Class I overweight (25- <27.5 kg/m2)
 Class II overweight (27.5- <30 kg/m2)
 Obese (30+ kg/m2)
Potential
heterogeneity

Exposure Assessment: ESR
 Venous blood collected at examination, from
which ESR was measured
 Non-specific marker of inflammatory response
 ESR categories:
 Low inflammation (ESR <10 mm/hr)
 Medium inflammation (ESR 10- <15 mm/hr)
 High inflammation (ESR 15+ mm/hr )

Outcome Ascertainment
 CRC cases identified by linkage to the Swedish
national cancer registry
 Men followed from date of conscription until:
 Date of CRC diagnosis
 Date of death
 Date of emigration
 January 1, 2010
 Average follow-up of 35 years
 885 cases of invasive CRC
 501 colon cancers
 384 rectal cancers

Analyses
 Cox regression
 Covariates
selected from
available registry
data
Variable
Age at conscription
Household crowding
Disease status at baseline conscription
Systolic and diastolic BP
Muscular strength
Physical working capacity
Cognitive function
Erythrocyte volume fraction
ESR (in analyses of BMI)
BMI (in analyses of ESR)

Study Design
1969-1976 201
0
BMI & ESR
Measurement
Men not followed into late adulthood.
Ages 16-20 in 1969-76.
CRC
?

Late Adolescent ESR, BMI & CRC
Cohort
N (%)
Case
N (%)
Model 1a
HR (95% CI)
Model 2b
HR (95% CI)
Model 3b,c
HR (95% CI)
Body Mass Index (kg/m2)
Underweight (<18.5) 27,879
(11.6)
92 (10.4) 0.91 (0.74, 1.14) 0.86 (0.68, 1.08)
Normal Weight (18.5-<25) 193,679
(80.9)
698 (78.9) 1.00 (Ref) 1.00 (Ref)
Class I Overweight (25-
<27.5)
11,853
(4.95)
48 (5.42) 1.12 (0.84, 1.50) 1.15 (0.85, 1.55)
Class II Overweight (27.5-
<30)
3,694
(1.54)
27 (3.05) 2.03 (1.38, 2.98) 2.08 (1.40, 3.07)
Obese (30+) 2,359
(0.99)
20 (2.26) 2.38 (1.53, 3.72) 2.38 (1.51, 3.76)
P-trend: <0.001 P-trend: <0.001
Erythrocyte Sedimentation Rate
Low (1-10) 230,520
(96.3)
837 (94.6) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref)
Moderate (11-14) 4,797
(2.00)
24 (2.71) 1.43 (0.95, 2.16) 1.40 (0.93, 2.10) 1.38 (0.91,
2.10)
High (15-89) 4,147
(1.73)
24 (2.71) 1.66 (1.10, 2.50) 1.63 (1.08, 2.45) 1.48 (0.95,
2.29)
P-trend: 0.004 P-trend: 0.006 P-trend: 0.03
ABBREVIATIONS: 95% CI (95% Confidence Interval); HR (Hazard Ratio)
a Model adjusted for age and analysis of erythrocyte sedimentation rate further adjusted for erythrocyte volume fraction
b Model adjusted for age, erythrocyte sedimentation rate, erythrocyte volume fraction, BMI, household crowding, cognitive
function,
physical working capacity, muscular strength, disease status, systolic blood pressure, and diastolic blood pressure
c Excludes the first 10 years of follow-up, as well as all persons diagnosed with ulcerative colitis or Crohn’s disease in this
10-year
period; after excluding the first 10 years of follow-up and further excluding cases diagnosed with ulcerative colitis or
Crohn’s disease

The Second Annual Early Age Onset Colorectal Cancer Summit

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