The Second Annual Early Age Onset Colorectal Cancer Summit

PowerPoint Presentation

YOUNG ADULT CRC: A GLOBAL CHALLENGERebecca Siegel MPH American Cancer SocietyDeborah Alsina Bowel Cancer UKT. Peter Kingham MD FACS Memorial Sloan Kettering Cancer CenterAung Ko Win MBS MPH PhD Melbourne School of Population and Global Health

Increasing colorectal cancer incidence in young adults in the US

Rebecca Siegel, MPHEarly-onset CRC SummitMarch 19, 2016

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Among 2 second-degree relatives40 years

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ConclusionCRC incidence rates continue to increase in young adults

ACTION ITEMSEarly screening when appropriateIncrease awareness among clinicians and young adults to facilitate earlier detectionKnow the symptomsRectal bleedingAbdominal painChange in bowel habitsEtiologic research known risk factors dont explain

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Thank you!

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Screening test use in ages 40-49 yearsSource: NHIS

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Why doesnt 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 levelrare before 50 (absolute risk 0.3% vs 5% for those 50+)serious adverse events (perforation, adverse reaction to sedation, etc)cost

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Harms & limitations of colonoscopy screening33% of patients report at least 1 GI symptom following the procedureSerious adverse event rate: 2.8 per 1,000 Adverse reaction to the sedativeBleeding if a polyp or tissue sample is takenPerforation of the colon wallScreening wont detect all cancers

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ACS screening guidelines average riskMen and women, ages 50+ FrequencyFecal occult blood test (FOBT) with at least 50% test sensitivity for cancer, or fecal immunochemical test (FIT) with at least 50% test sensitivity for cancerAnnualStool DNA testEvery 3 yearsFlexible sigmoidoscopyEvery 5 yearsDouble contrast barium enemaEvery 5 yearsColonoscopyEvery 10 yearsCT colonographyEvery 5 years

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35-3930-3425-2920-24Early-onset CRC incidence trends elsewhere

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Data sources for screening

Factors that influence population cancer trendsDetection/imagingpracticesRisk factorsScreening behaviors

MortalityIncidenceTreatment

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Colorectal cancer risk factors: medical and family historyRelative riskFamily history 1 first-degree relative2.2 More than 1 relative4.0 Relative with diagnosis before age 453.9Medical historyInflammatory bowel disease Crohn disease2.6 Ulcerative colitis Colon2.8 Rectum1.9Diabetes 1.2

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Increase risk:Relative riskTrendAlcohol consumption (heavy vs. nondrinkers)1.6Obesity1.2Red meat consumption1.2Processed meat consumption1.2?Smoking (current vs. never)1.2

Colorectal cancer risk factors: behavioralDecrease risk:Relative riskTrendPhysical activity (colon)0.7Milk/total dairy consumption0.8Fruit consumption0.9?Vegetable consumption0.9?Total dietary fiber (10 g/day)0.9?

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Deborah AlsinaExecutive Director

Bowel Cancer UK

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Charity of the Year 2013/2014

Young Adult CRC: A Global Challenge

Deborah AlsinaChief ExecutiveBowel Cancer UK

2ND ANNUAL EARLY AGE ONSET CRC SUMMIT

Thank you for inviting me.

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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

I need to give a health warning whilst Im going to try to stick to talking about colorectal or colon cancer in the UK we talk more about bowel cancer unhelpfully so its likely to creep into my descriptions.44


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

Work in all four nations of the UK45


What we do

We support research

We educate

We campaign

We are determined and ambitious

We do 3 core thingsDetermined & ambitious charity. Why/

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Colorectal cancer in the UK

The UKs 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

We havent reached tipping point where incidence is declining as it is here in the US. In part due to our screening programme which uses FOBt and has a 50% missed cancer rate.

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Around 60% of younger bowel cancer patients are diagnosed with either Stage 3 or Stage 4 bowel cancer, a higher proportion than people of any other age apart from those over the age of 90.

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Routes to diagnosis for under 50s

Screen DetectedGP Referral Urgent GP ReferralNon-urgentOther Out-patientInpatient ElectiveEmergency PresentationUnknown0%19%27%9%5%34%4%

Over a third of young people are diagnosed in Emergency. With this backdrop we decided to conduct research into why younger patients were being diagnosed late. Around 3 and half years ago we conducted our first focus groups, one to one interviews, surveys with younger patients and their families to find out what the issues were for them. We also consulted extensively with clinicians, academics and policy makers.

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Never Too Young

Launched Never Too Young April 2013 with the aim of improving the diagnosis, treatment and care of younger bowel cancer patients. Published several different reports and briefings on our findings and of course, much will be similar to here in the US so I thought I would highlight some of our policy related activity.50

Delays in diagnosis

OF course we want to understand why younger patients are being diagnosed late and our 2015 survey gave us some insights.. 56% of respondents to our survey went within 6 weeks of developing symptoms compared with 39% in 2013.

However, 44% waited over 3 months or didnt see their GP at all. The main reasons people gave for putting off going to the GP were that they thought their symptoms would go away or that they were not worried about their symptoms.51

Over 50% did only have to see their GP less than 3 times before referral.Yet 47% saw their GP 4 or more times or ended up being diagnosed as an emergency. 52

Gender delays54% 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.

Laura easily reassured when she was told at 29 her symptoms were nothing. When she was diagnosed 3 years later already very advanced.Her on her wedding day, one month before she died, 3 years ago53

Solutions: Awareness & education

As of March 2015Broadcast 32 million peoplePrint 11 million peopleSocial media 125,000Webpage views 185,000Celebrity campaign (Ricky Gervais, Stephen Fry, Sir Chris Hoy etc) 17 million

Raising awareness to dispel myths around the disease e.g. that its only an older persons disease. Also to create the environment for policy change.Weve created films, infographics, developed news stories that have been picked up on national and regional broadcast and print media.Noticing greater support for the campaign, not just from the public but also from health care providers and policy makers in the UK.54

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

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Risk Assessment Tool for Colorectal Cancers

This Risk Assessment Tool used by GPs on all CRC patients doesnt work for under 50s. So we are developing one specific to this age group. Because symptoms can be similar for IBD and CRC Professor Hamilton and team have reviewed the presenting symptoms of thousands of patients and developed a risk score for different combinations of symptoms. So if you used this chart if a patient came in with rectal bleeding on more than one occasion they would be assigned a risk score of 6.8%. In the UK our referral threshold is 3% risk so they would be referred.Our under 50 RAT publishing in June and will show different pattern.56

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

Concerned about all higher risk groups (IBD, strong family history and genetics) focused on genetics because through our research it became apparent that we are not identifying people with genetic conditions well.

Campaign to change this resulted in the RCPath guidance Yet we know that despite this around 50% of centres do not offer genetic testing.57

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??

Shocking lack of consensus about how to identify or when to test. Hope the new NICE guidance we are part of developing will help to address some of this.Also a major problem in the UK, once people are identified ensuring they receive the surveillance screening they need due to a lack of endoscopy capacity.58

Overall, only 68% of respondents were happy with their treatment and care, yet 89% were not given information on all the issues that affected them. For example, 1 in 2 were not given fertility advice 1 in 2 felt isolated, 1 in 3 people said that most of the information they received was targeted at older people.

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Solutions: a guide & films for people diagnosed under 50

Developed guide and films specifically to address the information gap felt by patients.

What have I learnt from 3 years of campaigning on these issues. Change takes time. Needs persistence, focus and determination but well worthwhile as the prize is great.

Leave you with a quote from a young 32 year old patient, charlotte who in her blog wrote about what she was looking forward to as her treatment ended.60


I cant 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 futureCharlotte (32)

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Thank you

Deborah [email protected] 44 207 940 1768@deborahalsina

Any questions?63

Colorectal cancer in NigeriaT. Peter Kingham MD FACSDirector, Global Cancer Disparity InitiativesMemorial 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 LMICBy 2050 70% of the predicted 24 million people with cancer will reside in LMICLifestyle changes, life expectancy higher, infectious disease treatments improvedHow do we improve outcomes of these patients?GuidelinesTrainingSurgeryKingham, Lancet Oncology, 2013

Cancer case fatality is high in LMICRatio 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): 801-803Farmer et al. Lancet. 2010. 376(9747):1187-93

In 2002 7.6 million world-wide cancer deaths vs 5.6 million from AIDS, malaria, and TB

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Tertiary care hospital in Malawi

Gyorki, Archives of Surgery, 2012

Late stage patients

CRC in NigeriaCharacteristics of CRC among Nigerians early age of onsetaggressive disease patternbulky tumorslate presentation and diagnosis

Investigating the outcomes and biology of CRC in Nigeria is worthwhile

Increasing Incidence of CRCIlorin, 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

Number of CasesYear

Ibrahim, Nigerian J of Clin Practice, 2011

Ibrahim Teaching hospital in Nigeria; 241 total cases; found 40% of CRC cases in last 4 years of study

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Comparison of Nigerian and American patients

Saluja, Surgery, 2013

Stage-matched Survival

North America Stage III

West Africa Stage IIINorth America Stage IVWest Africa Stage IV 0 2 4 68 10Years after DxProportion Survivingp < 0.01p < 0.011.0

0.8

0.60.4

0.2

survival stratified by stage at presentation (Stage III 62% nigeria vs 88% north america, stage IV 10% nigeria vs 45% north america) 74

Who gets CRC in West Africa?Prospective data collectionA multicenter study involving 4 tertiary health facilities in South west of Nigeria and MSKCC, New York.OAUTHC Ile-IfeUITH IlorinLAUTECH OsogboFMC OwoUniversity of IbadanEach hospital has a team comprised of Surgeons, Pathologists, Radiologists No medical oncologists

Consortium created in Oct 2013

Nigerian patients present at young ageMedian agesNigeria: 53 years USA: 68 years

% younger than 50 years:Nigeria: 41%USA: 17%

# of patientsKingham, unpublished data

USANigeria

Rectal cancer is most common in Nigeria

65% elective, 35% emergencyLocation#PercentageLeft colon42%Transverse colon116%Sigmoid colon2314%Right colon3823%Rectum9357%

Patients present late in NigeriaPresenting stage% Nigeria(n=145)% USA(SEER)I0%39%II9%36%IIIa27%-IV64%20%

Metastatic pattern is differentSiteNigeriaMSKCCPeritoneal 63%5%Liver 60%48%

Mortality rates in Nigeria are highNo 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 patients50 yearsN=106Rectal bleeding33 (46%)75 (71%)Right colon15 (21%)25 (24%)Rectum 35 (49%)57 (54%)StageII3 (4%)8 (8%)III18 (25%)23 (22%)IV36 (50%)56 (53%)DOD21 (29%)35 (33%)NED12 (17%)22 (21%)

Is the biology different?

Purified dna, then uses 5-microsatellite marker genotyping platform. MSI low if 30% of markers are unstable83

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

How do we identify earlier stage patients?

Symptoms of patients with rectal bleedingSymptomsN=100-change in stool caliber48%-pellet like stool24%-None52%Weight loss over 6 months45%Hemorrhoids 71%Polyps21%CRC present20%---Stage 245%---Stage 335%---Stage 420%

Pts with cancerN=20Pts without cancerN=80P valueSaw MD for bleeding16 (80%)67 (83.8%)Duration of rectal bleeding (median months)6 (2-24)6 (0.25-360)Change in stool caliber limit of detection for op

Maryland- (Helzouer)-- 1974 DDE is total of p,p'-DDT, o,p DDT, op DDE and DDE (of which majority would be DDE); 1989 DDE is p,p'-DDT +p,p'-DDE

New York (wolff)-- geometric mean is tabled for DDT as given in wolff and berkowitz 2000- probably somewhat lower than actual median--very close to median see table 8

Where results for cases and controls combined are not given, then results for controls are given.

ddt to dde ratio0.26415094340.12105263160.10.11666666670.10.1250.04166666670.04545454550.060.0389610390.15686274510.10447761190.0208333333

Ratio of DDT to DDTRatio

DDE by place and time5.31.71.91.61.212.41.20.441.21.150.822.510.770.511.690.760.410.670.48

p,p'-DDE

ddt by place and time1.40.230.160.140.10.30.050.020.150.030.080.070.01

p,p'-DDT

DDE and DDT log scale5.31.41.7Maryland 19741.90.231.60.161.20.1410.12.40.31.20.050.440.021.2Maryland 19891.15W. NY 19890.82U.S. Nurses 19902.510.150.770.030.510.081.69N. Carolina, African Amer 19950.76N. Carolina, whites0.41Connecticut 19960.670.070.480.01

p,p'-DDEp,p'-DDT

DDE lip adju (3)5.31.42.40.31.20.141.20.051.719741.219890.770.030.4119960.8219901.1519890.670.07

Yearp,p'-DDE (micrograms/gram)Lipid-adjusted p,p'-DDE by Year of Blood Draw

DDE lip adju (2)5.31.42.40.31.20.141.20.051.719741.219890.770.030.4119960.8219901.1519890.670.07

Yearp,p'-DDE (micrograms/gram)Lipid-adjusted p,p'-DDE by Year of Blood Draw

place labled5.31.41.7Maryland 19741.20.142.40.31.20.051.2Maryland 19891.15W. N.Y.19890.82U.S. Nurses 19900.770.030.41Connecticut 19960.670.07

p,p'-DDEp,p'-DDT

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Colorectal Cancer Case(n=2,301)Population / Spouse Controls(n=1,819)

Study Centers, n (%)

Ontario756 (32.9)484 (26.6)

Mayo Clinic323 (14.0)72 (4.0)

Seattle776 (33.7)890 (48.9)

Melbourne 446 (19.4)373 (20.5)

Sex , n (%)

Female1191 (51.8)975 (53.6)

Male1110 (48.2)844 (46.4)

Age at interview, years

Mean (SD)44.0 (5.7)45.5 (7.0)

Family history of CRC, n (%)

No1934 (84.1)1661 (91.3)

Yes367 (16.0)158 (8.7)

Adjusted OR (95% CI)P value

SexFemale1 (ref)

Male0.98 (0.84 1.15)0.81

Education attainmentNo or incomplete high school 1 (ref)

Completed high school0.87 (0.68 1.12)0.29

University degree or vocational school0.78 (0.61 1.01)0.06

Family history of colorectal cancerNo1 (ref)

Yes2.04 (1.65 2.51)

The Second Annual Early Age Onset Colorectal Cancer Summit

Health & Medicine

Transcript of The Second Annual Early Age Onset Colorectal Cancer Summit