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The Second Annual Early Age Onset Colorectal Cancer Summit

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This ground breaking program provided both survivors and health care professionals the opportunity to leverage each other's insights and an opportunity for all to hear "state-of-the-science" presentations on the epidemiology, pathogenesis, genomics and optimal multidisciplinary care of EAO-CRC.

The 2016 EAO CRC Summit featured keynote addresses from leading clinicians, epidemiologists and researchers from Europe, Africa, Australia and the nation's leading cancer centers and advocacy organizations.

Published in: Health & Medicine
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The Second Annual Early Age Onset Colorectal Cancer Summit

  1. 1. 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
  2. 2. Increasing colorectal cancer incidence in young adults in the US Rebecca Siegel, MPH Early-onset CRC Summit March 19, 2016
  3. 3. Among <50 years: 14,200 cases and 3,300 deaths Estimated numbers of new cases & deaths in 2016
  4. 4. 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
  5. 5. Anatomy of the colorectum (right-side) (left-side)
  6. 6. 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
  7. 7. 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
  8. 8. 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
  9. 9. 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:
  10. 10. 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
  11. 11. 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
  12. 12. 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 Incidencerateper100,000 2.6 in 1991 4.8 in 2012 Source: SEER 9 delay-adjusted rates, 1975-2012; 3-yr moving average. Distal colon 2.1% annually since 1994 Rectum 2.7% annually since 1991 Proximal colon
  13. 13. 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.
  14. 14. 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 Incidencerateper100,000 3.6% annually, 2003-2012 3.0% annually, 2003-2012
  15. 15. 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 Source: SEER 13 delay-adjusted rates, 1992-2012; 3-year moving average. 0 2 4 6 1992-94 2010-12 Rectal cancer incidence rate NHW Hispanic API NHB
  16. 16. Trends in young adults by 10-year age group 40-49 1.9% annually since 1994 30-39 2.2% annually since 1988 20-29 3.8% annually since 1987 0 5 10 15 20 25 Incidencerateper100,000people 0 0.5 1 1.5 2 2.5 20-29 years Source: SEER 9 delay-adjusted rates, 1975-2012; 3-year moving average. 20-29 years 6% 30-39 years 20% 40-49 years 74%
  17. 17. 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
  18. 18. 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
  19. 19. 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 Incidencerateper100,000 Colon 50-54 55-59 Source: SEER 9 delay-adjusted rates, 1975-2012; 3-yr moving average. 50-54 -0.8% annually, 2003-2012 +2.4% annually, 2003-2012 55-59 +0.7% annually, 2003-2012 -2.7% annually, 2003-2012
  20. 20. Increasing risk in successive generations since mid-century 1988 vs 1943 birth cohort: colon, 3X higher risk rectum, 4X higher risk
  21. 21. 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
  22. 22. State variation in incidence rates by age 50+ years20-49 years
  23. 23. 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.
  24. 24. 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
  25. 25. 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+
  26. 26. 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
  27. 27. 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
  28. 28. 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
  29. 29. 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
  30. 30. Thank you!
  31. 31. 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
  32. 32. 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
  33. 33. 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
  34. 34. 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. 35. 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
  36. 36. 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
  37. 37. Factors that influence population cancer trends Detection/imaging practices Risk factors Screening behaviors MortalityIncidence Treatment
  38. 38. 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 Inflammatory bowel disease Crohn disease 2.6 Ulcerative colitis Colon 2.8 Rectum 1.9 Diabetes 1.2
  39. 39. 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 ?
  40. 40. Deborah Alsina Executive Director Bowel Cancer UK
  41. 41. 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
  42. 42. 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
  43. 43. 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
  44. 44. Charity of the Year 2013/2014 What we do • We support research • We educate • We campaign • We are determined and ambitious
  45. 45. 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
  46. 46. 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%
  47. 47. Never Too Young
  48. 48. Delays in diagnosis
  49. 49. 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.
  50. 50. 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
  51. 51. 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
  52. 52. Risk Assessment Tool for Colorectal Cancers
  53. 53. 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
  54. 54. 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??
  55. 55. Solutions: a guide & films for people diagnosed under 50
  56. 56. 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)
  57. 57. Charity of the Year 2013/2014
  58. 58. Charity of the Year 2013/2014 Thank you Deborah Alsina Deborah.alsina@bowelcanceruk.org.uk 00 44 207 940 1768 @deborahalsina
  59. 59. Colorectal cancer in Nigeria T. Peter Kingham MD FACS Director, Global Cancer Disparity Initiatives Memorial Sloan Kettering Cancer Center
  60. 60. • Cancer in low- and middle-income countries (LMIC) • African Research Group for Oncology (ARGO) • Young patients with colorectal cancer (CRC)
  61. 61. 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
  62. 62. 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
  63. 63. Tertiary care hospital in Malawi Gyorki, Archives of Surgery, 2012
  64. 64. Late stage patients
  65. 65. 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
  66. 66. 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
  67. 67. Comparison of Nigerian and American patients Saluja, Surgery, 2013
  68. 68. 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
  69. 69. 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
  70. 70. 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
  71. 71. USA Nigeria
  72. 72. 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%
  73. 73. Patients present late in Nigeria Presenting stage % Nigeria (n=145) % USA (SEER) I 0% 39% II 9% 36% IIIa 27% - IV 64% 20%
  74. 74. Metastatic pattern is different Site Nigeria MSKCC Peritoneal 63% 5% Liver 60% 48%
  75. 75. 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%)
  76. 76. 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%)
  77. 77. Is the biology different?
  78. 78. Gene mutations found in Nigerian (Blue) and MSKCC (Red) patients
  79. 79. How do we identify earlier stage patients?
  80. 80. 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%
  81. 81. 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
  82. 82. 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
  83. 83. 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
  84. 84. 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
  85. 85. 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
  86. 86. Colorectal Cancer Worldwide
  87. 87. 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
  88. 88. Age-specific CRC incidence, 2015 Source: Australian Institute of Health and Welfare 90%10% 2-3%
  89. 89. CRC incidence and mortality, 1968 to 2012 Source: Australian Institute of Health and Welfare
  90. 90. • 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
  91. 91. Bowel Cancer in Young Adults in Australia
  92. 92. 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
  93. 93. 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 Young, Win, Rosty, et al. J Gastroenterol Hepatol. 2015;30(1):6- Age-specificincidenceper100000
  94. 94. 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 Young, Win, Rosty, et al. J Gastroenterol Hepatol. 2015;30(1):6-
  95. 95. CRC incidence in ASIA (1955-1999) Sung et al. Lancet Oncol. 2005;6(11):871-6.
  96. 96. RC incidence in ASIA (1993-1997) Sung et al. Lancet Oncol. 2005;6(11):871-6.
  97. 97. CRC incidence in ASIA (1983-2002) Center M, Jemal A, Ward E. Cancer Epidemiol Biomarkers Prev. 2009;18(6):1688-94.
  98. 98. Early-Onset CRC Incidence in JAPAN (1976-1994) Takada et al. Dis Colon Rectum. 2002;45(9):1249-54.
  99. 99. Early-Onset CRC Incidence in JAPAN (1978-2004) @ Confidential Unpublished data
  100. 100. Early-Onset CRC Incidence in KOREA (1999-2009) Shin et al. Cancer research and treatment. 2012;44(4):219-26.
  101. 101. CRC Incidence in KOREA vs JAPAN (1999-2012) Yoon et al. Epidemiology and health. 2015;37:e2015038.
  102. 102. Seydaoglu et al. Turkish Journal of Gastroenterology. 2013;24(6):521-31. Early-Onset CRC Incidence in TURKEY (1993-2008)
  103. 103. Early-Onset CRC in SINGAPORE
  104. 104. Early-Onset CRC in ASIAN COUNTRIES
  105. 105. 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.
  106. 106. 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
  107. 107. 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 Young, Win, Rosty, et al. J Gastroenterol Hepatol. 2015;30(1):6-
  108. 108. 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 Young, Win, Rosty, et al. J Gastroenterol Hepatol. 2015;30(1):6-
  109. 109. Australian Bowel Cancer Screening Guidelines
  110. 110. National Bowel Cancer Screening Program
  111. 111. 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 Young, Win, Rosty, et al. J Gastroenterol Hepatol. 2015;30(1):6-
  112. 112. 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 Young, Win, Rosty, et al. J Gastroenterol Hepatol. 2015;30(1):6-
  113. 113. Acknowledgement
  114. 114. © Copyright The University of Melbourne 2009
  115. 115. 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
  116. 116. 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
  117. 117. 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
  118. 118. 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
  119. 119. 0% 3% 49% 48% Stage 1 Stage 2 Stage 3 Stage 4 Initial Stage at Diagnosis
  120. 120. 46% 23% 11% 20% Emergency Room Primary Care OB / GYN Gastroenterologist How were you diagnosed?
  121. 121. 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
  122. 122. 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?
  123. 123. 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%)
  124. 124.  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?
  125. 125. “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?
  126. 126. 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?
  127. 127. 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?
  128. 128. 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
  129. 129. • 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!
  130. 130. 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
  131. 131. 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.
  132. 132. • 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
  133. 133. 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
  134. 134. Standard to improve psychosocial care for cancer survivors Health and Medicine Division (HMD), formerly IOM, National Academies of Science, Engineering and Medicine, 2008
  135. 135. Psychosocial needs of cancer survivors & services to address them Health and Medicine Division (HMD), formerly IOM, National Academies of Science, Engineering and Medicine, 2008
  136. 136. • 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
  137. 137. • 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
  138. 138. • 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
  139. 139. • 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
  140. 140. “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.” Health and Medicine Division (HMD), formerly IOM, National Academies of Science, Engineering and Medicine, 2008
  141. 141. GETTING YOUR AFFAIRS IN ORDER: A Legal Perspective • March 19, 2016
  142. 142. 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
  143. 143. Objectives • Provide overview of common concerns for young adults with cancer: –Employment Rights and Responsibilities –Disability Income –Advanced Directives and Wills –Debt 150
  144. 144. 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
  145. 145. 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
  146. 146. 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
  147. 147. 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
  148. 148. Advanced Planning • What legal documents should I have prepared to protect me and help my family assist me if needed? 155
  149. 149. 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
  150. 150. 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
  151. 151. 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
  152. 152. 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
  153. 153. 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
  154. 154. 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
  155. 155. 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
  156. 156. 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
  157. 157. 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
  158. 158. 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
  159. 159. 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
  160. 160. 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
  161. 161. 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
  162. 162. 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)
  163. 163. 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?
  164. 164. 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
  165. 165. 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.
  166. 166. 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”
  167. 167. 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)
  168. 168. 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
  169. 169. Important Considerations • Body Image • Sexual Functioning • Quality of Life Goals may differ from older patients • Fertility • Social Isolation
  170. 170. 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
  171. 171. 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
  172. 172. 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
  173. 173. 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
  174. 174. 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
  175. 175. 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
  176. 176. Program Development Support Group Implementation: Young Adult Couples YoungAdult Patients Young Adult Caregivers Young Adult Partner’s Bereavement
  177. 177. Contact Information Carolyn Fulton, LCSW-R fultonc@mskcc.org 646-888-3532
  178. 178. Fertility Preservation Before Cancer Treatment: Developing a Program to Improve Practice
  179. 179. 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
  180. 180. 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
  181. 181. 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)
  182. 182. Professional guidelines highlight the need for clinicians to address fertility
  183. 183. 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
  184. 184. A systematic approach can help in developing a program to help clinicians address fertility Plan Develop an Infrastructure Implement Evaluate
  185. 185. A systematic approach can help in developing a program to help clinicians address fertility Plan Develop an Infrastructure Implement Evaluate
  186. 186. 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
  187. 187. 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
  188. 188. A systematic approach can help in developing a program to help clinicians address fertility Plan Develop an Infrastructure Implement Evaluate
  189. 189. 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
  190. 190. Develop an infrastructure 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
  191. 191. Develop an infrastructure Develop resources for clinicians – 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
  192. 192. Develop an infrastructure Develop resources for clinicians – 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
  193. 193. Develop an infrastructure Develop resources for clinicians – 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
  194. 194. Develop an infrastructure Develop resources for clinicians – A clearly defined process for referring interested patients to reproductive specialist • Internal versus external provider • Electronic, email, phone • Alliance for Fertility Preservation – Fertility Scout
  195. 195. Develop an infrastructure Develop resources for clinicians – 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)
  196. 196. Develop an infrastructure 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)
  197. 197. Develop an infrastructure 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
  198. 198. A systematic approach can help in developing a program to help clinicians address fertility Plan Develop an Infrastructure Implement Evaluate
  199. 199. 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
  200. 200. 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
  201. 201. 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
  202. 202. A systematic approach can help in developing a program to help clinicians address fertility Plan Develop an Infrastructure Implement Evaluate
  203. 203. 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
  204. 204. 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?
  205. 205. Early Age Onset Colorectal Cancer: Chemotherapy During Pregnancy Cynthia Gail Leichman, MD March 19, 2016
  206. 206. 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
  207. 207. Chemotherapy During Pregnancy 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
  208. 208. Chemotherapy During Pregnancy 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)
  209. 209. Chemotherapy During Pregnancy 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
  210. 210. Chemotherapy During Pregnancy 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
  211. 211. Chemotherapy During Pregnancy 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
  212. 212. Chemotherapy During Pregnancy 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
  213. 213. Chemotherapy During Pregnancy November 5,2015
  214. 214. Study Overview Chemotherapy During Pregnancy • 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.
  215. 215. Study Design and Recruitment. Amant F et al. N Engl J Med 2015;373:1824-1834 Chemotherapy During Pregnancy 3 CRC
  216. 216. Characteristics of the Children at Baseline. Amant F et al. N Engl J Med 2015;373:1824-1834 Chemotherapy During Pregnancy 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
  217. 217. Cancer Treatment during Pregnancy for All Children and Those Categorized as Small for Gestational Age. Amant F et al. N Engl J Med 2015;373:1824-1834 Chemotherapy During Pregnancy
  218. 218. Cognitive Outcome. Amant F et al. N Engl J Med 2015;373:1824-1834 Chemotherapy During Pregnancy 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
  219. 219. Echocardiographic Data and Other Measurements of Cardiac Function at 36 Months. Amant F et al. N Engl J Med 2015;373:1824-1834 Chemotherapy During Pregnancy
  220. 220. Conclusions Chemotherapy During Pregnancy • 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.
  221. 221. Chemotherapy During Pregnancy 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
  222. 222. Chemotherapy During Pregnancy 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
  223. 223. 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
  224. 224. 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
  225. 225. APC Change-based predictedincidence rates of colon cancer by agecompared with incidence rate in 2010 Bailey RB, JAMA 2015
  226. 226. 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 Inflammatory bowel disease • 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
  227. 227. 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
  228. 228. 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?
  229. 229. 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
  230. 230. 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%)
  231. 231. 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%)
  232. 232. 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
  233. 233. Risk factor related studies 18 observational studies • 8 cohort • 10 case control Areas of study • Obesity • Diabetes • Occupational exposures • Physical activity • Dietary exposures
  234. 234. 12 studies related to obesity and EAO CRC
  235. 235. 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
  236. 236. 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
  237. 237. 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
  238. 238. Diabetes, physical activity, dietary factors, occupational exposures 1 cohort study 5 case control studies
  239. 239. 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
  240. 240. 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)
  241. 241. 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 828 cases, 818 controls 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 147 cases, 147 controls Physical activity; dietary factors; dust/fumes [strongest for wood and metal dusts]
  242. 242. 1. Rosato et al, 2013 Risk factors for young-onset CRC 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 Study objective: To investigate risk factors for colorectal cancer in early-onset cancers, to provide quantitative estimates for major selected risk factors.
  243. 243. Rosato et al, 2013 Risk factors for young-onset CRC 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 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)
  244. 244. 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 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 Risk factors for young-onset CRC
  245. 245. 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 No significant associations with physical activity, overweight, and diabetes and young onset colorectal cancer. Rosato et al, 2013 Risk factors for young-onset CRC
  246. 246. 2. Cox et al, 2011 School milk and risk of colorectal cancer: A national case-control study Year First author Title Age Study population Risk factor outcomes 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 Study objective: To determine whether school milk consumption in childhood decreased the risk of adult colorectal cancer
  247. 247. Cox et al, 2011 School milk and risk of colorectal cancer: A national case-control study Year First author Title Age Study population Risk factor outcomes 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 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)
  248. 248. 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 Title Age Study population Risk factor 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 20 cases, 54 controls Living with a spouse/significant other, pelvic irradiation, FDR with CRC, having had prior sigmoid or colonoscopy
  249. 249. 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.
  250. 250. 4. La Vecchia et al, 1994 A case-control study of diabetes mellitus and cancer risk Year First author Title Age Study population Risk factor outcomes 1994 LaVecchia A case-control study of diabetes mellitus and cancer risk <75 Integrated series of case-control studies in Northern Italy Network of teaching and general hospitals in greater Milan 828 cases, 818 controls Diabetes mellitus Study objective: To provide further quantitative information on the impact of diabetes on the risk of cancers of several sites.
  251. 251. La Vecchia et al, 1994 A case-control study of diabetes mellitus and cancer risk Year First author Title Age Study population Risk factor outcomes 1994 La Vecchia A case-control study of diabetes mellitus and cancer risk <75 Integrated series of case-control studies in Northern Italy Network of teaching and general hospitals in greater Milan 828 cases, 818 controls 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
  252. 252. 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)
  253. 253. 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
  254. 254. 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?
  255. 255. 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
  256. 256. 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
  257. 257. 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
  258. 258. 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
  259. 259. 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
  260. 260. 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 Sardo Molmenti et al, manuscript in preparation
  261. 261. 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 Sardo Molmenti et al, manuscript in preparation
  262. 262. 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 Sardo Molmenti et al, manuscript in preparation
  263. 263. 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
  264. 264. 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)
  265. 265. 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
  266. 266. Background
  267. 267. Rationale  Colorectal cancer (CRC) is the third most common cancer among men and women in the US Siegel et al, CA Cancer J Clin,
  268. 268. 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
  269. 269. Body Mass Index & CRC  Convincing evidence that adult body mass index is positively associated with CRC risk BMI CR C
  270. 270. 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
  271. 271. Inflammation & CRC  Chronic inflammation implicated in CRC etiology  Various lines of evidence point to the involvement of inflammation early in colorectal carcinogenesis
  272. 272. 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
  273. 273. Kantor ED et al, Gut,
  274. 274. 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
  275. 275. 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
  276. 276. Methods
  277. 277. 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
  278. 278. Details on Conscription Men completed extensive examinations Recorded in the Swedish Military Conscription Register
  279. 279. 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)
  280. 280. 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
  281. 281. 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 )
  282. 282. 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
  283. 283. 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)
  284. 284. Study Design 1969-1976 201 0 BMI & ESR Measurement Men not followed into late adulthood. Ages 16-20 in 1969-76. CRC ?
  285. 285. Results
  286. 286. 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
  287. 287. 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
  288. 288. 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

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