Early Age Onset (EAO) Working Meeting
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Meeting summary slides: Shareable slides highlighting takeaways from the meeting
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Early Age Onset (EAO) Working Meeting
- 1. Fight Colorectal Cancer Early Age Onset (EAO) Working Meeting February 1, 2019 Denver, Colorado Leads: Andrea (Andi) Dwyer Reese Garcia Sharyn Worrall, Anjee Davis
- 2. Fight CRC • Strong advocate network of patient/survivor diagnosed under the recommended screening age • Fight CRC represents patients and has a responsibility to take action • The Early Age Onset Colorectal Cancer Work Group meeting initiated resulting from the increase in EAO CRC-building off the momentum of partner organizations
- 3. Siegel R: 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 40% since 1987 Young-Onset CRC Incidence is Increasing Incidence/100,000 Incidence/100,000 ≈15,000 new YO-CRCs
- 4. Objectives: Review the current practice and research in the field and what we think we know. To identify things that can/should be done now based on what we know To define some of what we need to know (causation, identification, course, prevention) Begin developing a strategic plan and hypothesize a research agenda around these issues. 2017 EAO CRC Strategy Session (December 6, 2017) What: NCCRT convened a strategic meeting to focus on the concerning trend of young-onset colorectal cancer. Participants: • 30+ attendees- experts/stakeholders • Funding from ACS, Colon Cancer Challenge Foundation, Entertainment Industry Foundation, National Colorectal Cancer Research Alliance Purpose: To assess how the NCCRT and its member organizations could most effectively align to address the issue Background: EAO CRC Strategy Session
- 5. Short-term Action Items • Research • Conduct landscape of on-going research • Convene group of investigators to identify key study components; study design; data sources and funding opportunities • Adoption of evidenced-based practices • Disseminate and evaluate tool kit from Jackson Laboratories • Create new messages for providers and patients to emphasize reality of CRC in young adults and increase • Improve communication around advanced polyps – e.g. work of AA WG
- 6. Screening Guidelines • “Colorectal Cancer Screening Initiation before the age of 50 years: A Microsimulation Analysis” published in Cancer, May 2018. • Result of collaborative efforts of Fight CRC, the American Cancer Society, Memorial Sloan Kettering in the United States, and Erasmus University in the Netherlands. • Helped inform guidelines updates to begin at 45 years of age for average risk adults.
- 7. Patient Advocacy Organizations Fight CRC conducted survey of nearly 500 patients to examine EAO, polyps, and family history • 15% self-classified as not a CRC patient/survivor, but have had one or more polyp • 69.35% (n=43) reported having family members who also have had polyps and/or CRC Colorectal Cancer Alliance conducted a survey assessing EAO • 67% of patients reported that they saw at least 2 physicians or more before they were correctly diagnosed with CRC. • 71% diagnosed at an advanced stage of the disease, stages III or IV (metastatic). Both organizations reported the most common symptoms in young onset includes constipation, blood in stool, bloating, rectal bleeding, and diarrhea.
- 8. About The Work Group • A dedicated interactive working meeting to discuss necessary steps to explore the research opportunities to explore etiology of sporadic colorectal cancer in those under 50 year old. • > 45 experts and 4 patient advocates in Denver, CO attended for a discussion on the current state of science and future research direction for EAO CRC
- 9. Agenda Development and Attendees • Goal to assemble a multidisciplinary group • Survey distribution to understand previous and current research being conducted in the field of EAO CRC • One-on-one phone calls to discuss the work and interests in EAO CRC research • Mandatory webinars to familiarize the group with the current data, introduce working members and help ensure the meeting goals were clear and the Workgroup arrived prepared to work • Professional moderator assisted in development and flow of the day
- 10. Meeting Objectives • Determine the prioritized risk factors to be studied • Determine the means by which we can study these priorities with existing studies and/or data repositories • Determine the means by which we can study these priorities with new studies • Understand the perspectives of policy makers and funders on our conclusions
- 11. Lectures • Introduction and Objectives: Andrea (Andi) Dwyer, Fight Colorectal Cancer Director of Health Promotion in a joint appointment of the University of Colorado Cancer Center- Meeting Leader • Describe Epidemiologic Risk Factors and Novel Research Approaches: Caitlin Murphy, PhD, MPH, Department of clinical Sciences, UT Southwestern Medical Center • Summarize Molecular Markers: Genetic and Epigenetic Research: C. Richard Boland, MD, Professor of Medicine, UCSD School of Medicine • Insights on Evidence-based Screening Recommendations: Ann G. Zauber, PhD, Memorial Sloan Kettering
- 12. Activities Participants spent the remainder of the day in multi- disciplinary group activities, reviewing findings between each to share among the group at large.
- 13. Exposure Demographics Genetics Timing of Exposure Outcome Medications (e.g. antibiotics, aspirin) Sex Pathogenic mutations (including high and low penetrant mutations) In-utero Colon vs. rectum Weight Race/ethnicity VUS Infancy Incidence Tobacco Use Age Epigenetic alterations Childhood Mortality Alcohol Use Geographic location Family History Adolescence Patient survival Chronic conditions (e.g., IBD, diabetes) Gene-environment interactions Adulthood Dietary patterns Specific nutrients (e.g. calcium) Occupation Physical activity/sedentary behavior Gut microbiota, dysbiosis Viral or bacterial infection (e.g. H pylori, HPV) Environmental exposure Other
- 14. • Large overlap between groups regarding priority risk factors between table groups Overview Risk Factor Cocktails Table 1 Diet in childhood Antibiotic use in childhood Obesity Gene-environment interactions Table 2 Diet in childhood Medications used in childhood ------- --------- Table 3 Diet in childhood Antibiotic use in childhood ------- --------- Table 4 Diet in childhood Microbiome in childhood Weight in childhood --------- Table 5 Inflammatory exposures (include?) Microbiome BMI Somatic mutations (include?) Online Diet in childhood Microbiome Gene environment interaction ---------
- 15. Risk Factor Combinations • Major risk factors included: • Diet in childhood • Antibiotic use in childhood • The microbiome • Obesity/weight in childhood • Gene-environment interactions • Explore relationship between: • Diet and weight in childhood • Antibiotic use and microbiome in childhood • Microbiome, diet, antibiotic use vs. gene- environment interactions • Outcomes to study: • Incidence of CRC • Development of adenomas
- 16. Risk Factor Combinations • Major risk factors included: • Diet in childhood • Antibiotic use in childhood • The microbiome • Obesity/weight in childhood • Gene-environment interactions • Explore relationship between: • Diet and weight in childhood • Antibiotic use and microbiome in childhood • Microbiome, diet, antibiotic use vs. gene- environment interactions • Outcomes to study: • Incidence of CRC • Development of adenomas
- 17. Section 1
- 18. Risk Factor Combinations • Major risk factors included: • Diet in childhood • Antibiotic use in childhood • The microbiome • Obesity/weight in childhood • Gene-environment interactions • Explore relationship between: • Diet and weight in childhood • Antibiotic use and microbiome in childhood • Microbiome, diet, antibiotic use vs. gene- environment interactions • Outcomes to study: • Incidence of CRC • Development of adenomas
- 19. Section 2
- 20. Conclusions • All attendees (100%) indicated that they made new connections with someone who helped inform their research perspective for early-age onset colorectal cancer research and learned about new resources or opportunities related to the study of EAO CRC. • 93% of attendees made connections to initiate or advance research studies or plans • Fight CRC served as a catalyst to bridge collaborations • Fight CRC is positioned to bring together committed partners at all levels, integrating the patient voice, and addressing future research needs in EAO CRC.
- 21. Next Steps • Continue to convene the EAO workgroup • Plan and seek funding for prospective cohort study, potentially from the NCI • Fight CRC -work with policy makers for common data metrics and elements for EAO research • Genomic analyses of tumor vs tissues from cases identified in institutions, finalize list of resources, publicly and not publicly available • Publish meeting summary and next steps to inform the research and medical community • Explore additional opportunities for implementation of the medical and public health interventions that will impact EAO (beyond research)
- 22. Thank you to the following individuals… Research/Patient Advocates Jessica Martin Karen Wehling Violet Kuchar Curt Pesmen Fight CRC Staff Andrea (Andi) Dwyer Anjee Davis Sharyn Worrall Reese Garcia In-Person attendees Dennis Ahnen Swati Patel Ann Zauber Heather Hampel C. Richard Boland Jose Perea García Caitlin Murphy Mingyang Song Josh Demb Hisham Hussan Caleb Levell Paul Limburg Luis Diaz Andrea Cercek Chris Lieu Richard Hayes Patrick Blatchford Jordan Karlitz Anil Wali Claire Palles Noel de Miranda Yin Cao Jeffrey Lee Phillip Buckhaults Steve Waring Jan Lowery Ryan Soisson Rebecca Siegel Patrick Mahoney Betsy Risendal Elsa Weltzien Garth Sundem Online Attendees Phil Daschner Roberto Flores Holli Loomans Christine Molmenti Cindy Sears Dusty Deming Contributors Scott Kopetz Matthew Young Paul Schroy Sanmir Gupta Andrew Chan Richard Goldberg Bob Smith Ian Tomlinson Kathy Helzlsouer Doug Corley
Editor's Notes
- Fight CRC is
- Note difference in axis
- Fight CRC worked with ACS and others to attend the NNRT meeting in 2017 to help explore next steps in early age onset initiatiaves
- There were short-term action items noted from this NNRT meeting and Fight CRC took the next steps in helping conduct a landscape of current and ongoing research and hold a discussion and convene a group of investing to advance the research agenda.
- Fight CRC worked closely to help advance and advocate for the funding and efforts to explore early age onset colorectal cancer and influence on screening guidelines.
- Fight CRC and other advocacy agencies have performed surveys and analysis to understand EAO and the patient experience.
- The meeting was very limited in didactic presentations, we had already done most of the planning and sharing before the meeting, these were a few presentations for framing the day and to help and brief on the most salient themes.
- The groups were asked to consider primary risk factors and contextual elements that should be explored for study, the following chart provides the detail provided at the beginning of the day.
- Each color code shows the similar themes
- This graphic shows an overview of the major risk factors that were prioritized and the relationships between each of risk factors, or “cocktails” worth exploring. Each group was given a list of well-established risk factors including exposures, demographics, genetics, timing of exposure, and outcomes which can be seen on slide 13 and were asked to create a cocktail of no more than three risk factors. It’s worth noting that each of these risk factors are color coded to match the contextual elements from the graphic on slide 13. The five major risk factors that arose from the first activity were diet in childhood, weight in childhood, antibiotic use in childhood and the microbiome (both in childhood and unspecified age), and gene-environment interactions. . Specifically, attendees highlighted the need to explore “cocktails, or relationships, between diet and weight in childhood, antibiotic use and the microbiome in childhood, and the relationship between microbiome and gene-environment interactions, diet and gene-environment interactions, and antibiotic use and gene-environment interactions, these interactions can be seen on the next two slides. Primary outcome measures were the incidence of colon or rectal cancer or the development of adenomas.
- This graphic shows an overview of the major risk factors that were prioritized and the relationships between each of risk factors, or “cocktails” worth exploring. Each group was given a list of well-established risk factors including exposures, demographics, genetics, timing of exposure, and outcomes which can be seen on slide 13 and were asked to create a cocktail of no more than three risk factors. It’s worth noting that each of these risk factors are color coded to match the contextual elements from the graphic on slide 13. The five major risk factors that arose from the first activity were diet in childhood, weight in childhood, antibiotic use in childhood and the microbiome (both in childhood and unspecified age), and gene-environment interactions. . Specifically, attendees highlighted the need to explore “cocktails, or relationships, between diet and weight in childhood, antibiotic use and the microbiome in childhood, and the relationship between microbiome and gene-environment interactions, diet and gene-environment interactions, and antibiotic use and gene-environment interactions, these interactions can be seen on the next two slides. Primary outcome measures were the incidence of colon or rectal cancer or the development of adenomas.
- This graphic zooms in on the interactions between weight and Diet and Diet and gene-environment interactions. When exploring diet in childhood, it was noted that it would be important to look at differences in race/ethnicity and geography, and to stratify by MMR status and colon vs. rectum location.
- This graphic shows an overview of the major risk factors that were prioritized and the relationships between each of risk factors, or “cocktails” worth exploring. Each group was given a list of well-established risk factors including exposures, demographics, genetics, timing of exposure, and outcomes which can be seen on slide 13 and were asked to create a cocktail of no more than three risk factors. It’s worth noting that each of these risk factors are color coded to match the contextual elements from the graphic on slide 13. The five major risk factors that arose from the first activity were diet in childhood, weight in childhood, antibiotic use in childhood and the microbiome (both in childhood and unspecified age), and gene-environment interactions. . Specifically, attendees highlighted the need to explore “cocktails, or relationships, between diet and weight in childhood, antibiotic use and the microbiome in childhood, and the relationship between microbiome and gene-environment interactions, diet and gene-environment interactions, and antibiotic use and gene-environment interactions, these interactions can be seen on the next two slides. Primary outcome measures were the incidence of colon or rectal cancer or the development of adenomas.
- This graphic zooms in on the interactions between the microbiome and antibiotic use, gene-environment interactions and antibiotic use, and gene-environment interactions and the microbiome. When investigating antibiotic use in childhood, it was noted that differences in race/ethnicity should be explored. Primary areas of stratification when investigating antibiotic use included MMR status, and location of the tumor or adenoma (colon vs. rectum).