Mayo Clinic and Alaska: Collaborative Health Care Activities with a Focus in Cancer

1. Mayo Clinic and Alaska: Collaborative Health Care Activities with a Focus in Cancer Steven Alberts, MD MPH Medical Oncology Mayo Clinic - Rochester

2. Disclosures • Relevant Financial Relationship(s) • None • Off Label Usage • None

3. Learning Objectives • Understanding of the collaborative activities of the Mayo Clinic in Alaska • Appreciation of the occurrence of specific cancers in Alaska Native People • Recognition of potential areas of collaboration

4. Outline of Presentation • Mayo Clinic History and Current Activities • Mayo Clinic Cancer Center • Cancer in Alaska Native People • Mayo Clinic and collaborative activities in Alaska – Focus on cancer

5. Overview of the Mayo Clinic • Historical Points of Interest • Present Day

6. Founding of the Mayo Clinic

7. Mayo - History • 1864: Dr. William Worrall Mayo moves to Rochester to examine new recruits for the Union Army • 1883, 1888: Dr. Mayo’s two sons, William J. and Charles H., join him in practice after finishing medical school

8. Founding of the Mayo Clinic • December,1876 Mother Alfred commissioned to establish an academy in Waseca, MN. In 1877 she also established a mission house and day school in Rochester, Minnesota • 1883: Tornado strikes Rochester. Mother Alfred Moes, of the Sisters of Saint Francis, proposes to build and staff a hospital if Dr. William Worrall Mayo and his sons will provide medical care. Saint Mary’s Hospital opens in 1889 with 27 beds

9. Mayo - History • 1892: More physicians are invited to join, thus beginning the concept of an integrated group practice. The team approach naturally leads to a division of labor, specialists in different fields working together • 1905: Louis Wilson, M.D., develops a rapid way to diagnose surgical specimens (quick-frozen tissue stained with methylene blue), which allows Mayo surgeons to explore, diagnose and repair, all in one operation

10. Mayo - History • 1914: Mayo isolates thyroxin, the principal active component of the thyroid gland • 1920: Mayo develops a system for grading cancer on a numerical basis that is adopted worldwide and still used today • 1934: Edward Kendall, Ph.D., isolates cortisone, a hormone from the suprarenal cortex that will later be used to treat rheumatoid arthritis with dramatic results • 1950: Edward Kendall, Ph.D., and Philip Hench, M.D., are awarded the Nobel Prize for the isolation and first clinical use of cortisone

11. Mayo - History • 1919: The Mayo’s turn over the assets of Mayo Clinic to the nonprofit Mayo Properties Association, the forerunner of Mayo Foundation • 1915: Doctors come from all over the world to observe and learn, leading to the organization of one of the world’s first formal graduate training programs for physicians, the Mayo School of Graduate Medical Education

12. Mayo - History • Early 1900’s rapid growth of infrastructure

13. Mayo - History • 1939: Will and Charlie Mayo pass away within 2 months of each other

14. Mayo - History • Current Era

15. Mayo – Present Day • Current Era • 2 hospitals • Dedicated laboratory and research buildings

16. Mayo – 3 Locations • 1986: Mayo Clinic in Jacksonville, FL opens • 1987: Mayo Clinic in Scottsdale, AZ opens

17. Education Research Patient Care “The best interest of the patient is the only interest to be considered, and in order that the sick may have the benefit of advancing knowledge, union of forces is necessary.” (Dr. W. J. Mayo)

18. Mayo Clinic Activities • Mayo Clinic is the first and largest integrated, not-for-profit medical group practice in the world • Over $8 billion in gross revenues • 3,800 physicians and scientists and 50,900 allied health staff • 3,600 students, residents, and fellows • Over 1 million patients seen each year

19. Mayo Clinic Research Activities • New protocols reviewed by the Institutional Review Board • 2,513 • Active human research studies • 8,117 • Research publications and review articles in peer-reviewed journals • 5,430 • Physicians and medical scientists • 391 • Students • 548

20. Mayo Clinic Cancer Center NCI Designated Comprehensive Cancer Center

21. Mayo Clinic Cancer Center • 1973: Mayo Clinic Cancer receives NCI designation • 2002: Mayo Clinic is the first multicenter clinic to receive “comprehensive cancer center” designation for its entire cancer program.

22. Mayo Clinic Cancer Center • NCI Recognized Programs • Cancer Prevention and Control • Cell Biology • Developmental Therapeutics • Gastrointestinal Cancers • Genetic Epidemiology and Risk Assessment • Gene and Virus Therapy • Hematologic Malignancies • Immunology and Immunotherapy • Neuro-Oncology • Women’s Cancers

23. Mayo Clinic Cancer Center • Over the last 10 years MCCC activities supporting translational research and clinical trials have included, • 6 P50 SPORE grants, • U10 NCCTG Chairs grant, • N01 Phase II contract, • U10 CCOP Research Base grants, • U01 Phase I grant, • Chemoprevention Network (CPN) contract, • Multiple R01 and R21 grants, as well as, numerous foundation grants

24. Mayo Clinic Cancer Center • Clinical Research – Clinical Trials Program • 242 studies open to accrual and 419 studies closed to accrual but still actively collecting data • Approximately 1,500 patients enrolled to clinical treatment trials each year

25. Mayo Clinic Cancer Center (MCCC) • Cancer - major component of Mayo’s clinical practice • New cancer diagnoses each year - 16,000+ • Approximately 20,000 cancer patients receive treatment each year at Mayo • Cancer - 1/3 of Mayo’s total research portfolio • Cancer Care and Research • Care occurs primarily in the Department of Oncology, Department of Radiation Oncology, and Division of Hematology, and Department of Surgery • Research in the Cancer Center

26. Cancer Center Accomplishments Publications • Over 7,000 publications during the last 5 year period • Increase in high impact publications • Clinical journals (e.g., JAMA, NEJM, J ClinOncol) • Scientific journals (e.g., Science, Nature, Cell) Research funding • Increase in overall peer-reviewed funding (2003 - 2010)$77.6 million to $145 million • Increase in NCI funding (2003 - 2010)$56.3 million to $106 million • Total Funding > $200 Million

27. Alaska and Mayo Clinic Connection Mayo Clinic Alaska Native People

28. Mayo Clinic Activities in Alaska • Adult and Pediatric Cardiac Clinics, 1963 - 198­0 • Teams of Mayo Cardiac physicians traveled to Alaska on an annual basis to conduct pediatric and adult cardiac clinics, including assessment of surgical candidates for referral to the Mayo Clinic • The cardiac and surgery clinics were first coordinated by the Alaska Territorial Office and then the State of Alaska, with the assistance of handicapped and crippled children programs • The clinics continued until Alaska medical facilities were able to provide the needed surgical services in-state

29. North American Nasopharyngeal Cancer (NPC) Study, 1979-1984 • ANMC researchers collaborated with Mayo Clinic, Rochester, MN staff (ENT, pathology, microbiology, immunology, etc.) on a national study of etiology of NPC including the relationship of the cancer to the Epstein-Barr virus

30. Design of Radiology Department for the New Alaska Native Medical Center • ANMC Chief Radiologist John Midthun consulted with Mayo Clinic Radiologist Bernie King for the design and implementation of the PACS digital imaging system at the new Alaska Native Medical Center which opened 1996

31. Yukon-Kuskokwim Health Corporation: "Promoting Community Wellness", 1999 • Thomas Kottke, MD, Mayo Clinic Cardiovascular Disease Specialist, traveled to Bethel to provide support and training of Community Health Aides/ Practitioners (CHA/Ps) at a regional conference encouraging community level wellness initiatives

32. Cancer in Alaska Native People

33. Cancer in Alaska Native People

34. Alaska Native Tumor Registry • Population-based registry • Includes information on AN people living in Alaska at the time of diagnosis of cancer from 1969 to the present • Contributes to the National Cancer Institute Surveillance, Epidemiology and End Results (SEER) Program since 1999 Anne Lanier, MD MPH Janet Kelly, MS MPH

35. Causes of Death in Alaska Native People Mortality data for years 2004-2007; Source: NCHS; Alaska Native Tumor Registry, 2010

36. Cancer-related Mortality (Cancer in Alaska Native People 1969-2008. 40-Year Report. http://anthctoday.org/epicenter/)

37. Cancer Death Rates by Gender • Cancer remains the leading cause of death among Alaska Native people. The all cancer mortality rate has exceeded the US white cancer mortality rate for more than 30 years. There have not been any significant declines. • The leading cause of cancer death is lung cancer; where the mortality rate is 40% higher in Alaska Native people than US whites (Cancer in Alaska Native People 1969-2008. 40-Year Report. http://anthctoday.org/epicenter/)

38. Alaska Native Cancer Sites which are Higher than US White Rates, 1999-2006 * All are significantly different from US Rates

39. Alaska Native Cancer Sites which are Lower than US White Rates, 1996-2000 * All rates are significantly different from US Rates

40. Cancer Incidence in Indian Health Service Areas, 1994-2004

41. Cancer Incidence Rates in AI/AN by IHS Region in Contract Health Service Delivery Area Counties, 1999-2004 All sites, men *NHW= non-Hispanic Whites from all CHSDA counties; source: Wiggins, et al., 2008

42. All Sites Cancer Incidence Rates in AI/AN by IHS Region in Contract Health Service Delivery Area Counties, 1999-2004 All sites, women *NHW= non-Hispanic Whites from all CHSDA counties; source: Wiggins, et al., 2008

43. Mayo Clinic and Alaska Interactions

44. Colorectal Cancer Incidence in AI/AN People

45. Colon Cancer – Risk Factors • Defined Risk Factors • Diet: Consumption of animal fat, meat, and protein and a concomitant decreased consumption of fiber • Tobacco: 1.4-fold increase risk of death from colorectal cancer in smokers compared to non-smokers (IntJ Cancer 124:2406-15, 2009) • Hereditary Factors: Accounts for approximately 15% of colorectal cancer across populations

46. Colon Cancer – Molecular Changes (Gastroenterology 143:1442-60, 2012)

47. Assessing Molecular Changes in Alaska Native People with Colorectal Cancer • CRC from 329 Alaska Native people • (165 Eskimo, 111 Indians, and 53 Aleut) evaluated for defective DNA mismatch repair (MMR), testing tumors for altered protein expression (hMLH1, hMSH2, and hMSH6) and for the presence of microsatellite instability (MSI) • Findings • 46 (14%) showed both MSI and altered protein expression; 42 (91%) with a loss of hMLH1, 3 (7%) hMSH2, and 1 (2%) hMLH1/hMSH6. (Cancer Epidemiol Biomarkers Prev 2007;16(11):2344–50)

48. Assessing Molecular Changes in Alaska Native People with Colorectal Cancer • Findings Continued • Tumors with loss of hMLH1further evaluated for hMLH1 promoter hypermethylation and for the BRAF-V600E mutation • (23 of 27) tested positive for the V600E alteration • Conclusion • CRC with defective MMR among the Eskimo sample fit the typical profile for hMLH1-related cancer associated with sporadic CRC, whereas the pattern in the Aleut and Indian suggests the possibility that germ line hMLH1 mutations may be present

49. Patterns of Care Study • Care provided to AN people with colorectal cancer consistent with national guidelines • Appropriate incorporation of molecular markers

50. Screening and Prevention • Colorectal cancer is a potentially preventable cancer • Importance of screening • Reducing risk factors • Chemoprevention