©2013 MFMER | slide-1 Mayo Clinic and Alaska: Collaborative Health Care Activities with a Focus in...

©2013 MFMER | slide-1

Mayo Clinic and Alaska: Collaborative Health Care Activities with a Focus in CancerSteven Alberts, MD MPHMedical OncologyMayo Clinic - Rochester


Disclosures

• Relevant Financial Relationship(s)• None

• Off Label Usage• None


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


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


Overview of the Mayo Clinic

• Historical Points of Interest

• Present Day


Founding of the Mayo Clinic


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


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


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


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


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


Mayo - History

• Early 1900’s rapid growth of infrastructure


Mayo - History

• 1939: Will and Charlie Mayo pass away within 2 months of each other


Mayo - History

• Current Era


Mayo – Present Day

• Current Era• 2 hospitals• Dedicated

laboratory and research buildings


Mayo – 3 Locations

• 1986: Mayo Clinic in Jacksonville, FL opens

• 1987: Mayo Clinic in Scottsdale, AZ opens


Education

Patient Care

Research

“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)


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


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


Mayo Clinic Cancer CenterNCI Designated Comprehensive Cancer Center


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.



• 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



• 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



• 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


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


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 Clin Oncol)• 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


Alaska and Mayo Clinic Connection

Mayo Clinic Alaska Native People

http://mayoweb.mayo.edu/brand-standards/Images/mayo-brand-stock-photos/buildings/3086990-109.jpg


Mayo Clinic Activities in Alaska

• Adult and Pediatric Cardiac Clinics, 1963 - 198 0• 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


• 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


• 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


• 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


Cancer in Alaska Native People


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


Cancer21%

Heart Disease14%

UnintentionalInjury13%Suicide

7%COPD

4%Cerebrovascular Disease

4%

Chronic Liver2%

Pneumonia and Influenza

2%

Diabetes2%

Homicide2%

All other causes29%

Causes of Death in Alaska Native People

Mortality data for years 2004-2007; Source: NCHS; Alaska Native Tumor Registry, 2010


Cancer-related Mortality

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


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



1.0

2.0

3.0

4.0

5.0

6.0

Odds

Rati

o*

Alaska Native Cancer Sites which are Higher than US White Rates, 1999-2006

* All are significantly different from US Rates


0

0.2

0.4

0.6

0.8

1

Odds

Rati

o*

Alaska Native Cancer Sites which are Lower than US White Rates, 1996-2000

* All rates are significantly different from US Rates


Cancer Incidence in Indian Health Service Areas, 1994-2004


Cancer Incidence Rates in AI/AN by IHS Region in Contract Health Service Delivery Area Counties, 1999-2004

0

100

200

300

400

500

600

700

Southwest Pacific East Alaska N. Plains S. Plains All IHS NHW*

Ag

e-A

dju

ste

d R

ate

per

100,0

00

*NHW= non-Hispanic Whites from all CHSDA counties; source: Wiggins, et al., 2008

All sites, men


All Sites Cancer Incidence Rates in AI/AN by IHS Region in Contract Health Service Delivery Area Counties, 1999-2004

0

100

200

300

400

500

600

Southwest Pacific East Alaska N. Plains S. Plains All IHS NHW*

Ag

e-A

dju

sted

Rat

e p

er 1

00,0

00

*NHW= non-Hispanic Whites from all CHSDA counties; source: Wiggins, et al., 2008

All sites, women


Mayo Clinic and Alaska Interactions


Colorectal Cancer Incidence in AI/AN People

0 20 40 60 80 100

SEER White

Alaska

Bemidji

Billings

Portland

Oklahoma

Navajo

Incidence per 100,000

Women

Men


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 (Int J Cancer 124:2406-15, 2009)

• Hereditary Factors: Accounts for approximately 15% of colorectal cancer across populations


Colon Cancer – Molecular Changes

(Gastroenterology 143:1442-60, 2012)


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)


Assessing Molecular Changes in Alaska Native People with Colorectal Cancer

• Findings Continued• Tumors with loss of hMLH1 further 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


Patterns of Care Study Men Women

AK Native US White AK Native US White

Localized 41.1% 40.3% 39.4% 38.6%

Regional 34.6% 35.8% 35.9% 37.2%

Distant 20.7% 18.5% 21.2% 17.8%

Unstaged 3.7% 5.4% 3.5% 6.4%

• Care provided to AN people with colorectal cancer consistent with national guidelines

• Appropriate incorporation of molecular markers


Screening and Prevention

• Colorectal cancer is a potentially preventable cancer

• Importance of screening• Reducing risk factors• Chemoprevention


Screening

• Development of colorectal cancer• Opportunity for early detection

(Source: NIH Transformative R01 Program)


• Based on tumor exfoliation• Whole colonocytes• Proteins• Metabolites• RNA• DNA

• Nearly 100% discrimination of CRC and adenomas from normal mucosa

• Highly sensitive assay technique, QuARTS (quantitative allele-specific real-time target and signal amplification)


Stool DNA

• Identified 85% of patients with CRC and 54% of patients with adenomas ≥1 cm with 90% specificity (aggregate 87% detection rate for CRC stages I−III).

• Detection rates increased with adenoma size: 54% ≥1 cm, 63% >1 cm, 77% >2 cm, 86% >3 cm, and 92% >4 cm (P < .0001).

• Based on receiver operating characteristic analysis, the rate of CRC detection was slightly greater for the training than the test set (P = .04), whereas the rate of adenoma detection was comparable between sets.

• Sensitivities for detection of CRC and adenoma did not differ with lesion site

(Gastroenterology. 2012 Feb; 142(2): 248-56)

Training Set

Test Set


Colon Cancer in Alaska Native People



Rates of tobacco use are higher in AN people. Recent Behavioral Risk Factor Surveillance System (BRFSS) survey the rate of smoking in AN people is 45% compared to 21% in non-Native Alaskans


• Yukon-Kuskokwim Neonatal Tobacco Exposure Pilot project, 1998

• Mayo Nicotine Dependence Center Director Richard Hurt, MD and staff and YKHC program director Caroline Renner, MPH, collaborated on a pilot study to assess the impact of exposure of newborn infants to spit tobacco used by mothers during pregnancy and delivery.


• Iqmik: high pH of the punk fungus ash (pH 10.9) allows almost 100% of the nicotine to be in the freebase form

• Y-K Delta Alaska Native people are introduced to Iqmik at a very young age as it is frequently given to infants and children

• Substantial nicotine in neonates without exposure to the gaseous phase constituents of tobacco smoke

• Neurobehavioral effects of nicotine withdrawal observed in neonates born to Alaska Native women who use Iqmik and other forms of tobacco during pregnancy

(Journal of Maternal-Fetal and Neonatal Medicine 17(4): 281–289, 2005)


2000 2001 2002 2003-04 2005 2006-07 2008 2009 2010

• Start of Mayo, ANTHC, YKHC collaboration

• Meeting with AN leadership

• Needs Identified

• Focus groups conducted

• Key informant interviews

• Community priorities

• Study on nicotine exposure in pregnant women and newborns

• Adolescent focus groups

• Adolescent prevalence study

• Chemical assessment of ash

• Pregnant women prevalence study

• R21 grant to develop behavioral intervention for pregnant women

• NIDA and OWHR funded

• Community led youth tobacco cessation retreat

• R21 grant to evaluate efficacy of youth tobacco cessation retreat

• NIDA funded

• R01 level project to develop a biomarker feedback intervention for pregnant women

• NCI U54


• Pregnant Women• Pilot intervention with pregnant women indicated low

rate of participation and success• New interventions being developed and piloted

(Journal of Cancer Education 27(Suppl 1): S86-90, 2012)

• Youth Focus Group - Motivators to quit tobacco• Perceived adverse health effects of tobacco,• Improved self-image and appearance, • Potential to be a future role model as a non—tobacco user for

family and friends. • Findings being used to develop tobacco cessation programs

for Alaska Native youth(Health education & behavior 36:711 -723, 2009)


Breast Cancer


Breast Cancer Risk Factors

• Risk factors: • Age: menarche, first birth, menopause• Parity• Family history of breast cancer• Hormone replacement therapy• Lactation• Hysterectomy• Prior breast biopsy• Smoking status• Ethnic group• Breast Density


• Mammogram density has also not been studied in Alaska Native women

• The breast tissue parenchymal pattern as depicted on a mammogram is a factor that is influenced by hormonal breast cancer risk factors such as age at first birth, parity, menopause, and HRT3

• Density is a strong independent indicator of breast cancer risk


• Retrospective review of a sample of all sequential screening mammography examinations that were performed at the Alaska Native Medical Center between January and August of 1998 (n: 662 women)

• Aleut and Indian women were less likely to have high-density mammograms than were Eskimo women (P 0.0448).

• No significant differences were found between ethnic group for conventional breast cancer risk factors


(Mayo Clinic Proceedings 88(1): 68-73, 2013)

• Pilot study to provide telemedicine-based consultations for women at high risk for breast cancer

• Now service offered by Mayo Breast Clinic


Other Current Activities

• Annual Cancer Conference at ANMC (1998 – Present)

• Native American Programs at Mayo Clinic• Native C.I.R.C.L.E. (Cancer Information Resource Center for

Learning and Education): serves as a national resource for information and educational materials specifically targeting the American Indian/Alaska Native (AI/AN) population.

• Native WEB (Women Enjoying the Benefit) focuses on increasing cervical and breast cancer screening.

• Spirit of Eagles is a multi-faceted national AI/AN cancer initiative developed with the support of the NCI Leadership Initiative on Cancer and the current NCI Community Network Program.

©2013 MFMER | slide-1 Mayo Clinic and Alaska: Collaborative Health Care Activities with a Focus in...

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