Mayo Clinic and Alaska:
Collaborative Health Care Activities
with a Focus in Cancer
Steven Alberts, MD MPH
Medical Oncology
Mayo Clinic - Rochester
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Disclosures
• Relevant Financial Relationship(s)
• None
• Off Label Usage
• None
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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
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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
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Overview of the Mayo Clinic
• Historical Points of Interest
• Present Day
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Founding of the Mayo Clinic
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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
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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
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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
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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
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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
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Mayo - History
• Early 1900’s rapid growth of infrastructure
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Mayo - History
• 1939: Will and Charlie Mayo pass away within 2 months
of each other
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Mayo - History
• Current Era
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Mayo – Present Day
• Current Era
• 2 hospitals
• Dedicated
laboratory
and research
buildings
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Mayo – 3 Locations
• 1986: Mayo Clinic in
Jacksonville, FL opens
• 1987: Mayo Clinic in
Scottsdale, AZ opens
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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)
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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
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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
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Mayo Clinic Cancer Center
NCI Designated Comprehensive Cancer Center
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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.
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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
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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
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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
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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
CP13193
86-25
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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
CP13193
86-26
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Alaska and Mayo Clinic Connection
Mayo Clinic
Alaska Native People
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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 instate
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• 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
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• 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
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• 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
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Cancer in Alaska Native People
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Cancer in Alaska Native People
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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
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Causes of Death in Alaska Native People
All other causes
29%
Heart Disease
14%
Homicide
2%
Diabetes
2%
Pneumonia and
Influenza
2%
Chronic Liver
COPD
2%
4%
Cerebrovascular
Disease
4%
Cancer
21%
Suicide
7%
Unintentional
Injury
13%
Mortality data for years 2004-2007; Source: NCHS; Alaska Native Tumor Registry, 2010
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Cancer-related Mortality
(Cancer in Alaska Native People 1969-2008. 40-Year Report.
http://anthctoday.org/epicenter/)
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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/)
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Alaska Native Cancer Sites which are
Higher than US White Rates, 1999-2006
6.0
Odds Ratio*
5.0
4.0
3.0
2.0
ng
Lu
ne
y
K
id
s
nc
re
a
gu
s
Pa
Es
op
ha
ha
ry
nx
ve
r
O
ra
l/P
Li
l
or
ec
ta
C
ol
ac
h
om
St
G
al
lb
la
dd
er
1.0
* All are significantly different from US Rates
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Alaska Native Cancer Sites which are
Lower than US White Rates, 1996-2000
1
Odds Ratio*
0.8
0.6
0.4
0.2
Ly
m
ph
om
a
m
ia
Le
uk
e
ry
O
va
ru
s
U
te
de
r
ar
y
B
la
d
ta
te
U
rin
Pr
os
N
S
n/
B
ra
i
M
el
a
no
m
a
0
* All rates are significantly different from US Rates
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Cancer Incidence in
Indian Health Service
Areas, 1994-2004
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Cancer Incidence Rates in AI/AN
by IHS Region in Contract Health Service
Delivery Area Counties, 1999-2004
All sites, men
700
Age-Adjusted Rate per 100,000
600
500
400
300
200
100
0
Southwest
Pacific
East
Alaska
N. Plains
*NHW= non-Hispanic Whites from all CHSDA counties; source: Wiggins, et al., 2008
S. Plains
All IHS
NHW*
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All Sites Cancer Incidence Rates in AI/AN
by IHS Region in Contract Health Service
Delivery Area Counties, 1999-2004
600
All sites, women
Age-Adjusted Rate per 100,000
500
400
300
200
100
0
Southwest
Pacific
East
Alaska
N. Plains
*NHW= non-Hispanic Whites from all CHSDA counties; source: Wiggins, et al., 2008
S. Plains
All IHS
NHW*
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Mayo Clinic and Alaska Interactions
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Colorectal Cancer Incidence in AI/AN
People
Navajo
Oklahoma
Portland
Billings
Women
Bemidji
Men
Alaska
SEER White
0
20
40
60
80
100
Incidence per 100,000
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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 nonsmokers (Int J Cancer 124:2406-15, 2009)
• Hereditary Factors: Accounts for approximately 15%
of colorectal cancer across populations
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Colon Cancer – Molecular Changes
(Gastroenterology 143:1442-60, 2012)
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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)
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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
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Patterns of Care Study
Men
Localized
Regional
Distant
Unstaged
AK Native
41.1%
34.6%
20.7%
3.7%
US White
40.3%
35.8%
18.5%
5.4%
Women
AK Native
US White
39.4%
38.6%
35.9%
37.2%
21.2%
17.8%
3.5%
6.4%
• Care provided to AN people with colorectal cancer
consistent with national guidelines
• Appropriate incorporation of molecular markers
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Screening and Prevention
• Colorectal cancer is a potentially preventable
cancer
• Importance of screening
• Reducing risk factors
• Chemoprevention
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Screening
• Development of colorectal cancer
• Opportunity for early detection
(Source: NIH Transformative R01 Program)
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• 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)
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Stool DNA
Training Set
• 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.
Test Set
• Sensitivities for detection of CRC and
adenoma did not differ with lesion site
(Gastroenterology. 2012 Feb; 142(2): 248-56)
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Colon Cancer in Alaska Native People
(Cancer in Alaska Native People 1969-2008. 40-Year Report.
http://anthctoday.org/epicenter/)
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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
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• 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.
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• 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)
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2000
2001
• Start of Mayo,
ANTHC, YKHC
collaboration
• Meeting with AN
leadership
• Needs Identified
2002
2003-04
• Study on nicotine
exposure in
pregnant women
and newborns
• Focus groups
conducted
• Key informant
interviews
• Community
priorities
2005
2006-07
• Pregnant women
prevalence study
• Adolescent focus
groups
• Adolescent
prevalence study
• Chemical
assessment of ash
2008
2009
• Community led
youth tobacco
cessation retreat
• R21 grant to develop
behavioral
intervention for
pregnant women
• NIDA and OWHR
funded
2010
• R01 level project to
develop a biomarker
feedback
intervention for
pregnant women
• NCI U54
• R21 grant to
evaluate efficacy of
youth tobacco
cessation retreat
• NIDA funded
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• 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)
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Breast Cancer
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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
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• 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
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• 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
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• Pilot study to provide
telemedicine-based
consultations for women at
high risk for breast cancer
• Now service offered by Mayo
Breast Clinic
(Mayo Clinic Proceedings 88(1): 68-73, 2013)
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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.
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