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AACE Kennedy Lecture
Jerome W. Yates, MD, MPH
National Vice President, Research
American Cancer Society
September, 2008,
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Bryl James Kennedy MD1921 - 2003
B.J. to Everyone
Major Force in Medical and Geriatric Oncology
Usually Smiling and Always a Gentleman!
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BJ Kennedy - Leadership
• Charter Member of ASCO 1964
• Medical Oncology Specialty ’69-’74
• ASCO President 1987
• ASCO – “Older Population” Mtg. 2000
“Aging is not a Disease”
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Barriers to optimal Cancer Care for the Elderly
AWARENESS ACCESS
-Risk Assessment
FH, Age, Biomarkers
-Resources-Manpower
DIAGNOSIS
-Over & Under Dx
(Morphology Standard)
-Resilience
INDOLENT DISEASE
Evidence Based Therapies - Research COSTETHICS
TREATMENTSURVIVAL CARE PALLIATION/FUTILITY
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Are you covered?
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50 100 150 200 250 300 350 400 450 500
Invasive Cardiology
Diagnostic Radiology
Orthopedic Surgery
Gastroenterology
Anesthesiology
Hematology-oncology
Urology
Dermatology
Otorhinolaryngology
General Surgery
Opthalmology
Obsterics-Gynecology
Emergency Medicine
Psychiatry
General Internal Medicine
General Pediatrics
Family Medicine-General Practice
Specialty
Median Salary(thousands of U.S. dollars)
Source: Median Salary According to Medical Specialty, 2006. Data are from the Medical Group Management Association, 2008 report based on 2007 data. NEJM 359:6, 2648, August 7, 2008.
Year = 2006
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With the Care Giver?
? Theft
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Number of Chronically Disabled AmericansAge 65 and Over
6.4
7.58.3
9.4 9.5 9.6
6.47 7.1 7 7.1 7.2
0
2
4
6
8
10
1982 1988 1994 1996 1998 2000
No Change
Decline
(Percentages)
Source: National Long Term Care Survey 1982-1999 (Kenneth Manton, Ph.D.).
Total Population
Age 65+26.9 Million
Total PopulationAge 65+
30.8 Million
Total Population
Age 65+33.1 Million
Total PopulationAge 65+
35.3 Million
(projected)
If disability rate did not change since 1982
Based on declining disability rate since 1982
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Risks to the Elderly
• Genetic PredispositionsGenetic Predispositions• Environmental Exposures
– Tobacco– Obesity– Poverty
• Discrimination (Lack of Education and/or Navigation)• Access to Care (transportation, Support, Rehabilitation)• Affordable Stimulatory Activities
• Previous Cancers• Faulty Preventive and Treatment Plans• Ethical Conflicts
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Telomeres and Telomerase?
Telomerase is the natural enzyme which promotes telomere repair. It is however not active in most cells. It certainly is active though in stem cells, germ cells, hair follicles and in 90 percent of cancer cells. Telomerase functions by adding bases to the ends of the telomeres. As a result of this telomerase activity, these cells seem to possess a kind of immortality.
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C. Elegans - roundworm
Gene elt3 transcription factor ( lengthens life)
elt5 & elt6 transcription factor (turns off elt3)
These genes aid development of skin and intestines!
Surface Integrity
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Stickle FishIt’s not all in the genes!
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EPIGENETICS & CANCER PREVENTION
EPIGENETIC (UNRELATED TO GENETIC
VARIATION & PASSED ON TO
DAUGHTER CELLS)
GENETICTUMOR -SUPPRESOR
CHRONIC INFLAMMATION
MALIGNANCY
PROLIFERATION
Tumor suppressor genes –P16, MLH1, VHL, ECAD may be inactivated by promoter DNA methylation (Prevention hypomethelators or anti-inflammatory Drugs)
Toyota M, Issa, JP. Epigenetic Changes in solid and hematopoietic tumors. Sem Oncol 2005;32:521-530
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Young, healthy – normal epigenetic patterns
Tissues look normal, patches of faulty gene expression – aquired epigenetic changes
Cancers initiated in these abnormal epigenetic fields – early neoplastic transformation
Aging,diet, exposures, etc.
Aging,diet, exposures, etc.
EPIGENETIC MODULATION
Issa, J, Cancer Prevention: Epigenetics Steps Up to the Plate, Cancer Prev Res 2008;1(4) Sept.
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Risks to the Elderly
• Genetic Predispositions• Environmental ExposuresEnvironmental Exposures
– TobaccoTobacco– ObesityObesity– Poverty
• Discrimination (Lack of Education and/or Navigation)• Access to Care (transportation, Support, Rehabilitation)• Affordable Stimulatory Activities
• Previous Cancers• Faulty Preventive and Treatment Plans• Ethical Conflicts
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CANCER PROGRESSION
HOST WITH ENVIRONMENTAL FACTORS
INDOLENT CANCERS INVASIVE CANCERS
SUPPRESSION AGGRESSIVE PROPERTIES
BIOMARKERS
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Actual Causes of Death in the United States in 1990 and 2000
0
50,000
100,000
150,000
200,000
250,000
300,000
350,000
400,000
450,000
Tobacco Poor Diet andPhysicalActivity
AlcoholConsumption
Microbial Toxic Agents
No. (%) in 1990*
No. (%) in 2000**
Sources: *McGinnis, J. Michael, and Foege, William H., Actual causes of death in the United States. JAMA (1993) 270: 2207-2212. **Mokdad, Ali H., Marks, James S., Stroup, Donna F., and Gerberding, Julie L., 2004.
19% 18
.1%
14%
16.6
%
5%
3.5% 4%
3.1%
3% 2.3%
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Risks to the Elderly
• Genetic Predispositions• Environmental Exposures
– Tobacco– Obesity– PovertyPoverty
• Discrimination (Lack of Education and/or Navigation)Discrimination (Lack of Education and/or Navigation)• Access to Care (transportation, Support, Rehabilitation)Access to Care (transportation, Support, Rehabilitation)• Affordable Stimulatory ActivitiesAffordable Stimulatory Activities
• Previous Cancers• Faulty Preventive and Treatment Plans• Ethical Conflicts
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Risks to the Elderly
• Genetic Predispositions• Environmental Exposures
– Tobacco– Obesity– Poverty
• Discrimination (Lack of Education and/or Navigation)• Access to Care (transportation, Support, Rehabilitation)• Affordable Stimulatory Activities
• Previous CancersPrevious Cancers• Faulty Preventive and Treatment Plans• Ethical Conflicts
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1990 1995 2000 2005 2010 2015 2020 2025 2030 2035 2040 2045 20500
10
20
30
40
50
60
70
80
90Millions
Aged 100+
Aged 85-99
Aged 75-84
Aged 65-74
U.S. Population Aging 65 Years and Older: 1990 to 2050
U,S. Census Bureau, Current Population Reports, P25-1095, 1993 YEAR
Population, Past and Future
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PROJECTED CANCER CASESBY AGE GROUPS (2000-2050)
0
500
1000
1500
2000
2500
3000
2000 2010 2020 2030 2040 2050
85+
75-84
65-74
50-64
<50
CANCER, May 15, 2002, 94:2786
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The New Longevity: Life Expectancy from Age 65
17.1
22
16.3
20.1
16
19.2
15.3
19
15.1
18.4
12.2
15.5
0
5
10
15
20
25
Japan Canada UnitedStates
Germany Chile Hungary
Male
Female
Source: Centers for Disease Control and Prevention, Health, United States, 2003.
Years
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Risks to the Elderly
• Genetic Predispositions• Environmental Exposures
– Tobacco– Obesity– Poverty
• Discrimination (Lack of Education and/or Navigation)• Access to Care (transportation, Support, Rehabilitation)• Affordable Stimulatory Activities
• Previous Cancers• Faulty Preventive and Treatment PlansFaulty Preventive and Treatment Plans• Ethical Conflicts
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Co-morbiditySame Age – Different Risks!
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DISPARITY –AGE & PHYSIOLOGIC AGE
Birth 30 40 60 70 80 100
chronologic age
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Score of 0 Score of 1 Score of 2 Component of Acronym
Skin color
blue all over blue at extremitiesbody pink(acrocyanosis)
no cyanosisbody and extremities pink
Appearance
Heart rate
absent <100 >100 Pulse
Reflex irritability
no response to stimulation
grimace/feeble cry when stimulated
sneeze/cough/pulls away when stimulated
Grimace
Muscle tone
none some flexion active movement Activity
Breathin absent weak or irregular strong Respiration
Obstetrical Outcome Research Needed the Apgar Score
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Adult scoring systemsIntensive Care Assessment
These scoring systems can be used on patients age 15 and up.•APACHE II was designed to provide a morbidity score for a patient. It is useful to decide what kind of treatment or medicine is given. Methods exist to derive a predicted mortality from this score, but these methods are not too well defined and rather imprecise. •SAPS II was designed to provide a predicted mortality, that does not reflect the expected mortality for a particular patient, but is good for benchmarking. In a rather simple way, it makes it possible to provide a single number that describes the morbidity of a number of patients. •SAPS III was designed to provide a realistic predicted mortality for a particular patient or a particular group of patients. It does this by calibrating against known mortalities on an existing set of patients, for a specific definition of mortality (like 30-days mortality). This way, it can answer questions like "Did we improve our quality of care from 2004 to 2005?" or "If hospital A's patients had been treated at hospital B, would they have a better or a worse mortality?".
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Chronic Disease Score
Needed Foundation for a New
Approach to Clinical Research
Cancer and the Elderly !
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Guralnik’s Chair Test
11.19
13.69
16.69 16.7
0
2
4
6
8
10
12
14
16
18
4 Points 3 Points 2 Points 1 Point
Seconds
Source: Data derived from a study at the National Institute on Aging and participants were 71 and older.
5 Squats to Standing
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We Need and Apgar Score for the Older Population! – hypothetical approach
• 2 for normal ADL & Social Function
• 2 for normal Cognition (Clock Test)
• 2 for normal Muscle Strength (Hand Grip)
• 2 for normal Age adjusted Blood, Liver, Lung and Kidney Function (simple screen)
• 1 for no severe chronic disease
• 1 for not requiring acute treatment
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Clinical Trials in the Elderly
• Ageism or Bias against trial entry• Better cancer classification
(chromosomes, genetics, proteomics)• Improved pharmacology, predictable
toxicity, efficacy and cost of treatment• Stratification Score for Population Studies• Specialized Assessment Instruments –
toxicity, physical and social function, and satisfaction
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Barriers to optimal Cancer Care for the Elderly
AWARENESS ACCESS
-Risk Assessment
FH, Age, Biomarkers
-Resources-Manpower
DIAGNOSIS
-Over & Under Dx
(Morphology Standard)
-Resilience
INDOLENT DISEASE
Evidence Based Therapies - Research COSTETHICS
TREATMENTSURVIVAL CARE PALLIATION/FUTILITY
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Treatment Benefit vs. Morbidity
BENEFIT
MORBIDITY
DEATH
RECOVERY
Time
+
–
ELDERLY
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AGE RELATED COMORBIDITY REQUIRES
VARIABLE EXPERTISE FOR OPTIMAL MANAGEMENT!
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Importance of Comorbid Conditions (cont.)
• Increase with age
• Resilience (covert comorbidity) to toxic treatments decreases with age
• Overt comorbidity affects treatment selection
• May hamper patient recovery
• One aspect of case mix evaluationASCO
Balducci L, Yates J. Oncology (Huntingt). 2000;14(11A):221-227
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Risks to the Elderly
• Genetic Predispositions• Environmental Exposures
– Tobacco– Obesity– Poverty
• Discrimination (Lack of Education and/or Navigation)• Access to Care (transportation, Support, Rehabilitation)• Affordable Stimulatory Activities
• Previous Cancers• Faulty Preventive and Treatment Plans• Ethical ConflictsEthical Conflicts
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Optimal Cancer Care- Who will Pay?
MULTIDISCIPLINARY CAREPRACTICE VOLUME
TRACKING OUTCOMES
DECREASE MORBIDITY & MORTALITY
TEAMS
QUALITY IMPROVEMENT
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COMMUN ITY ORGANIZATIONS
SCHOOLS – all levels
PUBLIC HEALTH ORGANIZATIONS
SELF-EDUCATION
MEDICINE - COMMUNITY
- ACADEMIC
PUBLIC HEALTH SCHOOLS
ORGANIZATIONS - ACS
INTERDISCIPLINARY
TRAINING PROGRAMS
INFORMED PERSON PROVIDER TEAM
PREVENTION PROMOTE SELF-MANAGEMENT
EARLY DETECTION INTERDISCIPLINARY FACILITATION
STATE-OF-THE-ART ACCESS TO TREATMENT
PALLIATIVE CARE INTERDISCIPLINARY CARE
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Financial Barriers for Elderly with Active Cancer Care
• No Drug Benefit
• Diagnostic Procedures – 20% Co-payment
• Out of Pocket Costs– Transportation (+ Income Loss For Drivers)– Role Reversal (Others to care for Spouse)– Hospital Deductible Payments
• Adjuvant Therapies (Tamoxifen, Growth Factors, Pain Medications)
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Cost of Care of the Elderly
• About 30% of Medicare Budget Spent on 5% of Patients Destined to Die in that Year*
• 30-40% of last year of health care costs occur in the last month of life*
• Better methods of Defining Medical Futility would eliminate some Expenditures.
* Emanuel EJ & Battin MP. N Engl. J.Med.1998;339:167-172
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Contributing Factors
• Equipment Costs –e.g., MRI, Spiral CT• Supply Costs – Plastics tied to Oil Prices• Nurses Salaries – Shortage likely to
persist– Salary Differential in Specialties – ICU, NP
• Information Systems – Privacy Costs• Managing High Risk Populations
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Budget Rationing of Care
• At the Present Spending Level an Increase to 30% of G.N.P. by 2030
UNLESS THERE IS:
• Increased Personal Costs– Directly - through higher deductibles– Indirectly – through care shifting to families
• Shrinking Coverage based on Age• Dual System – Wealthy versus the Poor
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ETHICS
Real Applications
Reciprocal Behavior = “Golden Rule”
Universal Application = “Order or Chaos”
Theoretical Applications
Philosophy
Theology
Political
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PRINCIPLES OF MORALITY
• Respect for autonomy
• “Do no harm”
• Weigh benefit versus risk and cost
• Justice = Fairness = “Harmony”
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RELIGION POLITICS & The Courts
RECIPROCITY
UNIVERSALITY
ETHICS
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MEDICAL FUTILITYA FOREIGN CONCEPT
• PATIENTS
• FAMILIES
• PHYSICIANS
• BUT NOT TO THE PAYERS!
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PRIOR DIRECTIVES
• HEALTH CARE PROXY
• POWER OF ATTORNEY (?Durable)
• “LIVING WILL”
• DO NOT RESUSCITATESHOULD DISCUSS EARLY
WHEN THE PATIENT HAS CAPACITY!!!!!
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Future Research Directions
• Molecular Targets for Diagnosis, Prognosis & Treatment
• Incentives for Drug & Biologic Development• Coping with an Aging Population- Research
– Stratification Score– Early Detection– Managing Comorbidity– Palliative Care
• Ethical Dilemmas-Privacy, Profits, Rationed Care
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Future Practical Changes• Will Need Public (Academic) –Private Alliances to Develop the
leads from Genetic Research• Develop New Markers for Early Diagnosis, Prognosis &
Treatment Selection• Methods to Stratify the Elderly to Facilitate the Adoption of
Guidelines • Tie Reimbursement to Quality Assurance• Models for Reimbursement Reform for Chronic Disease
Management – Cognitive Skills & Time – Remove Distorted Incentives for Providing
Technical Procedures – Innovative Assisted Living Arrangements– Team Care Including the Elderly and their Families
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Geriatrics and OncologyToday’s Needs
• Bilateral Training (Oncologists & Geriatricians)• Research on Aging and Cancer
– Cancer Biology (e.g. Breast and Prostate)– Falls, Cognitive Diminution, Incontinence & Sexual Function– Clinical Trials
• Data on Cost and Efficacy of Screening and Early Detection
• Social Support (Income, Transportation, Home Care, Who?)
• Optimal Environment ( Hazards, Exercise, Nutrition, Rx Care)
• Reimbursement (interdisciplinary management)
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Collision of Entitlements (medicare) and Demographics (Aging & Survival)
“The Perfect Storm of 1991” – Predicted but Ignored
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The Clock Ticks For All!
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B.J. Kennedy, MD(1921-2003)
His time ran out but not his influence!
Clinician Diligent
Scientist Tenecious
Leader Honest