AACE Kennedy Lecture

Jerome W. Yates, MD, MPH

National Vice President, Research

American Cancer Society

September, 2008,

Bryl James Kennedy MD1921 - 2003

B.J. to Everyone

Major Force in Medical and Geriatric Oncology

Usually Smiling and Always a Gentleman!

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”

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

Are you covered?

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

With the Care Giver?

? Theft

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

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

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.

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

Stickle FishIt’s not all in the genes!

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

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.

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

CANCER PROGRESSION

HOST WITH ENVIRONMENTAL FACTORS

INDOLENT CANCERS INVASIVE CANCERS

SUPPRESSION AGGRESSIVE PROPERTIES

BIOMARKERS

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%

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

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

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

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

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

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

Co-morbiditySame Age – Different Risks!

DISPARITY –AGE & PHYSIOLOGIC AGE

Birth 30 40 60 70 80 100

chronologic age

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

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?".

Chronic Disease Score

Needed Foundation for a New

Approach to Clinical Research

Cancer and the Elderly !

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

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

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

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

Treatment Benefit vs. Morbidity

BENEFIT

MORBIDITY

DEATH

RECOVERY

Time

+

–

ELDERLY

AGE RELATED COMORBIDITY REQUIRES

VARIABLE EXPERTISE FOR OPTIMAL MANAGEMENT!

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

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

Optimal Cancer Care- Who will Pay?

MULTIDISCIPLINARY CAREPRACTICE VOLUME

TRACKING OUTCOMES

DECREASE MORBIDITY & MORTALITY

TEAMS

QUALITY IMPROVEMENT

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

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)

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

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

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

ETHICS

Real Applications

Reciprocal Behavior = “Golden Rule”

Universal Application = “Order or Chaos”

Theoretical Applications

Philosophy

Theology

Political

PRINCIPLES OF MORALITY

• Respect for autonomy

• “Do no harm”

• Weigh benefit versus risk and cost

• Justice = Fairness = “Harmony”

RELIGION POLITICS & The Courts

RECIPROCITY

UNIVERSALITY

ETHICS

MEDICAL FUTILITYA FOREIGN CONCEPT

• PATIENTS

• FAMILIES

• PHYSICIANS

• BUT NOT TO THE PAYERS!

PRIOR DIRECTIVES

• HEALTH CARE PROXY

• POWER OF ATTORNEY (?Durable)

• “LIVING WILL”

• DO NOT RESUSCITATESHOULD DISCUSS EARLY

WHEN THE PATIENT HAS CAPACITY!!!!!

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

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

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)

Collision of Entitlements (medicare) and Demographics (Aging & Survival)

“The Perfect Storm of 1991” – Predicted but Ignored

The Clock Ticks For All!

B.J. Kennedy, MD(1921-2003)

His time ran out but not his influence!

Clinician Diligent

Scientist Tenecious

Leader Honest