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AACE Kennedy Lecture. Jerome W. Yates, MD, MPH National Vice President, Research American Cancer Society September, 2008, . Bryl James Kennedy MD 1921 - 2003. B.J. to Everyone Major Force in Medical and Geriatric Oncology Usually Smiling and Always a Gentleman!. BJ Kennedy - Leadership.
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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 ACCESS -Risk Assessment FH, Age, Biomarkers -Resources-Manpower DIAGNOSIS -Over & Under Dx (Morphology Standard) -Resilience AWARENESS INDOLENT DISEASE TREATMENT SURVIVAL CARE PALLIATION/FUTILITY Evidence Based Therapies - Research ETHICS COST
Year = 2006 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.
With the Care Giver? ? Theft
(Percentages) If disability rate did not change since 1982 Based on declining disability rate since 1982 (projected) Total Population Age 65+ 26.9 Million Total Population Age 65+ 30.8 Million Total Population Age 65+ 33.1 Million Total Population Age 65+ 35.3 Million Source: National Long Term Care Survey 1982-1999 (Kenneth Manton, Ph.D.).
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 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 Surface Integrity Gene elt3 transcription factor ( lengthens life) elt5 & elt6 transcription factor (turns off elt3) These genes aid development of skin and intestines!
EPIGENETICS & CANCER PREVENTION CHRONIC INFLAMMATION PROLIFERATION EPIGENETIC (UNRELATED TO GENETIC VARIATION & PASSED ON TO DAUGHTER CELLS) TUMOR -SUPPRESOR GENETIC MALIGNANCY 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
EPIGENETIC MODULATION Young, healthy – normal epigenetic patterns Aging,diet, exposures, etc. Tissues look normal, patches of faulty gene expression – aquired epigenetic changes Aging,diet, exposures, etc. Cancers initiated in these abnormal epigenetic fields – early neoplastic transformation Issa, J, Cancer Prevention: Epigenetics Steps Up to the Plate, Cancer Prev Res 2008;1(4) Sept.
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 Conflicts
CANCER PROGRESSION HOST WITH ENVIRONMENTAL FACTORS AGGRESSIVE PROPERTIES SUPPRESSION INDOLENT CANCERS INVASIVE CANCERS BIOMARKERS
Actual Causes of Death in the United States in 1990 and 2000 18.1% 16.6% 19% 14% 5% 3.5% 4% 3.1% 2.3% 3% 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.
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 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 Cancers • Faulty Preventive and Treatment Plans • Ethical Conflicts
U.S. Population Aging 65 Years and Older: 1990 to 2050 Population, Past and Future Millions 90 Aged 100+ 80 Aged 85-99 70 60 50 Aged 75-84 40 30 20 Aged 65-74 10 0 1990 1995 2000 2005 2010 2015 2020 2025 2030 2035 2040 2045 2050 YEAR U,S. Census Bureau, Current Population Reports, P25-1095, 1993
PROJECTED CANCER CASESBY AGE GROUPS (2000-2050) CANCER, May 15, 2002, 94:2786
The New Longevity: Life Expectancy from Age 65 Years Source: Centers for Disease Control and Prevention, Health, United States, 2003.
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 Conflicts
Co-morbidity Same 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 morbidityscore 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 5 Squats to Standing Source: Data derived from a study at the National Institute on Aging and participants were 71 and older.
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 ACCESS -Risk Assessment FH, Age, Biomarkers -Resources-Manpower DIAGNOSIS -Over & Under Dx (Morphology Standard) -Resilience AWARENESS INDOLENT DISEASE TREATMENT SURVIVAL CARE PALLIATION/FUTILITY Evidence Based Therapies - Research ETHICS COST
Treatment Benefit vs. Morbidity + RECOVERY BENEFIT ELDERLY Time MORBIDITY – DEATH
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 evaluation Balducci L, Yates J. Oncology (Huntingt). 2000;14(11A):221-227 ASCO
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 Conflicts
Optimal Cancer Care- Who will Pay? MULTIDISCIPLINARY CARE TEAMS PRACTICE VOLUME DECREASE MORBIDITY & MORTALITY TRACKING OUTCOMES 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”
ETHICS POLITICS & The Courts RELIGION RECIPROCITY UNIVERSALITY
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 RESUSCITATE SHOULD 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