ASCO Advanced Course

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1 EVALTUATION OF AGING: PHYSIOLOGIC AGE LODOVICO BALDUCCI M.D. H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE

2 NCCN GUIDELINES SOME FORM OF GERIATRIC ASSESSMENT FOR INDIVIDUALS AGED 70+ ADJUSTMENT OF CHEMOTHERAPY DOSES TO RENAL FUNCTION IN INDIVIDUALS AGED 65+ PROPHYLACTIC FILGRASTIM OR PEGFILGRASTIM IN INDIVIDUALS AGED 65+ RECEIVING MODERATELY TOXIC CHEMOTHERAPY. MAINTENANCE HEMOGLOBIN 12 GM/DL PREFERENTIAL USE OF CAPECITABINE, WEEKLY TAXANES, GEMCITABINE, PREMETREXED, VINORELBINE

3 GERIATRIC ASSESSMENT PATIENT LIFE EXPECTANCY TREATMENT TOLERANCE CANCER: AGGRESSIVNESS CHEMOSENSITIVITY

4 SPECIFIC QUESTIONS Is the patient going to die with cancer or of cancer? Will the patient live long enough to suffer the complications of cancer Is the patient able to tolerate the treatment? What are the short and long term complications of the treatment? Who is the caregiver? Is he/she able to provide assistance to the patient?

5 GOALS OF TREATMENT Increased survival Increased active life expectancy Symptom management Preservation of existential meaning

6 The older patient

7 inflammation Disease Functional susceptibility dependence Entropy Stress tolerance Fractality Geriatric syndromes inflammation

8

9 Fractality Nervous system Respiratory system Cardiovascular system Cell generation

10

11 Age as a landmark AGE 70

12 Geriatric Evaluation Laboratory (Markers of inflammation, osmolarity) Clinical Comprehensive Geriatric Evaluation Tests of physical function Screening for frailty

13 Figure 2. Age regression coefficients and their 95% CIs estimated from linear models predicting level of inflammatory markers Ferrucci, L. et al. Blood 2005;105: Copyright 2005 American Society of Hematology. Copyright restrictions may apply.

14 INFLAMMATION, SURVIVAL AND FUNCTION NORMAL IL6 DD IL6+DD COHEN ET AL, AM J MED, 2003

15 Cancer and aging: ADL

16 Cancer and age: IADL

17 Cancer and age:geriatric SYNDROMES depression Dizziness delirium dementia Failure to thrive incontinence Falls Neglect and abuse

18 Valutazione geriatrica e aspettativa di vita RISK FACTORS Odd ratio SCORE AGE Male sex 2 2 comorbidity Diabetes Cáncer Respiratory disease CHF BMI < 25 Smoking Function grooming Financial management Walking one block Push and pull weighty objects LEE ET AL, JAMA, 2006

19 CGA AND FOUR YEARS MORTALITY RATE o 3 2 o >10 > LEE ET AL, JAMA, 2006

20 OTHER BENEFITS OF GERIATRIC ASSESSMENT Detection reversible comorbidity nutrition Disability and handicap Caregiver Treatment goals

21 FRAILTY INDEX AND CHRONOLOGIC AGE Mitzinski et al, 2004, J Gerontol Med Sci

22 Frailty A condition of increased Susceptibility to stress. Minor stress may lead to Disability and deconditioning FRAILTY

23 The older patient?

24 Cancer and age: functional screen of the older person THE CARDIOVASCULAR HEALTH STUDY (CHS) FIT PRE-FRAIL FRAIL

25 Cancer and age: the CHS parameters UNINTENTIONAL WEIGHT LOSS (> 10 LBS IN 1 YEAR) SELF-REPORTED EXHAUSTION WEAKNESS (GRIP STRENGTH) SLOW WALKING SPEED LOW PHYSICAL ACTIVITY.

26 Cancer and age: survival of Fit, pre-frail and Frail in the CHS fit pre-frail frail Fried et al, J Gerontol, 2001, 3, M146

27 COMORBIDITY DECREASED LIFE EXPECTANCY DECREASED TOLERANCE OF TREATMENT COMORBIDITY AND CANCER GROWTH COMORBIDITY, POLYPHARMACY AND DRUG INTERACTIONS

28 COMORBIDITY OF RELEVANCE CARDIOVASCULAR DISEASES ANEMIA DEPRESSION CANCER

29 Anemia and aging man woman 5 0 < Guralnik et al, Blood, 2004, NHANES III

30 Anemia and aging: ethnic variations men 15 women 10 total 5 0 white black hispanic others Guralnik et al, 2004, Blood, NHANES III

31 Increased prevalence of anemia with age epese olmsted italian tamiras

32 Anemia prevalence in nursing homes Chen et al, % Chernetsky et al, % Kalchthaler & Tan, % Joosten et al, % Bird et al, % Celestin-Roux, %

33 Definition of anemia and sex distribution of hemoglobin Uomini: <13 g/dl Man 15.2 ± 0.9 g/dl Frequency Donne: <12 g/dl Woman 13.3 ± 0.9 g/dl Hb Level (g/dl) 1. World Health Organization. Geneva, Switzerland; Dallman et al. In: Iron Nutrition in Health and Disease. London, UK: John Libbey & Co; 1996:65-74.

34 Causes of anemia ANIA JOOSTEN NHANESIII Infections 23% 13% - aci 17% 33% 20% Iron deficiency 8% 17% 20% Nutritional 8% 11% 14% Renal 8% 8% 12% insufficiency Unknown 36% 18% 34%

35 Anemia of unknown causes Renal insufficiency MDS Hypogonadism Aplastic anemia Stem cell exhaustion Relative erythropoietin ti insufficiency i Absolute erythropoietin insufficiency

36 quartile piu alto quartile piu basso Prevalenza Anemia e testosterone uomo donna quartile piu alto FERRUCCI ET AL, ARCH INTERN MED, 2006 quartile piu' basso Rischio in 3 anni

37 Aging and relative erythropoietin insufficiency Ferrucci et al, 2005, Am J Med

38 Aging and absolute erythropietin insufficiency controllo sidero inf cr insuff ren insuff eri Ferrucci et al, Br J Haematol, 2007

39 Consequences of anemia Death Fatigue and functional dependence Dementia Cardiovascular complications Falls Iatrogenic complications delirium myelosuppression

40 Anemia and aging: mortality Chaves et al >65, 2004 <13.4 Kikuchi et al > 70, 2000 < 12 Izsak et al > 85, 2000 <12 Ania et al >70, 1999 <12 Zakai et al > 65, 2005 < 13.7 men < 12.6 women Penninx et al >65, 2006 WHO criteria Longo et al > 65, 2005 WHO criteria

41 Conclusions Chronologic age is a landmark Physiologic age can be assessed with a CGA and laboratory tests. Frailty is a real condition and should be the focus of most studies Anemia is a common comorbidity of aging. Anemia from specific causes should be reversed. The role of ESAs is unestablished

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