too many assessments; too little time
TRANSCRIPT
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Too many assessments; too little time
Lodovico Balducci M.D.
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Définition de la ChimiothérapieDéfinition de la Chimiothérapie
• Les médicine administrent desLes médicine administrent des médicaments dont ils savent très peu, à des malades dont ils savent moins pourdes malades dont ils savent moins, pour guérir des maladies dont ils ne savent rien
François Marie Arouet
AKA V lt iAKA Voltaire
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Définition de la ChimiothérapieDéfinition de la Chimiothérapie
• Les médicine administrent desLes médicine administrent des médicaments dont ils savent très peu, à des malades dont ils savent moins pourdes malades dont ils savent moins, pour guérir des maladies dont ils ne savent rien
François Marie Arouet
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What do we know about older icancer patients
• Physiologic age and cancer treatmentPhysiologic age and cancer treatment• Frailty
Q lit f Lif• Quality of Life
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Physiologic age and cancer treatment
• Mortality RiskMortality Risk• Risk of chemotherapy-related
complicationscomplications• Functional outcome
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Expectative de vie
Facteurs de risque
Odd ratio Compte
AGE60 64 1 9 160-6465-6970-7475-7980-8485
1.92.83.75.48.316 2
12345785
Sexe Masculine16.2
27
2
DiabètesCancer
1.82 1
12Cancer
Maladies chroniques du poumonCHFBMI < 25Fumeur
2.12.3
2.31.72 1
22212
Fumeur 2.1
FonctionFaire sa toiletteGestion financièreM h i i lé
2.01.92 1
222
LEE ET AL, JAMA, 2006
Marcher au moine un isoléPousser ou traîner des objets lourdes
2.11.5
21
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Mortalité a 4 années selon le compte total
8090
50607080
80
20304050 >80
70-7950-69
010
1 o2
3o4
5 6 8 9 >102 o4
LEE ET AL, JAMA, 2006
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Heme ModelHeme Model
Item 0 points 1 point 2 pointsDBP ≤ 72 > 72
IADL 26–29 10–25
LDH* 0–459 > 459
Chemotox 0–0.44 0.45–0.57 > 0.57
*ULN 618*ULN = 618
DBP = diastolic blood pressure; LDH = lactate dehydrogenase; ULN = upper limit of normal.
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Heme ModelHeme Model
Trend p < 0.001Cstat 0.65–0.77
Int. low Int. high HighLow
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Non Heme ModelNon-Heme ModelItem 0 points 1 point 2 pointsItem 0 points 1 point 2 points
ECOG PS 0 1–2 3–4
MMS 30 < 30
MNA > 27.5 0–27.5
Chemotox 0–0.44 0.45–0.57 > 0.57
ECOG PS = Eastern Cooperative Oncology Group performance status;MMS = mini-mental status; MNA = mini-nutritional assessment.
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Non Heme ModelNon-Heme Model
Trend p < 0.001Cstat 0.62–0.66
Low Int. low Int. high High
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Predictive Model IIPredictive risk factors for grade 3–5 chemotherapy toxicity
in older adults with cancerRisk factors for grade 3–5 toxicity OR (95% CI) ScoreAge ≥ 73 years 1.8 (1.2–2.7) 2GI/GU 2 2 (1 4 3 3) 3
in older adults with cancer
GI/GU cancer 2.2 (1.4–3.3) 3Standard dose 2.1 (1.3–3.5) 3Poly–chemotherapy 1.8 (1.1–2.7) 2Haemoglobin (male: < 11, female: < 10) 2.2 (1.1–4.3) 3Creatinine Clearance (Jelliffe – ideal wt) < 34 2.5 (1.2–5.6) 31 or more falls in last 6 months 2.3 (1.3–3.9) 3Hearing impairment (fair or worse) 1.6 (1.0–2.6) 2Limited in walking 1 block (MOS) 1.8 (1.1–3.1) 2Assistance required in medication intake 1.4 (0.6–3.1) 1Decreased social activity (MOS) 1.3 (0.9–2.0) 1
Possible score range: 0–25Hurria et al. J Clin Oncol. 2010;28 Suppl 15s:[abstract 9001].
Data presented at ASCO 2010.GI = gastrointestinal; GU = genitourinary; MOS = months of study.
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Model Performance:Prevalence of Toxicity by Score
“High” 83%( ≥ 12)
ROC: 0.72
Prevalence of Toxicity by Score)
100% “Mid” 53%(6–11)
( ≥ 12)
92%
iciti
es (%
60%
80%
“Low” 27%
( )
63%
76%
92%
e 3–
5 to
xi
40%
60% %(0–5)
45%
63%
Gra
de
0 4 5 6 8 9 11 12 13 ≥ 140%
20% 31%21%
Total scoreN = 39 N = 64 N = 123 N = 36N = 50N = 1610–4 5 6–8 9–11 12–13 ≥ 14
ROC = receiver operating characteristic.
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Number of chemotherapy cycles in relation to GA
Test Baseline < 4 cycli (n=74)
≥ 4 cycli (n=118)
p-value
GFI < 4 57% 67% 0.15≥ 4 43% 33%
MNA 24-30 51% 75% 0 001MNA 24 30 51% 75% 0.001< 24 49% 25%
MMSE > 24 89% 97% 0.04≤ 24 11% 3%
IQ-CODE
< 3.3 80% 87% 0.20
≥ 3.3 20% 13%
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Hazard ratio for mortalitycorrected for sex age purpose of chemotherapy type ofcorrected for sex, age, purpose of chemotherapy, type of
malignancy
Test Baseline HR (95% C I ) p valueTest Baseline HR (95% C.I.) p-valueGFI ≥ 4 2.00 (1.26-3.17) 0.004MNA < 24 2.54 (1.55-4.15) < 0.001MMSE ≤ 24 0.92 (0.44-1.93) 0.82IQ-CODE < 3.3 0.93(0.49-1.73) 0.81
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A. Aaldriks et al. CROH 2011;79:205-212
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Survival breast cancer (n = 63)Survival breast cancer (n 63)
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L’exemple meilleur d’étude phase III chez le sujet âgéephase III chez le sujet âgée
N HR 95% LCL
95% UCL p
All (B:A) 451 0 639 0 515 0 792 0 000046All (B:A) 451 0.639 0.515 0.792 0.000046
PS 0/1 329 0.622 0.479 0.806 0.0003
PS 2 122 0.646 0.439 0.951 0.0268
Age ≤ 80 yr 337 0.668 0.519 0.859 0.0016
Age > 80 yr 114 0 559 0 368 0 851 0 0067Age > 80 yr 114 0.559 0.368 0.851 0.0067
Adenocarcinoma 229 0.712 0.518 0.979 0.0365
Other histology 222 0.539 0.399 0.727 0.000053
Smokers 356 0.631 0.498 0.800 0.0001
N k 94 0 625 0 368 1 060 0 0810Never smokers 94 0.625 0.368 1.060 0.0810
Weight loss < 5 % 198 0.610 0.431 0.864 0.0053
Weight loss ≥ 5 % 246 0.732 0.553 0.968 0.0287
ADL = 6 351 0.593 0.462 0.761 0.000042
ADL 6 87 0 655 0 417 1 029 0 0665ADL < 6 87 0.655 0.417 1.029 0.0665
MMS ≥ 24 372 0.601 0.473 0.764 0.000032
MMS < 24 70 0.909 0.540 1.530 0.7188
Favorsdoublet
Favorssingle
OS – The univariate hazard ratio was derived from a Cox model with a single treatment covariate
doublet single
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treatment has an independent effect on survival,
even after adjustment for patient characteristics
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Other issues related to physiologic age
• Does cancer treatment accelerate age?Does cancer treatment accelerate age?• Caregiver• Relationship with laboratory studies• Relationship with laboratory studies
(circulating cytokines, telomere length, allostatic index)allostatic index)
• Which abbreviated CGA if any• Management of the deconditioned and frail• Management of the deconditioned and frail
patient• Cancer independent life-expectancy• Cancer independent life-expectancy
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ConclusionsConclusions
• GFI and VES 13 have low negativeGFI and VES 13 have low negative predictive values: 40% and 48%
• aCGA has high negative predictive values• aCGA has high negative predictive values for GDS, cognition, ADL and IADLGFI d VES 13 t f l• GFI and VES 13 are not very useful as a screening tool in a group of cancer
ti t ld th 70 ith hi hpatients older than 70 years with a high risk of vulnerability
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FRAILTY - DEFINITIONSFriedA state of age-related physiologic vulnerability resulting from impaired homeostatic reserveand a reduced capacity of the organism towithstand stress.
RockwoodA precarious balance easily perturbed.
ClippA breeze could tip him over.
FDOCFrailty may be a syndrome……..
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Questions about frailtyQuestions about frailty
• Frailty and vulnerabiltyFrailty and vulnerabilty• Frailty and Somatopause
F ilt l d k• Frailty as a landmark
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Is this classification still workable in l ?oncology?
• FitFit• Vulnerable
F il• Frail• Moribund
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Frailty and OncologyFrailty and Oncology
• Frailty cancer incidence and prevalenceFrailty cancer incidence and prevalence• Frailty as consequence of cancer
F ilt f• Frailty as a consequence of cancer treatment
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Quality of lifeyHe puts his stamina down to ginger curry, tea and “being happy”.“The secret to a long and healthy life isThe secret to a long and healthy life is to be stress-free. Be grateful for everything you have, stay away from people who are negative, stay smiling and keep running ”and keep running.
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Aging and QOLAging and QOL
• Quality of life or quality of health?Quality of life or quality of health?• Is quality of health = active life
expectancy?expectancy?
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