Too many assessments; too little time
Lodovico Balducci M.D.
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
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
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
Physiologic age and cancer treatment
• Mortality RiskMortality Risk• Risk of chemotherapy-related
complicationscomplications• Functional outcome
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
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
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.
Heme ModelHeme Model
Trend p < 0.001Cstat 0.65–0.77
Int. low Int. high HighLow
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.
Non Heme ModelNon-Heme Model
Trend p < 0.001Cstat 0.62–0.66
Low Int. low Int. high High
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.
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.
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%
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
A. Aaldriks et al. CROH 2011;79:205-212
Survival breast cancer (n = 63)Survival breast cancer (n 63)
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
treatment has an independent effect on survival,
even after adjustment for patient characteristics
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
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
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……..
Questions about frailtyQuestions about frailty
• Frailty and vulnerabiltyFrailty and vulnerabilty• Frailty and Somatopause
F ilt l d k• Frailty as a landmark
Is this classification still workable in l ?oncology?
• FitFit• Vulnerable
F il• Frail• Moribund
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
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.
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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