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?