1

Cancer du sein et sujet âgé

Docteur Etienne BrainOncologie Médicale

Hôpital René Huguenin / Institut CurieSaint-Cloud, France

etienne.brain@curie.fr

A frailty revealed…

• 2006: Mrs BON… IR… 84 yo– No previous medical history (high blood sugar?)– Husband: 86 yo w/ severe advanced Parkinson, 2 children– Breast self exam � T1c N0 M0 left breast– 54 kg/167 cm

• Conservative surgery + axillary lymph node dissection– Invasive ductal carcinoma, 17 mm, SBR II, 8 N-– ER- PgR-, Ki 67 40%, HER2-

• Adjuvant strategy– Chemotherapy with anthracylines (GERICO 06)? + XRT

• Scoring– Oncologist: PS 0 � “Easy! Go for it“– Geriatrician

• Functional status, cognition, nutrition, GDS � OK• However ! 3 falls < 1 year

2

… treatment decision process

• LVEF by MUGA scan normal• Not in GERICO 06 trial, but OK for the oncology staff!• The lady “accepted”….

… treatment decision process & respect

• LVEF by MUGA scan normal• Not in GERICO 06 trial, but OK for the oncology staff!• The lady “accepted”…. but DID she?

• Central venous access + 1 cycle of AC-like chemo �febrile neutropenia + severe stroke (cardiac arythmia?)– Chemotherapy stopped

– Husband placed in nursing home

– Delayed XRT

– Recovered with neurological sequelae

– Seniors residence

– No relapse so far (last visit early 2015)

3

Binder-Foucard INCa report 2013

De Angelis Lancet Oncol 2013

Relative survival accounts for mortality from causes other than the relevant cancer, which can vary widely between countries

Breast

Ovary

4

20071991 2002

2013 2015

• Most common shortcut in statistics

“1 in 8 women will develop BC in their lifetime”instead of

“If everyone lived beyond the age of 70, 1 in 8 of those women would get or have had BC”

• Since BC risk increases w/ age, lifetime risk changes depending on age

– Age 20-29 1 in 2,000– Age 30-39 1 in 229– Age 40-49 1 in 68– Age 50-59 1 in 37– Age 60-69 1 in 26– Ever 1 in 8

Worldwidebreastcancer.com

5

Phénotype

Plus de formes hormonosensibles (RH+)Moins de formes agressives (triple négatif, HER2+++)

0

10

20

30

40

50

60

70

80

90

100

20 - 29 30 - 39 40 - 49 50 - 59 60 - 69 70 - 79 > 80

ER+PgR+ER-PgR-

Age

Grann Cancer 2005

• 205.736 femmes, cancers du sein > 20A• SEER 1990-2000• Récepteurs hormonaux (RH)

� Aux oestrogènes (RO ou RE, ou ER en anglais) et à la progestérone (RP ou PgR en anglais)� Négatifs (RH-) si tous les 2 sont absents� Positifs (RH+) si l’un ou l’autre est présent (RO ou RP)

6

Cheang, Clin Cancer Res 2008; Durbecq, CROH 2008

• British Columbia Cancer Agency• 1986-1992• 4,046 pts

• Jules Bordet• 2,723 pts

Les traitements

7

En pratique…

• 1.009 MBC65-74A 500> 75A 509

• 107 oncologues

Freyer Ann Oncol 2006

Le cancer du sein de la femme âgée se prête volontiers à

l’hormonothérapie car il est plus souvent RH+

Mais entre anti-aromatase (letrozole/FEMARA, anastro zole/ARIMIDEX, exemestane/AROMASINE et anti-oestrogène (tamoxifène) ,

la question de l’observance est majeure (et donc l’aju stement à la tolérance)

En contexte adjuvant/précoce, l’hormonothérapie se do nne 5 ans en général (discussion sur les extensions au delà)

En contexte métastatique, l’hormonothérapie est le tra itementgénéralement de première intention (phénotype RH+ fré quent)

8

SERM = Anti-oestrogènesSelective Estrogen Receptor Modulators

• > 35 ans d’utilisation• Standard

Déplétion en oestrogènes au mieuxréalisée par une inhibition spécifiquede l’aromatase qui convertit lesprécurseurs des oestrogènesen oestradiol et oestrone

Analogues dela LHRH

Progestatifs

Castration

Age Tamoxifène vs 0 Chimiothérapie vs 0

Rechute Mortalité Rechute Mortalité

< 40 44±10 39±12 40±6 29±7

40-49 29±7 24±9 36±4 30±5

50-59 34±5 24±7 23±3 15±4

60-69 45±5 35±6 13±3 9±4

≥ 70 51±12 37±15 12±11 13±12

Réduction (%) des risques annuels de rechute / mort alité

EBCTCG Lancet 1998 & 2005

Leçons des méta-analyses

9

• TAM / 0

15105

60 %

50 %

40 %

30 %

20 %

10 %

rech

ute

26,5

38,3

45,0

24,7

15,1

33,2

contrôle

TAM 5A

• IA / TAM

Réduction du risque de rechute

Bénéfice absolu à 10 ans

RO+ 41 % 13,6 %

Réduction du risque de rechute

Bénéfice absolu à 10 ans

RO+ Post-MP

20 % 5 %

AI 5A

ATAC

0,30 0,50 0,60 0,80 1,00 1,25 1,50 2,00

BIG 1-980,82 (0,67-0,99) 0,045143<<<< 65

0,79 (0,64-0,97) 0,022867≥≥≥≥ 65

<<<< 65 5137

≥≥≥≥ 65 4229

ITA

0,20

≤≤≤≤ 65 nr nr

>>>> 65 nr nr

0,63 (0,40-1,00) 0,051265

≥≥≥≥ 60 0,58 (0,39-0,87) 0,081959ABCSG / ARNO

<<<< 60

nr nr

nr nr

nr

nr

No analysis according age in IES and ABCSG-6

TAM superiorAI superior

HR (CI 95%) pN

Bénéfice des IA selon l’âge

10

COMPLIANCEis the issue!!!

TAM AINeurocognition

Sexuality

Hot flushes

Thrombosis & embolism

Uterus cancer

Gynecological tractus

Vaginal discharge

Cataract

Arthralgias & myalgias

Osteoporosis

Fractures

Dryness

Cardiovascular

Lipid profile

?

Fractures

Etude Suivi(m)

AnnéessousTAM

IA(%)

Comparateur(%)

p

ATAC 68 0 ANA (11.0) TAM (7.7) < 0.0001

ATAC 33 0 ANA (5.9) TAM (3.7) < 0.0001

ARNO 95ABCSG 8

28 2-3 ANA (2) TAM (1) 0.015

BIG 1-98 25.8 0 LET (5.6) TAM (4.0) < 0.001

IES 55.7 2-3 EXE (7.0) TAM (4.9) 0.003

MA.17 30 4-6 LET(5.3) Placebo (4.6) 0.25

Et jusqu’à 80% d’arthralgies en plus….(20.3% vs 12.3%, p < 0.001 BIG 1-98)

11

Copyright © American Society of Clinical Oncology

Morales, L. et al. J Clin Oncol; 26:3147-3152 2008

Getting a grip on aromatase inhibitor–associated arthr algiasDawn L. Hershman

Futur homonothérapie

• Probables questions de doses– Everolimus– Inhibiteur CDK 4/6

22

12

La chimiothérapie, c’est plus compliqué…

Car index thérapeutique plus étroit que l’hormonothéra pie

Des doses généralement ajustées (inférieures)

Physiological variations x PK & PD

Mechanism Consequences

AbsorptionGastric dumping and secretions �

Absorption of proteins, vitaminsand drugs �

MetabolismHepatocytes, blood flow, CYP P450 activity �Interactions (CYP P450)

Protein synthesis, (de-) activation of drugs and carcinogens �

Distribution H2O, albumin, Hb �Vd hydrosolubles drugs �

Vd liposolubles drugs �

ExcretionGFR, tubular filtration �Biliary excretion �

Renal elimination of drugsexcreted by kidney �

Biliary elimination �

Balducci. Oncologist 2000; Wildiers. Clin Pharmacoki net 2003; http://www.ema.europa.eu

13

Les grands médicaments

• Anthracyclines (adriamycine, épirubicine, schémas FEC 100 ou AC)– Myélotoxicité– Cardiotoxicité

• Alkylants (cyclophosphamide/Endoxan®, schéma FEC 100 ou AC)– Myélotoxicité– Attention à la fonction rénale

• Taxanes (docetaxel/Taxotère®, paclitaxel/Taxol®)– Myélotoxicité– Neuropathie– Onycholyse– Rétention hydrique

• Antimétabolites (5-flurorouracile, forme orale = capecitabine/Xeloda®)– Syndrome mains pieds– Diarrhée

25

Chimiothérapie

• Des doses spécifiques– CMF et adaptation du CPA à la fonction rénale– Xeloda® 1000 mg/m² x 2/J– Taxol® < 80 mg/m²/s– Taxotère® : PK identique mais risque accru de

neutropénie ± fièvre > 65A• q3w 75 mg/m² 63% et 16% vs 30% et 0%

• qw 35 mg/m² > 50% grade ≥ 3 (RD : 26 mg/m²)

• q2w 50 mg/m² GERICO-04

Gelman JCO 1984, Crivellari JCO 2000, Bajetta JCO 2005Del Mastro Ann Oncol 2005, ten Tije JCO 2005

14

La chimiothérapie adjuvante « marche » si on est attentif aux

effets secondaires…

DFS

OS

• CALGB (1975-1999)

• 4 randomized trials

• 6487 pts> 65 yo 542 (8%)> 70 yo 159 (2%)

• Results– Benefit identical– Toxicity careful!!

• Toxic deaths 1.5%

Adjuvant chemo for breast cancerAll

All

≤50

≤50

≥65

≥6551-64

51-64

Muss, JAMA 2005

15

0

0.2

0.4

Cumulative proportion with event

0.6

0.8

1.0Hazard ratio (>65: ≤6≤6≤6≤65) = 2.2595% CI of (>65: ≤≤≤≤65) = (1.04–4.86)Log rank p-value = 0.029Wilcoxon p-value = 0.78

0 200 300 400 700 800 900 1000Cumulative dose of doxorubicin (mg/m 2)

600500100

468172

345110

29692

10328

61

41

203

5912

431!51

≤≤≤≤65*>65*

*Patients at risk

≤≤≤≤65

>>>>65

Doxorubicine, CHF and age

• 630 patients (3 phase III) with 32 CHF– 26% >550 mg/m²

– >50%: reduction of LVEF <30% w/CT

• HRage 2.25 (1.04–4.86) vs 3.28 (1.4–7.65) if >400 mg/m²

Swain. Cancer 2003

Doxorubicin, CHF and age

• SEER 1992-2002: 43,338 women 66-80 years, no CHF history– stage I to III BC, chemotherapy vs no– AC: younger, fewer comorbidities, advanced (p=.001)– CHF10 years (%)

Pinder J Clin Oncol 2007

ACN = 4,712

Other chemoN = 3,921

No chemoN = 34,705

38.4 32.5 29

• 66-70 years HR 1.26 (95% CI, 1.12-1.42) if AC• 71-80 years no impact of CT type

Baseline HR (95%CI)

Age (decade) 1.79 (1.66-1.93)

Black 1.40 (1.30-1.50)

Trastuzumab 1.46 (1.21-1.77)

Hypertension 1.45 (1.39-1.52)

Diabetes 1.74 (1.66-1.83)

Coronary 1.58 (1.39-1.79)

Left XRT 1.04 (0.98-1.11)

16

Meta-analysis2012

EBCTCG Lancet 2012

• Decrease of BC mortality ~ 33%– 4 anthra + 4 taxanes > 4 anthra

• RR 0·86, SE 0·04, 2p=0·0005– 4 anthra + 4 taxanes ~ 8 anthra

• RR 0·94, SE 0·06, 2p=0·33– 4 AC = 6 CMF

• RR 0·98, SE 0·05, 2p=0·67– FAC ou FEC > CMF

• RR 0·78, SE 0·06, 2p=0·0004– 4 FAC > 4 AC ou CMF (vs no CT)

• RR 0·64, SE 0·09, 2p<0·0001• RR 0·78, SE 0·09, 2p=0·01• RR 0·76, SE 0·05, 2p<0·0001

• No influence– Age (but mostly < 70 yo)– pT, pN– Differentiation, ER– TAM

• Impact varies according to risk– Low risk ���� reduced absolute

benefit

… mais principalement si ER- !

17

Giordano* Elkin

No. total

No. w/CT

I-III, ∀∀∀∀ ER , 65+41,390

4,500

I-III, ER-, 66+5,081

1,711

pN ER HR (95% IC) HR (95% IC)pN0 ∀∀∀∀ 1.05 (0.85-1.31) NA

pN+ + 1.05 (0.85-1.31) NA

both - NA 0.85 (0.77-0.95)

pN+ - 0.72 (0.54-0.96) 0.76 (0.65-0.88)

pN+ > 70 yo - 0.74 (0.56-0.97)

Giordano & Elkin. J Clin Oncol 2006

Adjuvant chemotherapy and mortality

Adjuvant chemo is useful FIRST

in ER-, pN0 or pN+, even > 70 yo

*: BC specific mortality

We may try to avoid the risk of cardiotoxicity induced by

anthracyclines: TC & liposomal doxorubicin

18

Copyright © American Society of Clinical Oncology

Jones, S. et al. J Clin Oncol; 27:1177-1183 2009

Fig 1. Disease-free survival (DFS) and overall surv ival (OS) (A) DFS by treatment; (B) DFS by treatmen t and age; (C) OS by treatment: 1 day; (D) OS by trea tment and age

GERICO 06 (EUDRACT N°2005-000069-20, PHRC national 2005)

MC MC MC MC XRT

ADLTolerance

CGAADL + MNA +MMS + GDS +

CIRSG

QLQ-C30Willingness

CGAADL + MNA +MMS + GDS +

CIRSG

QLQ-C30WillingnessTolerance

CGAADL + MNA +MMS + GDS +

CIRSG

QLQ-C30WillingnessTolerance

1 & 2 yearDFS & OS

ADLTolerance

ADLTolerance

± trastuzumab

if HER2+++

trastuzumabif HER2+

q3w q3w q3w

4 cycles of “AC-like” chemoIn MC, M stands for liposomal non pegylated doxorubic in

19

1. Neutropénie fébrile 15%2. Risque dénutrition 15% vs 38%3. Impact QoL (social & role

functioning)4. Tolérance cardiaque du

trastuzumab5. Pas d’EPP6. DFS3A 85%

… faire une bonne chimio !

20

CALGB / CTSU 49907CALGB / CTSU 49907

• 9/2001-12/2006

• 633 pts ≥ 65 yo

– 65% 70+

– 55% pT > 2 cm

– 71% pN+

– 68% ER+

• Non-inferiority trial

• Median folow up 2.4 years

• Capecitabine vs standard

– RFS3A 68% vs 85%

– OS3A 86% vs 91%

– Toxicity 33% vs 64%

• Capecitabine

– 76% compliance (> 80%)

• AC & CMF > capecitabine

– Interaction +++ if ER-

– HRRFS 4.39 (95% CI: 2.9-6.7)

– HROS 3.76 (95% CI: 2.23-6.34)j

Muss NEJM 2009

> 65A6 CMF or 4 AC

6 capecitabine

All

ER-

ER+

DFS OS

Muss, NEJM 2009

CALGB / CTSU 49907 (AC or CMF vs X)

21

Kaplan–Meier survival analysis.

F. Perrone et al. Ann Oncol 2015;annonc.mdu564

© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Mean differences in QoL scores of items presenting statistically significant differences at one or more time-points.

F. Perrone et al. Ann Oncol 2015;annonc.mdu564

© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Green bars: CMFBlue bars: weekly docetaxel

22

General recommendations for adjuvant chemo in elderly

• Focus on ER-

• Regimen– Validated 4 AC, 6 CMF– Option 4 TC– Capecitabine no– Docetaxel qw no– Sequential regimen no data– Liposomal doxorubicin ?

• Primary prophylaxis of febrile neutropenia w/ G-CSF

Targeted treatments

Lack of specific data!But clinical evidence for benefit

23

Tyrosinekinase

domain

Ligand-bindingdomain

Erb-B1EGFRHER1

Erb-B2HER2/neu

Erb-B3HER3

Erb-B4HER4

TransTrans--membranemembrane

TGF-αEGFEpiregulinBetacellulinHB-EGFAmphiregulin

Heregulin(neuregulin-1)

Heregulin(neuregulin-1)EpiregulinHB-EGFNeuregulins-2,3,4

Domaine de liaison

ATP

Domaine C Terminal(sites de phosphorylation) Transduction

du signal

Région trans-membranaire

Domaine extra-cellulaire

Domaine intra-cellulaire

Substrats deTyrosine Kinase

phosphorylés

Noyau

Membranecellulaire

LigandDomaineTyrosineKinase

Structure et fonction de l’EGF-R

Trastuzumab

Piccart NEJM 2005

> 60 yo ≤≤≤≤ 16%

24

The incidence of CHF from the Finnish Herceptin Stud y (FINHER), Herceptin Adjuvant trial (HERA), Breast Cancer International Collaborative Group trial 006 (006) with TCH and AC-TH analyzed separately, the No rth

Central Cancer Treatment Group trial 9831 (N9831), and NSABP B-31 (B-31).

Bird B R H , Swain S M Clin Cancer Res 2008;14:14-24

©2008 by American Association for Cancer Research

• NSABP B31– Age

– 2% < 50 yo vs 5.4% > 60 yo– LVEF > 4 AC

– 12% if LVEF < 55%– Concomitant > sequential– Hypertension comedications

• B31/N9831– 6.7% pts who had completed AC had a lower LVEF or

developed cardiac symptoms preventing the initiation of TZT

– 1/3 pts who started TZT discontinued it: 4.7% with symptomatic CHF, 14.2% with confirmed asymptomatic decline in LVEF, and the rest for noncardiac reasons

• SEER database• 2,028 patients ≥ 66, stage I-III, 2005-2009, trastuzumab

– 71.2% < 76

– 66.8% w/o comorbidities (Charlson)

– 85.2% w/ chemotherapy

– 81.7% w/ complete trastuzumab treatment (> 9 months)

– Factors correlated w/ incomplete treatment• Age 80+ vs 66-70 OR 0.40 (0.30-0.55)• Comorbidities 2 vs 0 OR 0.65 (0.49-0.88)

Vaz-Luiz. J Clin Oncol 2014

25

- 2 gr 3 LVSD (0.5%) (95% CI, 0.1%-1.8%)- 13 significant asymptomatic LVEF decline (3.2%) (95% CI, 1.9%-5.4%)

Tolaney NEJM 2015

BCIRG 006: Mean LVEF and Cardiac Safety

� No cardiac related deaths on any arm

Slamon D, et al. SABCS 2015. Abstract S5-04. Slide credit: clinicaloptions.com

66

65

64

63

62

61

60

59

58

LVE

F p

oint

s %

0 12 24 36 48 60 72 84

Mos since randomization

AC -> T (N = 1019)AC -> TH (n = 1043)TCH (n = 1032)

(N = 1019)(N = 1043)(N = 1032)

26

NEOSPHERE417 EBC HER2+, randomized phase II 1:1:1:1

1. Docetaxel + trastuzumab2. Docetaxel + trastuzumab + pertuzumab3. Trastuzumab + pertuzumab4. Docetaxel + pertuzumab

Gianni, Lancet Oncol 2012

pCR increased if double HER2 blockade

General recommendations for adjuvant chemo & tratsuzumab in elderly

• Focus on ER-

• Regimen– Validated 4 AC, 6 CMF– Option 4 TC– Capecitabine no– Docetaxel qw no– Sequential regimen no data– Liposomal doxorubicin ?

• Primary prophylaxis of febrile neutropenia w/ G-CSF

• No restriction on trastuzumab if chemo indicated– 4 TC + trastuzumab– Paclitaxel qw x 12 + trastuzumab– TCH x 6??? (carboplatin AUC 6!)

27

Miles Breast Cancer Res Treat 2013

Pertuzumab

Verma N Engl J Med 2013Dieras J Clin Oncol 2014

Barrios ASCO 2015

T-DM1

Kamilla 194 pts 65-69, 78 pts 70-74, 120 pts 75+

28

Bevacizumab(Avastin®)

Miller N Engl J Med 2007

> 65 yo ≤ 20%

MBC L1

ATE eventsChemo only

N = 782

Chemo + beva

N = 963

Global 1.7 3.8

No risk factor 1.0 1.8

< 65 yo 1.4 2.1

≥≥≥≥ 65 yo (N = 279) 2.5 7.1

Previous history of ATE 3.4 15.7

≥≥≥≥ 65 yo and previous history 2.2 17.9

Scappaticci. J Natl Cancer Inst 2007

ATE and bevacizumab (various cancers)(ATE = arterial thrombo embolism)

29

%< 70

N = 2018

70+

N = 233*

HTN grade ≥ 3 4.2 6.9

Proteinuria grade ≥ 3 1.5 4.0

ATE (A or V) 3.3 2.9

Stop for toxicity

ATE

CHF

15

1.8

0.3

23

2.9

0.6

HTN 1.8 2.9

Biganzoli. Annals Oncol 2011

ATHENA: CT wo/anthracyclines + beva(breast cancer only)

*175 (7.8%) 70+, 51 (2.3%) 75+, 7 (0.3%) 80+

30

Signatures ?

40 %

15 %

Mammaprint®

25,000 genes, 78 tumours, 70 genes, 17 pN0, all < 5 5 yo

van’t Veer, Nature 2002; van de Vijver, NEJM 2002

295 pts < 53 yo

31

MINDACT

• 6,600 pts < 70

– FEB 2007-AUG 2011– 11,291 registered pts– 6,673 enrolled (59.1%)

Biganzoli, Lancet Oncol 2012

32

Problèmedémographique

Rechercheclinique

peureprésentée

Mortalitéspécifique

et effetssecondairessignificatifs

Phénomène hétérogène

Espérance de vie ou

pronostic « hors cancer »

?

Definition of “old” x ageing heterogeneity

Age Top 25 th%Fit

50th%Intermediate

Lowest 25 th%Sick

50 40 33 24.5

70 21.3 15.7 9.5

75 17 11.9 6.8

80 13 8.6 4.6

85 9.6 5.9 2.9

90 6.8 3.9 1.8

95 4.8 2.7 1.1

Women life expectancy

Walter JAMA 2001

33

Multimorbidities across age

Piccirillo Critical Rev Oncol Haematol 2008

dementia CHF

solid tumour AIDS

diabetes HBP

Competing causes of mortality

Deaths attributed to the primary cancer (solid dots) and those attributed to comorbidity (open circles)

Cumulative probability of

death

Cumulative probability of

death vs attained age

Competing HR of death

Kendal Cancer 2008

Prostate NHLBreast

34

Comprehensive Geriatric Assessment CGA

Assessment Instrument Administration Prognosis

Dependency, functionalstatus

PS, Activity of Daily Living (ADL), Instrumental ADL

Self administered +

ComorbidityCharlson Comorbidity Index (CCI), Cumulative Illness rating Scale-Geriatric(CIRS-G)

Self- or interviewer-administered or chart-based

+

Economic / social support

Life conditions, relatives, care-giversInterviewer-administered or chart-based

?

CognitionFolstein Mini-mental State Examination(MMSE)

Interviewer-administered

+

functional status

Depression Geriatric Depression Scale (GDS) Self administered +

Polypharmacy ListInterviewer-administered or chart-based

?

Nutrition Mini Nutritional Assessment (MNA), BMIInterviewer-administered

+

Geriatricsyndromes

Dementia, delirium, fallsinterviewer-administered or chart-based

+

functional status

Mobility/falls Timed-up-and-go test, Tinetti, gait speed Performance-tests ?

A frailty revealed… and assessed

• 2006: Mrs BON… IR… 84 yo– No previous medical history (high blood sugar?)– Husband: 86 yo w/ severe advanced Parkinson, 2 children– Breast self exam � T1c N0 M0 left breast– 54 kg/167 cm, BMI 19.4 (<25)

• Conservative surgery + axillary lymph node dissection– Invasive ductal carcinoma, 17 mm, SBR II, 8 N-– ER- PgR-, Ki 67 40%, HER2-

• Adjuvant strategy– Chemotherapy with anthracylines (GERICO 06)? + XRT

• Scoring– Oncologist: PS 0 � “Easy! Go for it“– Geriatrician

• Functional status, cognition, nutrition, GDS � OK• However ! 3 falls < 1 year

+5

+1

+1

���� Lee 7 ~ 50% 4-yr mortality

35

6 key messages for elderly BC patients

1. Age and standard approach upfront influence treatment decision

– In 40% cases: but not always in the right direction!

2. Under and over-treament are frequent

3. Access to innovation is unbalanced

4. Comprehensive Geriatric Assessment = enforceable & not opposable

– Brings to clinicians new information in > 2/3 cases

– Modifies clinical decision in 20-25% cases (function & nutrition)

5. Geriatric problems are far more frequent than usually believed

– 2/3 impaired G8, +50% functional dependence or risk of malnutrition, +40%

significant comorbidities, 20% depression, +10% cognitive dysfunctions,

polypharmacy, etc.

6. Competing risks for mortality

– Call for some degree of assessment of life expectancy to balance treatment decision

� Need for specific research