What Should the Oncologist Ask - PowerPoint Presentation

Slide1

What Should the Oncologist Ask

the Geriatrician and Possibly Expect?

Etienne GC Brain, MD PhDInstitut CurieSaint-Cloud, France

www.siog.org

etienne.brain@curie.fr

1

Slide2

Therapeutic

nihilism

Elderly

patients

do not

receive

any treatment

The intermediate position?

Elderly

patients

may benefit from treatmentsBlind therapeutic enthusiasmElderly patients receive futile/non beneficial treatments Place and role of geriatrician and oncologist

Pelike

from Attica 480–470 BCMusée du Louvre

Current dilemna & extreme positions

2

Slide3

Oncologist

Cancer diagnosisCurative vs palliativeTreatmentFollow up

Roles & sharing of responsabilities

Geriatrician

Holistic view

Comorbidities

Frailty, impact & reversibility

Recommendations

Together = personalized treatment plan

Which treatment?

Which dose?

Which supportive cares?

Where?

Slide4

Is the patient

going to die from cancer or from

other causes?Is the patient at risk of treatment

- or cancer-related complications?How to deal with patients presenting impaired cognitive functions?

Best tools to evaluate end-organ functions?What does frailty stand for?

Can one assess satisfaction in older patients?What is a geriatric assessment and what does it bring?

Can a geriatric assessment be short?How to get organized?

Is there any best endpoint for clinical research in older patients?

Questions from oncologists perspective

Slide5

Assessment

Instrument

Administration

Prognosis

Dependency

,

functional

status

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

Self

administered

+

Comorbidity

Charlson

Comorbidity

Index (CCI), Cumulative

Illness

rating

Scale-Geriatric

(CIRS-G)

Self- or interviewer-administered or chart-based

+

Economic

/ social supportLife conditions, relatives, care-givers?CognitionFolstein Mini-mental State Examination (MMSE)Interviewer-administered+functional statusDepressionGeriatric Depression Scale (GDS)Self administered+PolypharmacyList?NutritionMini Nutritional Assessment (MNA), BMIInterviewer-administered+Geriatric syndromesDementia, delirium, falls+functional statusMobility/fallsTimed-up-and-go-test, TinettiPerformance-tests?

"Comprehensive" geriatric assessment

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Age

Top 25

th%

Fit

50

th

%

Intermediate

Lowest 25

th

%

Sick

50403324.57021.3

15.7

9.5

75

17

11.9

6.8

80

13

8.6

4.6

85

9.6

5.92.9906.83.91.8954.82.71.1Women life expectancyAgeing makes us unique!Walter JAMA 20016

Slide7

dementia

CHF

solid

tumour

AIDS

diabetes

HBP

Multimorbidities

across age

Piccirillo

Critical Rev

Oncol

Haematol

2008

7

Slide8

Competing causes for mortality

Kendal Cancer 2008

8

Slide9

New problems?

Kenis

Ann Oncol 20139

1820 patients

Median

age

76

40%

breast

cancer

21% colorectal cancer

13% haematological malignancy"Geriatric defects

" in 51% casesVery often

not identified < treatment starts!

Slide10

58% grade ≥ 3 toxicity

Risk increased w/ increasing risk score

AUC/ROC 0.65 (95%CI 0.58-0.71) ~ development cohort 0.72 (95%CI 0.68-0.77) (P = .09)No association between PS and chemo toxicity (P = .25)

A true predictive model for

chemo-related grade 3-5 toxicity

Hurria

J

Clin

Oncol 201610

Slide11

Risk score

vs

Karnofsky PSHurria J Clin Oncol 2011

11

Slide12

Post-surgery delirium & GA

Brouquet

Ann Surg 201012

118 patients 75+ (MMSE > 10/30)

Major

surgery

for CRC,

gastric

,

biliary

&

pancreas

24% postoperative delirium

Slide13

Cognitive impairment & dementia

13

Decreased

survival

(

Eagles

Br

Med J 1990)

Condition

worsening

with chemotherapy (Shagen Cancer 1999)Decrease of tolerance to chemotherapy (Monfardini Cancer 1996)

Increased

risk for post-surgery delirium

(Meziere Ann Fr Anesth

Reanim

2013)

Slide14

Fit

patient

Frail patient

14

Slide15

Syndrome of advancing age

characterized byImmune dysregulationChronic inflammationSarcopenia (≠ cachexia)Increased cellular senescenceLoss of resilienceState of decreased physiological reserves

Caused by cumulative decline across multiple organ systems Resulting in a decreased resistance to stressors & destabilizing eventsCan be described by

geriatric assessment± frailty screening tool

Frailty

definition

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Slide16

Frail

Dependence

≥ 3 comorbiditiesGeriatric syndromeGA

Vulnerable

1

functional

dependence

± 1-2 comorbidities

FitIndependence

No comorbidityStandard treatmentSimilar treatment

tolerance/benefit

Adjusted

treatmentDecreasedtreatment tolerance BSCPoor treatmenttolerance Will the patient tolerateand benefit from treatment? LE > cancerLE < cancer

if

poor

tolerance

Balducci

Oncologist 2000

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Slide17

MNA

Self-

rated

health

Polymedication

Age

strata

MNA

MNA

MNA

MNA

Soubeyran PLOS 2014

http://www.eprognosis.org/

G8 as a screening tool  LE estimate

Slide18

≥ 75

yo

1st visitNew cancer or relapse

G8Physician

± nurse

≤ 14/17

> 14/17

Primary

focus on*:

systemic

treatment

?

Decision 1YESNOStandard health caresvigilance and geriatriciansought according to needs

GA

* But not

exclusively

Adjusted

health

cares

± MDTB 2 and

decision

2

Geriatric

interventionsStreamlining geriatrician timeInvolvement of oncologistsImpactDecisions 1 and 2Geriatric interventionsDay hospital in geriatric oncologyMDTB 1 + geriatricianAdapted recommendations for patient’s referral for GA at Institut CurieMDTB: multi disciplinary tumor board

Slide19

≥ 75

yo

1st visitNew cancer or relapse

G8Physician

± nurse

≤ 14/17

> 14/17

GA

Streamlining

geriatrician

time

Involvement of oncologistsImpactGeriatric interventionsDay hospital in geriatric

oncology

MDTB + geriatrician

Ideal

recommendations

for

patient’s

referral

for GA

at

Institut Curie

MDTB: multi disciplinary tumor boardMDTB ± geriatricianSystemictreatment?Standard health caresvigilance and geriatriciansought according to needsAdjusted health caresGeriatric interventions

Slide20

Systematic review (Medline &

Embase

)

1,654 reports 

10 studies3 w/ GA performed by geriatrician7 w/ GA performed by cancer specialist, healthcare worker or (research) nurse

Change in oncologic treatment: 6 studiesModification of initial treatment plan: 39% patients

2/3 w/ less intensive treatment (irrespective of performer)High role of functional & nutritional status

Implementation of non-oncologic interventions defined according to GA: 7 studiesAll but one: interventions suggested for > 70% patients

Social 38%, medication 37%, nutritional 26%Psychological, cognitive impairment, mobility and falls risk, previously unidentified comorbid conditions: all ~ 20%GA impact on

treament decision & interventions

Hamaker

Acta

Oncol 201420

Slide21

Demonstrate

the impact of GA

on cancer prognosis in elderly patients

PREPARE program (Pierre Soubeyran

, French PHRC 2013-2014)

Initial cares with first or second line chemotherapy

L1: breast, colorectal gastric, lung, prostate, bladder, ovarian,

myeloma, NHL

L2: breast, colorectal, prostate, myeloma, NHL

Co-primary endpoints: 1-yr OS (+10%) & HrQoL (+10 points)

P Soubeyran

> 14

 Standard treatment≤14Standard treatmentCase management("G8-guided", nurse, geriatrician, etc.)

> 70

yoL1 or L2

R1:1

G8

21

N = 1500

N = 1200

Slide22

Social environment

: Q1 “do you live alone?” + Q2 “do you have a person or caregiver able to provide care and support?”Autonomy: Activities of Daily Living (ADL) (abnormal if <6/6) and 4-Instrumental ADL (IADL) (abnormal if <4/4)

Mobility: Timed Up and Go test (TUG) (abnormal if >20 sec)Nutrition: unintentional weight loss (>10% in 6 months) and BMI (< 21)Cognitive status: Mini-Cog (abnormal if <4/5)

Mood: Mini-Geriatric Depression Scale (Mini-GDS) (abnormal if ≥ 1/4)Comorbidities: updated

Charlson index score

National & International validation

Geriatric

COre

DatasEt (G-CODE)

(Delphi/RAND + Consensus Methods)

DIALOG = GERICO + UCOG =

intergroup of clinical research in GO labeled by INCa in 2014 & 2017Paillaud Eur J Cancer 2018

Slide23

Acceptability &

willingness

West Haven Veterans Affairs226 patients 60+: attitudes toward burden of treatment, possible outcomes

, and likelihood- Limited life expectancy (cancer, congestive heart failure, or chronic obstructive pulmonary disease)- Burden of treatment (length of the hospital stay, extent of testing, and invasiveness of interventions)1. Low-burden

treatment (restoring participant's current state of health) vs no treatment resulting in

death 98.7% accept treatment

2. High-burden treatment

vs no treatment resulting in death

11% decline3 & 4. Low-burden treatment vs survival with severe functional or cognitive impairment

74-89% decline1

2

3

4Fried NEJM 2002The likelihood of adverse functional and cognitive outcomes of treatmentrequires explicit consideration in older ones23

Slide24

Tumour

extent

T & NPatientpreference& acceptability

TumourbiologyLuminal A/BHER2 & TNBC

Gene expression profile

Generalhealth

status

Geriatric assessment

Life expectancyTreatment toxicity

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Slide25

Age and standard

approach

upfront

influence

treatment

decision

Not

always

in the right direction: u

nder and over-treament are frequent (over > under)!Geriatric problems are far more frequent than usually believed2/3 impaired G8, +50% functional dependence or risk of malnutrition, +40% significant comorbidities, 20% depression, +10% cognitive dysfunctions, polypharmacy, etc.Geriatric assessment = enforceable & not opposableBrings to clinicians new information in > 2/3 casesModifies clinical decision in > 25% cases (function & nutrition)Competing risks for

mortality

Call for some degree of assessment of life expectancy

to balance treatment decision

Access to innovation

is

unbalanced

Need

for

specific

research

Key messages for older cancer patients25

Slide26

Young patient

Social and family obligations (children)

Quantity of life +++Elderly patientQoL+++IndependenceStaying

at home

Oncology

Therapies

and innovation

Toxicity

,

response, survival

RECIST

NCI CTC v4.0

Survival (DFS, PFS, DDFS, OS)Fast-moving world"Molecular portrait" of tumour & GEPGeriatricsSymptoms, diagnosisQuality of survival, i.e. amount of life with good QoL

CognitionFunctional status

QoLNutrition, etc.Requiring time"Global portrait" of patient & GA

GA

versus

or

+

?

Genomic

defects

targeted

therapy

GA

defectstargetedgeriatricinterventionTwo Worlds Confronting One Another?26

Slide27

FEC, AACR, FAC, ASCO, anti-PDL1, anti-PD1, CMF, SABCS, PD-1, PDL1, DXR, PK/PD, CEX, 5FU CDDP,

Calvert AUC, ESMO, Chatelut

AUC, CTC, TILs, population PK, EORTC, FOLFIRI, ctDNA, FOLFOX 7, CPA, DFS, CALGB, DDFS, OS, TTP, NCI, CYP P450, JCO, JNCI, HER2, PI3K, mTOR, Phase 0, ECCO, ib and ab, Unicancer

, EORTC, SWOG, CALGB, etc.

Charlson

, CIRSG, CGA, AD, MCI, MNA, GDS, MMS, ADL, IADL, GFI, CMR2, JAGS, EUGMS, G8, CARG,

Oncodage

, VES-13,

TRFs

, JGO, NIA, SoFOG, Walter’s score,

Lee’s

score, CRASH, etc.

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Slide28

FEC, FAC,

SoFOG

, ADL, IADL, CMF, SABCS, DXR, PK/PD, CEX, G8, EORTC, 5FU CDDP, MCI, Calvert and Chatelut AUC, CARG, GDS, population PK, AD, FOLFIRI, MMS, FOLFOX, CPA, CRASH, SWOG, DFS, OS, TTP, NCI, GERICO, TILs, CARG, anti-PDL1, anti-PD1, EORTC TFE, JCO, JNCI, Charlson, JGO, CIRSG, PD-1, PDL-1,

ctDNA, EGS, EGA, MNA, GFI, Unicancer, Lee’s score, JAGS, etc.

To be practice changing,

let us be practice sharing!

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Slide29

Optimising

treatment in older cancer patientsis precision medicine too

!

6th edition26-29/06/2019

29

SIOG Global Policy Meeting 14

th

November (UN venue)

SIOG Annual Conference 15

th-16th November (International Conference Centre Geneva CICG)