Relevance for the management of cancer patientsScreening tools Relevance for the management of cancer patients Pierre Soubeyran, MD, PhD Institut Bergonié, Université Bordeaux

Screening toolsRelevance for the management

of cancer patients

Pierre Soubeyran, MD, PhDInstitut Bergonié, Université Bordeaux

Disclosure

Research Support/P.I. Roche, TEVA

Employee No relevant conflicts of interest to declare

Consultant No relevant conflicts of interest to declare

Major Stockholder No relevant conflicts of interest to declare

Speakers Bureau No relevant conflicts of interest to declare

Honoraria SPECTRUM, Pierre Fabre

Scientific Advisory Board TEVA, CELGENE

What is the final goal ?

• Better treat patients

– Ensure tumor control, as much as possible

– Limit the risk of adverse events

• which may lead to dependencies or even death

• Maintain quality of life

– Patient is still leaving at home

– Still autonomous with no sequellae

– Cancer is controlled (cured ?)

How to screen patients

to design treatment

with appropriate efficacy / toxicity ratio ?

5

Available data for screening

• Standard evaluation– Performance status

• At baseline

• A few months before

– Organ function• Creatinine clearance

• Liver tests…

– Nutritional status• Weight, albumin…

• Geriatric assessment– Designed for the oldest

– To be implemented in oncology

6

How many Risk Groups ?

• Heterogeneous population

• Three groups (or even more)

– Fit

– Intermediate

– Frail

How to design screening tools ?

• Various solutions– Identify a specific vulnerable profile

• Vulnerable geriatric profile

– Questionnaires, Fried criteria

• Non feasibility of a specific treatment

– Or Identify predictors of unacceptable events

• Early death, functional decline, toxicity

Balducci’s conceptApproach for a phenotype

• >70 and at least one factor

– > 80

– ≥3 comorbidities grade 3

– At least one comorbidity grade 4

– Dependent for at least one activity (ADL)

– At least one geriatric syndrome

S Monfardini, Ann Oncol 2005; 16: 1352-8

Balducci’s conceptDefinition of a phenotype

Balducci’s conceptA Tucci’s prospective study - 84 patients >65 y

A Tucci. Cancer 2009

• >70 and at least one factor– > 80

– comorbidities grade 3 - 4

– Dependent for at least one activity (ADL)

– At least one geriatric syndrome

Fit for haematologists and geriatricians

Unfit for haematologists and geriatricians

Fit for haematologists and unfit for geriatricians

Balducci’s conceptA Tucci’s prospective study - 84 patients >65 y

A Tucci. Cancer 2009

Oncologists’ approachFeasibility of chemotherapy

• >70 and at least one factor

– Poor performance status (WHO 3-4)

– Cardiac contra-indication to doxorubicin

– Low creatinine clearance (<50 ml/mn)

– Neutropenia or thrombocytopenia

– Severe comorbidities

Soubeyran P, J Ger Oncol 2011;2:36-44

Characteristics of the patients

Aggressive lymphomas

• Italian Group

– Median age 83 (70-96)

– Geriatric assessment

• >80: 73%

• Dependent : 56%

• Severe comorb.: 43%

– aaIPI 2-3 56.7%

• PS 2-4 60%

• Stage III-IV 56.6%

• Abnormal LDH 46.7%

• EORTC Group

– Median age 78.5 (70-92)

– Geriatric assessment

• >80: 34.3%

• Dependent : 53%

• Severe comorb.: 18.7%

– aaIPI 2-3 72%

• PS 2-4 69%

• Stage III-IV 50%

• Abnormal LDH 66%

Limits of these classifications

• Designed by physicians empirically

• Significant risk to be wrong

– Patient classified in the wrong category

– Because of thresholds…

Another approachPredictors of unacceptable events

• Events which would have changed your initial

decision, would you have known it may occur later…

– Early death

– Functional decline

– Hospitalization for toxicity

– Early death

– Functional decline

– Hospitalization for toxicity

• Identification in patients

with1st line chemotherapy

of predictive factors for

Another approachPredictors of unacceptable events

P Soubeyran, J Clin Oncol 2012; 30: 1829-34

MNA and TGUG

add to

Stage and Sex

for prediction

of early death

Another approachPredictors of early death

S Hoppe, J Clin Oncol 2013; 31: 3877-82

IADL and GDS15 are the

only predictors

of early

functional decline

Another approachPredictors of functional decline

20

Arti Hurria, J Clin Oncol 2011;29:3457-65Martine Extermann, Cancer 2012;118:3377-86

IADL, MMS, MNA and MAX2

or

IADL and physical activities

predict severe toxicity

Another approachPredictors of toxicity

21

Thrombocytopenia and Malnutrition

predict severe toxicity

OR 95% CI P-value

MNA <24 4.194 1.7 - 10.3 0.0018

Platelets 3.763 1.3 - 10.8 0.0140

Treatment strategy 0.509 0.26 - 0.99 0.0465

T Warkus, Proc SIOG 2011

Another approachPredictors of hospitalization for toxicity

How to decide?

Adverse events to avoidControl the disease

Life expectancy

Too many patients to evaluate

Need for Screening tools

CGA is

time-consuming

Most CGA tools

are useful

Questionnaire VES13

Questionnaire VES13

G8 questionnaire

Eight questions

Performed by a nurse

5 to 10 minAppetite, weight loss, BMIMobilityMood and cognitionNumber of medicationsSelf-related healthAge

Abnormal if ≤14Preliminary analysisSe: 89.6% ; Sp: 60.4%

Carine Bellera, Ann Oncol 2012;23:2066-72

The ONCODAGE study

27

Setting: Patients >70 with cancer

Impaired MGA if

≥ one abnormal questionnaire

– CIRS-G : at least one grade ≥≥≥≥ 3

– ADL : score ≤ 5

– IADL : score ≤ 7

– Timed Get up and Go : > 20 s

– MNA : score ≤ 23,5

– MMSE : score ≤ 23

– GDS-15 : score ≥≥≥≥ 6

Gold standard: Impaired Multidimensional Geriatric Assessment (MGA)

Pierre Soubeyran, Proc ASCO 2011

CGA is time-consumingScreening tools

28

Setting: Patients >70 with cancer

Impaired MGA if

≥ one abnormal questionnaire

– CIRS-G : at least one grade ≥≥≥≥ 3

– ADL : score ≤ 5

– IADL : score ≤ 7

– Timed Get up and Go : > 20 s

– MNA : score ≤ 23,5

– MMSE : score ≤ 23

– GDS-15 : score ≥≥≥≥ 6

Gold standard: Impaired Multidimensional Geriatric Assessment (MGA)

Se Sp PPV NPV K Time(mn)

G8 76.6%(74-79)

64.4%(58.6-70)

89.6%(87.6-91.5)

40.7%(36.1-45.4)

0.65 4.4 +/- 2.9

VES13 68.7%(65.9-71.4)

74.3%(68.8-79.3)

91.5%(89.4-93.3)

37.1%(33.2-41.3)

0.64 4.3 +/- 4.6

Pierre Soubeyran, Proc ASCO 2011

N

%

Abnormal

VES13

Normal

VES13Total

Abnormal MGA784

55.02

357

25.05

1141

80.07

Normal MGA73

5.12

211

14.81

284

19.93

Total 857

60.14

568

39.86

1425

100.00

Weaknesses – G8 / VES13

N

%

Abnormal

G8Normal G8 Total

Abnormal MGA874

61.33

267

18.74

1141

80.07

Normal MGA101

7.09

183

12.84

284

19.93

Total975

68.42

450

31.58

1425

100.00

N

%

Abnormal

VES13

Normal

VES13Total

Abnormal MGA784

55.02

357

25.05

1141

80.07

Normal MGA73

5.12

211

14.81

284

19.93

Total 857

60.14

568

39.86

1425

100.00

Weaknesses – G8 / VES13

N

%

Abnormal

G8Normal G8 Total

Abnormal MGA874

61.33

267

18.74

1141

80.07

Normal MGA101

7.09

183

12.84

284

19.93

Total975

68.42

450

31.58

1425

100.00

What does G8 detect ?

• Detection of

– Abnormal MNA 94,4%

– Abnormal ADL 93,6%

– Abnormal TGUG 91,3%

– Abnormal GDS15 84,8%

– Abnormal IADL 84,5%

– Abnormal MMS 80,5%

– CIRS-G grade 3 – 4 77,4%

What does G8 detect ?

• False negative characteristics

– 53,1% with only one abnormal quest. median : 1

• 18,4% for true positives median : 3

– 136 patients with grade 3-4 comorbidities

• Vascular 49,3%

• Cardiac 15,4%

• Respiratory 14%

• Metabolic 11,8%

Confirmation

Kenis C et al. J Clin Oncol 2014, 32: 19-26

• 937 patients

• At least two abnormal

tests among:

– Live alone, ADL, IADL, MMS,

GDS15, MNA, CCI

Confirmation

Kenis C et al. J Clin Oncol 2013 In Press

Survie à un an

Flemish version of the

Triage Risk Screening Tool

Flemish version of the

Triage Risk Screening Tool

SIOG Review of screening tools

What to do when the screening

tool is positive ?

After Screening

40

Evaluation and cautious

management

G8 Screening>14

≤ 14

Sta

nd

ard

Ma

na

ge

me

nt

41

Sta

nd

ard

Ma

na

ge

me

nt

Selection procedureMGA ? CGA ? Other ?

G8 Screening>14

≤ 14

Cautious ManagementOncologist + Geriatrician

After Screening

42

Consultation

Screening G8Pretreatment work-up

Geriatric evaluation

Geriatric synthesisTreatment feasibility

Adaptation of non specific treatmentAdverse events to avoid

MultidisciplinaryOncology meeting

Treatment plan

After Screening

Conclusion

• CAUTION

– Screening is not geriatric assessment

– Thresholds are not the reality of daily life

• All these tools are made to HELP the

oncologist take the right decision

• Not to replace him in the decision process

– Still physicians

– With many different patients