Post on 24-Sep-2020
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