Radiological evaluation aasld 2011

BLINDED INDEPENDENT CENTRAL RESPONSE ASSESSMENT

USING RECIST, MODIFIED RECIST, AND CHOI CRITERIA

IN PATIENTS TREATED WITH SORAFENIB FOR ADVANCED

HEPATOCELLULAR CARCINOMA

Mohamed Bouattour, Johanna Wassermann, Onorina Bruno,

Béatrice Larroque, Laurent Castera, Chantal Dreyer, Valérie Vilgrain,

Jacques Belghiti, Eric Raymond, Sandrine Faivre

Beaujon University Hospital

Clichy, France

AASLD 2011

No disclosure to declare

AASLD 2011

RECIST do Not Capture the True Benefit of

Sorafenib in HCC

• Sorafenib improves survival but yields low objective

response rate by RECIST (< 5%)1,2

• Sustained survival despite NO response by RECIST

suggest that RECIST are inappropriate to capture the true

benefit of sorafenib3

• Modified RECIST (mRECIST)4 are used to assess vascular

effects of TACE5 and CHOI criteria were proposed to

evaluate necrosis induced by targeted agents in HCC6

1 Llovet JM ; N Engl J Med 2008 2 Cheng AL ; Lancet Oncol 2009 3 Edeline J, Cancer 2011

AASLD 2011

4 Lencioni R ; Semin Liver Dis. 2010 5 Gillmore R, J Hepatol 2011 6 Faivre S, Clin Cancer Res 2011

Objectives

• At the first tumor evaluation, are mRECIST and CHOI

criteria predicting overall survival in patients with

HCC treated with sorafenib?

• Can mRECIST and CHOI criteria reallocate to the

objective response group, patients who were

inappropriately considered non-responders by

RECIST?

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Study Method/Radiological Evaluation

• Retrospective single center cohort analysis

• January 2007- December 2009

• Beaujon Hospital

• Baseline evaluation within 6 weeks prior to sorafenib

• First tumor evaluation by CT-scan 2-3 months after

sorafenib initiation

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Radiological Evaluation

• Quality control criteria

– Multiphasic CT-scan fully available for central review

– Central Review of data by a radiologist highly experienced in

liver cancers, blinded to clinical data

– Evaluation of tumor response by RECIST, mRECIST, and CHOI

criteria

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RECIST mRECIST CHOI criteria

HU

Results: Study Population Selection

Patients with BCLC B-C, Child-Pugh A-B, advanced

hepatocellular carcinoma treated with sorafenib

from 2007 to 2009

(n=82)

Non-evaluable patients (n=22) – Non-evaluable CT scan (n=9)

– Target lesions in pretreated area (n=9)

– No target lesion (n=3)

– Missing data (n=4) • Lost of follow up

• Early death

Patients evaluated in this study

(n=60)

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Patient Characteristics

Median age, years 61 (37-77)

Sex M/F 52/8

Etiology, % (number of patients)

Viral

Alcohol

48 (29)

23 (14)

Child Pugh Score, % (number of patients)

A

B

80 (48)

20 (12)

BCLC stage , % (number of patients)

B

C

33 (20)

67 (40)

Pathological diagnosis, % (number of patients) 88 (53)

Extrahepatic Spread , % (number of patients) 35 (21)

Prior treatments, % (number of patients)

None

Surgery

Radio Frequency Ablation

Trans-Arterial Chemo-Embolization

32 (19)

27 (16)

5 (3)

36 (22)

Median duration of sorafenib, months 5.7

Median time for the first evaluation, months 2.1

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Venn diagram of tumor response according to three criteria

2 10 15 RECIST n=2

mRECIST n=12

CHOI criteria n=27

mRECIST and CHOI Criteria Identify

More Responder Patients Than RECIST

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0

10

20

30

40

50

60

70

RECIST mRECIST CHOI

3

21

45

62

48

23

3530

32

Response Rates by

RECIST, mRECIST, and CHOI Criteria

Progressive Disease

Stable Disease

Objective response

% o

f re

sp

on

se

rate

s b

y e

ac

h c

rite

ria

N=60 N=60 N=56* *4 pts non evaluable

At the first tumor evaluation, are mRECIST

and CHOI criteria predicting overall survival

in patients with HCC treated with sorafenib?

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Responses by RECIST Criteria Correlate with

Survival

0

0,1

0,2

0,3

0,4

0,5

0,6

0,7

0,8

0,9

1

0 5 10 15 20 25 30 35 40 45

Objective response (PR/CR)

Stable Disease

Progressive Disease

RECIST

p=0.0012

Pro

bab

ilit

y o

f su

rviv

al

Duration of survival, months

Can mRECIST and CHOI criteria reallocate

to the objective response group, patients

who were inappropriately considered non-

responders by RECIST?

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Examples of discrepancies

Between methods of evaluation

Baseline Stable

RECIST

Response

mRECIST

Response

CHOI criteria

↘ HU

Baseline Progression Response Response

↘ HU

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0

5

10

15

20

25

30

0

5

10

15

20

25

30

0

5

10

15

20

25

30

Response by RECIST

Progressive Disease

Stable Disease

Objective response

Responders

RECIST (n=2)

Responders

mRECIST (n=12)

Responders

CHOI (n=27)

Many Stable and Some Progressive Diseases

by RECIST Are Objective Responses

by mRECIST and CHOI Criteria

Objective responses according to each criteria

Nu

mb

er

of

pa

tie

nts

wit

h o

bje

cti

ve

re

sp

on

se

2 2 2

9

1 22

3

3.3%

21.4%

45%

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Conclusion

• Response rate using mRECIST and CHOI criteria correlates with survival in advanced HCC patients treated with sorafenib

• mRECIST and CHOI criteria identify patients with true benefit (partial responders with higher survival) among “RECIST-stable” and “RECIST-progressive” patients

• mRECIST and CHOI criteria compared to RECIST increase the number of partial responders who also are patients with a median overall survival >14 months

AASLD 2011