This study evaluated 60 patients with advanced hepatocellular carcinoma treated with sorafenib using RECIST, modified RECIST (mRECIST), and Choi criteria to assess tumor response. mRECIST and Choi criteria identified more patients with objective responses compared to RECIST, including some considered non-responders by RECIST. Objective responses by mRECIST and Choi correlated with longer survival, suggesting they better capture treatment benefit compared to RECIST. The study concludes mRECIST and Choi criteria can reclassify some RECIST non-responders as true partial responders with significant survival benefit from sorafenib.

1. 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

2. AASLD 2011
No disclosure to declare

3. 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 LlovetJM ; N Engl J Med 2008 4 Lencioni R ; Semin Liver Dis. 2010
2 Cheng AL ; Lancet Oncol 2009 5 Gillmore R, J Hepatol 2011
3 Edeline J, Cancer 2011 6 Faivre S, Clin Cancer Res 2011
AASLD 2011

4. 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?
AASLD 2011

5. 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
AASLD 2011

6. 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
RECIST mRECIST CHOI criteria
HU
AASLD 2011

7. 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)
AASLD 2011

8. Patient Characteristics
Median age, years 61 (37-77)
Sex M/F 52/8
Etiology, % (number of patients)
Viral 48 (29)
Alcohol 23 (14)
Child Pugh Score, % (number of patients)
A 80 (48)
B 20 (12)
BCLC stage , % (number of patients)
B 33 (20)
C 67 (40)
Pathological diagnosis, % (number of patients) 88 (53)
Extrahepatic Spread , % (number of patients) 35 (21)
Prior treatments, % (number of patients)
None 32 (19)
Surgery 27 (16)
Radio Frequency Ablation 5 (3)
Trans-Arterial Chemo-Embolization 36 (22)
Median duration of sorafenib, months 5.7
Median time for the first evaluation, months 2.1
AASLD 2011

9. mRECIST and CHOI Criteria Identify
More Responder Patients Than RECIST
Venn diagram of tumor response according to three criteria
15 10 2 RECIST n=2
mRECIST n=12
CHOI criteria n=27
AASLD 2011

10. Response Rates by
RECIST, mRECIST, and CHOI Criteria
70 Objective response
% of response rates by each criteria
60 Stable Disease
62 Progressive Disease
50
40 48
45
30
35 32
30
20
23
21
10
3
0
RECIST mRECIST CHOI
N=60 N=56* AASLD 2011 N=60 *4 pts non evaluable

11. At the first tumor evaluation, are mRECIST
and CHOI criteria predicting overall survival
in patients with HCC treated with sorafenib?
AASLD 2011

12. Responses by RECIST Criteria Correlate with
Survival
1
0,9
0,8 RECIST
Probability of survival
0,7
0,6 Objective response (PR/CR)
0,5
Stable Disease
Progressive Disease
0,4
0,3
0,2
0,1
p=0.0012
0
0 5 10 15 20 25 30 35 40 45
Duration of survival, months

14. Can mRECIST and CHOI criteria reallocate
to the objective response group, patients
who were inappropriately considered non-
responders by RECIST?
AASLD 2011

15. Examples of discrepancies
Between methods of evaluation RECIST mRECIST CHOI criteria
Baseline  Stable  Response  Response
↘ HU
Baseline  Progression  Response  Response
↘ HU
AASLD 2011

16. Many Stable and Some Progressive Diseases
by RECIST Are Objective Responses
by mRECIST and CHOI Criteria
Objective responses according to each criteria
45%
Number of patients with objective response
30
3
25 Response by RECIST
Progressive Disease
20 21.4%
15 22 Stable Disease
1
Objective response
10
3.3%
9
5
2 2 2
0
Responders Responders Responders
RECIST (n=2) AASLD 2011 (n=27)
mRECIST (n=12) CHOI

17. 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