1. DEBIRI TACE Patterns and Predictors of Response
Robert Jones
Declaration
Robert Jones is a consultant to Biocompatibles UK LTD.

2. Pathological response to chemotherapy predicts survival
100 90 80 70 60 50 40 30 20 10
Major response
Complete response
Minor
response
% survival 1 2 3 4 5 6 7 8 9 10
Years
Blazer, JCO 2008

3. Pathological Response Rates after Treatment70 60 50 40 30 20 10
55%
55%
FOLFOX/FOLFIRI
DEBIRI-TACE
36%
% patients
30%
15% 9%
Minor
Major
Complete
Pathological response

4. Metabolism of Irinotecan (CPT-11)
APC
SN-38
CYP3A4
Blood
CPT-11
CES2
Topo-1

5. “…tumour CES2 expression may contribute to variable response to irinotecan containing chemotherapy”
Clinical Cancer Research 2002; 8:

6. “…23 fold variation in CES-2 expression in colon cancers, which directly correlated with conversion from irinotecan to SN-38”
Clinical Cancer Research 2003; 9:

7. “Absolute levels of CES-2 appear highest in hepatic parenchyma, with colorectal primary tumour having levels two to three fold lower ”
British Journal of Cancer 1999; 80:

8. “Only 10% of cells need to express CES-2 for 48% growth suppression…
“Only 10% of cells need to express CES-2 for 48% growth suppression…..bystander growth suppression may play a role in the effect of CPT-11 ”
Journal of Clinical Investigation 1998; 101:

9. Hypothesis
Variation in pathological response to DEBIRI-TACE is due to inter-patient variation in metabolism of Irinotecan
Metabolism within tumour
Metabolism in surrounding tissue

10. Identification of Biomarkers
Prognostic
Predictive

11. Fresh metastatic tumour
Fresh hepatic tissue
FFPE primary tumour

12. Metabolomic Analysis
n=3

13. Immunohistochemistry
Primary tumour
Metastatic tumour
Hepatic parenchyma
CES-2 in primary colorectal cancer
CYP3A4 in hepatic parenchyma

14. Proteomic Analysis

15. Summary Wide variation in response to DEBIRI-TACE
Exploration of reasons behind variation in response will define approach to treatment
Identification of potential biomarkers of response will help guide personalisation of therapy