1. 4 YEARS SURVIVAL OF 100 HCC PATIENTS TREATED WITH DC BEAD: A RETROSPECTIVE ANALYSIS Marta Burrel Vascular Interventional Unit Barcelona Clinic Liver Cancer Group Hospital Clínic. Barcelona, Spain.

2. Very early stage (0) Single< 2cm. Carcinoma in situ HCC Portal pressure/ bilirubin Okuda 3, PST >2, Child-Pugh C Terminal stage (D) Okuda 1-2, PST 0-2, Child-Pugh A-B Stage A-C Stage D Normal Single 3 nodules <3cm Associated diseases Increased NoYes Early stage ( A) Single or 3 nodules < 3cm, PS 0 Intermediate stage ( B) Multinodular, PS 0 Advanced stage (C) Portal invasion, N1,M1, PS 1-2 Stage 0 PST 0, Child-Pugh A BCLC Classification and Treatment Schedule Resection PEI/RFSorafenibTACE Symptomatic treatment Liver Transplantation (CLT / LDLT) Curative Treatments: 50% - 75% at 5 years RCT: 40% - 50% at 3 yr vs 10% at 3yr Forner et al. Semin Liver Dis. 2010 Feb;30(1):61-744

3. Lo et al. Hepatology 200235(5):1164-71Llovet et al. Lancet 200218;359(9319):1734-9 Survival probability TACE Control 1 year 82%63% 2 years 63%27% 35% objective response > 6 months Independent prognostic factor Survival probability TACE Control 1 year 57%32% 2 years 31%11% Lipiodol TACE improves survival in a selected group of HCC patients

4. Favors treatment Favors control Lin, Gastroenterology 198863 GETCH, NEJM 1995 159 Llovet, Lancet 2002 503 Pelletier, J Hepatol 1998 312 Bruix, Hepatology 1998 239 OVERALL 503 10 1 0.10.01100 0.5 2 2p=0.017 Heterogeneity: Q:7.73 P=0.14 Random effects model (DerSimonian & Laird) OR (95% CI) Author,Journal, year Cumulative (pts) Lo, Hepatology 2002 391 2p=0.086 Median survival : ~ 20 months Systematic Review of RCT for Unresectable HCC Llovet and Bruix. Hepatology 2002

5. Varela 2007 J Hepatology Poon 2007 Clin Gastroenterol Hepatology Malagari 2008 CVIR # patients273562 Tumor size (mm)46 (8-150)76 (25-220)56 (30-90) Tumor responseRC 29% RP 75% RO (IT) 66,6% RC 14,3% RO 42,9% RC 12,2% RO 80,7% Survival 12 m 24 m 92,5% 88,9% 12 m 24 m 30 m 97% 91% 88% Cohort studies with TACE-DC Beads. Improved Objective Response. Better tolerance

6. Bland Embolization (n=41) Compensate cirrhosisChild-Pugh A –BECOG o-1Number of nodulesNo difference in both groups Randomization N=87 TACE with DCB (n=43) Malagari et al.Cardiovasc Intervent Radiol. 2010 Jun;33(3):541-51. Epub 2009 Nov 24. TACE-DEB better than Bland Embolization Local response. Overall Response (p=0.04) Fewer recurrence. At 9 months (p=0.002) Longer TTP (p=0.008) Chemoembolization vs Bland Embolization

7. Doxorubicin-Related Side Effects: Precision V End Point: Negative Lammer et al. Cardiovasc Intervent Radiol (2010), 33(1):41-52 TACE - DC Beads: Randomised Studies

8. SURVIVAL DATA AFTER TACE IN PATIENTS WITH HEPATOCELLULAR CARCINOMA (HCC) IN 2010: IMPACT ON CLINICAL PRACTICE AND RESEARCH

9. OBJECTIVES - Evaluate the survival of HCC patients treated with TACE- DEB following a strict selection (preserved liver function, absence of cancer related symptoms, extrahepatic spread or vascular invasion) - Evaluate causes of untreatable progression (UTP)

10. PATIENTS AND METHOD HCC patients treated by TACE-DEB between February 2004 and March 2010 Retrospective review of: - baseline characteristics - development of treatment related adverse events - overall survival

11. RESULTS - 97 patients evaluated - Median follow up 24.4 months (2.6-79.6) - At the time of evaluation 31 patients had died 2 received transplantation 22 had received Sorafenib because of progression not amenable for TACE

12. Results: Characteristics of patients CharacteristicAll (n=97) BCLC-A (n=46) BCLC-B (n=51) Age (years)68,2 [34-81] 68,2 [42- 80] 67 [34-81] Gender (male / female)85/1239/746/5 Etiology (VHC/Alcohol/others) 58/23/4/1227/11/6/ 231/13/3/4 Child-Pugh (A/B/C)93/445/148/3 BCLC stage (A/B)46/5146/00/51 Bilirrubin (mg/dl)1 [0,4-2,8] 0,85 [0,4- 2,4] Albumin (g/dL)42 [29-64] 40,5 [31- 47] 42 [29-64] AFP (ng/ ml) 15,5 [1-78847] 11,5 [1-2422] 18,5 [1-78847]

13. Median whole cohort survival : 47.7 months (95%CI: 36.6-58.8) Results: Survival Survival (months) 80,0060,0040,0020,000,00 1,0 0,8 0,6 0,4 0,2 0,0 Censurado Función de supervivencia

14. OS 54.2 months for stage A OS 40.2 months for stage B Survival after censoring follow-up at the time of transplant or Sorafenib 40.2 months for BCLC A 31.9 months for BCLC B Results: Survival

15. Early (<1 month) Abscess Ischemic cholecystitis Subcapsular hematoma Severe pain Pancreatitis Hepatic artery dissection 111111111111 Late ( >1 month) Hepatic artery dissection Biliary dilatation Abscess 112112 Related death1 n=10 Results: Complications

16. TACE No objective response Objective response Treatable (i.e. additional small HCC) Untreatable (i.e. vascular invasion, M1) or Liver failure/contraindication TACE HCC progression controlled 2nd-line option Progression Retreatment strategy Prof Bruix.Personal communication Evolutionary events after TACE The untreatable progression concept

17. Causes of untreatable progression leading to Sorafenib administration Significant progression after TACE Biliary dilatation related to tumor Extrahepatic spread Technically not feasible Intolerance to previous TACE-DEB 10 3 5 3 1 n= 22

18. J Lammer et al. Cardiovasc Intervent Radiol. 2010 Feb;33(1):41-52. Precision V: Potential patients with UTP

19. 1.Current survival of non-ressectable HCC patients within stages A and B is 47,7 months 2.Current survival of BCLC B patients is 40,2 months 3.These new data update the previous survival results obtained from Lipiodol-TACE, which impacts in clinical practice and research purposes CONCLUSIONS