The role of adjuvant TACE after curative liver resection for HCC

1. The role of adjuvant TACE after curative liver resection for HCC Anthony Fong Prince of Wales Hospital

2. Hepatocellular Carcinoma 1. Surgeon. 2005 Jun;3(3):210-5. The continuing challenge of hepatic cancer in Asia. Lai EC, Lau WY. J Am Coll Surg. 2007 Jul;205(1):27-36. 2. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin 2005; 55: 74–108 5th most common cancer in the world > 500,000 new cases per year 600,000 people die globally due to HCC each year

3. Curative treatment for HCC • Surgical resection / transplantation • Loco-regional ablation • Radiofrequency ablation • Microwave ablation

4. Surgical resection 1. Lang H, Sotiropoulos GC, Brokalaki EI, Schmitz KJ, Bertona C, Meyer G, Frilling A, Paul A, Malagó M, Broelsch CE. Survival and recurrence rates after resection for hepatocellular carcinoma in noncirrhotic livers. J Am Coll Surg. 2007 Jul;205(1):27-36. 2. Dupont-Bierre E, Compagnon P, Raoul JL, Fayet G, de Lajarte-Thirouard AS, Boudjema K. Resection of hepatocellular carcinoma in noncirrhotic liver: analysis of risk factors for survival. J Am Coll Surg 2005; 201: 663–70 3. mamura H, Matsuyama Y, Tanaka E et al. Risk factors contributing to early and late phase intrahepatic recurrence of hepatocellular carcinoma after hepatectomy. J Hepatol 2003; 38: 200–7. • Poor survival rate despite curative resection • 5-year survivals of 39% - 50% • High recurrence rate • 1,3,5 years recurrence rate : 30.1%, 62.3%, 79% respectively

5. Adjuvant Therapy

6. Adjuvant Therapy • Adjuvant therapy: • TACE • Systemic chemotherapy • Immunotherapy • Interferon • Acyclic retinoid acid

7. TACE TransArterial ChemoEmbolization

8. TACE Llovet JM, Bruix J Systematic review of randomized trials for unresectable hepatocellular carcinoma: Chemoembolization improves survival Hepatology 37:429, 2003 Survival benefit in un-resectable HCC ? TACE as an adjuvant treatment

9. TACE as adjuvant therapy after curative liver resection

10. TACE as adjuvant therapy Izumi R, Shimizu K, Iyobe T et al. Postoperative adjuvant hepatic arterial infusion of Lipiodol containing anticancer drugs in patients with hepatocellular carcinoma. Hepatology 1994; 20: 295–301. Lai EC, Lo CM, Fan ST, Liu CL, Wong J. Postoperative adjuvant chemotherapy after curative resection of hepatocellular carcinoma: a randomized controlled trial. Arch Surg 1998; 133: 183–8. Li Q, Wang J, Sun Y, Cui YL, Juzi JT, Qian BY, Hao XS.Postoperative transhepatic arterial chemoembolization and portal vein chemotherapy for patients with hepatocellular carcinoma: a randomized study with 131 cases.Dig Surg. 2006;23(4):235-40. Zhong C, Guo RP, Li JQ et al. A randomized controlled trial of hepatectomy with adjuvant transcatheter arterial chemoembolization versus hepatectomy alone for Stage IIIA hepatocellular carcinoma. J Cancer Res Clin Oncol 2009; 135: 1437–45. Peng BG, He Q, Li JP, Zhou F. Adjuvant transcatheter arterial chemoembolization improves efficacy of hepatectomy for patients with hepatocellular carcinoma and portal vein tumor thrombus. Am J Surg 2009; 198: 313–8.

11. TACE as adjuvant therapy Patient selection – tumor extent Timing for TACE Chemotherapy agent Side effects

12. Patient selection for adjuvant TACE

13. TMN Staging for HCC • T-staging • T1 - Solitary tumor without vascular invasion • T2 - Solitary tumor with vascular invasion or multiple tumors none more than 5 cm • T3 - Multiple tumors more than 5 cm or tumor involving a major branch of the portal or hepatic vein(s) • T4 - Tumor(s) with direct invasion of adjacent organs other than the gallbladder or with perforation of visceral peritoneum • N-staging • N0 - Indicates no nodal involvement • N1 - Indicates regional nodal involvement • M-staging • M0 - Indicates no distant metastasis • M1 - Indicates metastasis presence beyond the liver

14. p = 0.0237 p = 0.5327 p = 0.04 p = 0.10 p = 0.345 p = 0.004 p = 0.048 p = 0.0094

15. Patient selection for adjuvant TACE • High risk tumor • Tumor size (>5 cm) • Vascular invasion • Multiple tumor nodules

16. Timing for TACE

17. Timing for TACE

18. Timing for TACE 4 weeks after hepatectomy Single course already showed survival benefit

19. Chemotherapy agent

20. Agent for TACE Doxorubicin Cisplatin Doxorubicin Cisplatin Carboplatin Carboplatin Epirubicin Doxorubicin

21. Agent for TACE Doxorubicin (Adriamycin) / Epirubicin Mitomycin 5-FU Cisplatin / Carboplatin

22. Agents for TACE Cleared rapidly by the liver. Large difference in concentration between the liver and systemic circulation Effective primarily at high doses

23. Side effects

25. Side effects Fever Nausea / vomiting Impaired liver function Leukopenia Pain Local complications

26. Meta-analysis

28. Meta-analysis - Abstract

29. Our experience

30. Our experience • 13 Patients underwent adjuvant TACE after liver resection of curative intent • Criteria of adjuvant TACE : • Large tumor (>5 cm) • Satellite nodules • Vascular invasion • Close surgical margin

32. Our experience

33. Our experience 2 Patients had recurrence (15%) Both from lung metastasis Disease free survival : 3 mths / 15 mths 1 mortality from recurrence (Overall survival 15mths)

34. Conclusion Role of adjuvant TACE after curative liver resection is still controversial Some trials showed promising results in patients with advanced disease TACE is well tolerated in most studies Need further large scale study for evaluation

35. Thank you