CHEMOEMBOLISATION USING IODIZED OIL(LIPIODOL ) BASED TECHNIQUES

Transcription

1 CHEMOEMBOLISATION USING IODIZED OIL(LIPIODOL ) BASED TECHNIQUES Peter Huppert Department of Radiology, Neuroradiology and Nuclear Medicine Klinikum Darmstadt ATH Universities of Frankfurt and Heidelberg/Mannhein Germany

2 Disclosure Speaker name: Peter Huppert, M.D. I have the following potential conflicts of interest to report: X Consulting: Guerbet Employment in industry Stockholder of a healthcare company Owner of a healthcare company Other(s)

3 Rational of Transarterial Chemoembolization Dual blood supply with arterial vessels feeding tumors Selective arterial drug delivery and devascularization R art = Regional advantage of arterial drug delivery (x-times compared to systemic delivery) clearance CL R art = Q A (1 - E r ) flow reduction extraction Collins 1994 drug R art 5-FU 80 Irinotecan 60 Doxorubicin 4 Mitomycin 3 Cisplatin 2

4 Lipiodol is part of conventional TACE Emulsion = water-in-oil suspension: water phase: oily phase: Embolics: Gelfoam, particles Drug(s): Doxorubicin/Epirubicin, Cisplatin, Mitomycin Iodized oil (Lipiodol ) = oily phase

5 Key of success: Preparation of W/O-Emulsion & continuous refreshing Water-in-Oil: 1:2-3 (3 cc Epirubicin+6-9 cc Lipiodol )* Slowly injection of water phase into oily phase* 3-way-stopcock: 2 syringes 10cc, Pumping-method : >30 times *Deschamps F et al.: Parameters for stable water-in-oil Lipiodol emulsion for liver transarterial chemo-embolization. Cardiovasc Intervent Radiol 2017;40:

6 Lipiodol-TACE is superselective TACE Angiographical work up of supply Coaxial microcatheter use Flow-guided injections grade 3 S7 S1 grade 1b Intended result: Intense & complete uptake of iodized oil Grade 1-3 of Maki-classification

7 The Way of Iodized Oil & Portal Venous Overflow 6/2009 6/ /2010 The Way of iodized oil: Arterial feeder Peribiliary arterial plexus Sinusoids Portal venuoles Tumor vessels Portal venous overflow

8 Intense uptake of Lipiodol in HCC EPR-effect (enhanced permeability and retention): - interstitial deposition of macromolecules - caused by enhanced permeability of tumor vessels - lack of lymphatic drainage in tumors - deposition of iodized oil in satellites Id e JM, Guiu B: Use of Lipiodol as a drug-delivery system for transcatheter arterial chemoembolization of hepatocellular carcinoma: A review. Crit Review Oncol/Hematol 2013;88:530-49

9 ctace in case of PV Infiltration 10/ /2005 9/2010 1/2006 7/ years old male Child-Pugh-Score 6 8 cm HCC infiltrating right PV 5 x TACE (Intervals: 3-5 mo.) Survival 63 months In case of good liver function PV infiltr. is no contraindication for selective TACE + 60 Mo. 8/2010

10 Extrahepatic supply can be treated by CTACE Right inferior phrenic artery

11 Lipiodol -TACE: from the Beginning to Evidence First report Konno 1982* First choice treatment in asia ** High efficacy of superselektive ctace*** *Konno T, Maeda H, Yokoyama et al.: Use of a lipid lymphographic agent Lipiodol as a carrier of high molecular weight antitumor agent SMANCS for hepatocellular carcinoma. Gan To Kagaku Ryoho 1982;9: **Satake M, Uchida H, AraiY et al.: Trancatheter arterial chemoembolization (TACE) with Lipiodol to treat hepatocellular carcinoma: Survey results from the TACE study group of Japan. Cardiovasc Intervent Radiol 2008;31: *** Golifieri R, Cappelli A, Cucchetti A et al.: Efficacy of selective transarterial chemoembolization in inducing tumor necrosis in small (<5cm) hepatocellular carcinomas Hepatology 2011;53(5): Matsui O, Kadoya M, Yoshikawa J et al.: Small hepatocellular carcinoma: treatment with subsegmental transcatheter ambolization. Radiology 1993;188:79-83 Murakawi R, Yoshimatsu S, Yamashita Y et al.: Transcatheter hepatic subsegmental arterial chemoembolization therapy using iodized oil for small hepatocellular carcinomas. Correlation between Lipiodol accumulation pattern and local recurrence. Acta Radiol 1994;35:576-80

12 Lipiodol -TACE: from the Beginning to Evidence Metaanalyses: prove of clinical efficacy: mrecist % OR, median survival 19 Mo Camma C, Schepis F, Orlando A et al.: Transarterial chemoembolization for unresectable hepatocellular carcinoma: Meta-Analysis of randomized controlled trials. Radiology 2002;224:47-54 Bruix J, Llovet JM: Prognostic prediction and treatment strategy in hepatocellular carcinoma. Hepatology 2002;35: Llovet JM, Bruix J: Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival. Hepatology 2003;37: Reidy DL, Schwartz JD: Therapy for unresectable hepatocellular carcinoma: Review oft he randomized clinical trials I: Hepatic arterial embolization and embolization-based therapies in unresectable hepatocellular carcinoma. Anti-Cancer Drugs 2004;15: Bruix J, Sherman M: Management of hepatocellular carcinoma. Hepatology 2005;52: Lencioni R, de Baere T, Soulen MC et al.: Lipiodol transarterial chemoembolization for hepatocellular carcinoma: a systematic review of efficacy and safety data. Hepatology 2016;64:106-16

13 The break through studies Llovet et al. Lancet (2002), 359; Lo et al. Hepatology (2002), 35; pts.: BSC 37 pts.: Embolization GF 40 pts.: TACE: Doxo mg/m 2, 10 cc iodized oil, GF 40 pts. BSC 40 pts. TACE Cisplatin 1-30 mg, iodized oil 1-30 (mean 10) cc, GF Embx. TACE BSC TACE BSC Response 6Mo. (WHO) 43% 35% 0 p=.004 Survival 1a 75% 82% 63% p=.009 2a 50% 63% 27% p=.009 3a 29% 29% 17% p=.009 mean (mo.) p=.005 Response 3Mo. (WHO) 39% 6% p=.01 Survival 1a 57% 32% p=.005 2a 31% 11% p=.005 3a 26% 3% p=.005

14 Conv. TACE vs. BSC in HCC : Phase III-Studies (Random effectsmodel pooledor, 95 % CI) fav. TACE 1,0 fav. BSC GETCH 1995 Pelletier 1998 Lo 2000 Llovet 2002 Pooled OR 0,1 0,2 0,3 0,4 0,5 0,6 0,7 0,8 0,9 1,0 1,1 1,2 1,3 adapted from: Llovet et al 2003, Hepatology 37;

15 Conv. TACE vs. BSC in HCC : Phase III-Studies (Random effectsmodel pooledor, 95 % CI) Survival benefit: 6-10 fav. months TACE 1,0 fav. BSC GETCH 1995 Pelletier 1998 Lo 2000 Llovet 2002 Pooled OR 307 / 387 (79%) excluded 791 / 903 (88%) excluded Lo et al. Hepatology (2002), 35; Patients: 40 TACE: Cis 1-30 mg, iodized oil 1-30 cc, GF Llovet et al. Lancet (2002), 359; Patients: 40 TACE: Doxo mg/m 2, 10 cc iodized oil, GF 0,1 0,2 0,3 0,4 0,5 0,6 0,7 0,8 0,9 1,0 1,1 1,2 1,3 adapted from: Llovet et al 2003, Hepatology 37;

16 Negative Predictors & Contraindications diffuse type of HCC compact type of HCC infiltrative type of HCC arterioportal shunts

17 Positive Predictors & Long Term Survival Nodular type Selective feeder 5/2006 8/2006 5/2007 8/2010 nodular type /pseudoencapsulation selective feeder size <10 cm Child A-B no central PV infiltration, no extrahepatic mts. Survival today: 12 years. S.M

18 Summary Advantages of conventional Lipiodol-TACE Proven survival benefit in comparison to BSC of 6-12 months Clear feed back by iodized oil uptake in CT: guiding retreatment Limited serious side effects even in multinodular and hughe tumors Low cost / procedure 4/2009 3/2010

19 Thank You for Attention!

20 CHEMOEMBOLISATION USING IODIZED OIL(LIPIODOL ) BASED TECHNIQUES Peter Huppert Department of Radiology, Neuroradiology and Nuclear Medicine Klinikum Darmstadt ATH Universities of Frankfurt and Heidelberg/Mannhein Germany