Combination therapy of TACE and PEI, TACE and RFA, and PEI and RFA for treatment of HCC

Transcription

1 Combination therapy of TACE and PEI, TACE and RFA, and PEI and RFA for treatment of HCC Poster No.: C-0747 Congress: ECR 2014 Type: Authors: Keywords: DOI: Educational Exhibit S. W. Jeon, J. H. Kwon, M. J. Kim; Daegu/KR Multidisciplinary cancer care, Cirrhosis, Cancer, Treatment effects, Education, Ablation procedures, Ultrasound, Percutaneous, CT, Management, Liver, Abdomen /ecr2014/C-0747 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. Page 1 of 13

2 Learning objectives It has been well-known that combination of the two of RFA, PEI, and TACE produces a synergistic effect. The combination of TACE and PEI, TACE and RFA, or PEI and RFA is more effective than each of the monotherapies in preventing incomplete necrosis, especially in advanced disease or when tumors are in close proximity to large vessels or vital structures. So we illustrate technique, advantage, disadvantage, role, and limitation of each combination therapy. Background 1. Understanding and rationale of combination therapy for treatment of HCC Liver cancer is the fifth most common cancer in the world and its incidence is increasing worldwide. But only about 30% of patients can benefit from curative therapies such as resection or liver transplantation due to poor liver function, as well as multiplicity of tumors. Therefore, non-surgical locoregional therapies have been used worldwide, such as transcatheter arterial chemoembolization(tace), percutaneous ethanol injection(pei) and radiofrequency ablation(rfa). They are minimally invasive options that can achieve the successful tumor eradication and preservation of liver function. Recent evidence suggests that combination therapy has a synergistic effect in treating hepatocellular carcinoma(hcc), especially for: (1) larger lesions that do not respond adequately to either procedure alone; (2) tumor at risky location or difficult to be treated by either procedure alone. 2. Principle, technique, advantage and disadvantage of each monotherapy 2.1. TACE(transcatheter arterial chemoembolization) Principle and technique: Usually the normal liver parenchyma has dual blood supply from the portal vein and hepatic artery. Two-third from portal vein and one-third from hepatic artery. But during hepatocarcinogenesis, most HCC show a deterioration of arterial blood flow and are eventually fed Page 2 of 13

3 mainly by arterial flow(fig. 1). So TACE exploits hepatic artery to deliver chemotherapic agent such as 5-fluorouracil, mitomycin C, doxorubicin, or cisplantin without damaging the normal liver parenchyma. TACE is based on the synergistic effect of arterial occlusion and local chemotherapy by using microcatheter technology. The purpose of embolization is to prevent the washout of the chemotherapic agent at the site of tumor and to induce ischemic necrosis. Well knowned embolic materials for occlusion of the hepatic artery are metallic coils, Gelfoam, lipiodol, polyvinyl alcohol, starch microspheres, or collagen particles. Advantage: Can make selective arterial occlusion which induces ischemic tumor necrosis while minimizing damage to the liver tissue with preserved liver function. Disadvantage: Can not be done for patients with severely compromised liver function, such as: (1) Child-Pugh classification C or late B; (2) massive HCC or HCC involving major portal veins coexistence of inferior vena cava thrombosis (IVTT) and/or portal vein tumor thrombosis (PVTT). In these situations, TACE shows a high risk of ischemic liver insufficiency or a lack of efficacy PEI(percutaneous ethanol injection) Principle and technique: Most HCCs arise in a background of cirrhosis caused by hepatitis virus or alcohol. The patients with underlying cirrhotic liver need percutaneous ablation because of minimal invasiveness and ready reproducibility. The principle of PEI is percutaneous injection of absolute ethanol (99.9%) into HCC for making tumor necrosis. Needle targeting into tumor is performed by ultrasonography or CT-guidance. Advantage: Can be performed in any portion of the liver because of less invasive rather than RFA. The effect of PEI reveal nearly equal result of 5- year survival rates compared with surgical resection for small (<3cm) HCC. In patients with large HCC, high-dose PEI would be a valid alternative for volume debulking. Disadvantage: Incomplete necrosis is more frequent than RFA because diffusion of ethanol is affected by the capsule or septa of HCC that can make uneven and imcomplete necrosis RFA(radiofrequency ablation) Principle and technique: The principle of RFA is percutaneous insertion of electrode into HCC which can produce heat for thermal cytotoxicity and Page 3 of 13

4 tumor necrosis. Use of electrical currents in the radiofrequency range to make heat. Most HCCs arise in a cirrhotic liver and often is surrounded by a capsule. The tumor capsule functions as thermal insulators like oven, resulting in higher peak temperatures and more effective ablation, so-called oven effect. Electrode targeting into tumor is performed by ultrasonography or CT-guidance. Advantage: Complete necrosis is more frequent with fewer treatment sessions rather than PEI because heat effect distributes homogeneously in all directions and are less affected by intratumoral septa than PEI. So RFA can makes better overall survival and disease-free survival rate with lower local recurrence rate. Disadvantage:Has some limitations by tumor location such as: (1) close (<1 cm) to vital adjacent structures (bowel loops, stomach, main bile ducts, GB, kidney, etc); (2) abutting on large vessels (3) located subcapsularly or exophytically. Also has less effectiveness in large HCC and relatively higher complication rate than PEI. Images for this section: Page 4 of 13

5 Fig. 1: Intranodular hemodynamic change during hepatocalcinogenesis in cirrhotic liver Page 5 of 13

6 Findings and procedure details 3. Principle, technique, advantage and disadvantage of each combination therapy 3.1. TACE plus PEI Principle and technique: TACE performed followed by PEI. PEI performed at 7 to 10 days after TACE because recovery of side effects of TACE without recanalization of tumor vessels when PEI will be performed. The Principle of TACE plus PEI is increasement of ethanol diffusion secondary to tumor necrosis and disruption of intratumoral septa produced by TACE before the PEI. In addition, embolization may reduce ethanol wash-out. Advantage: (Fig. 2) Significantly improve the survival rate in patients with HCC (3-8cm), compared to PEI alone. Also has benefit to HCCs(larger than 3 cm) at risky or difficult to ablate by RFA, especially in HCCs larger than 5 cm. Disadvantage: No advantage in small HCC (less than 3cm) compared to PEI alone TACE plus RFA Principle and technique: TACE performed followed by RFA. RFA performed at 7 to 10 days after TACE because recovery of side effects of TACE without recanalization of tumor vessels when RFA will be performed. The principle of TACE plus RFA is diminishment of blood flow and heat sink effect facilitating a larger zone of ablation during RFA. In addition, thermal therapy may also potentiate the effects of chemotherapy. Advantage: (Fig. 3) Significantly improve the survival rate in patients with HCC (3-5cm), compared to RFA alone or TACE alone. Also has benefit to HCCs(larger than 3 cm) at risky or difficult to ablate by RFA only. Disadvantage: No advantage in small HCC (less than 3cm) 3.3. PEI plus RFA compared to RFA alone. Page 6 of 13

7 Principle and technique: PEI performed followed by simultaneous application of RFA. In high risk location to RFA, PEI needle is located on the tumor closest to the blood vessel or vital structure. On the other hand, RFA electrode is located on the tumor at least 10mm away from vital structures. The principles of PEI plus RFA is diffusion of ethanol into areas not reached by RFA. In addition, destruction of small vessels and tissue desiccation by PEI can produce less tissue cooling effect and more increased ablation zone during RFA. Advantage: (Fig. 4) Significantly improve the survival rate in patients with large HCC (3.1-5cm) or high risk located HCC compared to RFA alone. PEI plus RFA reveal more higher primary effective rate than RFA only ( 92% > 85%) in these patients. Disadvantage: No advantage in small HCCs (less than 3cm) or large HCCs( cm). 4. Choice among various treatment modalities Consider advantage and disadvantage of each therapy, tumor and patient characteristics such as tumor size, number, location, margin, whether conspicuous at US or CT or not or patient's hepatic function (Fig. 5). The number of HCC # 3 and the size of HCC < 3cm: First treatment of choice is ultrasonography or CT-guided RFA. But if tumor locate at risky area or having difficulty to be ablated with RFA, ultrasonography or CT-guided PEI should be considered first. The number of HCC > 3 or the size of HCC # 5cm: First treatment of choice is TACE. But in cases of compromised liver function or the tumor had no therapeutic effect by TACE, PEI plus RFA should be considered first. The size of HCC # 3cm: If tumor size is 3-5cm, TACE plus RFA or PEI plus RFA are firstly considered. If tumor size is 5-8cm, TACE plus PEI is first treatment choice. If tumor had risk to be ablated with RFA, TACE plus PEI or PEI plus RFA should be considered. And if tumor had no therapeutic effect by TACE, PEI plus RFA can be performed. Images for this section: Page 7 of 13

8 Fig. 2: Successful combination therapy of TACE plus PEI in a 76-year-old man with high risk located HCC and remnant viable portion after TACE. (a) Axial contrast enhanced CT scan before combination therapy of TACE plus PEI shows a 3.4cm sized enhancing hepatocellular carcinoma(hcc, black arrow) at segment II nearby the IVC and liver Page 8 of 13

9 capsule. (b) Axial contrast enhanced CT scan after TACE shows partially accumulated iodized oil in the HCC. Anterior to accumulated iodized oil, there is ill-defined enhancing area, suggesting viable HCC (white arrow). (c,d) Axial unenhanced CT images obtained during followed PEI after TACE shows the side-hole needle positioned in the viable HCC with a CT guidence. (e) Dynamic CT scan 1 day after combination therapy shows complete ablation of HCC with no residual tumor. (f) Repeated CT scan 3 months after shows complete necrosis of the area of previous index HCC without local recurrence and remnant viable HCC. Fig. 3: Successful combination therapy of TACE plus RFA in a 71-year-old man with remnant viable HCC after TACE. (a) Axial contrast enhanced CT scan before combination therapy of TACE plus RFA shows a 3.8cm sized enhancing hepatocellular carcinoma(hcc, black arrow) at segment VIII. (b) Axial contrast enhanced CT scan after TACE shows partially accumulated iodized oil in the HCC. Posterior to accumulated iodized oil, there is ill-defined enhancing area, suggesting viable HCC (white arrow). (c) Axial unenhanced CT image obtained during followed RFA after TACE shows the electrode positioned in the viable HCC with a right lateral approach. (d) Dynamic CT scan 1 day after combination therapy shows complete necrosis of the area of the index HCC. (e) Repeated CT scan 1 year after shows complete necrosis of the area of previous index HCC without local recurrence and remnant viable HCC. Page 9 of 13

10 Fig. 4: Successful combination therapy of RFA and PEI in a 70-year-old man with high risk located HCC. (a,b) Axial and coronal contrast enhanced CT scans before combination therapy of PEI plus RFA show a 4.0cm sized enhancing hepatocellular carcinoma(arrow) at segment VI nearby the right kidney. (c) Axial unenhanced CT image obtained during PEI shows the side-hole needle positioned in the tumor. Focal low density area nearby the needle tip reveal tumor necrosis by the injected ethanol. (d) Page 10 of 13

11 Axial unenhanced CT image obtained during followed RFA after PEI shows the electrode positioned in the tumor with a right lateral approach. (e) Dynamic CT scan 1 day after combination therapy shows complete necrosis of the area of index tumor. (f) Repeated CT scan 6 months after shows complete necrosis of the area of previous index tumor without local recurrence. Fig. 5: Flow diagram for choice among various treatment modalities Page 11 of 13

12 Conclusion Combination therapy is more effective than each of monotherapies, and each combination therapy has own inherent advantage, disadvantage, role, and limitation. Personal information References 1. Lai EC, Fan ST, Lo CM, Chu KM, Liu CL, Wong J: Hepatic resection for hepatocellular carcinoma: an audit of 343 patients. Ann Surg 1995; 221: Lo CM, Ngan H, Tso WK, Liu CL, Lam CM, Poon RT, et al.: Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology 2002; 35: Dettmer A, Kirchhoff TD, Gebel M, Zender L, Malek NP, et al: Combination of repeated single-session percutaneous ethanol injection and transarterial chemoembolisation compared to repeated single-session percutaneous ethanol injection in patients with nonresectable hepatocellular carcinoma. World J Gastroenterol 2006;12: Choi BI: Hepatocarcinogenesis in liver cirrhosis: imaging diagnosis. J Korean Med Sci 1998;13: Cha DI, Lee MW, Rhim H, Choi D, Kim YS, et al: Therapeutic efficacy and safety of percutaneous ethanol injection with or without combined radiofrequency ablation for hepatocellular carcinomas in high risk locations. Korean J Radiol. 2013;14(2): Mulier S, Ni Y, Jamart J, Ruers T, Marchal G, Michel L: Local recurrence after hepatic radiofrequency coagulation: multivariate meta-analysis and review of contributing factors. Ann Surg 2005; 242: Okuda K, Ohtsuki T, Obata H, Tomimatsu M, Okazaki N, Hasegawa H, et al.: Natural history of hepatocellular carcinoma and prognosis in relation to treatment: Study of 850 patients. Cancer 1985; 56: Page 12 of 13

13 8. Lencioni RA, Allgaier HP, Cioni D, Olschewski M, Deipert P, Crocetti L, et al.: Small hepatocellular carcinoma in cirrhosis: randomized comparison of radio-frequency thermal ablation versus percutaneous ethanol injection. Radiology 2003; 228: McGahan JP, Browning PD, Brock JM, Tesluk H: Hepatic ablation using radiofrequency electrocautery. Invest Radiol 1990; 25: Liem MS, Poon RT, Lo CM, Tso WK, Fan ST: Outcome of transarterial chemoembolization in patients with inoperable hepatocellular carcinoma eligible for radiofrequency ablation. World J Gastroenterol 2005; 11: Teratani T, Yoshida H, Shiina S, Obi S, Sato S, Tateishi R, et al.: Radiofrequency ablation for hepatocellular carcinoma in so-called high-risk locations. Hepatology 2006; 43: Buscarini L, Buscarini E, Di Stasi M, Vallisa D, Quaretti P, Rocca A: Percutaneous radiofrequency ablation of small hepatocellular carcinoma: long-term results. Eur Radiol 2001; 11: Livraghi T, Goldberg SN, Lazzaroni S, Meloni F, Solbiati L, Gazelle GS: Small hepatocellular carcinoma: treatment with radio-frequency ablation versus ethanol injection. Radiology 1999; 210: Wong SN, Lin CJ, Lin CC, Chen WT, Cua IH, Lin SM: Combined percutaneous radiofrequency ablation and ethanol injection for hepatocellular carcinoma in high-risk locations. Am J Roentgenol 2008; 190: Page 13 of 13