TACE Combined With Iodine-125 Seeds Implantation for HCC

Portal vein tumour thrombus (PVTT) is a common complication of hepatocellular carcinoma (HCC). PVTT has a profound adverse effect on prognosis, with a very short median survival time (2-4 months). The presence of PVTT also limits treatment options, such as liver transplantation and curative resection. Although the Barcelona Clinic Liver Cancer group recommended sorafenib as a standard therapy for advanced-stage HCC, the optimal treatment for HCC with PVTT remains largely controversial. Some studies have reported a survival benefit in patients with PVTT who underwent transarterial chemoembolization (TACE), even in patients with main portal vein (MPV) tumor thrombus. Iodine-125 brachytherapy had also showed promising efficacy as a new method for unresectable HCC with PVTT. Results of our previous study indicated that TACE combined with Iodine-125 seeds implantation might be a good choice for selected patients with PVTT. Thus, we conduct this study to farther evaluate the effect of TACE combined with Iodine-125 seeds implantation for HCC with PVTT. 270 patients with HCC and PVTT will be included and randomized to two group: group 1, patients received TACE combined with Iodine-125 seeds implantation; group 2, patients received TACE alone. TACE and Iodine-125 seeds implantation will be performed with a standardized procedure. Iodine-125 seeds implantation into PVTT (guided by CT) will be conducted 7 days after TACE. All patients revisit our institutions for follow-up examinations including contrast enhanced CT/MRI and laboratory tests every 4-6 weeks after the first treatment. Patients who have a tumor response rating of complete response will be required to revisit 3 months interval. At each visit, TACE or Iodine-125 seeds implantation is repeated if the following criteria are reached: 1) images indicating viable intrahepatic tumor tissue or PVTT; 2) Child-Pugh class A or B, and no contraindication to TACE and Iodine-125 seeds implantation. The primary end point of this study is overall survival. The secondary end points are time to tumor progression, disease control rate, duration of portal patency and adverse events. All adverse events are graded in accordance with Common Toxicity Criteria Adverse Events Version (CTCAE) 4.03.

Sex

All

Minimum age

18 Years

Maximum age

75 Years

Inclusion Criteria:

1. clinical diagnosis of HCC;
2. age between18 and 75 years;
3. type I PVTT, type II PVTT, or type III PVTT within 1.5cm extending in the main portal vein (if obstructive PVTT involve both the left and right portal vein or main portal vein, multiple collateral vessels are required);
4. Child-Pugh class A or B;
5. Eastern Cooperative Group performance status (ECOG) score of 0-2;
6. neutrophilic granulocyte count ≥ 1.5×10\^9/L, platelet count ≥ 30×10\^9/L, and hemoglobin level ≥ 85g/L;
7. serum bilirubin ≤ 51.3 μmol/L, albumin ≥ 28g/L, ALT and AST ≤ 5 times of the upper normal limit, and creatinine ≤ 20g/L;
8. prothrombin time ≤18s or international normalized ratio \< 1.7.

Exclusion Criteria:

1. diffuse HCC;
2. extrahepatic metastasis;
3. obstructive PVTT involving both the left and right portal vein or main portal vein without collateral vessels,
4. type III PVTT affecting the main portal vein more than 1.5cm, or type IV PVTT;
5. previously surgery (resection or liver transplantation), local-regional therapies (e.g., radiofrequency ablation), intra-arterial chemoinfusion, TACE, radiotherapy, systemic chemotherapy, or molecular targeted drug therapy for HCC;
6. serious medical comorbidities.

• BACKGROUNDEl-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 2007 Jun;132(7):2557-76. doi: 10.1053/j.gastro.2007.04.061. PMID 17570226
• BACKGROUNDJemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A, Feuer EJ, Thun MJ. Cancer statistics, 2005. CA Cancer J Clin. 2005 Jan-Feb;55(1):10-30. doi: 10.3322/canjclin.55.1.10. PMID 15661684
• BACKGROUNDPirisi M, Avellini C, Fabris C, Scott C, Bardus P, Soardo G, Beltrami CA, Bartoli E. Portal vein thrombosis in hepatocellular carcinoma: age and sex distribution in an autopsy study. J Cancer Res Clin Oncol. 1998;124(7):397-400. doi: 10.1007/s004320050189. PMID 9719503
• BACKGROUNDCheung TK, Lai CL, Wong BC, Fung J, Yuen MF. Clinical features, biochemical parameters, and virological profiles of patients with hepatocellular carcinoma in Hong Kong. Aliment Pharmacol Ther. 2006 Aug 15;24(4):573-83. doi: 10.1111/j.1365-2036.2006.03029.x. PMID 16907890
• BACKGROUNDMinagawa M, Makuuchi M. Treatment of hepatocellular carcinoma accompanied by portal vein tumor thrombus. World J Gastroenterol. 2006 Dec 21;12(47):7561-7. doi: 10.3748/wjg.v12.i47.7561. PMID 17171782
• BACKGROUNDLlovet JM, Bustamante J, Castells A, Vilana R, Ayuso Mdel C, Sala M, Bru C, Rodes J, Bruix J. Natural history of untreated nonsurgical hepatocellular carcinoma: rationale for the design and evaluation of therapeutic trials. Hepatology. 1999 Jan;29(1):62-7. doi: 10.1002/hep.510290145. PMID 9862851
• BACKGROUNDSchoniger-Hekele M, Muller C, Kutilek M, Oesterreicher C, Ferenci P, Gangl A. Hepatocellular carcinoma in Central Europe: prognostic features and survival. Gut. 2001 Jan;48(1):103-9. doi: 10.1136/gut.48.1.103. PMID 11115830