Transarterial chemoembolization combined with sorafenib for advanced hepatocellular carcinoma with portal vein tumor thrombus: A prospective control study

JVIR

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Scientific Session

Tuesday

27.8%), and presence of multiple factors (all p40.05). Listing MELD was 10.6 ⫾ 3.1 for T v 10.7 ⫾ 3.1 for D (p¼0.87). AFP 4 200 ng/ml was 7.9% for T v 22.2% for D (p¼0.09). TACE cycles were 2.3 ⫾ 1.3 for T v 2.5 ⫾ 1.5 for D (p¼0.68). Mean days listed was 241 ⫾ 159 (range 65-785) for T v 324 ⫾ 360 (range 55-1491) for D (p¼0.35). Blood types are outlined in the Table. The distribution of all blood types was similar for T and D (p¼0.92) as was type O versus other types (p¼0.56). At logistic regression, blood type (p¼0.85), listing MELD (p¼0.95), TACE cycle number (p¼0.54) and days listed (0.17) did not predict D. Chemoembolization of Hepatocellular Carcinoma as a Bridge to Liver Transplantation: Derived Benefit Is Independent of Blood Type Blood Type Entire Group Transplant Drop-off

O 49.4% 47.6% 56.6%

A 39.5% 38.1% 44.4%

B 8.6% 11.1% 0%

AB 2.5% 3.2% 0%

Conclusion: In similarly matched groups receiving similar TACE cycles, D was independent of blood type including those associated with longer wait times. The rate of D following TACE compared favorably to historic controls.

8:16 AM

Abstract No. 130

R. Lokken, N. Fidelman, R.K. Kerlan, Jr.; Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA Purpose: To determine incidence and risk factors of irreversible hepatotoxicity after transarterial chemoembolization (TACE) with doxorubicin-eluting beads (DEB) for hepatocellular carcinoma (HCC) in a patient population with high prevalence of hepatic dysfunction. Materials and Methods: Records of 48 consecutive patients with HCC who underwent 76 DEB-TACE procedures from 20112012 were retrospectively reviewed. Forty-seven (60.3%) and 26 (33.3%) of the procedures were performed in patients with total bilirubin of 42mg/dl and 43mg/dl respectively. Mean Model for End-Stage Liver Disease (MELD) score prior to TACE was 12.7 (median 13, standard deviation 4.0). Portal vein thrombus, hepatofugal flow, or transjugular intrahepatic portosystemic shunt (TIPS) was present prior to 17 procedures (21.8%). Thirty procedures (38.5%) were performed in patients with ascites. TACE was delivered to a segmental or subsegmental hepatic artery (50 procedures; 64.1%), two segmental hepatic arteries (23; 29.5%), or three segmental arteries (3; 3.8%). Hepatotoxicity was defined as new or worsening ascites or NCI Common Terminology Criteria for Adverse Events grade 3 or 4 toxicity of bilirubin, AST, ALT, creatinine or INR. Rates for death or urgent liver transplantation within 6 weeks of DEB TACE and irreversible hepatotoxicity were determined.

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Results: Reversible hepatotoxicity developed after 13 procedures (16.7%) in 10 patients (20.8%). Irreversible hepatotoxicity developed after 11 procedures (14.1%) in 11 patients (22.9%). One patient required an urgent liver transplant in the setting of irreversible hepatotoxicity within 6 weeks of DEB-TACE. No patient died within 6 weeks of DEB-TACE. Conclusion: DEB-TACE can be performed safely in patients with baseline hepatic dysfunction.

8:24 AM

Abstract No. 131

Transarterial chemoembolization in liver transplant candidates with and without marginal hepatic reserve D.N. Tran, E. Garwood, N. Fidelman; Radiology, UCSF, San Francisco, CA Purpose: In liver transplant candidates TACE can be used as a bridging treatment until an organ becomes available. However, many of these patients often have hepatic dysfunction. Our purpose is, therefore, to determine the rate of adverse outcomes following TACE in this patient population. Materials and Methods: From 2005-2009, 205 consecutive transplant candidates underwent 351 TACE procedures. The procedures were categorized as high-risk if the patients met one of the following criteria: pre-TACE bilirubin 42mg/dl, INR 41.5, creatinine 41.2 mg/dl, platelet count o60k, MELD score 415, Childs-Pugh class B or C, presence of ascites, or portal venous thrombus. Hepatotoxicity was defined as worsening ascites, encephalopathy, or NCI Common Terminology Criteria for Adverse Events grade 3 or 4 toxicity of bilirubin, AST, ALT, creatinine or INR. The primary outcome was irreversible hepatotoxicity leading to urgent liver transplantation or death within 6 weeks of the procedure. Results: Of the 351 TACE procedures, 236 procedures were determined to be high-risk in 133 patients (38-77 years old; 106 males and 27 females) and 115 procedures were determined to be low-risk in 72 patients (38-78 years old; 51 males and 21 females). The high-risk patients developed irreversible hepatotoxicity in 25 of the procedures (10.5%), 7 of which lead to an urgent liver transplant or death (3.0%). In comparison, the lowrisk patients developed irreversible hepatotoxicity in 1 procedure (0.9%), none of which lead to an urgent liver transplant or death (0%). Conclusion: TACE can be performed safely in liver transplant candidates with baseline hepatic dysfunction. However, poor hepatic reserves increase the risk of irreversible hepatotoxicity, which may require urgent liver transplantation or lead to death. Future work studying specific risk factors may guide the selection of high-risk liver transplant candidates for TACE treatment.

8:32 AM

Abstract No. 132

Transarterial chemoembolization combined with sorafenib for advanced hepatocellular carcinoma with portal vein tumor thrombus: A prospective control study J. Chen, K. Zhu, X. Meng, W. Huang; the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China

TUESDAY: Scientific Sessions

Hepatotoxicity and mortality following transarterial chemoembolization with doxorubicin-eluting beads in patients with hepatocellular carcinoma and marginal hepatic reserve

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TUESDAY: Scientific Sessions

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Tuesday

Scientific Session

Purpose: To assess the efficacy and safety of transarterial chemoembolization (TACE) combined with sorafenib for advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). Materials and Methods: 106 patients with advanced HCC were enrolled in this study. Among them, 45 were treated with TACE and sorafenib (TþS group), 61 were treated with TACE alone (T group). In TþS group, sorafenib was orally administered 3-5 days after first TACE (400 mg twice daily). Sorafenib was not interrupted during follow-up TACE treatments. PVTT was classified as follows: tumor involving the main portal vein (type A), right/left portal vein (type B), segmental branches of portal vein (type C) and without portal vein invasion (type D). Baseline characteristics, disease control rate (DCR), time to tumor progression (TTP), overall survival (OS) and adverse events (AEs) were compared for the two groups. Results: The baseline characteristics between TþS group and T group were similar (P40.05). DCR in TþS group was significantly higher than in T group (P¼0.001). With the exception of patients with type A, the median TTP and OS of patients with type B, type C and type D were significantly improved in TþS group than in T group (Po0.05). In TþS group, liver function tests at 1 month and 6 months after treatment were not significantly changes compared to pre-treatment (P40.05); however in patients with type A, liver function at 1 month after treatment deteriorated significantly. 37 patients (82.2%) experienced AEs related to sorafenib. Among them, 9 required sorafenib dose reductions for grade 3 hand-foot skin reactions in 5 patients and grade 3/4 diarrhea in 4 patients; 4 required sorafenib interruption for gastrointestinal hemorrhage. Conclusion: TACE combined with sorafenib in patients with advanced HCC was safe. Patients without main portal vein invasion can obtain benefit from the combined treatment, which have a longer TTP and OS than TACE alone. However, in patients with main portal vein invasion, although sorafenib is recommended according to Barcelona Clinic Liver Cancer therapy guide, our results do not support the combination therapy in these patients.

8:40 AM

Abstract No. 133

Sorafenib combined with transarterial chemoembolization for advanced hepatocellular carcinoma Y. Zhao1, W. Wang1, S. Guan2, H. Li3, D. Fan1, G. Han1; 1 Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China; 2The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; 3 Henan Tumor Hospital, Zhengzhou, China Purpose: Data on the efficacy and safety of sorafenib in combination with transarterial chemoembolization (TACE) are limited, particularly for advanced hepatocellular carcinoma (HCC) patients. We evaluated the outcome of the combination therapy in advanced HCC patients with preserved liver function, determined the predictors of survival, and proposed a new prognostic score to stratify the advanced HCC. Materials and Methods: In the multicenter retrospective singlearm study, 222 consecutive HCC patients receiving the combination therapy were enrolled between June 2008 and July 2011.

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JVIR

Results: Chronic hepatitis B was the predominant cause of HCC (86%). 80% patients were in Barcelona Clinic Liver Cancer (BCLC) stage C and 86% patients were at Child-Pugh (CP) A class. The median number of TACE procedure was 2 (range 1-8); and the median duration of sorafenib treatment was 8.1 months (range 0.1-33.9). After a median follow-up of 10.4 months, 148 patients had died. The overall median survival was 12 months (95% CI 10.1-13.9); and it was 13.1 months in CP-A patients and 7.6 months in CP-B patients. The overall incidence of adverse events (AEs) was 87%; and the most common AEs were diarrhea (50%), hand-foot-skin reaction (40%), rash (39%), and fatigue (33%). In 177 BCLC-C patients, performance status, the number of HCC nodules, Child-Pugh score and macrovascular invasion were significantly associated with overall survival and were included in the final score. Risk scores (R)¼ 5*(Vascular invasion: 0 if no, 1 yes) þ 6*(CP: 0 if A, 1 if B) þ 7*(No. of lesions: 0 if 1-2, 1 Z3) þ 8*(ECOG: 0 if 0, 1 Z1). Conclusion: Sorafenib in combination with TACE should be considered a safe and effective therapy for advanced HCC with well-preserved liver function. It is necessary to stratify the BCLC stage C to achieve the individualized optimal treatment. Further validation of the new subgroup of BCLC-C stage is warranted in an independent patient cohort.

8:48 AM

Abstract No. 134

Prospective phase II trial of sorafenib combined with doxorubicin eluting bead-transarterial chemoembolization for patients with unresectable hepatocellular carcinoma: efficacy analysis A. Feng, D. Reyes, I. Kamel, V. Gowdra Halappa, C. Corona Villalobos, D. Cosgrove, N. Bhagat, J. Hebert, T. Wahlin, J. Foltz, T. Pawlik, J.H. Geschwind; The Johns Hopkins University School of Medicine, Baltimore, MD Purpose: This study reports the final analysis (n¼50) of a prospective phase II study evaluating the efficacy of the combination of sorafenib and doxorubicin eluting bead transarterial chemoembolization (DEB-TACE) in patients with unresectable hepatocellular carcinoma (HCC). Materials and Methods: Therapeutic protocol consisted of 6week cycles with sorafenib at 800 mg/day beginning 1 week prior to DEB-TACE with up to four DEB-TACE treatments within 6 months. Tumor response was assessed by RECIST and EASL criteria using contrast enhanced MRI at baseline and at 1 month follow-up. Time to untreatable progression(TTUP) was defined as the interval from the initiation of sorafenib therapy until inability of patient to further receive intra-arterial therapy. Overall survival (OS) and TTUP were calculated with the Kaplan-Meier method; outcomes were stratified by BCLC A/B and C and compared with the log-rank test. Results: DEB-TACE in combination with sorafenib was successfully performed in 50 patients: mean 62 yrs(range, 31-88yrs), Child-Pugh A/B(92%/8%), BCLC A/B/C(10%/28%/62%), ECOG 0/1 (52%/48%), HCV/HBV(44%/8%), mean tumor burden 20%, mean tumor size 7.2 cm(range, 1.0-17.6cm), and mean tumor enhancement 78%. Patients were enrolled for a median of 3 (range, 1-22) cycles including a median of 1(range, 0-6) DEBTACE procedure. Median dose regimen was 400 mg QD and median dose taken while on study was 318 mg/day(range, 100 -