Comparison of chemoembolization with and without radiation therapy and sorafenib for advanced hepatocellular carcinoma with portal vein tumor thrombosis: a propensity score analysis.

PURPOSE: To compare efficacy of transarterial chemoembolization with and without radiation therapy (RT) versus sorafenib for advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). MATERIALS AND METHODS: This single-center retrospective study involved 557 patients with HCC with PVTT who initially received chemoembolization (1997-2002; n = 295), chemoembolization and RT (2003-2008; n = 196), or sorafenib (2009-2012; n = 66) according to eligibility criteria among an initial population of 617. The three groups were divided into three pairs (chemoembolization vs chemoembolization/RT, chemoembolization vs sorafenib, and chemoembolization/RT vs sorafenib), and time to progression (TTP) and overall survival (OS) were compared by propensity-score analyses. RESULTS: The chemoembolization/RT group had longer median TTP and OS than the chemoembolization-alone and sorafenib groups (P < .001). Multivariate Cox analysis revealed that chemoembolization/RT treatment was an independent predictor of favorable TTP and OS. In the matched cohort, median TTP and OS were significantly longer in the chemoembolization/RT group than the chemoembolization-alone group (102 pairs; TTP, 8.7 mo vs 3.6 mo [P < .001]; OS, 11.4 mo vs 7.4 mo [P = .023]) or the sorafenib group (30 pairs; TTP, 5.1 mo vs 1.6 mo [P < .001]; OS, 8.2 mo vs 3.2 mo [P < .001]), in agreement with the inverse probability of treatment weighted (IPTW) outcomes. In matching analyses, the chemoembolization-alone group had longer median TTP and OS than the sorafenib group (46 pairs; TTP, 3.4 mo vs 1.8 mo [P < .001]; OS, 5.9 mo vs 4.4 mo [P = .003]). There was no significant difference in terms of OS with the IPTW approach (P = .108), but there was one in terms of TTP (P < .001). CONCLUSIONS: Within the limitation of a retrospective study, the present data indicate that transarterial chemoembolization combined with RT could be considered as an alternative to the standard sorafenib in the treatment of patients with advanced-stage HCC with PVTT.

Predisposing factors of hepatocellular carcinoma recurrence following complete remission in response to transarterial chemoembolization.

BACKGROUND AND AIM: The aim of our study was to determine the predictors of recurrences in hepatocellular carcinoma (HCC) patients who had achieved complete remission (CR) by transarterial chemoembolization (TACE). METHODS: A total of 220 consecutive HCC patients who had achieved CR by TACE were followed for a median 72 months. CR was defined as complete lipiodol uptake based on the results of lipiodol-computed tomography 4 weeks after TACE and no additional tumor staining on the follow-up angiography. Recurrence patterns were classified as local recurrence and secondary tumor, respectively, in relation to the location of recurrence; early and late recurrence were classified in relation to recurrence time. RESULTS: Recurrence of HCC was observed in 169 patients (77 %), of whom 91 (54 %) had local recurrences, 61 (36 %) had secondary tumor, and 17 (10 %) had both. There were 45 (27 %) early and 124 (73 %) late recurrences. Local recurrence developed more frequently in patients with early recurrence than in those with late recurrence (62 vs. 51 %, respectively), while secondary tumor was detected more commonly in patients with late recurrence than in those with early recurrence (39 vs. 29 %, respectively; P < 0.001). In multivariate analyses, multinodularity [hazard ratio (HR) 2.351, P = 0.023] and a persistently high serum alpha-fetoprotein level following CR (HR 3.173, P < 0.001) were significant predictors of early recurrence. Older age (≥ 60 years; HR 1.531, P = 0.043), advanced Child-Pugh class (HR 1.983, P = 0.002), and the association with cirrhosis (HR 1.756, P = 0.028) were predictors of late recurrence following CR. CONCLUSIONS: Early recurrences following CR by TACE may be due mainly to undetectable remaining tumors, whereas late recurrences may be caused by newly appearing tumors in patients with a background of advanced cirrhotic liver.

Genetic predisposition of hand-foot skin reaction after sorafenib therapy in patients with hepatocellular carcinoma.

BACKGROUND: Sorafenib currently sets the new standard for advanced hepatocellular carcinoma (HCC). It has been suggested that Asian patients with HCC have increased susceptibility to hand-foot skin reaction (HFSR) related to sorafenib therapy. The authors investigated the association between sorafenib-induced HFSR and genetic polymorphisms in Korean patients with HCC. METHODS: For this prospective cohort study, the authors enrolled 59 consecutive patients with intermediate stage HCC from 5 centers in Korea. All patients received sorafenib 400 mg twice daily in combination with transarterial chemoembolization (TACE). Genotyping was performed on a total of 49 single nucleotide polymorphisms (SNPs) in 8 candidate genes (minor allelic frequency ≥5%). Serum levels of vascular endothelial growth factor (VEGF) and tumor necrosis factor-alpha (TNF-α) were measured using enzyme-linked immunosorbent assays before therapy and 1 month after therapy. RESULTS: During a median treatment period of 18 months, 55 patients (93%) developed sorafenib-induced HFSR, including grade 1 reactions in 15 patients, grade 2 reactions in 27 patients, and grade 3 reaction in 13 patients. The SNPs TNF-α -308GG, VEGF -94GG, VEGF 1991CC, VEGF IVS3-28CC, and uridine diphosphate glucuronosyltransferase 1 family-polypeptide A9 (UGT1A9) IVS1-37431AA were associated significantly with the development of high-grade (grade 2 or 3) HFSR in univariate analysis (P < .05). In multivariate analysis, the SNPs VEGF 1991CC (odds ratio, 45.7), TNF-α -308GG (odds ratio, 44.1), and UGT1A9 IVS1-37431AA (odds ratio, 18.7) were identified as independent risk factors for the development of high-grade HFSR (P = .01, P = .02, and P = .02, respectively). He serum TNF-α level measured 1 month after sorafenib therapy was correlated significantly with the development of high-grade HFSR (odds ratio, 3.56; P = .026). CONCLUSIONS: Differences in the incidence of HFSR may have been caused by ethnic differences in genetic polymorphisms of the TNF-α, VEGF, and UGT1A9 genes, especially in relation to the expression of serum TNF-α after sorafenib therapy.