***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Objective To compare the treatment outcomes of sorafenib plus transarterial chemoembolization ( TACE ) vs TACE alone in patients with hepatocellular carcinoma ( HCC ) and hepatic vein tumor thrombus ( HVTT ) . Methods Twenty patients who were initially diagnosed with HCC and HVTT and received TACE combined with sorafenib during February 2009 to October 2013 were included in the study . To minimize selection bias , these patients were compared with 60 case-matched controls selected from a pool of 81 patients ( in a 1:3 ratio ) who received TACE alone during the same period . The primary end point was overall survival ( OS ) . The secondary end points were time to progression , disease control rate , and adverse events . Results After a median follow-up period of 12.5 months ( range , 1.03–44.23 months ) , the OS of the combined group was found to be significantly higher compared with the monotherapy group ( 14.9 vs 6.1 months , P=0.010 ) . The time to progression was found to be significantly longer in the combined group ( 4.9 vs 2.4 months , P=0.016 ) . Univariate and multivariate analyses revealed that the treatment allocation was an independent predictor of OS . Conclusion Sorafenib plus TACE was well tolerated and was more effective in treating patients with advanced HCC and HVTT . Future trials with prospect i ve larger sample s are required to vali date these results BACKGROUND In Japan and South Korea , transarterial chemoembolisation ( TACE ) is an important locoregional treatment for patients with unresectable hepatocellular carcinoma ( HCC ) .  Sorafenib , a multikinase inhibitor , has been shown effective and safe in patients with advanced HCC . This phase III trial assessed the efficacy and safety of sorafenib in Japanese and Korean patients with unresectable HCC who responded to TACE . METHODS Patients ( n=458 ) with unresectable HCC , Child-Pugh class A cirrhosis and ≥25 % tumour necrosis/shrinkage 1 - 3 months after 1 or 2 TACE sessions were r and omised 1:1 to sorafenib 400 mg bid or placebo and treated until progression/recurrence or unacceptable toxicity . Primary end-point was time to progression/recurrence ( TTP ) . Secondary end-point was overall survival ( OS ) . FINDINGS Baseline characteristics in the two groups were similar ; > 50 % of patients started sorafenib>9 weeks after TACE . Median TTP in the sorafenib and placebo groups was 5.4 and 3.7 months , respectively ( hazard ratio ( HR ) , 0.87 ; 95 % confidence interval ( CI ) , 0.70 - 1.09 ; P=0.252 ) .  HR ( sorafenib/placebo ) for OS was 1.06 ( 95 % CI , 0.69 - 1.64 ; P=0.790 ) . Median daily dose of sorafenib was 386 mg , with 73 % of patients having dose reductions and 91 % having dose interruptions . Median administration of sorafenib and placebo was 17.1 and 20.1 weeks , respectively . No unexpected adverse events were observed . INTERPRETATION This trial , conducted prior to the reporting of registration al phase III trials , found that sorafenib did not significantly prolong TTP in patients who responded to TACE . This may have been due to delays in starting sorafenib after TACE and /or low daily sorafenib doses BACKGROUND AND OBJECTIVES To compare the impact of concurrent TACE + sorafenib versus TACE alone on overall survival ( OS ) and time to progression ( TTP ) in patients with unresectable hepatocellular carcinoma ( uHCC ) . A secondary goal was to determine if sorafenib use increases the interval between courses of TACE . METHODS This study enrolled 150 patients with uHCC from June 2011 to June 2014 , including 50 treated with TACE + sorafenib and 100 treated with TACE alone .  Factors associated with OS and TTP were identified by univariate and multivariate Cox-regression model analyses . Average TACE interval was defined as TTP/TACE frequency . RESULTS The median OS ( 21.7 vs. 11.5 months ) and TTP ( 10.2 vs. 6.7 months ) were longer in the TACE + sorafenib group compared to the TACE group . Patients receiving combination therapy had higher survival rate ( P < 0.032 ) and longer average interval to TACE  ( P < 0.001 ) , but lower progression rate ( P < 0.001 ) . TACE + sorafenib therapy was associated with improved OS ( P ≤ 0.009 ) and TTP ( P ≤ 0.021 ) . The majority of AEs identified in patients receiving the combination therapy were classified as Grade s 1 and 2 , and skin-related reactions and fatigue were the most common . CONCLUSION Concurrent sorafenib with TACE provides survival benefits  over TACE monotherapy , which may be related to a prolonged interval between subsequent TACE courses . J. Surg . Oncol . 2016;113:672 - 677 . © 2016 Wiley Periodicals , Background We analyzed whether difference exist in the clinical manifestations and outcomes of hepatocellular carcinoma ( HCC ) according to the two major etiologies of HCC from a nationwide , population -based , r and om HCC registry . Methods Of the 31,521 new HCC cases registered at the Korea Central Cancer Registry between 2003 and 2005 , 4,630 ( 14.7 % ) were r and omly abstract ed , and followed up until December 2011 . Of those , 2,785 hepatitis B virus (HBV)-related and 447 hepatitis C virus (HCV)-related HCC patients were compared . Results The mean annual incidence rates of HBV- and HCV-related HCC incidence per 100,000 persons were 20.8 and 4.9 , respectively . The annual incidence rate of HBV-related HCC peaked at 50–59 age group ( 46.5 per 100,000 persons ) , while the annual incidence rate of HCV-related HCC increased gradually to the ≥70 year age group ( 13.2 per 100,000 persons ) . Large tumors ( ≥5 cm ) and portal vein invasion at initial diagnosis were more frequent in HBV-related HCC , while multiple tumors were more frequent in HCV-related HCC . In outcome analysis , HBV-related HCC showed poorer survival than HCV-related HCC [ median survival : 1.34 vs. 2.17 years , adjusted hazard ratio ( 95 % confidence interval ) : 0.88 ( 0.78–0.98 ) , P = 0.03 , adjusted for age , gender , Child-Pugh class , AJCC/mUICC stage , and initial treatment modality ] . However , when divided according to the AJCC/mUICC stage , survival difference was observed only for those with AJCC/mUICC stage IV tumor , but not for AJCC/mUICC stage I , II or III tumors . The treatment outcome of each modality ( resection , ablation , and transartherial chemoeombolization ) was comparable between the two etiologies . Conclusion HBV-related and HCV-related HCC have clear differences in clinical manifestation , requiring different screening strategy according to etiology to optimize HCC surveillance in HBV-endemic area . However , etiology did not affect treatment outcomes and long-term survival within the same stage except for far advanced tumors BACKGROUND & AIMS Transarterial chemoembolization with doxorubicin-eluting beads ( DC Bead ® ; DEB-TACE ) is effective in patients with Barcelona clinic liver cancer stage B hepatocellular carcinoma ( HCC ) . The multikinase inhibitor sorafenib enhances overall survival ( OS ) and time-to-tumor progression ( TTP ) in patients with advanced HCC . This exploratory phase II trial tested the efficacy and safety of DEB-TACE plus sorafenib in patients with intermediate stage HCC . METHODS Patients with intermediate stage multinodular HCC without macrovascular invasion ( MVI ) or extrahepatic spread ( EHS ) were r and omized 1:1 to DEB-TACE ( 150 mg doxorubicin ) plus sorafenib 400 mg twice daily or placebo . The primary endpoint was TTP by blinded central review . Secondary endpoints included time to MVI/EHS , OS , overall response rate ( ORR ) using modified response evaluation criteria in solid tumors , disease control rate ( DCR ) , time to unTACEable progression ( TTUP ) , and safety . RESULTS Of 307 patients r and omized , 154 received sorafenib and 153 received placebo .  Median TTP for subjects receiving sorafenib plus DEB-TACE or placebo plus DEB-TACE was similar ( 169 vs. 166 days , respectively ; hazard ratio ( HR ) 0.797 , p=0.072 ) . Median time to MVI/EHS ( HR 0.621 , p=0.076 ) and OS ( HR 0.898 , p=0.29 ) had not been reached . The ORRs for patients in the sorafenib and placebo groups with post-baseline scans were 55.9 % and 41.3 % , respectively , and the DCRs were 89.2 % and 76.1 % , respectively . TTUP was lower with sorafenib than with placebo ( HR 1.586 ; 95 % confidence intervals , 1.200 - 2.096 ; median 95 vs. 224 days ) . No unexpected adverse events  related to sorafenib were observed . CONCLUSION Sorafenib plus DEB-TACE was technically feasible , but the combination did not improve TTP in a clinical ly meaningful manner compared with DEB-TACE alone Abstract Objectives To investigate the safety of transarterial chemoembolisation ( TACE ) in combination with sorafenib in patients with hepatocellular carcinoma ( HCC ) . Methods Patients with Child – Pugh A/B liver function , ECOG performance status 0–2 and HCC treatable with TACE received continuous sorafenib 800 mg/day , and TACE with doxorubicin ( 75 , 50 and 25 mg/m2 according to serum bilirubin : < 1.5 , 1.5–3 , and > 3 mg/dL ) and lipiodol 2 weeks after sorafenib initiation and repeated every 4 weeks . Results Fifteen patients were included ( Child – Pugh A/B , n = 12/3 ; Barcelona Clinic Liver Cancer-A/B/C , n = 1/9/5 ; ECOG 0/2 , n = 14/1 ) . Median time on sorafenib was 5.2 months ( 2.6–7.4 months ) ; median number of TACE sessions was 3 . Common adverse events were abdominal pain ( n = 14 ) , weight loss ( n = 13 ) , alopecia ( n = 12 ) , fatigue ( n = 12 ) and hyperbilirubinaemia ( n = 11 ) . There were 32 serious adverse events ( grade ≥3 ) ; 9/10-unscheduled hospital admissions and 4/5 deaths were considered TACE-related . The study was stopped prematurely because of safety concerns . At 6 months , 2 and 5 patients had complete or partial responses ; 1 had stable disease . Median overall survival was 10.6 months ( 95 % CI : 5.2–16 months ) . Conclusion These findings do not support use of an intensive , high-dose doxorubicin-based TACE regimen in combination with sorafenib in this study population .Key Points• Transarterial chemoembolisation ( TACE ) is widely used in patients with hepatocellular carcinoma ( HCC ) • Various antiangiogenic and other agents have been used to augment this treatment • We tested lipiodol-TACE with bilirubin-adjusted doxorubicin dosing in combination with sorafenib • This trial was stopped prematurely because of safety reasons • Our safety results do not support the combination of sorafenib with this TACE BACKGROUND / AIMS This study assesses the safety , pharmacokinetics and efficacy of transarterial chemoembolization using drug eluting beads ( DEB ) , an embolizing device that slowly releases chemotherapy to decrease systemic toxicity . METHODS Twenty-seven Child-Pugh A cirrhotics ( 76 % male , 59 % HCV ) with untreated large/multifocal HCC received chemoembolization with doxorubicin loaded DEBs at doses adjusted for bilirubin and body surface ( range : 47 - 150 mg ) . Clinical and analytical data were recorded at 24 and 48 h , 7 , 14 and 30 days after first and second TACE . Response rate was assessed by CT at 6 months . Blood sample s were obtained in 13 patients at 5 , 20 , 40 , 60 , 120 min , 6 , 24 , 48 and 168 h to determine  doxorubicin Cmax and AUC . RESULTS DEB-TACE was well tolerated with an acceptable safety profile . Two cases developed liver abscess , one leading to death . Response rate was 75 % ( 66.6 % on intention-to-tre 
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These data may indicate positive TTP outcome in Asian patients but not in European patients while no positive findings regarding OS were observed in either region .
The most common AEs included fatigue , h and -foot skin reaction , diarrhoea and hypertension .
Conclusions Combination therapy may benefit unresectable HCC patients in terms of prolonged TTP and DCR .