***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 & 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 This prospect i ve non‐r and omized controlled trial aim ed to compare the efficacy of sorafenib in combination with transarterial chemoembolization ( TACE ) vs TACE alone for the treatment of patients with unresectable intermediate or advanced hepatocellular carcinoma PURPOSE To determine the safety and efficacy of transarterial chemoembolization ( TACE ) combined with sorafenib ( hereafter , TACE-sorafenib ) in patients with hepatocellular carcinoma ( HCC ) and portal vein tumor thrombus ( PVTT ) . MATERIAL S AND METHODS This study was approved by the institutional review board , and the requirement for informed consent was waived . The medical records of consecutive patients with HCC and PVTT who underwent TACE-sorafenib or TACE alone from January 2010 to December 2012 were retrospectively evaluated .  Sorafenib ( 400 mg ) was administered twice daily . Outcomes of patients who underwent TACE-sorafenib were compared with outcomes of patients who underwent TACE by using the Kaplan-Meier method according to types of PVTT : PVTT in the main portal vein ( type A ) , PVTT in the first-order portal vein branch ( type B ) , and PVTT in second- or lower-order portal vein branches ( type C ) . RESULTS Ninety-one patients were included in the analysis ; 46 patients underwent TACE-sorafenib and 45 underwent TACE . TACE-sorafenib showed significant survival benefits compared with TACE in patients with type B ( median survival , 13 months vs 6 months ; P = .002 ) or type C ( median survival , 15 months vs 10 months ; P = .003 ) PVTT . TACE-sorafenib and main PVTT were the independent prognostic factors for survival at uni- and multivariate analysis . Liver function after TACE-sorafenib worsened only in patients with main PVTT . Sorafenib-related adverse events of grade 3 or higher occurred in 16 patients ( 35 % ) . CONCLUSION TACE-sorafenib side effects were acceptable , and this treatment may improve overall survival in patients with HCC with first-order or lower-branch PVTT when compared with patients who underwent TACE alone The oncologic community is faced with a steady increase in the incidence of hepatocellular carcinoma ( HCC ) [ 1 ] . Liver cancer represents the sixth most common cancer in the world ( 749 000 new cases ) and the third cause of cancer-related death ( 692 000 cases ) . The incidence varies from 3 out of 100 000 in Western countries , to more than 15 out of 100 000 in certain areas of the world , mapping the geographical distribution of viral hepatitis B ( HBV ) and hepatitis C ( HCV ) , the most important causes of chronic liver disease and HCC [ 2 ] . Most cases arise in those regions with limited re sources . The incidence of HCC increases progressively with advancing age in all population s , with a strong male preponderance . The association of chronic liver disease and HCC represents the basis for preventive strategies , including universal vaccination at birth against hepatitis B , programs to stop transmission and early antiviral eradication of viral hepatitis B and C [ III , A ] . It is unclear whether HBV vaccination will result in a decline in HCC as was seen in Taiwan , given the importance of other risk factors in Europe , such as alcoholic and non-alcoholic fatty liver disease . The control of other risk factors for chronic liver disease and cancer is more difficult to implement , such as cutting down on the consumption of alcohol and programs aim ing at a healthier lifestyle in the light of the obesity p and emic [ 3 , 4 ] . In Africa , reduction of exposure to aflatoxin B1 , especially in HBV-infected individuals , may lower the risk of HCC . HCC may evolve from subclasses of adenomas , and in < 10 % of cases HCC occurs in a normal liver . Surveillance of HCC involves the repeated application of screening tools in patients at risk for HCC and aims for the reduction in mortality of this patient population . The success of surveillance is influenced by the incidence of HCC in the target population , the availability and acceptance of efficient diagnostic tests and the availability of effective treatment . Costeffectiveness studies suggest surveillance of HCC is warranted in cirrhotic patients irrespective of its etiology [ 5 ] . Surveillance of non-cirrhotic patients is also advocated , especially in HBV carriers with serum viral load > 10 000 copies/ml [ 6 ] or HCVinfected patients with bridging fibrosis ( F3 ) [ III , A ] . Patients with HCV infection and advanced fibrosis remain at risk for HCC even after achieving sustained virological response following antiviral treatment [ III , A ] . Japanese cohort studies have shown that surveillance by abdominal ultrasound result ed in an average size of the detected tumors of 1.6 ± 0.6 cm , with < 2 % of the cases exceeding 3 cm [ 7 ] . In the Western world and in less experienced centers , sensitivity of finding early-stage HCC by ultrasound is considerably less effective [ 8 ] . There are no data to support the use of contrast-enhanced computed tomography ( CT ) or magnetic resonance imaging ( MRI ) for surveillance . In many centers , ultrasound surveillance is complemented with the determination of serum alphafetoprotein ( AFP ) , which can lead to a 6%–8 % gain in the tumor detection rate but at the price of false-positive results . A r and omized , controlled trial ( RCT ) of Chinese patients with chronic hepatitis B infection compared surveillance ( ultrasound and serum AFP measurements every 6 months ) versus no surveillance [ 9 ] . Despite low compliance with the surveillance program ( 55 % ) , HCC-related mortality was reduced by 37 % in the surveillance arm . Considering the most appropriate surveillance interval , a r and omized study comparing a 3 
    Output:
    
Conclusions The combination of transarterial chemoembolizaiton and sorafenib significantly improves outcomes of unresectable hepatocellular carcinoma compared with transarterial chemoembolization monotherapy , especially in Asian region