***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 Transcatheter arterial chemoembolization ( TACE ) offers a survival benefit to patients with intermediate hepatocellular carcinoma ( HCC ) . A widely accepted TACE regimen includes administration of doxorubicin-oil emulsion followed by gelatine sponge — conventional TACE . Recently , a drug-eluting bead ( DC Bead ® ) has been developed to enhance tumor drug delivery and reduce systemic availability . This r and omized trial compares conventional TACE ( cTACE ) with TACE with DC Bead for the treatment of cirrhotic patients with HCC . Two hundred twelve patients with Child-Pugh A/B cirrhosis and large and /or multinodular , unresectable , N0 , M0 HCCs were r and omized to receive TACE with DC Bead loaded with doxorubicin or cTACE with doxorubicin . R and omization was stratified according to Child-Pugh status ( A/B ) , performance status ( ECOG 0/1 ) , bilobar disease ( yes/no ) , and prior curative treatment ( yes/no ) . The primary endpoint was tumor response ( EASL ) at 6 months following independent , blinded review of MRI studies . The drug-eluting bead group showed higher rates of complete response , objective response , and disease control compared with the cTACE group ( 27 % vs. 22 % , 52 % vs. 44 % , and 63 % vs. 52 % , respectively ) . The hypothesis of superiority was not met ( one-sided P = 0.11 ) . However , patients with Child-Pugh B , ECOG 1 , bilobar disease , and recurrent disease showed a significant increase in objective response ( P = 0.038 ) compared to cTACE . DC Bead was associated with improved tolerability , with a significant reduction in serious liver toxicity ( P < 0.001 ) and a significantly lower rate of doxorubicin-related side effects ( P = 0.0001 ) . TACE with DC Bead and doxorubicin is safe and effective in the treatment of HCC and offers a benefit to patients with more advanced disease PURPOSE To evaluate safety and efficacy of combined transarterial chemoembolization ( TACE ) with doxorubicin-eluting beads ( DEB ) and sorafenib in patients with advanced hepatocellular carcinoma ( HCC ) . PATIENTS AND METHODS A prospect i ve single-center phase II study was undertaken involving patients with unresectable HCC . The protocol involved sorafenib 400 mg twice per day combined with DEB-TACE . Safety and response were assessed . Results DEB-TACE in combination with sorafenib was successfully administered in 35 patients : mean age , 63 years ; Child 's A , 89 % ; Barcelona Clinic Liver Cancer stage C , 64 % ; Eastern Cooperative Oncology Group performance status of 0 and 1 , 46 % and 54 % , respectively ; and mean index tumor size , 7.7 cm ( st and ard deviation , ± 4.2 cm ) . Patients underwent 128 cycles of therapy ( sorafenib plus DEB-TACE , 60 cycles ; sorafenib alone , 68 cycles ) . Median number of cycles per patient was two ( range , one to five cycles ) ; median number of days treated with sorafenib was 71 ( range , 4 to 620 days ) . The most common toxicities during cycle one were fatigue ( 94 % ) , anorexia ( 67 % ) , alterations in liver enzymes ( 64 % ) , and dermatologic adverse effects ( 48 % ) . Although most patients experienced at least one grade 3 to 4 toxicity , most toxicities were minor ( grade 1 to 2 , 83 % v grade 3 to 4 , 17 % ) . Toxicity during cycle two was decreased . Over the course of the study , there were 40 sorafenib dose interruptions and 25 sorafenib dose reductions . Sorafenib plus DEB-TACE was associated with a disease control rate of 95 % ( Response Evaluation Criteria in Solid Tumors Group)/100 % ( European Association for the Study of the Liver [ EASL ] ) , with an objective response of 58 % ( EASL ) . CONCLUSION The combination of sorafenib and DEB-TACE in patients with unresectable HCC  is well tolerated and safe , with most toxicities  related to sorafenib  . Toxicity is manageable with dose adjustment of sorafenib . Preliminary efficacy data are promising Background / Objective : The survival benefit of treatment for unresectable hepatocellular carcinoma ( HCC ) with transcatheter arterial chemoembolization ( TACE ) combined with sorafenib remains uncertain . We compared the survival of patients treated with TACE and sorafenib  with that of patients treated with TACE alone . Methods : This was a post hoc analysis of the Study in Asia of the Combination of TACE with Sorafenib in Patients with HCC ( START ) trial . All patients who received TACE and interrupted dosing of sorafenib for early or intermediate-stage HCC in Taiwan from 2009 to 2010 were recruited into the TACE and sorafenib group . They were r and omly matched 1:1 by age , sex , Child – Pugh score , tumor size , tumor number , and tumor stage with patients from Taichung Veterans General Hospital in Taiwan who received TACE alone and who fulfilled the selection criteria of the START trial during the same time period ( control group ) . Patient survival [ cumulative incidence and hazard ratio ( HR ) ] of the 2 groups were analyzed and compared . Results : The baseline characteristics of the 36 patients in each group were similar  . Tumor response rates were significantly better in the TACE and sorafenib group ( P < .04 ) . Overall survival of the TACE and sorafenib group was also significantly better than that of the control ( TACE alone ) group over the 2 years [ 78 % , 95 % confidence interval ( 95 % CI ) 64–91 vs 49 , 95 % CI 32–66 ; P = .012 ] . In the multivariate regression analysis , TACE and sorafenib was found to be independently associated with a decreased risk of mortality ( HR 0.33 , 95 % CI 0.12–0.89 ; P = .015 ) . Multivariate stratified analyses verified this association in each patient subgroup ( all HR < 1.0 ) . Conclusion : With a high patient tolerance to an interrupted sorafenib dosing schedule , the combination of TACE with sorafenib was associated with improved overall survival in early – intermediate stage HCC when compared with treatment with TACE alone This r and omized , controlled trial assessed the efficacy of transarterial Lipiodol ( Lipiodol Ultrafluide , Laboratoire Guerbet , Aulnay-Sous-Bois , France ) chemoembolization in patients with unresectable hepatocellular carcinoma . From March 1996 to October 1997 , 80 out of 279 Asian patients with newly diagnosed unresectable hepatocellular carcinoma fulfilled the entry criteria and r and omly were assigned to treatment with chemoembolization using a variable dose of an emulsion of cisplatin in Lipiodol and gelatin-sponge particles injected through the hepatic artery ( chemoembolization group , 40 patients ) or symptomatic treatment ( control group , 40 patients ) . One patient assigned to the control group secondarily was excluded because of unrecognized systemic metastasis . Chemoembolization was repeated every 2 to 3 months unless there was evidence of contraindications or progressive disease . Survival was the main end point . The chemoembolization group received a total of 192 courses of chemoembolization with a median of 4.5 ( range , 1 - 15 ) courses per patient . Chemoembolization result ed in a marked tumor response , and the actuarial survival was significantly better in the chemoembolization group ( 1 year , 57 % ; 2 years , 31 % ; 3 years , 26 % ) than in the control group ( 1 year , 32 % ; 2 years , 11 % ; 3 years , 3 % ; P = .002 ) . When adjustments for baseline variables that were prognostic on univariate analysis were made with a multivariate Cox model , the survival benefit of chemoembolization remained significant ( relative risk of death , 0.49 ; 95 % CI , 0.29 - 0.81 ; P = .006 ) . Although death from liver failure was more frequent in patients who received chemoembolization , the liver functions of the survivors were not significantly different . In conclusion , in Asian patients with unresectable hepatocellular carcinoma , transarterial Lipiodol chemoembolization significantly improves survival and is an effective form of treatment 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 We prospect ively investigated the association between a change of serum vascular endothelial growth factor ( VEGF ) level after transcatheter arterial chemoembolization ( TACE ) and hepatocellular carcinoma ( HCC ) patient prognosis . The study involved 147 patients with unresectable HCC treated at the National Cancer Center , Korea , between July and December 2005 . Serum sample s were collected from each patient before TACE , and 1–2 days and 1 month after TACE . Serum VEGF concentrations were measured using an  enzyme‐linked immunosorbent assay ( ELISA )  . The loge(VEGF/platelets ) increased transiently 1–2 days after TACE and declined thereafter . Frequency of previous TACE did not correlate with loge(VEGF/platelets ) . This study found that loge(VEGF/platelets ) 1–2 days after TACE , but not loge(VEGF/platelets ) at baseline , was strongly correlated with vascular or nodal invasion and AJCC ( American Joint Committee on Cancer)/UICC ( International Union Against Cancer ) stage , and was significantly greater in men . Relative changes in serum VEGF/platelet levels 1–2 days after TACE ( ΔVEGF ) > 0.5 were directly correlated with tumor size , vascular invasion and modified UICC and AJCC/UICC stage ( P < 0.05 for each ) . Additionally , ΔVEGF > 0.5 was 
    Output:
    
Conclusions Combination therapy has significant advantages over TACE monotherapy in terms of improving TTP and OS