***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: PURPOSE This phase II study of sorafenib , an oral multikinase inhibitor that targets Raf kinase and receptor tyrosine kinases , assessed efficacy , toxicity , pharmacokinetics , and biomarkers in advanced hepatocellular carcinoma ( HCC ) patients . METHODS Patients with inoperable HCC , no prior systemic treatment , and Child-Pugh ( CP ) A or B , received continuous , oral sorafenib 400 mg bid in 4-week cycles . Tumor response was assessed every two cycles using modified WHO criteria . Sorafenib pharmacokinetics were measured in plasma sample s. Biomarker analysis included phosphorylated extracellular signal regulated kinase ( pERK ) in pretreatment biopsies ( immunohistochemistry ) and blood-cell RNA expression patterns in selected patients . RESULTS Of 137 patients treated ( male , 71 % ; median age , 69 years ) , 72 % had CP A , and 28 % had CP B. On the basis of independent assessment , three ( 2.2 % ) patients achieved a partial response , eight ( 5.8 % ) had a minor response , and 46 ( 33.6 % ) had stable disease for at least 16 weeks . Investigator-assessed median time to progression ( TTP ) was 4.2 months , and median overall survival was 9.2 months . Grade 3/4 drug-related toxicities included fatigue ( 9.5 % ) , diarrhea ( 8.0 % ) , and h and -foot skin reaction ( 5.1 % ) . There were no significant pharmacokinetic differences between CP A and B patients . Pretreatment tumor pERK levels correlated with TTP . A panel of 18 expressed genes was identified that distinguished " nonprogressors " from " progressors " with an estimated 100 % accuracy . CONCLUSION Although single-agent sorafenib has modest efficacy in HCC , the manageable toxicity and mechanisms of action support a role for combination regimens with other anticancer agents Background / Aims Transarterial chemoembolization ( TACE ) has long been used as a palliative therapy for unresectable hepatocellular carcinoma ( HCC ) .  High-dose hepatic arterial infusion chemotherapy ( HAIC ) has showed favorable outcomes in patients with intractable , advanced HCC . The aim of this study was to compare the effectiveness and safety of high-dose HAIC and conventional TACE using doxorubicin for advanced HCC . Methods The high-dose HAIC group comprised 36 patients who were enrolled prospect ively from six institutions . The enrollment criteria were good liver function , main portal vein invasion ( including vascular shunt ) , infiltrative type , bilobar involvement , and /or refractory to prior conventional treatment ( TACE , radiofrequency ablation , or percutaneous ethanol injection ) , and documented progressive disease . Patients received 5-fluorouracil ( 500 mg/m2 on days 1~3 ) and cisplatin ( 60 mg/m2 on day 2 every 4 weeks ) via an implantable port system . In the TACE group , 31 patients with characteristics similar to those in the high-dose HAIC group were recruited retrospectively from a single center . Patients underwent a transarterial infusion of doxorubicin every 4~8 weeks . Results Overall , 6 patients ( 8.9 % ) achieved a partial response and 20 patients ( 29.8 % ) had stable disease . The objective response rate ( complete response+partial response ) was significantly better in the high-dose HAIC group than in the TACE group ( 16.7 % vs. 0 % , P=0.030 ) . Overall survival was longer in the high-dose HAIC group than in the TACE group ( median survival , 193 vs. 119 days ; P=0.026 ) . There were no serious adverse effects in the high-dose HAIC group , while hepatic complications occurred more often in the TACE group . Conclusions High-dose HAIC appears to improve the tumor response and survival outcome compared to conventional TACE using doxorubicin in patients with intractable , advanced HCC 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 PURPOSE Despite the absence of conclusive data , portal vein ( PV ) thrombosis is considered a contraindication to transarterial chemoembolization ( TACE ) in patients with unresectable hepatocellular carcinoma ( HCC ) . The purpose of our study was to establish the safety of TACE in such patients and identify key prognostic factors and survival . MATERIAL S AND METHODS Data were prospect ively collected from 32 consecutive patients with unresectable HCC and PV thrombosis who underwent treatment with TACE .  History and physical examination , relevant laboratory values , and contrast material -enhanced magnetic resonance ( MR ) images were obtained before each TACE procedure . Repeated TACE was performed every 6 weeks unless patients developed a contraindication or MR imaging showed complete response . RESULTS Median overall survival was 9.5 months ( range , 3 - 50 months ) . Child-Pugh numerical disease stage was the prognostic factor most strongly related to survival . The 30-day mortality rate was zero and there was no evidence of TACE-related hepatic infa rct ion or acute liver failure . The 6- , 9- , 12- , and 18-month survival rates were 60 % , 47 % , 25 % , and 12.5 % , respectively . CONCLUSIONS PV thrombosis should not be considered a contraindication to TACE . Compared with historical control subjects who received traditional forms of treatment , the patients in the present study had extended survival . However , prospect i ve r and omized trials are necessary to show this conclusively and to show which subgroups benefit Transcatheter arterial chemoembolization ( TACE ) has been contraindicated for the treatment of patients with hepatocellular carcinoma ( HCC ) and main portal vein ( MPV ) obstruction because of the potential risk of hepatic insufficiency result ing from ischemia after TACE . The current controlled study was undertaken to assess the safety , efficacy , and predictive factors of favorable response to TACE in patients with HCC and MPV obstruction with good hepatic function and adequate collateral circulation around the MPV Background For patients with hepatocellular carcinoma ( HCC ) with portal vein tumor thrombosis ( PVTT ) , the survival benefit of transarterial chemoembolization ( TACE ) compared with conservative treatment largely remains controversial . The objective of this study was to determine whether TACE confers a survival benefit to patients with HCC and PVTT , and to uncover prognostic factors . Methods Between July 2007 and July 2009 , a prospect i ve two-arm nonr and omized study was performed on consecutive patients with unresectable HCC with PVTT . In one arm , patients were treated by TACE using an emulsion of lipiodol and anticancer agents ± gelatin sponge embolization . In another arm , patients received conservative treatment . Results A total of 164 patients were recruited for the study  ( TACE group , n = 84 ; conservative treatment group , n = 80 ) . Patients in the TACE group received a mean of 1.9 ( range , 1–5 ) TACE sessions . The overall median survival for all patients was 5.2 months , and the 12- and 24-month overall survival rates were 18.3 % and 5.6 % , respectively . The 12- and 24-month overall survival rates for the TACE and conservative groups were 30.9 % , 9.2 % , and 3.8 % , 0 % , respectively . The TACE group had significantly better survivals than the conservative group ( P < 0.001 ) . On subgroup analysis of segmental and major PVTT , the TACE group also had significantly better survivals ( P = 0.002 , P = 0.002 ) . The treatment type , PVTT extent , tumor size , and serum bilirubin were independent prognostic factors of survival on multivariate analysis . Conclusions TACE was safe and feasible in selected HCC patients with PVTT and it had survival benefit over conservative treatment The classifications of hepatocellular carcinoma ( HCC ) currently used are based on prognostic factors obtained from studies performed years ago when most tumors were diagnosed at advanced stages and the survival rates were substantially poor . Recent investigations have review ed the survival of early tumors properly selected to receive radical therapies and the natural outcome of nonsurgical HCC patients . These data enable a new staging system to be proposed , the Barcelona Clinic Liver Cancer ( BCLC ) staging classification , that comprises four stages that select the best c and i date s for the best therapies currently available . Early stage ( A ) includes patients with asymptomatic early tumors suitable for radical therapies -- resection , transplantation or percutaneous treatments . Intermediate stage ( B ) comprises patients with asymptomatic multinodular HCC . Advanced stage ( C ) includes patients with symptomatic tumors and /or an invasive tumoral pattern ( vascular invasion/extrahepatic spread ) . Stage B and C patients may receive palliative treatments/new agents in the setting of phase II investigations or r and omized controlled trials . End-stage disease ( D ) contain patients with extremely grim prognosis ( Okuda stage III or PST 3 - 4 ) that should merely receive symptomatic treatment BACKGROUND No effective systemic therapy exists for patients with advanced hepatocellular carcinoma . A preliminary study suggested that sorafenib , an oral multikinase inhibitor of the vascular endothelial growth factor receptor , the platelet-derived growth factor receptor , and Raf may be effective in hepatocellular carcinoma . METHODS In this multicenter , phase 3 , double-blind , placebo-controlled trial , we r and omly assigned 602 patients with advanced hepatocellular carcinoma who had not received previous systemic treatment to receive either sorafenib ( at a dose of 400 mg twice daily ) or placebo . Primary outcomes were overall survival and the time to symptomatic progression . Secondary outcomes included the time to radiologic progression and safety . RESULTS At the second planned interim analysis , 321 deaths had occurred , and the study was stopped . Median overall survival was 10.7 months in the sorafenib group and 7.9 months in the placebo group ( hazard ratio in the sorafenib group , 0.69 ; 95 % confidence interval , 0.55 to 0.87 ; P<0.001 ) . There was no significant difference between the two groups in the median time to symptomatic progression ( 4.1 months vs. 4.9 months , respectively , P=0.77 ) . The median time to radiologic progression was 5.5 months in the sorafenib group and 2.8 months in the placebo group ( P<0.001 ) . Seven patients in the sorafenib group ( 2 % ) and two patients in the placebo group ( 1 % ) had a partial response ; no patients had a complete response . Diarrhea , weight loss , h and -foot skin reaction , and hypophosphatemia were more frequent in the sorafenib group . CONCLUSIONS In patients with advanced hepatocellular carcinoma  , median survival and the time to radiologic progression were nearly 3 months longer for patients treated with sorafenib than for those given placebo . ( Clinical Trials.gov number , NCT00105443 . BACKGROUND Most cases of hepatocellular carcinoma occur in the Asia-Pacific region , where chronic hepatitis B infection is an important aetiological factor . 
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CONCLUSION TACE can be safely performed in advanced HCC patients with vascular invasion or extrahepatic spread and may improve their overall survival .
Patients with portal vein branch invasion and well-preserved liver function seemed to derive optimal benefit from treatment with TACE .