***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 
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    Input: 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 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 Until now , no effective systemic treatment options have been available for patients with unresectable advanced hepatocellular carcinoma ( HCC ) . In the Sorafenib Hepatocellular Carcinoma Assessment R and omized Protocol ( SHARP ) , patients with unresectable advanced HCC with Child – Pugh liver function class A and who had not received prior systemic therapy , received either oral sorafenib ( 400 mg twice daily ) or placebo until radiological and symptomatic progression . The two groups of patients were well balanced with respect to baseline characteristics . The study was stopped at the second planned interim analysis because of an advantage in the median overall survival ( 10.7 vs 7.9 months ; hazard ratio : 0.69 ; 95 % CI : 0.55–0.87 ; p < 0.001 ) and the median time to radiological progression ( 5.5 vs 2.8 months ; p < 0.001 ) in the sorafenib arm . However , sorafenib was not able to increase the time to symptomatic progression . In terms of toxicity , there were more cases of diarrhea , weight loss , h and –foot skin reaction and hypophosphatemia among the patients receiving sorafenib , the majority of which were of grade 1 or 2 severity . The SHARP trial has demonstrated that sorafenib is effective in prolonging median survival and time-to-progression in patients with advanced HCC and that it is generally well tolerated with a manageable adverse events profile BACKGROUND Assessment of the change in tumour burden is an important feature of the clinical evaluation of cancer therapeutics : both tumour shrinkage ( objective response ) and disease progression are useful endpoints in clinical trials . Since RECIST was published in 2000 , many investigators , cooperative groups , industry and government authorities have adopted these criteria in the assessment of treatment outcomes . However , a number of questions and issues have arisen which have led to the development of a revised RECIST guideline ( version 1.1 ) . Evidence for changes , summarised in separate papers in this special issue , has come from assessment of a large data warehouse ( > 6500 patients ) , simulation studies and literature review s. HIGHLIGHTS OF REVISED RECIST 1.1 : Major changes include : Number of lesions to be assessed : based on evidence from numerous trial data bases merged into a data warehouse for analysis purpose s , the number of lesions required to assess tumour burden for response determination has been reduced from a maximum of 10 to a maximum of five total ( and from five to two per organ , maximum ) . Assessment of pathological lymph nodes is now incorporated : nodes with a short axis of 15 mm are considered measurable and assessable as target lesions . The short axis measurement should be included in the sum of lesions in calculation of tumour response . Nodes that shrink to < 10 mm short axis are considered normal . Confirmation of response is required for trials with response primary endpoint but is no longer required in r and omised studies since the control arm serves as appropriate means of interpretation of data . Disease progression is clarified in several aspects : in addition to the previous definition of progression in target disease of 20 % increase in sum , a 5 mm absolute increase is now required as well to guard against over calling PD when the total sum is very small . Furthermore , there is guidance offered on what constitutes ' unequivocal progression ' of non-measurable/non-target disease , a source of confusion in the original RECIST guideline . Finally , a section on detection of new lesions , including the interpretation of FDG-PET scan assessment is included . Imaging guidance : the revised RECIST includes a new imaging appendix with up date d recommendations on the optimal anatomical assessment of lesions . FUTURE WORK A key question considered by the RECIST Working Group in developing RECIST 1.1 was whether it was appropriate to move from anatomic unidimensional assessment of tumour burden to either volumetric anatomical assessment or to functional assessment with PET or MRI . It was concluded that , at present , there is not sufficient st and ardisation or evidence to ab and on anatomical assessment of tumour burden . The only exception to this is in the use of FDG-PET imaging as an adjunct to determination of progression . As is detailed in the final paper in this special issue , the use of these promising newer approaches requires appropriate clinical validation studies 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 Disease progression of hepatocellular cancer ( HCC ) in patients eligible for liver transplantation ( LTx ) occurs in up to 50 % of patients , result ing in withdrawal from the LTx waiting list . Transarterial chemoembolization ( TACE ) is used as bridging therapy with highly variable response rates . The oral multikinase inhibitor sorafenib significantly increases overall survival and time-to-progression in patients with advanced hepatocellular cancer . Design The HeiLivCa study is a double-blinded , controlled , prospect i ve , r and omized multi-centre phase III trial . Patients in study arm A will be treated with transarterial chemoembolization plus sorafenib 400 mg bid . Patients in study arm B will be treated with transarterial chemoembolization plus placebo .  A total of 208 patients with histologically confirmed hepatocellular carcinoma or HCC diagnosed according to EASL criteria will be enrolled . An interim patients ' analysis will be performed after 60 events . Evaluation of time-to-progression as primary endpoint ( TTP ) will be performed at 120 events . Secondary endpoints are number of patients reaching LTx , disease control rates , OS , progression free survival , quality of live , toxicity and safety . Discussion As TACE is the most widely used primary treatment of HCC before LTx and sorafenib is the only proven effective systemic treatment for advanced HCC there is a strong rational to combine both treatment modalities . This study is design ed to reveal potential superiority of the combined TACE plus sorafenib treatment over TACE alone and explore a new neo-adjuvant treatment concept in HCC before LTx LBA154^ Background : The global SPACE trial was conducted to evaluate the efficacy and safety of S in combination with TACE with DEBDOX in patients ( pts ) with intermediate-stage HCC ( BCLC B ) . METHODS Pts were eligible if they had asymptomatic , unresectable , multinodular tumors without vascular invasion ( VI ) or extrahepatic spread ( EHS ) ; Child-Pugh A liver functional status ; and ECOG PS 0 . Pts were r and omized to receive S 400 mg bid or matching P continuously ( 1 cycle = 4 wks ) until progression . All pts received TACE with DEBDOX ( 150 mg doxorubicin ; Biocompatibles UK Ltd ) 3 - 7d after first dose of study drug , and then on d1 ( ±4d ) of months 3 , 7 , and 13 , and q6 months thereafter . The primary endpoint was time to radiologic progression ( TTP ) by independent review ( predefined alpha = 0.15 ) . Secondary endpoints were overall survival ( OS ) , time to VI/EHS , time to untreatable progression ( TTUP ) , and safety . RESULTS Of 452 pts screened , 307 were r and omized to S ( n=154 ) or P ( n=153 ) . The HR for TTP was 0.797 ( 
    Output:
    
Conclusion Combination of sorafenib and TACE showed survival and clinical benefits  in patients with HCC , though enhanced morbidity