***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: 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 Purpose The purpose of this study was to report toxicity and long-term survival outcomes of 2 prospect i ve trials evaluating mitomycin C ( MMC ) with 5-fluorouracil – based adjuvant chemoradiation in resected periampullary adenocarcinoma . Methods and material s From 1996 to 2002 , 119 patients received an adjuvant 4-drug chemotherapy regimen of 5-fluorouracil , leucovorin , MMC , and dipyridamole with chemoradiation on 2 consecutive trials ( trials A and B ) . Trial A patients received upfront chemoradiation ( 50 Gy split-course , 2.5 Gy/fraction ) followed by 4 cycles of the 4-drug chemotherapy with bolus 5-fluorouracil . Trial B patients received 1 cycle of the 4-drug chemotherapy with continuous infusion 5-fluorouracil followed by continuous chemoradiation ( 45 - 54 Gy , 1.8 Gy/fraction ) and 2 additional cycles of chemotherapy . Cox proportional hazards models were performed to identify prognostic factors for overall survival ( OS ) . Results Of the 62 trial A patients , 61 % had pancreatic and 39 % nonpancreatic periampullary carcinomas . Trial B ( n = 57 ) consisted of 68 % pancreatic and 32 % nonpancreatic periampullary carcinomas .  Resection margin and lymph node status were similar for both trials . Median follow-up was longer for trial A than trial B ( 197.5 vs 107.0 months ) , with median OS of 32.2 and 24.2 months , respectively . Rates of 3- , 5- , and 10-year OS were 48 % , 31 % , and 26 % in trial A and 32 % , 23 % , and 9 % in trial B. On multivariate analysis , lymph node – positive resection was the strongest prognostic factor for OS . A pancreatic primary and positive margin status were also associated with inferior survival ( P < .05 ) . Rates of grade ≥3 treatment-related toxicity in trials A and B were 2 % and 7 % , respectively . Conclusions This is the first study to report long-term outcomes of MMC with 5-fluorouracil – based adjuvant chemoradiation in periampullary cancers . Because MMC may be considered in DNA repair-deficient carcinomas , r and omized trials are needed to determine the true benefit of adjuvant MMC 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 Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more 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 , 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 This article introduces the approach of GRADE to rating  quality of evidence .  GRADE specifies four categories-high , moderate , low , and very low-that are applied to a body of evidence , not to individual studies . In the context of a systematic review , quality reflects our confidence that the estimates of the effect are correct . In the context of recommendations , quality reflects our confidence that the effect estimates are adequate to support a particular recommendation . R and omized trials begin as high- quality evidence , observational studies as low quality . " Quality " as used in GRADE means more than risk of bias and so may also be compromised by imprecision , inconsistency , indirectness of study results , and publication bias . In addition , several factors can increase our confidence in an estimate of effect . GRADE provides a systematic approach for considering and reporting each of these factors . GRADE separates the process of assessing quality of evidence from the process of making recommendations . Judgments about the strength of a recommendation depend on more than just the quality of evidence 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 Background / Aim : We evaluated the relationship of hepatic function with repeated transarterial catheter chemoembolization ( TACE ) and prognosis after sorafenib treatment in various patient cohorts . Methods : Study 1 comprised of 212 Barcelona clinic liver cancer stage-B ( BCLC-B ) HCC patients classified as Child-Pugh A ( CP-A ) and who had received repeated TACE treatments ( r-TACE ) ( naïve : recurrence = 66:146 ) . Study 2 comprised of 435 patients with unresectable HCC classified as CP-A in who sorafenib was introduced ( naïve : recurrence = 37:398 ; CP score 5:6 = 282:153 ; macro-vessel invasion [MVI]+ : extrahepatic metastasis [EHM]+ both negative = 124:226:143 ) .  Changes in hepatic function along with CP and albumin-bilirubin ( ALBI ) score/ grade during r-TACE in Study 1 , and prognosis after introducing sorafenib in Study 2 were evaluated . Results : Hepatic function worsened to CP-B in 9 - 14 % with each TACE procedure , while 18 - 21 % had a change of classification from ALBI-1 to ALBI-2 . When the prognosis of patients with the best CP score of 5 was analyzed , those with ALBI-1 ( n = 154 ) had a better outcome than those with ALBI-2 ( n = 128 ) ( MST 17.5 vs. 9.9 months ; p = 0.01 ) , while ALBI-1 ( n = 43 ) patients also showed a better outcome than ALBI-2 ( n = 34 ) patients with a CP score of 5 without M 
    Output:
    
The safety of MMC and 5‐Fu were suboptimal , and Adriamycin and HCPT were safer than Platinum .
The TACE(HCPT+THP ) + Sorafenib and TACE ( HCPT+EPI ) + Sorafenib arms had significantly different efficacy rates .
For efficacy outcomes , subgroups which included 5‐fluorouracil and hydroxycamptothecin ranked higher than other chemotherapy agents , while mitomycin C ranked the lowest .
In conclusion , for patients with advanced HCC , combination therapy with HCPT plus THP/EPI in TACE and Sorfenib may be used as a first‐line treatment