You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
hcc is a frequent cancer that is among the leading causes of cancer deaths   worldwide .
most cases are associated with an underlying liver disease , usually liver cirrhosis , and hcc is the leading cause of death among cirrhotic patients .
the treatment of hcc is based on various classification systems . in europe and in the us ,
the most commonly used staging system is the bclc allocation system , which links prognostic factors , stages ( 4 stages ) and therapeutic proposal . in the staging system ,
the intermediate stage is defined by large , unresectable or multinodular hcc in patients with excellent performance status ( ps 0 ) with child - pugh a or b liver cirrhosis . for these patients ,
tace was recommended for these patients after two positive , randomized controlled trials were reported which used either doxorubicin   or cisplatin   as the chemotherapeutic agent .
additionally , a meta - analysis   demonstrated an improvement in patients ' median overall survival from 16 months , with best supportive care alone , to 20 months after tace .
however , these studies suffered from a lack of standardization   in patient selection , chemotherapeutic agents used , retreatment schedule , discontinuing rules and the skill of the interventional radiologists . in europe , tace is usually restricted to intermediate stage patients , excluding those with decompensated cirrhosis ( stage b8 and over ) , extensive tumor , renal insufficiency , large tumor size ( > 10 cm ) , comorbidities and portal vein thrombosis . in a randomized phase
ii trial , a novel drug delivery system ( drug eluding beads ) loaded with doxorubicin was shown to have similar efficacy , but was better tolerated than conventional tace . moreover
, this technique seems reproducible and has been used with increasingly promising results , particularly in patients with minor tumor burden and well - compensated liver cirrhosis .
furthermore , the discontinuing rules are even less clear , and limited data are available on this subject , mainly because there are no well defined criteria for tace failure and refractoriness . taking into account the possible risks and the limited survival benefit of tace , physicians have to avoid adverse effects that will outweigh the survival benefit , and determine when continuing treatment is an ineffective therapeutic option .
moreover , studies that have demonstrated the efficacy of sorafenib   have shown that contraindications to or the discontinuing of tace is not associated with the end of treatment , because sorafenib has been demonstrated to be as efficient in patients after tace failure ; this concept of treatment stage migration   has led to sorafenib being offered to bclc stage b patients who have failed to respond to tace , or who have progressed after tace .
this paper will focus on the definition of tace failure or refractoriness from a european perspective .
the difference between failure and refractoriness is subtle , as both will lead to considerations that tace is not useful .
accordingly , we will consider a failure as a worsening of either the tumor size or liver function or performance status , and refractoriness as a lack of efficacy of the treatment .
in the study from lo et al . , tace was repeated every 2 to 3 months and was discontinued in cases of poor hepatic function , severe adverse effects , or progressive disease .
poor hepatic function was defined as the following : hepatic encephalopathy , ascites not controlled by diuretics , variceal bleeding , serum bilirubin over 50 mol / l , serum albumin level below 28
g / l or a prothrombin time of more than 4 seconds over the control .
the definition of progression was based on computer tomography ( ct ) scans of tumor size and an increase in the serum -fetoprotein levels by more than 25% . in this series ,
the reasons for discontinuation were as follows : progressive disease in 12 , death in 7 , poor liver function in 6 , adverse events in 6 , patient refusal in 3 , arteriovenous shunting in 2 , and hepatic artery thrombosis in 2 patients .
the 2-year overall survival was only 11% in the control group but was 31% in the tace group . in a multivariate analysis , only two factors were of prognostic value , namely the treatment group and the presence of a unilobar portal vein obstruction .
specifically , the 2-year overall survival was 27% in the absence of portal vein obstruction , but 5% in its presence . in the trial reported by llovet et al ,
tace was performed at baseline , 2 months , and 6 months followed by every 6 months thereafter .
treatment was discontinued at the patient 's request or if any of the following exclusion criteria developed : child - pugh c , active gastrointestinal bleeding , encephalopathy , refractory ascites , and the presence of vascular invasion , including segmental portal obstruction .
progressive disease led to the discontinuation of tace in cases of vascular invasion or extrahepatic spread .
the reasons for treatment discontinuation in the tace group were as follows : 9 cases of tumor progression ( including worsening of performance status ) , 8 cases of technical problems , 4 severe adverse events , 4 patient 's decision , 4 deaths and 2 cases of liver failure without progression .
the 2-year overall survival was 63% in the tace group and 27% in the control group , respectively .
tace is a loco - regional treatment , and some usual oncologic parameters , such as time to progression , are not valid , as local tumor progression can sometimes benefit from new tace sessions .
in contrast , major local progression , but also hepatic responses or stabilizations associated with portal vein invasion or extrahepatic progression , will not benefit from tace , but will require systemic treatment . according to bruix
,   untreatable tumor progression includes massive liver involvement , extrahepatic spread and vascular invasion as well as minor hepatic progression , if associated with impaired liver function or performance status .
it is obvious that extrahepatic metastases can develop despite tace efficacy with eventual complete response .
even though such cases are infrequent , they must be considered as tace failure because the disease itself was not fully controlled .
the toxicity and efficacy of retreatment with tace are related to tumor and liver parameters .
conducted a multivariate analysis , and found three prognostic factors namely an increase in aspartate transaminase ( ast ) level by more than 25% , an increase in the child - pugh score and the absence of tumor response , which were used to develop the art score , which calculates the prognosis if a second tace is given . in their series , patients with an art score of 0 - 1.5 points benefitted from a second tace session , while those with a score  2.5 did not benefit , respectively .
next , the authors proposed to combine the art score with a previous algorithm to better define patients who would benefit from the continuation of tace , and those who would require switching to another therapeutic option .
more recently , they demonstrated that the art score was also of value for deciding the potential benefit of undergoing a third tace .
for some authors , the art score is not considered as a universal point scoring system , particularly in japan , where tace is given to patients with a lower tumor burden than in austria or in france , and of whom the majority have hepatitis c virus - induced liver diseases .
if one considers tace to be a palliative treatment , the stabilization of disease can be considered a positive outcome .
in contrast , if tace is considered , in some instances , as a potential cure , stable disease would be considered a negative outcome , and it could be viewed that the disease is refractory to tace .
these two options are discussed in two different algorithms . for raoul et al . , stable disease after two tace sessions is considered as sufficient to propose a  wait - and - see policy  ; that is , patients will be followed - up closely to re - tace them if there is progression .
consider the absence of tumor response as tace refractoriness , and these patients will be treated by other means .
candidates for tace include bclc stage b patients with good performance status , child - pugh a or b7 liver cirrhosis , without extra hepatic spread or portal vein invasion ( including segmental thrombosis ) , with mild or low tumor burden .
after the first tace , in cases of severe adverse events or liver deterioration ( child - pugh score ) , the tace program is stopped and sorafenib is offered to these patients .
a contrast - enhanced ct scan or magnetic resonance imaging ( mri ) is performed 4 to 6 weeks after this first tace . in cases of progression
, tace has to be stopped , and sorafenib is considered the best option . in cases of stability or
response some days prior to the planned second tace , the art score will be calculated . in cases of high scores (  2.5 ) , it seems prudent to stop tace and switch to systemic treatments . if not , a second tace will be given , which will be followed 4 to 6 weeks later by a contrast enhanced ct or mri . in cases of controlled disease ( response or stable disease ) ,
a wait - and - see policy will be applied with a regular follow - up ( every 2 to 3 months ) .
if the tumor progresses , a third tace can be given , if the art score remains low .
if after the second tace there is evidence of untreatable tumor progression , including extrahepatic spread , portal vein thrombosis and the growth of the previously tace - treated lesion , sorafenib will be given . in cases of progression outside of the pre - treated field , a third tace can be given if indicated by the art score .
in conclusion , the definition of tace failure or refractoriness is very much dependent on the indications of tace .
in contrast to japan , in western countries , the diagnosis is frequently made at 
the goal of tace is usually to control the disease for several more months , and severe toxicity or minor progression usually leads to switching to another treatment , to avoid worsening of liver function and poorer outcome .
there is certainly room for improvement with the art score , but it can certainly be useful in such patients . in patients with very localized tumors treated with supra - selective tace and those with well - compensated cirrhosis , one single session can be very effective and can control the disease for months or years . in such cases , retreatment is certainly the best way to control the tumor for a prolonged period , but these patients are certainly more frequent in japan than in europe .
in europe , trans - arterial chemoembolization ( tace ) is usually given to patients with barcelona clinic liver cancer ( bclc )  intermediate stage  
 hepatocellular carcinoma ( hcc ) , and is associated with a modest improvement in median overall survival . in the two positive randomized trials that have been reported , 
 tace was stopped in cases of severe toxicity , worsening of liver cirrhosis or performance status and tumor progression , including local progression , extrahepatic spread and portal vein thrombosis . the necessity to stop tace leads to the concept of untreatable progression , which is characterized by massive liver involvement , extrahepatic spread , vascular invasion , impaired liver function or performance status . 
 more recently , the assessment for re - treatment with tace ( art ) score has been developed to determine which patients will not benefit from a second or a third tace therapy . 
 herein , we propose an algorithm that summarizes our experience with tace .