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Giovanis et al. Hepatoma Res 2018;4:10 I http://dx.doi.org/10.20517/2394-5079.2018.21 Page 3 of 13

Table 1. Patient unsuitable for TACE or with absolute contraindications to cTACE according to ESMO 2012 guidelines
Exclusion criteria for cTACE
Decompensated cirrhosis (Child-Pugh B ≥ 8), including:
-Jaundice
-Clinical encephalopathy
-Refractory ascites
Extensive tumour with massive replacement of both entire lobes
Severely reduced portal vein flow (e.g., portal vein occlusion or hepatofugal blood flow)
Technical contraindications to hepatic intra-arterial treatment (e.g., untreatable arteriovenous fistula)
Bilio-enteric anastamosis or biliary stents
Renal insufficiency (creatinine clearance < 30 mL/min)

cTACE: conventional transarterial chemoembolization; ESMO: European Society of Medical Oncology

Table 2. When to stop TACE? Definition of TACE failure/refractorines
Authors Criteria for definition of TACE failure/refractorines
Kudo et al. [62] Intrahepatic lesion (> 2 consecutive incomplete necrosis; > 2 consecutive appearances of a new lesion recurrence)
Appearances of vascular invasion
Appearance of EHS
Continuous elevation of tumor markers
Yamanaka et al. [63] TACE failure
Inability to select the feeding artery of the HCC because of arterial devastation; deterioration of liver function and/or
tumor thrombosis of the portal vein
TACE refractory
Repetitive tumor recurrence in the liver; appearance of vascular invasion; appearance of distant metastasis; continuous
increase in tumor marker levels after TACE
AISF et al. [64] The AISF expert panel considers failure of TACE the lack of objective response of the treated lesions after two procedures
(consider also a multi-disciplinary decisional setting)
Sieghart et al. [21] ART score
TACE: transhepatic arterial chemoembolization; ART: assessment for retreatment with TACE

be considered a curative therapy [16-18] . This loco-regional treatment may not represent the only therapeutic
option for this stage of patients because authors reported that TACE can deal good results in center
with good experience after a careful selection of patients, but may also present technical difficulties and
[19]
contraindication . Table 1 shows the main patients characteristics in which TACE is contraindicated,
absolute and relative contraindications generally include features of decompensated liver disease, extensive
bilobular tumor load and impaired integrity of the portal vein due to thrombosis or hepatofugal flow, as well
as untreated large varices, massive tumor diameter, and severe co-morbidities.

A point of discussion is when to establish TACE failure/refractoriness and, consequently, patient should be
switched to a different therapy. The lack of a clear definition of the right moment to stop the re-treatments
with TACE due to failure or refractoriness may lead to unnecessary overtreatment with TACE that may
[20]
worsen the liver function, precluding the opportunity to shift the patient to systemic treatments . Table 2
summarizes the criteria identified to define the failure of TACE by experts and guidelines. The assessment
for retreatment with TACE (ART) score is a simple validated algorithm useful for deciding the potential
benefit of undergoing a third TACE evaluating three prognostic factors: the increase in aspartate transaminase
(AST) level by more than 25%, the increase in the Child-Pugh score and the absence of tumor response.
TACE has a good prognostic effect on patients with ART score of 0-1.5, while patients with ART score ≥ 2.5
might have minor or even no prognostic benefits [21,22] .

Similarly, to TACE, the effectiveness of the intra-hepatic radioembolization (TARE) using microspheres
[23]
loaded with yttrium-90, may depend on the operator’s manual skills . Table 3 reports levels of evidence
associated to TARE by the principal international guidelines and recommendations; the use of TARE
in HCC is supported by data based on retrospective series and uncontrolled prospective studies. Two
randomized studies (SARAH and SIRVENIB), designed to show the superiority of TARE versus sorafenib,