Cardiovasc Intervent Radiol (2021) 44:1851–1867

https://doi.org/10.1007/s00270-021-02968-1

CIRSE STANDARDS OF PRACTICE

CIRSE Standards of Practice on Hepatic Transarterial

Chemoembolisation
Pierleone Lucatelli1 • Marta Burrel2 • Boris Guiu3 • Gianluca de Rubeis1,4 •

Otto van Delden5 • Thomas Helmberger6

Received: 2 January 2021 / Accepted: 4 September 2021 / Published online: 25 October 2021
 Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe
(CIRSE) 2021

Abstract This CIRSE Standards of Practice document is c-TACE Conventional transarterial

aimed at interventional radiologists and provides best chemoembolisation
practices for performing transarterial chemoembolisation. DEM-TACE Drug-eluting microsphere
It has been developed by an expert writing group under the transarterial chemoembolisation
guidance of the CIRSE Standards of Practice Commit- DSM-TACE Degradable starch microsphere
tee. It will encompass all technical details reflecting transarterial chemoembolisation
European practice of different TACE procedures (Lp- b-TACE Balloon-occluded transarterial
TACE, DEM-TACE, DSM-TACE, b-TACE) as well as chemoembolisation
revising the existing literature on the various clinical HCC Hepatocellular carcinoma
indications (HCC, mCRC, ICC, NET). Finally, new fron- ICC Intrahepatic cholangiocarcinoma
tiers of development will also be discussed. m-CRC Metastatic colorectal cancer
NET Neuroendocrine tumour
Keywords TACE
Standards of practice
HCC
MDCT Multidetector computed tomography
mCRC
ICC
NET MRI Magnetic resonance imaging
TIPS Transjugular portosystemic shunt
Abbreviations and Definitions BCLC Barcelona Clinic Liver Cancer
SOP Standards of practice ECOG Eastern Cooperative Oncology
Group
AST Aspartate transaminase
& Pierleone Lucatelli ALT Alanina transaminase
[email protected] cGT Gamma-glutamyltransferase
1
AFP Alfa-fetoprotein
Vascular and Interventional Radiology Unit, Department of
Radiological Oncological and Anatomo-Pathological
CBCT Cone beam computed tomography
Sciences, Sapienza University of Rome, Rome, Italy TARE Transarterial radioembolisation
2
Radiology Department, Hospital Clı́nic of Barcelona,
Transarterial Blockade of tumorous arterial flow
Barcelona, Spain chemoembolisation through embolic material which
3
Department of Radiology, Montpellier School of Medicine,
carried chemotherapeutic drugs.
St-Eloi University Hospital, Montpellier, France Conventional Performed with an emulsion of
4
Department of Diagnostic Radiology, Azienda Ospedaliera
TACE lipiodol (oil) and chemotherapeutic
San Camillo Forlanini, Rome, Italy drugs, then followed by the
5 administration of an embolic agent.
Department of Interventional Radiology, Amsterdam
University Medical Centers, Amsterdam, The Netherlands Drug-eluting Performed with permanent
6 microsphere microspheres loaded with
Institute for Diagnostic and Interventional Radiology and
Neuroradiology, Bogenhausen Hospital, Munich, Germany TACE chemotherapeutic drugs.

123
1852 P. Lucatelli et al: CIRSE Standards of Practice on Hepatic Transarterial Chemoembolisation

Degradable starch Performed with a resorbable carrier eluting microspheres (DEM). This device is capable of
microsphere TACE mixed with chemotherapeutic drugs. slowly releasing the loaded drug to the liver. DEM showed
Balloon-occluded Performed with a balloon a better safety profile with lower systemic drug-related
microcatheter microcatheter inflated prior toxicity, although without significant added value on local
TACE embolisation in combination with tumour control over cTACE [9]. Moreover, in recent years
either lipiodol or microspheres the use of a degradable embolic/carrier material (Degrad-
mixed with chemotherapeutic drugs. able Starch Microsphere or DSMTACE) has been proposed
for selected advanced HCC patients [10–12] intrahepatic
cholangiocarcinoma (ICC) [13] and metastases from col-
orectal cancer (mCRC) [14]. With regards to microcatheter
Introduction selection, in 2013, Irie et al. [15] developed the concept of
balloon-occluded TACE (b-TACE), a modified procedure,
The CIRSE Standards of Practice Committee established in which a balloon microcatheter is inflated within the
an expert writing group, which was tasked with updating arterial feeder(s) permitting pressure-driven embolisation.
the previous CIRSE Standards of Practice (SOP) document Nowadays, indications for TACE include primary and
on performing transarterial chemoembolisation (TACE) by secondary liver tumours, including HCC, ICC, mCRC and
Basile et al. [1]. CIRSE Standards of Practice documents metastases from neuroendocrine tumours (NET) [16, 17].
are not clinical practice guidelines or systematic reviews of HCC and ICC account for 9.1% of all cancer deaths
the literature. This SOP document is not intended to worldwide [16]. Half of all patients with CRC develop liver
impose a standard of clinical patient care but recommends metastases during the course of the disease [16]. The liver
a reasonable approach to best practices for performing is also the most common site of metastases from NET [18].
TACE. Considering the plethora of technical variations cur-
rently available, the aim of this document is to provide an
update on all techniques and new developments.
Methods

The writing group was established by the CIRSE Standards Patient Preparation
of Practice Committee, comprising members with inter-
nationally recognised expertise in TACE. A systematic Pre-Treatment Imaging
literature search was carried out using PUBMED and
EMBASE to identify relevant publications in English from According to international guidelines, multidetector com-
2012 to 2020. Recommendations were then formulated puted tomography (MDCT)/magnetic resonance imaging
through consensus. (MRI) is capable of establishing the diagnosis of HCC in
cirrhotic patients in lesions greater than 10 mm [19]. In
most other tumours (mCRC, ICC, NET), confirmatory
Background biopsy is usually preferred before planning a TACE ses-
sion. In addition, due to the increased use of precision
The history of TACE dates back to the late 1970s, with the medicine, evidence in favour of biopsy of suspected HCC
first evidence for TACE being published by Yamada et al. is accumulating [20].
in 1979 [2–4]. However, after forty years there is no At least one dynamic contrast-enhanced imaging tech-
standard technique regarding all aspects of the procedure nique (MDCT or MRI) should be performed prior to
including drugs, embolic materials, and microcatheter TACE, preferably within one month before the procedure.
selection, as demonstrated by a recently published inter- Several factors should be assessed: vascular anatomy,
national survey [5, 6]. In the treatment of hepatocellular size and number of liver tumour(s), extrahepatic spread and
carcinoma (HCC), doxorubicin is the most commonly used presence of absolute and/or relative contraindications for
chemotherapeutic agent, although several other drugs are TACE [1, 21, 22].
also used, including epirubicin, cisplatin, mitomycin C, and Vascular anatomy is best shown on MDCT imaging [23]
5-fluorouracil [7]. Concerning the embolic material, TACE and is not limited to identification of the anatomic variants
has classically been performed with an emulsion of lipiodol of the hepatic vasculature but also includes identification of
and chemotherapeutic drugs followed by gelfoam (con- parasitic tumour feeders. This is crucial for determining the
ventional TACE or cTACE [1]). In 2006, Hong et al. [8] appropriate catheter selection and deciding on treatment
were the first to report a new drug-delivery system: drug- plans.

123
P. Lucatelli et al: CIRSE Standards of Practice on Hepatic Transarterial Chemoembolisation 1853

With regards to tumour spread: size, numbers of lesions coagulopathy, severe renal insufficiency or severe reaction
(single vs multifocal; uni-lobar vs bilobar) and percentage to contrast media) [1, 17].
volume of tumour spread should be assessed. HCC lesions Relative contraindications for TACE include: TIPS,
greater than 3 cm are often associated with the need for segmental or subsegmental non-neoplastic portal vein
multiple treatments, and tumour involvement [50% of the thrombosis.
liver volume is associated with a poor prognosis [24]. Finally, patients with tumour burden [50% of liver
Presence and extension of portal vein thrombosis must be volume are unlikely to benefit from treatment.
assessed, as it influences prognosis and risk of the
procedure. Laboratory Findings
Finally, predisposing factors for liver abscess have to be
assessed in order to establish proper treatment. These Laboratory markers for diagnosing and assessing the extent
factors include: of potential hepatocytic damage, and monitoring therapy
effects on liver function are:
• dilation of the biliary tree
• biliary/gallbladder lithiasis • aminotransferases (ALT)
• presence of biliary prosthesis (plastic, metallic) • cholinesterase
• presence of a bilioenteric anastomosis • alkaline phosphatase (ALP)
• presence of transjugular intrahepatic portosystemic • c-glutamyl transferase (cGT)
shunt (TIPS) [1, 25]. • bilirubin
• albumin
• prothrombin time (e.g. PT is increased for a longer
Indications and Contraindications for TACE
period of time in hepatocellular insufficiency, and
diminished in cholestasis based on Vit K
Since TACE is usually implemented in complex, disease-
malabsorption)
stage related treatment algorithms, it is mandatory that the
• creatinine and electrolytes
therapy decision is made by a multidisciplinary tumour
board, which includes hepatologists, oncologists, surgeons, This panel of analysis may be repeated within 24–48
diagnostic and interventional radiologists. hours after the intervention, and throughout the clinical
With regards to HCC, indications for TACE follow the follow-up in order to detect potential treatment-related
Barcelona Clinic Liver Cancer (BCLC) recommendations. liver toxicity early.
They have recently been amended to include Stages 0-A as Serum alpha-fetoprotein (AFP) is the most widely used
well as Stage B in the transplant setting with a class of tumour marker in patients with HCC and has been proven
recommendation of IB and IA, respectively [26]. The aims to have capability of prefiguring the prognosis [29] and aid
of TACE could be: reducing the total tumour burden to in monitoring for tumour recurrence [30]. Recently it has
within the transplant criteria (down-staging), controlling been shown that protein induced by vitamin K absence,
tumour growth in a patient who is on the transplant list antagonist-II (PIVKA-II), effectively increases the detec-
(bridging), and increasing survival in patients not eligible tion rate of HCC as a valid complement to AFP and
for transplantation (palliative). imaging surveillance [31]. Carcinoembryonic antigen
Indications for TACE in ICC include surgically unre- (CEA) and carbohydrate antigen 19–9 (CA 19–9) are the
sectable or inoperable liver tumours with liver-only or markers usually employed in mCRC patients [32]. For
liver-dominant disease [17]. NETs, the commonly used serum markers are neuron-
In the setting of mCRC, patients with liver-limited dis- specific enolase (NSE) and chromogranin A [33].
ease in whom the available chemotherapeutic lines have Although there is no ultimate risk stratification tool,
failed, TACE may be also considered as a treatment option several scorings systems which take into account labora-
[27]. tory and clinical parameters are applied in clinical routine.
TACE can also be considered as an alternative therapy To estimate the procedure-related risk versus the thera-
to surgical resection of liver metastasis in patients with peutic benefit, the Child-Pugh score is well accepted for
NET and as an alternative to systemic treatment in those HCC in liver cirrhosis. According to the BCLC/EASL
patients with NETs with disease limited to the liver [28]. guideline, patients with Child-Pugh score of less than B8
Absolute contraindications for TACE include: portal are well suited for TACE [34], that is based on both clinical
vein neoplastic thrombosis or hepatofugal blood flow, and laboratory values. Recently, the albumin-bilirubin
impaired hepatic function (Child-Pugh B8 or greater), poor (ALBI) score has been proposed as a simple and objective
performance status (ECOG P2 or greater), contraindication method of assessment which removes the need for sub-
for arteriography (uncorrectable thrombocytopenia, jective clinical variables. It has been established as a

123
1854 P. Lucatelli et al: CIRSE Standards of Practice on Hepatic Transarterial Chemoembolisation

prognostic tool not only for HCC [35] but also for the hepatotoxicity of each agent. Discussion with microbiolo-
therapy of metastatic liver disease [36]. gist may be useful in complex cases involving multiple
Finally, there is increasing evidence that systemic organisms, antibiotic resistance or allergies. Guidelines on
inflammation correlates with cancer patients’ survival and the use of antibiotics in IR procedures are presented by
prognosis. In recent years, various markers of systemic Chehab et al. which is endorsed by CIRSE, SIR and CIRA
inflammatory response including cytokines, neutrophil to [44].
lymphocyte ratio (NLR) and platelet to lymphocyte ratio According to the Society of Interventional Radiology
(PLR) are being investigated as prognostic markers in and CIRSE Standards of Practice documents on peri-pro-
patients treated with TACE, but these markers are currently cedural bleeding [45, 46], TACE carries a moderate risk of
not used in clinical practice [37]. bleeding. Therefore, INR should be corrected to less than
1.5, and platelets transfusion recommended for counts less
Preparing the Patient than 50,000/ul, clopidogrel should be suspended for 5 days
before the procedure. Aspirin may be continued. Thera-
It is recommended that patients should fast [ 6 hours prior peutic dose low-molecular-weight heparin should be
to the procedure. withheld for 24 h.
As in any other invasive intervention, some standard
prerequisites are mandatory:
Treatment
• signed informed consent
• peripheral venous access
Vascular Access to Diagnostic Angiography
• pre-procedural safety checklist (e.g. CIRSE checklist)
and CBCT
[38]
• monitoring of basic circulation parameters (i.e. blood
Detailed knowledge on the normal and variant anatomy of
pressure, pulse rate, O2-saturation) [38]
the visceral and hepatic arterial anatomy and familiarity
with suitable catheters and guidewires, liquid and particu-
late embolic agents and applicable chemotherapeutics is
Medication and Peri-Procedural Care vital.
Multiphasic contrast-enhanced CT and MRI and cone
Periprocedural medication may include intravenous beam CT (CBCT) are helpful tools for pre-procedure
hydration, analgesia, anxiolytics, antibiotic prophylaxis planning [47]. CBCT has shown superior tumour and
(only for specific situations), dexamethasone [39], non- tumour feeder detection compared to digital subtraction
steroidal anti-inflammatory drugs (NSAID), anti-emetics angiography (DSA) [48], as well as permitting detection of
and gastric protection with proton pump inhibitors [40]. occult nodules [49], thus improving treatment outcomes
TACE in HCC has a low incidence of side effects. [50]. It is particularly useful for hypovascular lesions
However, procedures in younger patients, higher dosage of (mCRC and ICC) as it facilitates visualisation [51, 52]. A
applied chemotherapies, and in the absence of chronic liver summary of recommendations is shown in Table 2.
disease such as patients with mCRC, are more prone to Moreover, the increased availability of hybrid angio-
pain necessitating peri- and post-procedural analgesia graphic/computed tomography allowing to perform CT
[41, 42]. TACE with irinotecan in mCRC patients should hepatic arteriography and CT arterio-portography, may
not be performed without appropriate analgesia and improve tumour detection, pre-treatment planning and
anaesthetic support is advised. A proposed medication treatment outcome [53, 54].
protocol for mCRC patients is shown in Table 1 [40]. For
more information on the use of analgesia and sedation, TACE Techniques
please refer to the ‘‘CIRSE Standards of Practice on
Analgesia and Sedation for Interventional Radiology in Conventional Transarterial Chemoembolisation (cTACE)
Adults’’ [43]. or Lipiodol TACE
Routine antibiotic prophylaxis is not recommended.
However, in scenarios with an increased risk of developing Lipiodol (Guerbet, France) is an ethyl ester of iodized fatty
liver abscess, prophylactic antibiotics are recommended. acids of poppy seed oil. Lipiodol TACE, also called con-
These include biliary obstruction or the presence of a bil- ventional TACE (cTACE), consists of intra-arterial injec-
ioenteric anastomosis. The choice of agent is dependent on tion of a mixture of lipiodol and one of several anticancer
the suspected pathogens (upper gastrointestinal tract flora) drug(s), followed by the administration of an embolic
and consideration should be given to potential agent.

123
P. Lucatelli et al: CIRSE Standards of Practice on Hepatic Transarterial Chemoembolisation 1855

Table 1 A proposed protocol of Pre-procedure

periprocedural management
(modified by Iezzi et al. [40]) • i.v. access for hydration e.g. Sodium Chloride 0.9% 1500 ml/24 h intravenously
• Midazolam (1-3 mg iv)
• Dexamethasone (4-8 mg, not in patients with diabetes)
During procedure
• Monitoring vital signs: ECG, HR, SPO2, NIBP
• Fentanyl 50–100 mgc (0.7–14 mcg/kg)
• Ondansetron 4 mg slow iv infusion
• Paracetamol 1 g iv
• In case of vegetative reaction: Atropin i.v. Bolus
Post procedure
• i.v. hydration Sodium Chloride 0.9% 1500 ml/24 h
• Morphine 10 mg/24 h
• Ondansetron 4 - 8 mg (elastomeric pump)
• Dexamethasone (4 - 8 mg, not in patients with diabetes)
ECG: Electrocardiogram; HR Heart rate; SPO2 Sensor pulse oximetry; NIBP Non-
invasive blood pressure

Lipiodol-Based Emulsions Lipiodol has a plastic and (i.e. injection of the entire volume of doxorubicin into the
transient embolic effect [52, 55] but does not have a sig- entire volume of lipiodol) results in W/O emulsion in only
nificant cytotoxic effect on its own [56], which necessitates 6.25% cases, incremental (subsequent injections of aliquots
combination with anticancer agents. of doxorubicin in the entire volume of lipiodol) or con-
Most cytotoxic drugs are more soluble in water than in tinuous (continuous incorporation of doxorubicin using an
lipiodol, explaining why an emulsion (mixture of two liq- electric syringe pump at 1ml/min) injection allow obtaining
uids that are unmixable) is used for cTACE [57]. Two W/O emulsions in 93.7–100% cases [64]. As each drug has
different emulsion types can be distinguished: water-in-oil its own hydrophilic-lipophilic balance, these characteristics
(W/O) emulsion where the drug (water droplets) is ‘‘loa- may not apply to other cytotoxic drugs.
ded’’ in lipiodol (oily droplets), and the opposite oil-in-
water (O/W) emulsion. Emulsion Stability Intuitively, the more stable the emul-
Accumulating evidence shows that W/O emulsions sion, the higher chance for lipiodol to carry the drug into
result in: the tumour owing to its targeting ability for hypervascular
liver tumours. Unstable lipiodol-based emulsions result in a
• greater lipiodol accumulation within the tumour
distribution of anticancer drug within the arterial bed that is
[58, 59]
not guided by lipiodol [67]. On the contrary, stabilising
• greater drug-delivery capacity [60]
emulsions reduces systemic exposure [63, 64] and increa-
• greater embolic effect
ses early accumulation of the drug within the tumour [64].
• higher viscosity than O/W emulsions [55]
From a practical perspective, high ratios of lipiodol/drug
cTACE emulsion is usually prepared using the pumping also increased emulsion stability with both doxorubicin
technique through a three-way metal stopcock [61]. Lipi- [64] and idarubicin [63].
odol can cause cracking or crazing of polycarbonate three- Whatever the technique used to emulsify lipiodol and
way stopcocks, while polypropylene, polyamide, and doxorubicin, at least 20 pumping exchanges through the
polysulphide have higher durability [62]. In order to favour stopcock are needed to favour the production of ‘‘large’’
a W/O emulsion, the volume of lipiodol should be greater droplets [59] although any emulsification process basically
than the volume of drug in aqueous solution, ideally a 2:1 provides polydisperse coexistence of small and large dro-
or 3:1 lipiodol:drug ratio [63–65]. Instead of water for plets [57]. ‘‘Large’’ droplets (70–100 lm) limit the risk of
injection, non-ionic contrast medium can be used for reaching the lung, which can cause subsequent toxicity,
preparation of doxorubicin solution in order to improve and increase tumour:non-tumoural liver uptake [55].
stability of doxorubicin-lipiodol [66], but this preparation Given the instability of most lipiodol-drug emulsions,
is considered off-label by pharmacists. they should be prepared extemporaneously immediately
The speed of incorporation of doxorubicin in lipiodol is before transcatheter administration, and they may need to
crucial to favour W/O emulsions. While bolus injection be re-emulsified through the stopcock when phase

123
1856 P. Lucatelli et al: CIRSE Standards of Practice on Hepatic Transarterial Chemoembolisation

Table 2 Summary of recommendations for performing TACE

Step Procedure Consider

Arterial access Choose a safe and controllable access route. 4 or 5 Common femoral artery most common entry
Fr entry sheets sufficient since almost all point. Radial artery is an alternative but will
procedures will be performed superselectively require longer catheters and guidewires
by a microcatheter. Ultrasound-guided puncture
is preferred
Flush aortic angiogram Position a pigtail catheter approx. 5 cm cranial of Standard case work-up should include a
In selected cases only when feeding celiac trunk origin multiphasic MDCT/MRI to provide a roadmap
arteries are not identified on MDCT/ Contrast injection volume: 15–20 ml of arterial, portal venous and venous circulation
MRI, Injection rate: 8–15 ml/s
or when there is lack of tumour Duration of angiography: Until the portal vein is
enhancement on selective hepatic visible
angiography
Selective angiogram of SMA, celiac Selective 4–5 Fr angiographic catheters (e.g. Assessment of normal and variant vascular
trunk, common, right and left HA, Sidewinder or Cobra) - anatomy (e.g. replaced right HA) including
GDA, and potential aberrant vessels Contrast injection volume: 15–20 ml accessory arteries, additional arterial
anastomoses (e.g. left HA to GA), or
Injection rate: 3–5 ml/s
extrahepatic feeding arteries
PSI: 900–1000 superselective with microcatheter
(2.3–2.7 Fr) -
Injection volume: 10–15 ml
Injection rate: 1.5–3 ml/s
PSI 600–700
The use of microcatheters is mandatory to
minimise risk of vessel injury and to maintain
free antegrade flow
Definition of optimal vascular access CBCT is usually acquired with the angiographic CBCT is helpful in identification of tumours with
to the tumour catheter positioned in the proper hepatic artery complex feeding vessels
Tailor flow rate according to initial angiography Note that CBCT may not depict all relevant
(no reflux in the splenic artery e.g.: 3–5 ml/sec) tumour supply, depending on the catheter
Dilute contrast media to 30% position during CBCT
Injection duration approx. 15 s
Selective angiography for segmental or lobar
tumour distribution, and superselective
microcatheter position for immediate tumour
feeders. Match tumour configuration derived
from cross-sectional imaging and angiographic
display
‘‘Missing’’ tumour (typically subcapsular
tumours) parts may be supplied by extrahepatic
feeders or in watershed segment by contralateral
lobe
MDCT: Multidetector computed tomography; MRI Magnetic resonance imaging; SMA Super mesenteric artery; HA hepatic artery; GDA
Gastroduodenal artery; GA Gastric artery, PSI

separation is observed during the procedure. Most IRs use induce or enhance tumour ischaemia and prevent washout
less than 10 ml of lipiodol [5] for cTACE. For safety of the drug. Histological data showed increased necrosis in
reasons, it is recommended to use a total volume of less both the main tumour and daughter nodules with doxoru-
than 20 ml [68] in order to minimise the risk of pulmonary bicin cTACE, versus doxorubicin/lipiodol (without
lipiodol embolism, which can be fatal. embolisation) and lipiodol alone [56]. In a recent interna-
tional survey [5], spherical embolic particles were used by
Embolisation in cTACE Embolisation is widely adopted 47.9% responders followed by gelatine sponge particles by
as the second part of the cTACE procedure immediately 36.8%. There is paucity of data regarding the best embolic
after injection of lipiodol-based emulsion, in order to agent with literature recommending both agents. Gelatine

123
P. Lucatelli et al: CIRSE Standards of Practice on Hepatic Transarterial Chemoembolisation 1857

Table 3 Major adverse events in TACE (adapted from [1, 17, 160])
Adverse event Frequency Quality indicator threshold
[%] [%]

Technical Iatrogenic vessel damage \1 1

Puncture site related \7 5
Hepatic Liver infarction \1 1
Abscess (patent sphincter of Oddi) \2 1
Abscess (not patent SOO) *15 10
Biloma \1 1
Cholecystitis \1 1
Procedure Secondary HA occlusion (CTx related damage) 1–60 10
Liver failure 3–5 2
Extrahepatic Haematologic effects (e.g. neutropenia, leukopenia, thrombocytopenia…) *25 15
Pulmonary embolism \1 1
GI ulceration/haemorrhage \1 1
CM induced nephropathy *10 5
Death (within 30 days) *4 4
Other Skin injury (prolonged and or extensively repeated procedures with increased \1 1
radiation)
SOO, Sphincter of Oddi; HA, Hepatic artery; GI, Gastrointestinal; CM, Contrast media

sponge has the advantage of resorbability within 1–2 weeks DEM-TACE

[69], allowing for subsequent TACE session through the
same tumour feeders. Hand cutting of small (&1–1.5mm) Drug-eluting microspheres are embolic agents that allow
gelfoam pieces provides more uniform particle sizes and loading with anthracyclines (doxorubicin, epirubicin,
should be recommended when using the ‘‘pumping’’ idarubicin) and irinotecan through an ionic interaction of
technique through a three-way stopcock [70]. As the the cationic drug with the anionic functional groups of the
threshold separating intra-tumoural (smaller) from extra- microspheres. Currently, various types of drug-eluting
tumoural vessels (larger) is &300lm [71, 72], non-re- microsphere (DEM) are commercially available for use
sorbable calibrated microspheres ranging 100–300 lm are with doxorubicin, with some differences in elution and
recommended that favour intra-tumoural ischaemia while suspension characteristics [75].
preserving the patency of extra-tumoural arteries, and limit As a general rule, the maximum dose of doxorubicin
the risk of complications due to very small particle size, that can be administered safely to an adult patient in a
such as pulmonary embolism [73] or biliary ischaemia. single session is 150 mg [76]. Drug dosage does not require
Regardless of the choice of embolic agent, only a small adjustment according to body surface area (BSA) or
volume is usually required after administration of the lip- weight. According to this rationale, treatment priority
iodol-based emulsion. However, the occlusion by gelatine should be given to the target lesion. Each vial of DEM,
sponge is often temporary and flow may be restored within comprising of 2 ml of beads, is loaded with 50–75 mg
a few minutes. In addition, calibrated microspheres can doxorubicin or epirubicin. This equates to a loading dose of
take minutes to reach the core of the tumour and the rec- 25–37.5 mg doxorubicin per 1 ml of beads. Cardiac toxi-
ommendation is to wait at least 5 min prior to the final city of anthracyclines is cumulative and observed above a
embolisation to ensure a stronger embolic effect [61]. The certain threshold. For example, 450 mg/m2 for doxoru-
endpoint is a ‘‘tree-in-winter’’ appearance with occlusion bicin. Four sessions of 150 mg doxorubicin TACE can be
of small tumour-feeding radicals but preservation of flow performed safely with regard to cardiac toxicity, but not
in the major lobar and segmental arteries in order to pre- more [77, 78].
serve them for subsequent embolisation. With regards to With regards to DEM bead size, it is worth highlighting
what degree of portal vein visualisation should be achieved that since 2012, when the recommended size for a standard
during lipiodol injection, it has been demonstrated that procedure was usually 100–300 microns, there is a growing
grade 2 segmental visualisation correlates with lower body of literature reporting a comparable safety and effi-
recurrence rate [61, 74]. cacy profile of particle sizes smaller than 100 microns

123
1858 P. Lucatelli et al: CIRSE Standards of Practice on Hepatic Transarterial Chemoembolisation

[79–86]. Nevertheless, using beads less than 100 microns bead size is less than 100 microns [91]. Finally, the
requires caution when superselective catheterisation of the chemotherapy of choice is Irinotecan with the usual stan-
feeder is not achieved as there is increased risk of hepa- dard dose of 100 mg for each lobar treatment.
tobiliary complications [87]. Combinations of different When the treatment is considered finished, a final
calibre beads can offer the advantage of high-drug pene- angiography could be performed to assess tumour devas-
tration of tumour and effective obstruction of feeding cularisation. Alternatively, in order to save contrast media,
arteries [88]. unenhanced CBCT can be used to immediately assess the
DEM are administered using a 1–3 ml syringe, mixed deposition of the embolic agent.
with contrast. It is important to follow preparation steps
specific to each type of DEM according to the IFU of each DSM-TACE
manufacturer. In all cases, a good suspension of DEM is
required before delivery. Either contrast or saline/water can Degradable starch microspheres (Embocept, Phar-
be added depending on the concentration of beads and fluid maCept) consist of resorbable amilomer (hydrolysed potato
density. starch) based particles, ranging around average 45 ±7 lm,
The aim during infusion is to deliver the maximum that can be mixed with a wide range of chemotherapeutic
DEM into the target lesion. The infusion must be slow, agents [10, 92]. These particles act as carriers and show no
with smooth pulses, to the normal arterial flow to push the chemical binding with the selected drug. The microspheres
beads into the tumour feeders. Care should be taken to are enzymatically degraded by amylase in the blood with a
avoid sedimentation of the beads in the syringe by rotating half-life of about 35–50 minutes. The particles are com-
the syringe or using a three-way stopcock to gently suspend pletely resorbed after approximately 2 hours [10].
the beads in solution. The beads are administered under The drug is usually mixed immediately before admin-
continuous fluoroscopic monitoring until stagnation of flow istration using 4 ml out of a 7.5 ml DSM vial, then mixed
is achieved, counting 10 cardiac beats as a guide. At this in suspension with adjunctive contrast media (around
point, the injection should be stopped, regardless of the 15–20 ml). The solution is then infused via a coaxially
volume of beads administered, in order to avoid reflux of positioned microcatheter, to control reflux [93]. The treat-
embolic material [89]. ment consists of administering the total predicted dose of
As stated before, the basis of treatment relies on both drug, followed by the residual part of the DSM vial, used as
cytotoxic and anoxic effects, and as such, the treatment unloaded temporary embolic agent. The aim of embolisa-
endpoint is complete tumour devascularisation. Following tion with the non-loaded DSM is temporary cessation of
this logic, it has been suggested that if arterial stasis is not flow within the treated artery. Depending on the degree of
achieved after injection of the scheduled volume of DEMs, selectivity and vessel size, an additional second vial of
additional unloaded beads should be injected until the unloaded DSM may be needed, or alternatively gelfoam
endpoint of arterial stasis has been reached. However, there can be used. Embolisation to stasis is a crucial end-point to
is no definite evidence to support this statement and some allow adequate drug absorption within the target lesion.
groups recommend scheduling a repeat course of treatment. Since the half-life is short, the goal of the technique is to
There are no technical differences in transarterial deliver the maximum amount of drug to the liver and
chemoembolisation of HCC, ICC and NETs. With regards reduce the risk of post-embolisation syndrome from a
to functional NETs, it is important to note that TACE reduced ischaemic time [10].
should be performed early following somatostatin analogue Usually, administration is performed multiple times, at
(SSA) therapy, in order to improve hormonal symptom least twice for each treatment site. In case of bilobar
control and to prevent complications, such as carcinoid tumour spread and to avoid whole liver treatments that
crisis in serotonin secreting NETs [28]. could impair liver function, the lobe with greater tumour
There are several technical differences to consider in involvement is treated first, followed after 14 days by the
chemoembolisation of mCRC. First, delayed CBCT contralateral lobe. After two more weeks, the treatment
acquisition is integral in the patient work-up to ensure cycle can be repeated [93].
detection of all hypovascular lesions [52, 90]. Second, The main advantage of DSM-TACE is that it may be
depending on the extent and distribution of disease, it is used in patients with a bilirubin greater than 3 mg/dl and
decided to perform a single lobe (2 treatments at 4 weeks portal vein thrombosis [10].
interval) or a bilobar treatment (4 treatments, at 2 weeks
interval), with the first targeted to the lobe more involved B-TACE
by disease. Third, the embolisation endpoint is the delivery
of the planned dose of anticancer agent, not complete In 2013, Irie et al. [15] developed a variant of the TACE
occlusion of feeding vessels. Fourth, the recommended procedure using a temporary occlusion micro-balloon, the

123
P. Lucatelli et al: CIRSE Standards of Practice on Hepatic Transarterial Chemoembolisation 1859

so-called b-TACE. The concept of b-TACE is redistribu- Intra-Procedural and Immediate Post-Procedural Imaging
tion of blood flow towards the target lesion by performing a
pressure-driven embolisation, which occurs because of Lipiodol use combines both therapeutic effects and visi-
restoration of flow distal to the temporary occluded vas- bility on imaging owing to its own radio-opacity. Vascular
cular segment via collaterals (interlobar, intersegmental and tissue distribution can be visualised under fluoroscopy
arteries) [15, 94, 95]. Micro-balloons (Occlusafe, Terumo, to monitor treatment delivery in real-time. Outside any
Japan) are positioned proximal to all lesion feeders in order arterio-venous shunt, lipiodol can deposit in portal bran-
to maximise efficacy. During inflation of the micro-bal- ches (first distally) through arterio-portal communications
loon, invasive arterial pressure is monitored to detect a [57].
pressure drop. The mean arterial pressure threshold below Immediate post-treatment unenhanced CBCT or CT is
which the b-TACE effect will perform optimally, is recommended to document the precise anatomical area that
62 mmHg [96]. It should be remembered that the micro- has been treated and to predict tumour response [49, 101].
balloon maximum diameter is 4 mm. In addition, this may be helpful to depict incomplete tar-
The conventional endpoint of TACE cannot be evalu- geting and to guide further TACE sessions.
ated due to the inflated micro-balloon. Thus, composite
endpoints have been proposed: reflux despite the presence
of the inflated micro-balloon, inversion of flow into opened Outcomes
collaterals, perception of resistance, and maximum
threshold of drug [95]. b-TACE has the same risks as Clinical Results
cTACE and DEM-TACE (biloma, abscess, arterial dis-
section) with adjunctive potential risk of vascular injury Hepatocellular Carcinoma (HCC)
due to micro-balloon inflation. In addition, by allowing
access to the peribiliary plexus, terminal arteriosinus twigs TACE is recommended as the first-line therapy for inter-
and the vasa vasorum, b-TACE may have an increased risk mediate stage HCC (BCLC B) [34, 102, 103]. In compar-
of biliary and vascular damage. ison to best supportive care (BSC), cTACE showed a
decreased relative risk of death ranging from 0.45 (CI95%
Radiopaque Beads 0.25–0.81) [112 patients; early interrupted for cTACE
superiority over control group], to 0.49 (CI95% 0.29–0.81)
Contrary to cTACE, where lipiodol may be retained by [randomisation 1 vs. 1; 80 patients] and a superior overall
HCCs for several months, the contrast agent trapped survival in two RCTs [104, 105]. Moreover, two meta-
between beads rapidly dissipates after DEB-TACE, which analyses [106, 107] confirmed an improved 2-year survival
explains why the embolised territory cannot be directly rate for cTACE vs. BSC (OR 0.59 [CI95% 0.29–1.20]) and
visualised if CT or CBCT acquisition is not performed a reduced overall 2-year mortality rate (OR 0.54; [CI95%
immediately after the procedure. DC Bead LUMITM 0.33–0.89]).
(Biocompatibles UK Ltd, UK) is a drug-eluting technology Two randomised controlled trials comparing cTACE to
with iodine incorporated into its chemical structure, DEM-TACE (PRECISION V, a multicentre, prospective,
ensuring that it is permanently radiopaque [97]. Few randomised, single-blind, phase II study which enrolled
studies [97–99] have been published with radiopaque beads 212 patients and PRECISION Italia, a multicentre,
in humans. They showed safety and response rates com- prospective, randomised, open-label, active-controlled
parable to non-radiopaque beads, although no randomised study which enrolled 177 patients), revealed differences in
or comparative data are available. Some issues are still oncological outcome (DEM-TACE vs. c-TACE; complete
under debate, such as the difficulty to ensure reliable response 27% vs. 22%, objective response 52% vs. 44%,
imaging follow-up using CT [99] as well as the very dif- and disease control 63% vs. 52% p = 0.001). However, a
ferent pharmacokinetic profile of drug elution compared to better safety profile and reduced drug-eluted toxicity could
non-radiopaque beads [100]. This would imply that all be observed in the DEM-TACE group [9, 108]. These
prior phase I/II data published on doxorubicin-eluting findings were confirmed by a meta-analysis which failed to
microspheres are not valid with radiopaque beads, which demonstrate DEM-TACE superiority [109]. However,
theoretically necessitates specific clinical investigations. recent growing evidence shows promising results of DEM-
Therefore, its place still remains to be defined in the TACE TACE, using new material, over both cTACE and TARE
armamentarium. (overall survival at 2-years relative risk 0.89; [CI95%
0.81–0.99], p = 0.046 and 0.40 [CI95% 0.19–0.84]
p = 0.016, respectively) [110].

123
1860 P. Lucatelli et al: CIRSE Standards of Practice on Hepatic Transarterial Chemoembolisation

Few reports are present in literature regarding indica- survival rate of 70% (CI95% 49–87) for cTACE and 80%
tions, in particular, DSM-TACE was employed for HCC as (CI 95% 74–86) for DEM-TACE. Current smaller studies
first- [12, 92] or second-line treatment (after Sorafenib on DSM-TACE in CRC could demonstrate an objective
cessation) [10]. Moreover, Auer et al. [111] demonstrate, in response in 40.0% of patients and disease control in 64.9%
a small series, similar oncological results comparing with [14]. Latest available evidence on multicentre prospective
selective internal radiation therapy (SIRT) in multifocal controlled registries (CIREL cohort) demonstrated an
hepatocellular carcinoma. acceptable toxicity profile and a stable or improved health-
Limited evidence exists and no conclusive results were related quality of life [123]. Nevertheless, the evidence is
found for b-TACE in oncological response, in particular still too scarce for any recommendation.
using lipidiol–Ogawa et al. [112] and Irie et al. [113]
showed a better tumour response for b-TACE compared Intrahepatic Cholangiocarcinoma (ICC)
with cTACE, while Maruyama et al. [114] failed to
demonstrate a difference in tumour control between the In ICC clinical outcome data for hepatic arterial perfusion,
two techniques. To our knowledge, only two studies cTACE and TARE are still controversial [124]. While early
evaluated the combination of DEM-TACE with balloon studies report a median OS of 13 months without any
microcatheter [95, 115] reporting an objective response of difference between cTACE, bland, DEB-TACE and TARE
90% and 100%, respectively. Thus, there is no standard [125], more recent reviews describe a wider range between
indication for b-TACE procedure, however, some reports 12 and 25.2 months of OS for TACE and between 14.9 and
suggested better results for HCC [ 3 cm with higher pro- 43.7 months for TARE [126, 127]. Moreover, DSM-TACE
gression-free survival. In a retrospective European multi- showed a disease control rate in 44% of patients in 7
centric registry (96 patients b-TACE vs 434 patients non patients [12, 128]. Consequently, current guidelines do not
b-TACE with propensity score matching) b-TACE had a make any distinct recommendations regarding a specific
better complete response at 1 month (59.3% vs. 41.8%; transarterial treatment.
p = 0.026), a lower rate of retreatment (9.9%% vs. 22.0%;
p = 0.041) and a higher rate of post-embolic syndrome Neuroendocrine Tumour (NET)
(41.8% vs. 8.8%; p \ 0.001) [116]. Because the existing
evidence is still limited, micro-balloon or flow directing Most international guidelines endorse cTACE as a vali-
microcatheters should be used only in trials. dated treatment option either to control tumour symptoms
in secreting NETs and/or to control disease progression
Colorectal Liver Metastases (mCRC) [28, 33]. In cTACE, the median overall survival ranges
from 24 to 44 months in a retrospective series of 192
There is very limited evidence for cTACE in mCRC (RCT patients [129] reaching an overall survival rate of 36% at
112 patients). Several chemotherapy agents such as mito- 5 years, also in a retrospective report of 123 patients [130].
mycin C, mitomycin C plus irinotecan and mitomycin C In addition, Minh et al. [129] demonstrated a significantly
plus gemcitabine [117] had been applied resulting in 1- and longer median overall survival for cTACE (33.8 months)
2-year survival rates of 62% and 28% and a median time to compared with DEM-TACE (21.7 months, p \ 0.01) or
progression of 5 months [118] – comparable to standard Y90 (23.6 months, p = 0.02), whereas it remains unclear
systemic chemotherapy. In contrast, in a single-arm mul- which patient-specific parameters might explain these
ticentre study in 55 chemotherapy-naı̈ve patients applying results.
DEM-TACE loaded with irinotecan (DEBIRI), Martin
et al. [119] demonstrated a median time to progression of Procedure Specific Complications
11 months with an overall survival of 19 months. Fioren-
tini et al. [120] confirmed these results in a randomised Complications in the context of TACE occur in about 10%
controlled trail in 74 patients where DEBIRI resulted in a of cases and should be documented in a standardised
significantly longer overall survival in comparison to sys- fashion [131, 132].
temic FOLFIRI (22 months [CI 95% 21–23] vs. 15 months According to the time of occurrence, adverse events can
[CI 95% 12–18]). Moreover, Iezzi et al. [121] in a single be divided into:
centre study with 20 patients and 54 treatments, demon-
• intra-procedural (e.g. catheter/guidewire induced vas-
strated a role of DEBIRI ? systemic Capecitabine in
cular injury or haemorrhage, immediate vascular
chemotherapy-refractory patients (first or second line). In a
thrombosis, aberrant embolisation)
current meta-analysis, Levy et al. [122] highlighted com-
• peri-procedural (metabolic impairment), delayed (e.g.
parable response rates of 23% (CI 95% 9.7–36) for cTACE
liver failure, peribiliary necrosis)
and 36% (CI 95% 0–73) for DEM-TACE and 1-year

123
P. Lucatelli et al: CIRSE Standards of Practice on Hepatic Transarterial Chemoembolisation 1861

• minor and major (all events as abscess, bilioma, CT is associated with both tumour response [136] and
haemorrhage, liver failure, vascular damage that need survival [137].
some kind of intervention) (Table 3). The timing of post-procedural imaging is widely adop-
ted and accepted as 4 weeks from the completion of
In contrast to adverse events, post-embolisation syn-
treatment in the first instance [138]. Follow-up after that
drome (PES) is not considered a complication and is
should be performed every 3 months [34] as this has been
expected in about 30% of cases as an effect of an efficient
demonstrated to lead to a better overall survival in high-
chemoembolisation. PES is usually self-limiting and
risk HCC patients as compared to using longer imaging
should last only a few days within the first two weeks after
intervals [139]. Tumour response should be categorised
the procedure. It is typically characterised by nausea,
according to mRECIST criteria, as this takes the viable part
vomiting, fever, pain, and fatigue necessitating no or only
of the tumour (arterial enhancement) into account rather
symptomatic treatment. In rare, cases it may last up to four
than the size of both viable and non-viable tumours [140].
weeks post-TACE. Longer-lasting symptoms should
Tumour markers such as AFP and DCP may help to
prompt evaluation for other causes.
evaluate complete necrosis (therefore the effect of the
While most minor complications by definition do not
treatment) in partial response setting, especially in tumours
need any or only symptomatic treatment, the management
that actively produce these markers prior treatments, in
of major complications may necessitate a wide range of
which imaging may fail to demonstrate the residual/
radiological, medical, and surgical procedures. Vascular
necrosis proportion and may also detect recurrence before
complications as haemorrhage, dissection or pseudoa-
imaging demonstrates it [138].
neurysm of the celiac trunk or hepatic artery are rare and
For mCRC, RECIST version 1.1 [141] should be used
should whenever possible be treated by interventional
for assessing radiological response of oncological patients,
techniques. Infectious conditions, such as cholangitis,
but adjunctive evaluation using the Choi et al. criteria,
cholecystitis, but also initial abscesses, infected haeman-
which measure the attenuation coefficient may also be
giomas or bilomas are initially treated using antibiotics. In
quite useful as mCRC is usually hypovascular [142]. The
liquified infected fluid collections, percutaneous drainage is
timing and the duration of the radiological follow-up for
appropriate and a surgical intervention may be necessary in
mCRC in stage II and III depends on different guidelines
rare cases.
ranging from 6 to 12 months [133]. CEA is fundamental in
clinical follow-up and should be assessed every 3–6
months [133].
Post-procedural and Follow-up Care
For ICC, guidelines are less standardised in terms of
follow-up timeline as compared to other tumour types, but
Imaging Follow-Up
an imaging evaluation every 2–4 months for 2 years seems
reasonable, along with evaluation of CEA and CA19-9
Imaging Modalities
[135].
For NET, imaging after curative surgery should be
The type of imaging follow-up used for assessment of
performed every year for the first 3 years [28, 134], and
treatment response as well as the timing and frequency of
after TACE a more narrow imaging interval (3–6 months)
imaging follow-up varies depends on the nature of the
is not clearly stated by internationally accepted guidelines.
target tumour and may also be influenced by the use of
However, it seems reasonable to propose surveillance with
other tumour markers and metabolic imaging techniques.
3–6-month intervals in order to promptly identify radio-
Imaging follow-up is mainly performed with cross-sec-
logical recurrence, eligible for adjunctive treatment. For
tional techniques such as CT and MRI with nuclear
non-functioning NET, oncological markers are functionally
imaging (PET) playing a smaller role, mainly for mCRC
useless and, although serial evaluation seems reasonable,
and mNET [133, 135].
there is no robust evidence for its use [134].
Tumour Types
Re-TACE Planning and Scoring Systems
For HCC both MRI and CT are appropriate techniques, but
There is still an unmet need to recommend the treatment
MRI is the modality of choice for response evaluation in
schedule for TACE and whether it should be performed at
cTACE because tumour lipiodol deposition can make
regular intervals or on demand based on tumour response.
tumour enhancement difficult to appreciate on contrast-
The repetition of TACE procedures according to an
enhanced CT-scan, even though tumour lipiodol uptake at
aggressive schedule might induce liver failure in an unac-
ceptable proportion of patients and as imaging techniques

123
1862 P. Lucatelli et al: CIRSE Standards of Practice on Hepatic Transarterial Chemoembolisation

show high efficacy to detect residual viable tissue, it seems of doxorubicin for TACE of HCC. Unfortunately, the
reasonable to perform a subsequent TACE session only results of this trial have never been reproduced so far
when residual viable HCC is detected [34]. explaining why doxorubicin is not used for systemic
The decision whether treatment with TACE should be treatment of HCC
interrupted is complex. In recent years, various scoring 2. Conduct a randomised trial comparing drugs. Two
systems have been proposed to identify patients who are randomised trials comparing doxorubicin to epirubicin
poor candidates for repeat TACE treatment. The HAP and did not show any difference in terms of efficacy
STATE scores [143, 144] aim to identify poor candidates [150, 151]. The only positive randomised trial so far
before the first treatment session and the ART score aims to has been reported in 365 patients by Shi et al., showing
assess retreatment. The ‘‘six-and-twelve’’ score has been that a triple-drug (lobaplatin, epirubicin and mito-
developed more recently to select best candidates for mycin C) TACE regimen was associated with OS
TACE [145]. These scores have been questioned by dif- benefit as compared to single-drug (epirubicin) TACE
ferent groups, based on the fact that they don’t capture the [152].
established candidates to TACE according to guidelines or 3. Select the appropriate drug for HCC TACE to conduct
due to the lack of impact in clinical practice [146, 147]. a cytotoxicity study. Such a study was conducted in
Therefore, the decision on whether to re-treat patients 2011 to screen eleven drugs against three HCC cell
with TACE should be based on the concept of ‘‘untreat- lines [153] and reported that idarubicin was by far the
able progression’’ [148]. Thus, TACE should not be repe- most cytotoxic agent. Good safety profile and promis-
ated when substantial necrosis is not achieved after two ing clinical efficacy has been reported either for
rounds of treatment or when follow-up treatment fails to idarubicin cTACE [154], DEM-TACE [155] or
induce marked necrosis at sites that have progressed after chemolipiodolisation [156]. However, no prospective
an initial tumour response. Additionally, TACE should not randomised data are available so far.
be repeated in patients with tumour progression associated
with a clinical profile that prevents re-treatment, e.g.
Combination of TACE Plus Systemic Therapies
development of liver failure. Definitions of untreat-
able progression may include major progression (extensive
Randomised trials have evaluated the benefit of adding the
liver involvement, extrahepatic metastasis or vascular
following targeted therapies to TACE (either conventional
invasion) but also minor intrahepatic progression associ-
or using drug-eluting microspheres): sorafenib (SPACE,
ated with impaired liver function and performance status
TACE 2 and TACTICS trials), brivanib (BRISK-TA trial),
[34].
and orantinib (ORIENTAL trial) [157]. Despite the high
number of included patients (889 in the latter) in these
trials, none of them has shown positive results in terms of
Future Perspectives
OS improvement. Yet, there is a strong rationale for
combining anti-angiogenic molecules with TACE, known
New Drugs
to favour the release of pro-angiogenic factors (such as
VEGF), which in turn, may cause tumour progression.
In a recent worldwide survey regarding TACE for HCC,
Post-TACE serum VEGF levels have been linked to both
doxorubicin appeared as the most used cytotoxic agent
response and survival [158]. Except the TACTICS trial
(71.7% responders) especially in North America, Europe
[159] comparing TACE to sorafenib-TACE-sorafenib (in-
and Korea [6]. Pirarubicin was the most commonly used
terruption for 2 days before and after TACE) and showing
drug in China and epirubicin in Japan. It is important to
a benefit in PFS (25.2 vs. 13.5 months; p = 0.006), all
note that most of these drugs are not approved by health
combination trials with tyrosine-kinase inhibitors or anti-
authorities for locoregional treatment of HCC. Three dif-
angiogenics were all negative.
ferent methods can be used to select the optimal drug for
Immunotherapy has very recently become the new
HCC TACE:
standard for the treatment of advanced HCC. The extensive
1. Use of a drug that has shown a significant clinical research in this field has led to exploring the combination
efficacy when used intravenously. If this drug has high of various immune-checkpoint inhibitors, alone or in
hepatic extraction ratio, this may be a good candidate combination with TACE [157] durvalumab ? beva-
for TACE. One trial conducted in 1975 [149] on 14 cizumab (EMERALD-1 trial), nivolumab (TACE-3 trial),
HCC patients treated by IV doxorubicin reported Lenvatinib?pembrolizumab (LEAP-012 trial), nivolumab
tumour response in 11/14, among whom three showed ? ipilimumab (CheckMate 74W trial). The results of these
complete response. These results justified further use

123
P. Lucatelli et al: CIRSE Standards of Practice on Hepatic Transarterial Chemoembolisation 1863

phase III randomised trials are pending and might define microspheres (DSM) in hepatocellular carcinoma (HCC): multi-
new standards in the future. center results on safety and efficacy. Oncotarget.
2017;8(42):72613–20.
13. Goerg F, Zimmermann M, Bruners P, Neumann U, Luedde T,
Kuhl C. Chemoembolization with Degradable Starch Micro-
Funding This study was not supported by any funding. spheres for Treatment of Patients with Primary or Recurrent
Unresectable, Locally Advanced Intrahepatic Cholangiocarci-
Declarations noma: A Pilot Study. Cardiovasc Intervent Radiol.
2019;42(12):1709–17.
Conflict of interest Marta Burrel has been a paid speaker for BTG, 14. Schicho A, Pereira PL, Michalik K, Beyer LP, Stroszczynski C,
Guerbet and Terumo. Boris Guiu has recieved study funding from Wiggermann P. Safety and efficacy of transarterial chemoem-
Guerbet, Boston Scientific and Terumo. He has also acted as a con- bolization with degradable starch microspheres (DSM-TACE) in
sultant for Boston Scientific and Terumo. All other authors declare the treatment of secondary liver malignancies. Onco Targets
they have no conflict of interest. Ther. 2018;11:345–50.
15. Irie T, Kuramochi M, Takahashi N. Dense accumulation of
lipiodol emulsion in hepatocellular carcinoma nodule during
References selective balloon-occluded transarterial chemoembolization:
measurement of balloon-occluded arterial stump pressure. Car-
diovasc Intervent Radiol. 2013;36(3):706–13.
1. Basile A, Carrafiello G, Ierardi AM, Tsetis D. Brountzos E 16. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal
Quality-improvement guidelines for hepatic transarterial A. Global cancer statistics 2018: GLOBOCAN estimates of
chemoembolization. Cardiovasc Intervent Radiol. incidence and mortality worldwide for 36 cancers in 185
2012;35(4):765–74. countries. CA Cancer J Clin. 2018;68(6):394–424.
2. Yamada R, Nakatsuka H, Nakamura K, et al. [Super-selective 17. Gaba RC, Lokken RP, Hickey RM, et al. Quality Improvement
arterial embolization in unresectable hepatomas (author’s Guidelines for Transarterial Chemoembolization and
transl)] Nihon Igaku Hoshasen Gakkai zasshi. Nippon acta Embolization of Hepatic Malignancy. J Vasc Interv Radiol.
radiologica. 1979;39(5):540–3. 2017;28(9):1210–23.
3. Guan Y-S, He Q, Wang M-Q. Transcatheter arterial 18. Riihimaki M, Hemminki A, Sundquist K, Sundquist J, Hem-
chemoembolization: history for more than 30 years. ISRN minki K. The epidemiology of metastases in neuroendocrine
Gastroenterol. 2012;2012:1–8. tumors. Int J Cancer. 2016;139(12):2679–86.
4. Yamada R, Sato M, Kawabata M, Nakatsuka H, Nakamura K, 19. Mitchell DG, Bruix J, Sherman M, Sirlin CB. LI-RADS (Liver
Takashima S. Hepatic artery embolization in 120 patients with Imaging Reporting and Data System): Summary, discussion, and
unresectable hepatoma. Radiology. 1983;148(2):397–401. consensus of the LI-RADS Management Working Group and
5. Craig P, Young S, Golzarian J. Current Trends in the Treatment future directions. Hepatology. 2015;61(3):1056–65.
of Hepatocellular Carcinoma with Transarterial Embolization: 20. Di Tommaso L, Spadaccini M, Donadon M, et al. Role of liver
Variability in Technical Aspects. Cardiovasc Intervent Radiol. biopsy in hepatocellular carcinoma. World J Gastroenterol.
2019;2(9):1322–8. 2019;25(40):6041–52.
6. Young S, Craig P, Golzarian J. Current trends in the treatment of 21. Lencioni R, Petruzzi P, Crocetti L. Chemoembolization of
hepatocellular carcinoma with transarterial embolization: a cross- hepatocellular carcinoma. Semin Intervent Radiol.
sectional survey of techniques. Eur Radiol. 2019;29(6):3287–95. 2013;30(1):3–11.
7. Sahara S, Kawai N, Sato M, et al. Prospective evaluation of 22. Shin SW. The current practice of transarterial chemoemboliza-
transcatheter arterial chemoembolization (TACE) with multiple tion for the treatment of hepatocellular carcinoma. Korean J
anti-cancer drugs (epirubicin, cisplatin, mitomycin c, 5-fluo- Radiol. 2009;10(5):425–34.
rouracil) compared with TACE with epirubicin for treatment of 23. Schraml C, Kaufmann S, Rempp H, et al. Imaging of HCC-
hepatocellular carcinoma. Cardiovasc Intervent Radiol. Current State of the Art. Diagnostics. 2015;5(4):513–45.
2012;35(6):1363–71. 24. Golfieri R, Renzulli M, Mosconi C, et al. Hepatocellular carci-
8. Hong K, Khwaja A, Liapi E, Torbenson MS, Georgiades CS, noma responding to superselective transarterial chemoem-
Geschwind JF. New intra-arterial drug delivery system for the bolization: an issue of nodule dimension? J Vasc Interv Radiol.
treatment of liver cancer: preclinical assessment in a rabbit 2013;24(4):509–17.
model of liver cancer. Clini cancer res Official J Am Assoc 25. Miura JT, Rilling WS, White SB, et al. Safety and efficacy of
Cancer Res. 2006;12(8):2563–7. transarterial chemoembolization in patients with transjugular
9. Lammer J, Malagari K, Vogl T, et al. Prospective randomized intrahepatic portosystemic shunts. HPB. 2015;17(8):707–12.
study of doxorubicin-eluting-bead embolization in the treatment 26. Vogel A, Cervantes A, Chau I, et al. Hepatocellular carcinoma:
of hepatocellular carcinoma: results of the PRECISION V study. ESMO Clinical Practice Guidelines for diagnosis, treatment and
Cardiovasc Intervent Radiol. 2010;33(1):41–52. follow-up. Ann Oncol. 2018;29:238–55.
10. Iezzi R, Pompili M, Rinninella E, et al. TACE with degradable 27. Van Cutsem E, Cervantes A, Adam R, et al. ESMO consensus
starch microspheres (DSM-TACE) as second-line treatment in guidelines for the management of patients with metastatic col-
HCC patients dismissing or ineligible for sorafenib. Eur Radiol. orectal cancer. Ann Oncol. 2016;27(8):1386–422.
2019;29(3):1285–92. 28. de Baere T, Deschamps F, Tselikas L, et al. GEP-NETS update:
11. Gross A, Albrecht T. Transarterial Chemoembolisation (TACE) Interventional radiology: role in the treatment of liver metas-
with Degradable Starch Microspheres (DSM) and Anthracycline tases from GEP-NETs. Eur J Endocrinol. 2015;172(4):R151-
in Patients with Locally Extensive Hepatocellular Carcinoma 166.
(HCC): Safety and Efficacy. Cardiovasc Intervent Radiol. 29. Tangkijvanich P, Anukulkarnkusol N, Suwangool P, et al.
2020;43(3):402–10. Clinical characteristics and prognosis of hepatocellular carci-
12. Schicho A, Pereira PL, Haimerl M, et al. Transarterial noma: analysis based on serum alpha-fetoprotein levels. J Clin
chemoembolization (TACE) with degradable starch Gastroenterol. 2000;31(4):302–8.

123
1864 P. Lucatelli et al: CIRSE Standards of Practice on Hepatic Transarterial Chemoembolisation

30. Arai T, Kobayashi A, Ohya A, et al. Assessment of treatment 47. Lucatelli P, Corona M, Argiro R, et al. Impact of 3D Rotational
outcomes based on tumor marker trends in patients with recur- Angiography on Liver Embolization Procedures: Review of
rent hepatocellular carcinoma undergoing trans-catheter arterial Technique and Applications. Cardiovasc Intervent Radiol.
chemo-embolization. Int J Clin Oncol. 2014;19(5):871–9. 2015;38(3):523–35.
31. Yu R, Tan Z, Xiang X, Dan Y, Deng G. Effectiveness of 48. Pung L, Ahmad M, Mueller K, et al. The Role of Cone-Beam
PIVKA-II in the detection of hepatocellular carcinoma based on CT in Transcatheter Arterial Chemoembolization for Hepato-
real-world clinical data. BMC Cancer. 2017;17(1):608. cellular Carcinoma: A Systematic Review and Meta-analysis.
32. Michl M, Koch J, Laubender RP, et al. Tumor markers CEA and J Vasc Interv Radiol. 2017;28(3):334–41.
CA 19–9 correlate with radiological imaging in metastatic col- 49. Lucatelli P, De Rubeis G, Ginnani Corradini L, et al. Intra-
orectal cancer patients receiving first-line chemotherapy. procedural dual phase cone beam computed tomography has a
Tumour Biol. 2014;35(10):10121–7. better diagnostic accuracy over pre-procedural MRI and MDCT
33. Pavel M, Öberg K, Falconi M, et al. Gastroenteropancreatic in detection and characterization of HCC in cirrhotic patients
neuroendocrine neoplasms: ESMO Clinical Practice Guidelines undergoing TACE procedure. Eur J Radiol. 2020;124:108806.
for diagnosis, treatment and follow-up. Ann Oncol. 50. Lucatelli P, Argiro R, Bascetta S, et al. Single injection dual
2020;31(7):844–60. phase CBCT technique ameliorates results of trans-arterial
34. EASL Clinical Practice Guidelines. Management of hepatocel- chemoembolization for hepatocellular cancer. Transl Gastroen-
lular carcinoma. J Hepatol. 2018;69(1):182–236. terol Hepatol. 2017;2:83.
35. Johnson PJ, Berhane S, Kagebayashi C, et al. Assessment of 51. Schernthaner RE, Haroun RR, Duran R, et al. Improved Visi-
liver function in patients with hepatocellular carcinoma: a new bility of Metastatic Disease in the Liver During Intra-Arterial
evidence-based approach-the ALBI grade. J Clin Oncol. Therapy Using Delayed Arterial Phase Cone-Beam CT. Car-
2015;33(6):550–8. diovasc Intervent Radiol. 2016;39(10):1429–37.
36. Abdel-Rahman O. Prognostic Value of Baseline ALBI Score 52. Kan Z, Ivancev K, Hägerstrand I, Chuang VP, Lunderquist A.
Among Patients With Colorectal Liver Metastases: A Pooled In vivo microscopy of the liver after injection of Lipiodol into
Analysis of Two Randomized Trials. Clin Colorectal Cancer. the hepatic artery and portal vein in the rat. Acta Radiol.
2019;18(1):e61–8. 1989;30(4):419–25.
37. Rebonato A, Graziosi L, Maiettini D, et al. Inflammatory 53. Tanaka T, Arai Y, Inaba Y, et al. Current role of hybrid CT/
Markers as Prognostic Factors of Survival in Patients Affected angiography system compared with C-arm cone beam CT for
by Hepatocellular Carcinoma Undergoing Transarterial Che- interventional oncology. Br J Radiol. 2014;87(1041):20140126.
moembolization. Gastroenterol Res Pract. 54. Toyoda H, Kumada T, Sone Y. Impact of a Unified CT
2017;2017:4164130–4164130. Angiography System on Outcome of Patients with Hepatocel-
38. Lee MJ, Fanelli F, Haage P, Hausegger K, Van Lienden KP. lular Carcinoma. Am J Roentgenol. 2009;192(3):766–74.
Patient safety in interventional radiology: a CIRSE IR checklist. 55. de Baere T, Dufaux J, Roche A, et al. Circulatory alterations
Cardiovasc Intervent Radiol. 2012;35(2):244–6. induced by intra-arterial injection of iodized oil and emulsions
39. Ogasawara S, Chiba T, Ooka Y, et al. A randomized placebo- of iodized oil and doxorubicin: experimental study. Radiology.
controlled trial of prophylactic dexamethasone for transcatheter 1995;194(1):165–70.
arterial chemoembolization. Hepatology. 2018;67(2):575–85. 56. Takayasu K, Shima Y, Muramatsu Y, et al. Hepatocellular
40. Iezzi R, Kovacs A, Prenen H, Chevallier P, Pereira PL. carcinoma: treatment with intraarterial iodized oil with and
Transarterial chemoembolisation of colorectal liver metastases without chemotherapeutic agents. Radiology.
with irinotecan-loaded beads: What every interventional radi- 1987;163(2):345–51.
ologist should know. Eur J Radiol Open. 2020;7:100236. 57. Idée JM, Guiu B. Use of Lipiodol as a drug-delivery system for
41. Wang TC, Zhang ZS, Xiao YD. Determination of Risk Factors transcatheter arterial chemoembolization of hepatocellular car-
for Pain After Transarterial Chemoembolization with Drug- cinoma: a review. Crit Rev Oncol Hematol. 2013;88(3):530–49.
Eluting Beads for Hepatocellular Carcinoma. J Pain Res. 58. Deschamps F, Farouil G, Gonzalez W, et al. Stabilization
2020;13:649–56. Improves Theranostic Properties of Lipiodol()-Based Emul-
42. Benzakoun J, Ronot M, Lagadec M, et al. Risks factors for sion During Liver Trans-arterial Chemo-embolization in a VX2
severe pain after selective liver transarterial chemoembolization. Rabbit Model. Cardiovasc Intervent Radiol. 2017;40(6):907–13.
Liver Int. 2017;37(4):583–91. 59. de Baere T, Zhang X, Aubert B, et al. Quantification of tumor
43. Romagnoli S, Fanelli F, et al. CIRSE Standards of Practice on uptake of iodized oils and emulsions of iodized oils: experi-
Analgesia and Sedation for Interventional Radiology in Adults. mental study. Radiology. 1996;201(3):731–5.
Cardiovasc Intervent Radiol. 2020;43(9):1251–60. 60. Kan Z, Wright K, Wallace S. Ethiodized oil emulsions in hep-
44. Chehab MA, Thakor AS, Tulin-Silver S, et al. Adult and Pedi- atic microcirculation: in vivo microscopy in animal models.
atric Antibiotic Prophylaxis during Vascular and IR Procedures: Acad Radiol. 1997;4(4):275–82.
A Society of Interventional Radiology Practice Parameter 61. de Baere T, Arai Y, Lencioni R, et al. Treatment of Liver
Update Endorsed by the Cardiovascular and Interventional Tumors with Lipiodol TACE: Technical Recommendations
Radiological Society of Europe and the Canadian Association from Experts Opinion. Cardiovasc Intervent Radiol.
for Interventional Radiology. J Vasc Interv Radiol. 2016;39(3):334–43.
2018;29(11):1483-1501.e1482. 62. Kudo T, Monzawa S, Sugimura K. Evaluation of durability of
45. Patel IJ, Davidson JC, Nikolic B, et al. Consensus guidelines for three-way stopcocks to Lipiodol in making an emulsion for
periprocedural management of coagulation status and hemosta- transcatheter arterial chemo-embolization. Medical Journal of
sis risk in percutaneous image-guided interventions. J Vasc Kobe University. 2004;64:47–52.
Interv Radiol. 2012;23(6):727–36. 63. Boulin M, Schmitt A, Delhom E, et al. Improved stability of
46. Hadi M, Walker C, Desborough M, et al. CIRSE Standards of lipiodol-drug emulsion for transarterial chemoembolisation of
Practice on Peri-operative Anticoagulation Management During hepatocellular carcinoma results in improved pharmacokinetic
Interventional Radiology Procedures. Cardiovasc Intervent profile: Proof of concept using idarubicin. Eur Radiol.
Radiol. 2021;44(4):523–36. 2016;26(2):601–9.

123
P. Lucatelli et al: CIRSE Standards of Practice on Hepatic Transarterial Chemoembolisation 1865

64. Deschamps F, Moine L, Isoardo T, et al. Parameters for Patients at an Italian Center. J Vasc Interv Radiol.
Stable Water-in-Oil Lipiodol Emulsion for Liver Trans-Arterial 2017;28(11):1495–502.
Chemo-Embolization. Cardiovasc Intervent Radiol. 81. Aal AKA, Moawad S, Lune PV, et al. Survival Outcomes of
2017;40(12):1927–32. Very Small Drug-Eluting Beads Used in Chemoembolization of
65. Nakamura H, Hashimoto T, Oi H, Sawada S. Transcatheter oily Unresectable Hepatocellular Carcinoma. J Vasc Interv Radiol.
chemoembolization of hepatocellular carcinoma. Radiology. 2019;30(9):1325-1334.e1322.
1989;170(3 Pt 1):783–6. 82. Richter G, Radeleff B, Stroszczynski C, et al. Safety and Fea-
66. Tzeng WS, Wu RH, Chang SC, et al. Ionic versus nonionic sibility of Chemoembolization with Doxorubicin-Loaded Small
contrast media solvents used with an epirubicin-based agent for Calibrated Microspheres in Patients with Hepatocellular Carci-
transarterial chemoembolization of hepatocellular carcinoma. noma: Results of the MIRACLE I Prospective Multicenter
J Vasc Interv Radiol. 2008;19(3):342–50. Study. Cardiovasc Intervent Radiol. 2018;41(4):587–93.
67. Gaba RC, Baumgarten S, Omene BO, et al. Ethiodized oil 83. Balli H, Aksungur E, Khalatai B, Aikimbaev K. Super-Selective
uptake does not predict doxorubicin drug delivery after Transarterial Chemoembolization with Doxorubicin-Loaded
chemoembolization in VX2 liver tumors. J Vasc Interv Radiol. Drug-Eluting Beads Sized Below and Above 100 Microns in
2012;23(2):265–73. Hepatocellular Carcinoma: A Comparative Study. J Belg Soc
68. Chung JW, Park JH, Im JG, Han JK, Han MC. Pulmonary oil Radiol. 2019;103(1):47.
embolism after transcatheter oily chemoembolization of hepa- 84. Delicque J, Guiu B, Boulin M, Schwanz H, Piron L, Cassinotto
tocellular carcinoma. Radiology. 1993;187(3):689–93. C. Liver chemoembolization of hepatocellular carcinoma using
69. Louail B, Sapoval M, Bonneau M, Wasseff M, Senechal Q, TANDEM((R)) microspheres. Future Oncol.
Gaux JC. A new porcine sponge material for temporary 2018;14(26):2761–72.
embolization: an experimental short-term pilot study in swine. 85. Greco G, Cascella T, Facciorusso A, et al. Transarterial
Cardiovasc Intervent Radiol. 2006;29(5):826–31. chemoembolization using 40 lm drug eluting beads for hepa-
70. Katsumori T, Kasahara T. The size of gelatin sponge particles: tocellular carcinoma. World J Radiol. 2017;9(5):245–52.
differences with preparation method. Cardiovasc Intervent 86. Malagari K, Pomoni M, Moschouris H, et al. Chemoemboliza-
Radiol. 2006;29(6):1077–83. tion of hepatocellular carcinoma with HepaSphere 30–60 lm
71. Laurent A, Wassef M, Chapot R, et al. Partition of calibrated Safety and efficacy study. Cardiovasc Intervent Radiol.
tris-acryl gelatin microspheres in the arterial vasculature of 2014;37(1):165–75.
embolized nasopharyngeal angiofibromas and paragangliomas. 87. Deipolyi AR, Oklu R, Al-Ansari S, Zhu AX, Goyal L, Ganguli
J Vasc Interv Radiol. 2005;16(4):507–13. S. Safety and efficacy of 70–150 mum and 100–300 mum drug-
72. Lee KH, Liapi E, Vossen JA, et al. Distribution of iron oxide- eluting bead transarterial chemoembolization for hepatocellular
containing Embosphere particles after transcatheter arterial carcinoma. J Vasc Interv Radiol. 2015;26(4):516–22.
embolization in an animal model of liver cancer: evaluation with 88. Lucatelli P, Argirò R, De Rubeis G, et al. Polyethylene Glycol
MR imaging and implication for therapy. J Vasc Interv Radiol. Epirubicin-Loaded Transcatheter Arterial Chemoembolization
2008;19(10):1490–6. Procedures Utilizing a Combined Approach with 100 and 200
73. Bonomo G, Pedicini V, Monfardini L, et al. Bland embolization lm Microspheres: A Promising Alternative to Current Stan-
in patients with unresectable hepatocellular carcinoma using dards. J Vasc Interv Radiol. 2019;30(3):305–13.
precise, tightly size-calibrated, anti-inflammatory microparti- 89. Lencioni R, de Baere T, Burrel M, et al. Transcatheter treatment
cles: first clinical experience and one-year follow-up. Cardio- of hepatocellular carcinoma with Doxorubicin-loaded DC Bead
vasc Intervent Radiol. 2010;33(3):552–9. (DEBDOX): technical recommendations. Cardiovasc Intervent
74. Miyayama S, Matsui O, Yamashiro M, et al. Ultraselective Radiol. 2012;35(5):980–5.
transcatheter arterial chemoembolization with a 2-f tip micro- 90. Schernthaner RE, Lin M, Duran R, Chapiro J, Wang Z,
catheter for small hepatocellular carcinomas: relationship Geschwind JF. Delayed-Phase Cone-Beam CT Improves
between local tumor recurrence and visualization of the portal Detectability of Intrahepatic Cholangiocarcinoma During Con-
vein with iodized oil. J Vasc Interv Radiol. 2007;18(3):365–76. ventional Transarterial Chemoembolization. Cardiovasc Inter-
75. de Baere T, Plotkin S, Yu R, Sutter A, Wu Y, Cruise GM. An vent Radiol. 2015;38(4):929–36.
In Vitro Evaluation of Four Types of Drug-Eluting Micro- 91. Akinwande OK, Philips P, Duras P, Pluntke S, Scoggins C,
spheres Loaded with Doxorubicin. J Vasc Interv Radiol. Martin RC. Small versus large-sized drug-eluting beads
2016;27(9):1425–31. (DEBIRI) for the treatment of hepatic colorectal metastases: a
76. Varela M, Real MI, Burrel M, et al. Chemoembolization of propensity score matching analysis. Cardiovasc Intervent
hepatocellular carcinoma with drug eluting beads: efficacy and Radiol. 2015;38(2):361–71.
doxorubicin pharmacokinetics. J Hepatol. 2007;46(3):474–81. 92. Yamasaki T, Hamabe S, Saeki I, et al. A novel transcatheter
77. Volkova M, Russell R 3rd. Anthracycline cardiotoxicity: arterial infusion chemotherapy using iodized oil and degradable
prevalence, pathogenesis and treatment. Curr Cardiol Rev. starch microspheres for hepatocellular carcinoma: a prospective
2011;7(4):214–20. randomized trial. J Gastroenterol. 2011;46(3):359–66.
78. McGowan JV, Chung R, Maulik A, Piotrowska I, Walker JM, 93. Lucatelli P, De Rubeis G, Basilico F, et al. Sequential dual-
Yellon DM. Anthracycline Chemotherapy and Cardiotoxicity. phase cone-beam CT is able to intra-procedurally predict the
Cardiovasc Drugs Ther. 2017;31(1):63–75. one-month treatment outcome of multi-focal HCC, in course of
79. Veloso Gomes F, Oliveira JA, Correia MT, et al. Chemoem- degradable starch microsphere TACE. Radiol Med (Torino).
bolization of Hepatocellular Carcinoma with Drug-Eluting 2019;124(12):1212–9.
Polyethylene Glycol Embolic Agents: Single-Center Retro- 94. Aramburu J, Anton R, Rivas A, et al. Numerical zero-dimen-
spective Analysis in 302 Patients. J Vasc Interv Radiol. sional hepatic artery hemodynamics model for balloon-occluded
2018;29(6):841–9. transarterial chemoembolization. Int J Numer Method Biomed
80. Aliberti C, Carandina R, Lonardi S, et al. Transarterial Che- Eng. 2018;34(7):e2983.
moembolization with Small Drug-Eluting Beads in Patients with 95. Lucatelli P, Corradini LG, De Rubeis G, et al. Balloon-Occluded
Hepatocellular Carcinoma: Experience from a Cohort of 421 Transcatheter Arterial Chemoembolization (b-TACE) for
Hepatocellular Carcinoma Performed with Polyethylene-Glycol

123
1866 P. Lucatelli et al: CIRSE Standards of Practice on Hepatic Transarterial Chemoembolisation

Epirubicin-Loaded Drug-Eluting Embolics: Safety and Prelim- hepatocellular carcinoma using miriplatin, a lipophilic anti-
inary Results. Cardiovasc Intervent Radiol. 2019;42(6):853–62. cancer drug: Short-term results. Hepatol Res official J Japan Soc
96. Matsumoto T, Endo J, Hashida K, et al. Balloon-occluded Hepatol. 2016;46(3):E60-69.
transarterial chemoembolization using a 1.8-French tip coaxial 113. Irie T, Kuramochi M, Kamoshida T, Takahashi N. Selective
microballoon catheter for hepatocellular carcinoma: technical balloon-occluded transarterial chemoembolization for patients
and safety considerations. Minim Invasive Ther Allied Technol. with one or two hepatocellular carcinoma nodules: Retrospec-
2015;24(2):94–100. tive comparison with conventional super-selective TACE.
97. Reicher J, Mafeld S, Priona G, et al. Early Experience of Trans- Hepatol Res official J Japan Soc Hepatol. 2016;46(2):209–14.
arterial Chemo-Embolisation for Hepatocellular Carcinoma with 114. Maruyama M, Yoshizako T, Nakamura T, Nakamura M,
a Novel Radiopaque Bead. Cardiovasc Intervent Radiol. Yoshida R, Kitagaki H. Initial Experience with Balloon-Oc-
2019;42(11):1563–70. cluded Trans-catheter Arterial Chemoembolization (B-TACE)
98. Aliberti C, Carandina R, Sarti D, et al. Transarterial for Hepatocellular Carcinoma. Cardiovasc Intervent Radiol.
chemoembolization with DC Bead LUMITM radiopaque beads 2016;39(3):359–66.
for primary liver cancer treatment: preliminary experience. 115. Goldman DT, Singh M, Patel RS, et al. Balloon-Occluded
Future Oncol. 2017;13(25):2243–52. Transarterial Chemoembolization for the Treatment of Hepato-
99. Moschouris H, Malagari K, Dimakis A, Kiakidis T, Anagnos- cellular Carcinoma: A Single-Center US Preliminary Experi-
topoulou A. Transarterial Chemoembolization of HCC with ence. J Vasc Interv Radiol. 2019;30(3):342–6.
Radiopaque Microspheres: Evaluation with Computed Tomogra- 116. Golfieri R, Bezzi M, Verset G, et al. Retrospective European
phy and the Complementary Role of Contrast-Enhanced Ultra- Multicentric Evaluation of Selective Transarterial Chemoem-
sonography. Cardiovasc Intervent Radiol. 2020;43(7):1075–83. bolisation with and without Balloon-Occlusion in Patients with
100. Hagan A, Caine M, Press C, et al. Predicting pharmacokinetic Hepatocellular Carcinoma: A Propensity Score Matched Anal-
behaviour of drug release from drug-eluting embolization beads ysis. Cardiovasc Intervent Radiol. 2021;44(7):1048–59.
using in vitro elution methods. Eur J Pharm Sci. 117. Vogl TJ, Wissniowski TT, Naguib NN, et al. Activation of
2019;136:104943. tumor-specific T lymphocytes after laser-induced thermotherapy
101. Tacher V, Radaelli A, Lin M, Geschwind J-F. How I Do It: in patients with colorectal liver metastases. Cancer Immunol
Cone-Beam CT during Transarterial Chemoembolization for Immunother. 2009;58(10):1557–63.
Liver Cancer. Radiology. 2015;274(2):320–34. 118. Albert M, Kiefer MV, Sun W, et al. Chemoembolization of
102. Llovet JM, Brú C, Bruix J. Prognosis of hepatocellular carci- colorectal liver metastases with cisplatin, doxorubicin, mito-
noma: the BCLC staging classification. Semin Liver Dis. mycin C, ethiodol, and polyvinyl alcohol. Cancer.
1999;19(3):329–38. 2011;117(2):343–52.
103. Forner A, Reig ME, Rodriguez de Lope C, Bruix J. Current 119. Martin RC, Joshi J, Robbins K, et al. Hepatic intra-arterial
Strategy for Staging and Treatment The BCLC Update and injection of drug-eluting bead, irinotecan (DEBIRI) in unre-
Future Prospects. Seminars in liver disease. sectable colorectal liver metastases refractory to systemic
2010;30(1):061–074. chemotherapy: results of multi-institutional study. Ann Surg
104. Lo CM, Ngan H, Tso WK, et al. Randomized controlled trial of Oncol. 2011;18(1):192–8.
transarterial lipiodol chemoembolization for unresectable hepa- 120. Fiorentini G, Aliberti C, Tilli M, et al. Intra-arterial infusion of
tocellular carcinoma. Hepatology. 2002;35(5):1164–71. irinotecan-loaded drug-eluting beads (DEBIRI) versus intra-
105. Llovet JM, Real MI, Montaña X, et al. Arterial embolisation or venous therapy (FOLFIRI) for hepatic metastases from col-
chemoembolisation versus symptomatic treatment in patients orectal cancer: final results of a phase III study. Anticancer Res.
with unresectable hepatocellular carcinoma: a randomised con- 2012;32(4):1387–95.
trolled trial. Lancet. 2002;359(9319):1734–9. 121. Iezzi R, Marsico VA, Guerra A, et al. Trans-Arterial Che-
106. Llovet JM, Bruix J. Systematic review of randomized trials for moembolization with Irinotecan-Loaded Drug-Eluting Beads
unresectable hepatocellular carcinoma: Chemoembolization (DEBIRI) and Capecitabine in Refractory Liver Prevalent
improves survival. Hepatology. 2003;37(2):429–42. Colorectal Metastases: A Phase II Single-Center Study. Car-
107. Cammà C, Schepis F, Orlando A, et al. Transarterial diovasc Intervent Radiol. 2015;38(6):1523–31.
chemoembolization for unresectable hepatocellular carcinoma: 122. Levy J, Zuckerman J, Garfinkle R, et al. Intra-arterial therapies
meta-analysis of randomized controlled trials. Radiology. for unresectable and chemorefractory colorectal cancer liver
2002;224(1):47–54. metastases: a systematic review and meta-analysis. HPB.
108. Golfieri R, Giampalma E, Renzulli M, et al. Randomised con- 2018;20(10):905–15.
trolled trial of doxorubicin-eluting beads vs conventional 123. Pereira PL, et al. The CIREL Cohort: A Prospective Controlled
chemoembolisation for hepatocellular carcinoma. Br J Cancer. Registry Studying the Real-Life Use of Irinotecan-Loaded
2014;111(2):255–64. Chemoembolisation in Colorectal Cancer Liver Metastases:
109. Facciorusso A, Di Maso M, Muscatiello N. Drug-eluting beads Interim Analysis. CardioVasc Interv Radiol. 2020;44:50–62.
versus conventional chemoembolization for the treatment of 124. Bridgewater J, Galle PR, Khan SA, Llovet JM, Park JW, Patel T,
unresectable hepatocellular carcinoma: A meta-analysis. Pawlik TM, Gores GJ. Guidelines for the diagnosis and man-
Digestive Liver Dis. 2016;48(6):571–7. agement of intrahepatic cholangiocarcinoma. J Hepatol.
110. Yang B, Liang J, Qu Z, Yang F, Liao Z, Gou H. Transarterial 2014;60(6):1268–89.
strategies for the treatment of unresectable hepatocellular carci- 125. Hyder O, Marsh JW, Salem R, et al. Intra-arterial therapy for
noma: A systematic review. PLoS ONE. 2020;15(2):e0227475. advanced intrahepatic cholangiocarcinoma: a multi-institutional
111. Auer TA, Jonczyk M, Collettini F, et al. Trans-arterial analysis. Ann Surg Oncol. 2013;20(12):3779–86.
chemoembolization with degradable starch microspheres (DSM- 126. Filippi L, Schillaci O, Cianni R, Bagni O. Yttrium-90 resin
TACE) versus selective internal radiation therapy (SIRT) in microspheres and their use in the treatment of intrahepatic
multifocal hepatocellular carcinoma. Acta Radiol. cholangiocarcinoma. Future Oncol. 2018;14(9):809–18.
2020;62(3):313–21. 127. Labib PL, Davidson BR, Sharma RA, Pereira SP. Locoregional
112. Ogawa M, Takayasu K, Hirayama M, et al. Efficacy of a therapies in cholangiocarcinoma. Hepat Oncol.
microballoon catheter in transarterial chemoembolization of 2017;4(4):99–109.

123
P. Lucatelli et al: CIRSE Standards of Practice on Hepatic Transarterial Chemoembolisation 1867

128. Schicho A, Pereira PL, Pützler M, et al. Degradable Starch carcinoma: A multicentre observational study. J Hepatol.
Microspheres Transcatheter Arterial Chemoembolization 2019;70(5):893–903.
(DSM-TACE) in Intrahepatic Cholangiocellular Carcinoma 146. Terzi E, Terenzi L, Venerandi L, et al. The ART score is not
(ICC): Results from a National Multi-Center Study on Safety effective to select patients for transarterial chemoembolization
and Efficacy. Med Sci Monit. 2017;23:796–800. retreatment in an Italian series. Dig Dis. 2014;32(6):711–6.
129. Do Minh D, Chapiro J, Gorodetski B, et al. Intra-arterial therapy 147. Kudo M, Arizumi T, Ueshima K. Assessment for retreatment
of neuroendocrine tumour liver metastases: comparing conven- (ART) score for repeated transarterial chemoembolization in
tional TACE, drug-eluting beads TACE and yttrium-90 patients with hepatocellular carcinoma. Hepatology.
radioembolisation as treatment options using a propensity score 2014;59(6):2424–5.
analysis model. Eur Radiol. 2017;27(12):4995–5005. 148. Forner A, Gilabert M, Bruix J, Raoul JL. Treatment of inter-
130. Da Dong X, Carr BI. Hepatic artery chemoembolization for the mediate-stage hepatocellular carcinoma. Nature reviews Clin
treatment of liver metastases from neuroendocrine tumors: a Oncol. 2014;11(9):525–35.
long-term follow-up in 123 patients. Med Oncol. 149. Olweny CL, Toya T, Katongole-Mbidde E, Mugerwa J, Kyal-
2011;28(1):286–90. wazi SK, Cohen H. Treatment of hepatocellular carcinoma with
131. Gaba RC, Lewandowski RJ, Hickey R, et al. Transcatheter adriamycin. Preliminary commun Cancer. 1975;36(4):1250–7.
Therapy for Hepatic Malignancy: Standardization of Terminol- 150. Kawai S, Tani M, Okamura J, et al. Prospective and randomized
ogy and Reporting Criteria. J Vasc Interv Radiol. trial of lipiodol-transcatheter arterial chemoembolization for
2016;27(4):457–73. treatment of hepatocellular carcinoma: a comparison of epiru-
132. Filippiadis DK, Binkert C, Pellerin O, Hoffmann RT, Krajina A, bicin and doxorubicin (second cooperative study). The Coop-
Pereira PL. Cirse Quality Assurance Document and Standards erative Study Group for Liver Cancer Treatment of Japan.
for Classification of Complications: The Cirse Classification Semin Oncol. 1997;24:S6-38-s36-45.
System. Cardiovasc Intervent Radiol. 2017;40(8):1141–6. 151. Watanabe S, Nishioka M, Ohta Y, Ogawa N, Ito S, Yamamoto
133. Vera R, Aparicio J, Carballo F, et al. Recommendations for Y. Prospective and randomized controlled study of chemoem-
follow-up of colorectal cancer survivors. Clin Transl Oncol. bolization therapy in patients with advanced hepatocellular
2019;21(10):1302–11. carcinoma Cooperative Study Group for Liver Cancer Treatment
134. Singh S, Moody L, Chan DL, et al. Follow-up Recommenda- in Shikoku area. Cancer Chemother Pharmacol. 1994;33:S93-
tions for Completely Resected Gastroenteropancreatic Neu- 96.
roendocrine Tumors. JAMA Oncol. 2018;4(11):1597–604. 152. Shi M, Lu LG, Fang WQ, et al. Roles played by chemolipi-
135. Rahnemai-Azar AA, Pandey P, Kamel I, Pawlik TM. Monitor- odolization and embolization in chemoembolization for hepa-
ing outcomes in intrahepatic cholangiocarcinoma patients fol- tocellular carcinoma: single-blind, randomized trial. J Natl
lowing hepatic resection. Hepat Oncol. 2016;3(4):223–39. Cancer Inst. 2013;105(1):59–68.
136. Takayasu K, Arii S, Ikai I, et al. Overall survival after transar- 153. Boulin M, Hillon P, Cercueil JP, et al. Idarubicin-loaded beads
terial lipiodol infusion chemotherapy with or without for chemoembolisation of hepatocellular carcinoma: results of
embolization for unresectable hepatocellular carcinoma: the IDASPHERE phase I trial. Aliment Pharmacol Ther.
propensity score analysis. AJR Am J Roentgenol. 2014;39(11):1301–13.
2010;194(3):830–7. 154. Favelier S, Boulin M, Hamza S, et al. Lipiodol trans-arterial
137. Kim DY, Ryu HJ, Choi JY, et al. Radiological response predicts chemoembolization of hepatocellular carcinoma with idaru-
survival following transarterial chemoembolisation in patients bicin: first experience. Cardiovasc Intervent Radiol.
with unresectable hepatocellular carcinoma. Aliment Pharmacol 2013;36(4):1039–46.
Ther. 2012;35(11):1343–50. 155. Guiu B, Chevallier P, Assenat E, et al. Idarubicin-loaded Beads
138. Arora A, Kumar A. Treatment Response Evaluation and Follow- for Chemoembolization of Hepatocellular Carcinoma: The
up in Hepatocellular Carcinoma. J Clin Exp Hepatol. IDASPHERE II Single-Arm Phase II Trial. Radiology.
2014;4(Suppl 3):S126-129. 2019;291(3):801–8.
139. Liu W, Zheng Y, Zou R, et al. Impact of follow-up interval on 156. Guiu B, Jouve JL, Schmitt A, et al. Intra-arterial idarubicin_li-
patients with hepatocellular carcinoma after curative ablation. piodol without embolisation in hepatocellular carcinoma: The
BMC Cancer. 2018;18(1):1186. LIDA-B phase I trial. J Hepatol. 2018;68(6):1163–71.
140. Lencioni R, Llovet JM. Modified RECIST (mRECIST) assess- 157. Llovet JM, Kelley RK, Villanueva A, et al. Hepatocellular
ment for hepatocellular carcinoma. Semin Liver Dis. carcinoma Nat Rev Dis Primers. 2021;7(1):6.
2010;30(1):52–60. 158. Sergio A, Cristofori C, Cardin R, et al. Transcatheter arterial
141. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response chemoembolization (TACE) in hepatocellular carcinoma
evaluation criteria in solid tumours: revised RECIST guideline (HCC): the role of angiogenesis and invasiveness. Am J Gas-
(version 11). Eur J Cancer. 2009;45(2):228–47. troenterol. 2008;103(4):914–21.
142. Lucidarme O, Wagner M, Gillard P, et al. RECIST and CHOI 159. Kudo M, Ueshima K, Ikeda M, et al. Randomised, multicentre
criteria in the evaluation of tumor response in patients with prospective trial of transarterial chemoembolisation (TACE) plus
metastatic colorectal cancer treated with regorafenib, a sorafenib as compared with TACE alone in patients with hepa-
prospective multicenter study. Cancer Imaging. 2019;19(1):85. tocellular carcinoma: TACTICS trial. Gut. 2020;69(8):1492.
143. Kadalayil L, Benini R, Pallan L, et al. A simple prognostic 160. Sakamoto I, Aso N, Nagaoki K, et al. Complications associated
scoring system for patients receiving transarterial embolisation with transcatheter arterial embolization for hepatic tumors.
for hepatocellular cancer. Ann Oncol. 2013;24(10):2565–70. Radiographics. 1998;18(3):605–19.
144. Hucke F, Pinter M, Graziadei I, et al. How to STATE suitability
and START transarterial chemoembolization in patients with Publisher’s Note Springer Nature remains neutral with regard to
intermediate stage hepatocellular carcinoma. J Hepatol. jurisdictional claims in published maps and institutional affiliations.
2014;61(6):1287–96.
145. Wang Q, Xia D, Bai W, et al. Development of a prognostic score
for recommended TACE candidates with hepatocellular

123