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Della Corte et al. Hepatoma Res 2022;8:5 https://dx.doi.org/10.20517/2394-5079.2021.103 Page 9 of 15

Both in cTACE and DEB-TACE, treatment design may be lobar, segmental, or subsegmental, according to
the disease extension and distribution. Underlying liver function must be taken into account when planning
the treatment strategy, since lower volume of ischemia may be tolerated in cirrhotic patients; for this reason,
treatment schedule may be organized in sequential sessions (at least 2 weeks apart) if a large volume of liver
is involved, in order to allow healthy parenchyma to withstand the ischemic injury and preserve function.

Trans-arterial radioembolization
Trans-arterial radioembolization (TARE) consists in the intra-arterial injection of radioactive microspheres,
in order to selectively release a high radiation dose to liver tumor cells while maintaining an acceptable dose
to the healthy parenchyma . Inclusion criteria for TARE include, but are not limited to, ECOG
[72]
performance status of 0-2 and adequate liver function with bilirubin < 2.0 mg/dL. Some of the exclusion
criteria are the presence of shunts with gastrointestinal arteries not feasible for embolization and an
estimated radiation dose to the lungs > 30 Gy. Similar to TACE, the ideal candidates for TARE are patients
[73]
with unresectable liver-only or liver-dominant tumors , particularly if hypervascularization is evident on
preoperative imaging.

The procedure is divided in a work-up session and a treatment session, generally a week apart. In the
former, an accurate angiographic study, possibly aided by cone-beam-CT technology, is performed to
identify and possibly embolize extrahepatic feeders and shunts between hepatic and gastrointestinal
circulation. Following a good targeting of the lesion(s), albumin macroaggregates marked with technetium-
99 (99mTc-MAA) are injected intraarterially and the patient undergoes a single photon emission CT within
the same day to map 99mTc-MAA distribution and validate treatment feasibility. If the work-up has a
positive outcome, the treatment session consists in targeting the same vessels previously injected with
99mTc-MAA and infuse of yttrium-90 (Y-90) microspheres. In case of work-up failure, either a new work-
up procedure is scheduled or other treatment strategies are considered. TARE may be performed with either
[74]
glass or resin Y-90 charged microspheres, without significant differences in terms of safety or efficacy . In
both cases, bead size range is 20-30 microns, which allows radioisotope entrapment within the sinusoids
exerting its therapeutic effect by localized radiation rather than by ischemia as seen in TACE. The lower
ischemic effect allows the theoretical possibility of treating larger liver volumes than TACE, without altering
liver function as much.

Studies show median survivals ranging from 9 to 22 months [67,75] ; factors associated to worse survival after
TARE were having ECOG performance 1 or 2 [76-78] and infiltrative disease [76,78] . However, a considerable
heterogeneity of baseline data mainly regarding the inclusion of patients with both peripheral and
infiltrative disease, varying tumor burden, and patients who received previous systemic chemotherapy
constitute the main limit in drawing conclusions regarding its efficacy.

A meta-regression study by Cucchetti et al. showed that naïve patients had a 2-year survival of 50.4%
[79]
compared to 23.6% in patients previously treated with systemic CT. Survival was found to be longer in
patients with non-infiltrative type ICC; however, these data are not confirmed by the largest single center
[80]
[81]
cohort of patients (n = 85) available to date . The recent CIRT prospective trial enrolled 120 patients
with ICC and showed a median OS of 14.7 months and severe adverse events at thirty days (grade 4 and 5)
observed in less than 2.5% of patients. Of note is that 60.8% of these patients had received systemic CT.

In addition, TARE seems to have a favorable safety profile: post-radioembolization syndrome, hepatic
dysfunction, biliary complications, portal hypertension, radiation pneumonitis, gastrointestinal ulceration,
vascular injury, and lymphopenia are the most frequent adverse events even though they rarely occur,
[82]