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Page 10 of 15 Della Corte et al. Hepatoma Res 2022;8:5 https://dx.doi.org/10.20517/2394-5079.2021.103

especially when treatment planning and execution are properly performed.

Another fairly recent interesting application of TARE is in the neoadjuvant setting (i.e., in downstaging an
[83]
initially unresectable ICC rendering the surgical option feasible). A study by Riby et al. showed that
patients undergoing preoperative TARE could undergo resection with a comparable prognosis to patients
undergoing upfront surgery; furthermore, TARE showed benefit as downstaging treatment in terms of
survival compared with patients treated with chemotherapy.

HEPATIC ARTERY INFUSION CHEMOTHERAPY
Hepatic arterial infusion chemotherapy (HAIC) (i.e., injecting chemotherapeutic agents into the hepatic
artery without embolization) is an option to obtain effective drug delivery without the systemic side effects
seen with systemic chemotherapy. HAIC consists of a continuous infusion of floxuridine into the hepatic
arterial circulation administered through a surgically implanted pump at a predetermined flow rate .
[84]
Previous studies have demonstrated that HAIC is a promising option for advanced ICC and has shown
better tumor control than systemic chemotherapy .
[85]

Recently, studies involving agents other than floxuridine have been published; a study describing
intraarterial epirubicin and cisplatin combined with systemic 5-fluorouracil demonstrated an objective
response rate and median survival time of 36% and 15.4 months, respectively .
[86]

[87]
A study by Cai et al. compared the outcome of mFOLFOX-HAIC and TACE, demonstrating higher one-
year overall survival rates after the HAIC treatment compared with those after TACE treatment (1-year OS
rates: 60.2% vs. 42.9%, 2-year OS rates: 38.7% vs. 29.4%, P = 0.028).

HAIC was shown to have the highest rate of adverse events and liver-related toxicity among intra-arterial
therapies for ICC , therefore it has questionable safety profile. In general, its application is reserved to
[17]
extended bilobar disease, in case of non-response or poor compliance to systemic chemotherapy.

CHEMOSATURATION - PERCUTANEOUS HEPATIC PERFUSION
First studied for treatment of hepatic metastases from ocular melanoma , chemosaturation - percutaneous
[88]
hepatic perfusion with intra-arterial melphalan injection represents an emerging technique for disease
control in unresectable ICC. In this technique, a transfemoral catheterization of the hepatic artery is used
for chemoperfusion of the liver with melphalan. A transfemoral venous double-balloon catheter is inflated
to isolate the intrahepatic tract of the inferior vena cava. Venous blood from the liver, extracted through
side holes of the double-balloon catheter, is filtered via an extracorporeal hemofiltration circuit, while a
transjugular venous access is used for blood return.

A multi-institutional study by Marquardt et al. on a cohort of 26 patients with unresectable ICC
[89]
demonstrated an overall response rate of 20% and disease control in 53% of patients after first treatment
session, with a median OS of 26.9 months from initial diagnosis and 7.6 months from first treatment, and
median progression free survival of 4.1 months. Patients with liver-only disease exhibited a significantly
longer median OS compared to patients with loco-regional lymph node metastases (12.9 months vs. 4.8
months, respectively; P < 0.01). Regarding safety, no grade 3 or 4 adverse events occurred during the
procedure; however, hematological toxicity including thrombocytopenia and anemia, requiring transfusions
in the post-procedural period, were fairly common, and one patient with a tumor load > 40% of the liver
developed acute multi-organ failure after the treatment. Given its good response coupled with a mild
burden of systemic side effects, the application of this treatment strategy is limited to extended liver disease