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An et al. Hepatoma Res 2023;9:43 https://dx.doi.org/10.20517/2394-5079.2023.60 Page 5 of 12

Side effects of TARE
The side effect profile of TARE is typically minor, with most patients tolerating the procedure in the
outpatient setting. Mild symptoms of fatigue, nausea, and malaise are common in up to 20-40% of patients
post radioembolization, with these symptoms being referred to as “post-radioembolization syndrome”.
Non-target deposition of radioactive microspheres to the lungs and gastrointestinal tract is relatively rare,
but has the potential to cause gastrointestinal ulceration or radiation pneumonitis [36,37] . Radioembolization-
induced liver disease (REILD) is another rare but potentially serious post-radioembolization complication.
REILD occurs due to excessive radiation exposure to normal hepatic parenchyma and the risk for
development increases with a history of severe cirrhosis, prior liver external beam radiation therapy, or
multiple TARE procedures [38,39] .

Overall, post-treatment symptoms from TARE are typically better tolerated compared to those following
TACE procedures. A study by Mosconi et al. demonstrated an increased rate of clinical adverse events for
TACE compared to TARE (58.5% vs. 43%), particularly with post-embolization syndrome and post-embolic
[40]
liver abscesses . This finding suggests that TARE may be preferable in patients with a history of biliary
instrumentation or frail patients receiving concurrent systemic chemotherapy.

TRANS-ARTERIAL CHEMOEMBOLIZATION FOR INTRAHEPATIC CHOLANGIOCARCINOMA
Overview
TACE delivers chemotherapy and embolic material to liver tumors via the hepatic arteries. Selective delivery
of chemotherapy via the hepatic arteries that supply tumor allows a concentrated and localized dose of
[41]
chemotherapy to be administered with limited systemic delivery . Embolization and occlusion of arterial
branches supplying tumor also have the additional advantage of causing ischemia and necrosis within the
targeted lesions.

There are two different approaches to performing TACE: conventional TACE (cTACE) and drug-eluting
bead TACE (DEB-TACE). cTACE uses a chemotherapeutic agent mixed with ethiodized oil contrast called
lipiodol. Chemotherapeutic agents commonly utilized during cTACE include doxorubicin, cisplatin,
gemcitabine, and mitomycin-C [42,43] . DEB-TACE utilizes chemotherapy-coated microbeads which allow for
sustained drug release within the tumor [44,45] . Irinotecan and doxorubicin are commonly utilized
chemotherapeutic agents with DEB-TACE for intrahepatic cholangiocarcinoma . Both TACE approaches
[46]
combine the synergistic cytotoxic effects of high-dose, localized chemotherapy with the ischemic effects of
occluding the tumor arterial blood supply.

Clinical efficacy of TACE
Multiple studies have demonstrated median survival between 12 to 26 months post treatment with cTACE
in the setting of unresectable intrahepatic cholangiocarcinoma [40,43,47-50] . Park et al. compared patients with
intrahepatic cholangiocarcinoma who underwent cTACE (n = 72) vs. supportive therapy (n = 83) and
reported significantly improved survival for the cTACE cohort (12.2 months vs. 3.3 months) . Cisplatin
[51]
was the chemotherapy of choice utilized during chemoembolization and partial tumor response was noted
in 23% of patients who underwent TACE. Among patients undergoing TACE, survival was significantly
improved in patients with liver-only disease compared to those with extrahepatic metastases (13.3 months
vs. 11.3 months) and among patients with partial tumor response compared to those with no response (22
months vs. 10.9 months). Factors associated with decreased survival post TACE for unresectable
intrahepatic cholangiocarcinoma include increased tumor size (> 5 cm), history of prior major resection,
short interval tumor progression, poor tumor differentiation, and tumor hypo-vascularity [48,49,52] .