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Page 2 of 12 An et al. Hepatoma Res 2023;9:43 https://dx.doi.org/10.20517/2394-5079.2023.60

intrahepatic cholangiocarcinoma and hepatocellular carcinoma suggests that they share oncogenic
[2]
pathways . There are multiple risk factors for developing cholangiocarcinoma, including cirrhosis related
[3]
to alcohol use, primary sclerosing cholangitis, chronic viral hepatitis, and biliary parasitic infection . In
recent decades, the incidence of cholangiocarcinoma has been on the rise, particularly for intrahepatic
cholangiocarcinoma .
[1,4]
Intrahepatic cholangiocarcinoma has a poor overall prognosis, with less than a 10% median 5-year survival
after diagnosis . R0 surgical resection is a curative treatment option for intrahepatic cholangiocarcinoma.
[5]
The role of liver transplantation as a potential curative option for intrahepatic cholangiocarcinoma has also
been revisited in recent years . However, the majority of patients are not eligible for resection at the time of
[6]
[7,8]
diagnosis and recurrent disease is common following surgery, often occurring in the remnant liver . Early
detection of intrahepatic cholangiocarcinoma is difficult since many patients do not develop symptoms in
the early stages.

Systemic chemotherapy has limited efficacy in patients with unresectable disease. First-line chemotherapy
with cisplatin and gemcitabine has demonstrated median survival of less than 12 months in multiple
studies [9,10] . Some improvement over these results has been seen with the addition of durvalumab to
gemcitabine and cisplatin in the TOPAZ-1 study, as well as gemcitabine, cisplatin, and nab-paclitaxel,
although this regimen has a high grade III/IV adverse event rate [11,12] . Recent advances have also been made
in targeted systemic therapy options against IDH1 and FGFR2 mutations for intrahepatic
cholangiocarcinoma [13-15] . Treatment options offered by interventional radiology, including trans-arterial
radioembolization (TARE) and trans-arterial chemoembolization (TACE), are increasingly utilized in
current practice for unresectable diseases. Both TACE and TARE are minimally invasive procedures that
allow for endovascular delivery of chemotherapy or radiation selectively to liver tumors.

The rationale for TACE and TARE relies on the dual blood supply of the liver from the hepatic arteries and
portal veins. In healthy individuals, the liver receives approximately 75% of its blood flow from the portal
veins and 25% from the hepatic arteries . Hepatic tumors including hepatocellular carcinoma and
[16]
[17]
intrahepatic cholangiocarcinoma are predominantly vascularized by the hepatic arteries . This vascular
pattern allows trans-arterial interventions including chemoembolization and radioembolization to deliver
concentrated doses of chemotherapy or radiation directly to tumors while partially sparing normal liver
parenchyma and decreasing the risk of non-target systemic side effects.

This review provides an overview of trans-arterial chemoembolization and radioembolization for
intrahepatic cholangiocarcinoma, summarizes current evidence, and explores future directions for
locoregional therapies.

TRANS-ARTERIAL RADIOEMBOLIZATION FOR INTRAHEPATIC CHOLANGIOCARCINOMA
Overview
TARE is an endovascular intervention that delivers radioactive isotope-coated microspheres to tumors via
selective catheterization of the hepatic arteries . TARE may be performed in settings with interventional
[18]
radiology and nuclear medicine capabilities. Selective internal radiation therapy (SIRT) is another common
name for this procedure.

TARE was first described in 1965 and has demonstrated efficacy in the setting of primary and metastatic
hepatic tumors . Radioembolization is performed with microspheres impregnated with the radioactive
[19]
isotope Yttrium-90 ( Y), a high-energy beta emitter. Y decays to stable element Zirconium-90 with a half-
90
90