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Page 6 of 12 An et al. Hepatoma Res 2023;9:43 https://dx.doi.org/10.20517/2394-5079.2023.60

The median survival following DEB-TACE has been shown to be between 9 to 13 months for unresectable
intrahepatic cholangiocarcinoma, similar to studies with cTACE [53-56] . A meta-analysis of 1091 patients who
underwent cTACE and DEB-TACE for intrahepatic cholangiocarcinoma demonstrated a pooled objective
response rate of 51.2% for DEB-TACE and 29.4% for cTACE. Despite this large difference in response rate,
there was no statistically significant difference in survival between the two treatment methods . Similarly,
[57]
Wang et al. reported a prospective study comparing DEB-TACE and cTACE with irinotecan demonstrated
no significant difference in median overall survival of 11.5 months vs. 9.0 months, respectively . However,
[58]
this study did demonstrate a statistically significant advantage for DEB-TACE over cTACE in overall
response rate and progression-free survival. Venturini et al. compared DEB-TACE with doxorubicin vs.
irinotecan in 10 patients and demonstrated increased overall survival in patients who underwent irinotecan
DEB-TACE compared to doxorubicin DEB-TACE, although results were limited by small sample size .
[46]
Additional prospective studies are needed to further compare the efficacy of cTACE vs. DEB-TACE for
intrahepatic cholangiocarcinoma.

Scheuermann et al. compared survival in patients undergoing both cTACE and DEB-TACE vs. surgical
resection for intrahepatic cholangiocarcinoma . As expected, there was significantly improved median
[59]
survival in patients who underwent R0 surgical resection without lymph node metastases (37 months).
However, the authors demonstrated no significant difference in median survival between patients who
underwent TACE (11 months) vs. patients who had positive resection margins (11 months) or positive
lymph node metastases (9 months). A summary of studies examining TACE for intrahepatic
cholangiocarcinoma is included in Table 2.

Although TACE has the potential to improve survival in patients with unresectable intrahepatic
cholangiocarcinoma, the intervention remains palliative rather than curative. In a study of patients with
intrahepatic cholangiocarcinoma who underwent TACE prior to liver transplant, viable residual tumor was
[60]
demonstrated in 100% of explants (n = 13) . In addition, tumor necrosis was observed in only 7.6% of the
tumor volume post-TACE treatment for intrahepatic cholangiocarcinoma, which was significantly lower
than the degree of tumor necrosis observed in patients with hepatocellular carcinoma who underwent
TACE pre-transplant (75.1%). This finding may be secondary to the hypo-vascular nature of intrahepatic
cholangiocarcinoma relative to hepatocellular carcinoma, which may make the tumors less susceptible to
ischemic necrosis following TACE.

Side effects of TACE
Potential side effects of TACE include abdominal pain, nausea, fever, and liver enzyme elevation in up to
20% -40% of cases [61,62] . Additional systemic side effects such as anemia, alopecia, and myelosuppression are
uncommon, but have also been observed post-TACE due to systemic translocation of chemotherapeutic
agents . Together, these symptoms are referred to as “postembolization syndrome” and often self-resolve
[63]
in one to two days. TACE is often performed as an outpatient procedure; however, some patients require
overnight observation for symptom management. Major complications from TACE are relatively
uncommon, but may be secondary to non-target embolization and/or induced liver ischemia. Potential
major complications include hepatic abscess, cholecystitis, or gastrointestinal tract ulceration, which occur
in approximately 2%-5% of patients [63,64] .

SYSTEMIC CHEMOTHERAPY COMBINED WITH LOCOREGIONAL INTERVENTIONS
Palliative systemic chemotherapy remains the main treatment option for patients with unresectable
intrahepatic cholangiocarcinoma [9,65] . However, there is increasing evidence that locoregional therapies
including TACE and TARE in combination with palliative systemic chemotherapy may provide additional