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Page 4 of 10 Sullivan et al. Hepatoma Res 2018;4:68 I http://dx.doi.org/10.20517/2394-5079.2018.95

electroporation (IRE) may be considered for these lesions. IRE involves the application of an electric field
above a threshold that causes irreversible damage to the cell membrane but below the threshold causing
thermal damage thus minimizing coagulative necrosis. The non-thermal nature of this technique allows
[31]
potential application when lesions are near important structures . Large-scale clinical data remains
scarce for this technique, with retrospective studies showing local tumor progression rate within the first
year of 20%-34% [32,33] and progression free survival rate of 70% at 12 months [32,33] . Overall, the two thermal
ablation techniques (RFA and MWA) appear to provide similar outcomes for patients with HCC lesions
less than 3 cm located away from major vascular or biliary structures and while more data is required, the
IRE technique is promising as an alternative for small lesions located next to major structures.

Current practice advocates a minimally invasive approach to liver tumor ablation such that treatments
can usually be performed on an out-patient basis. For tumors lying deep in the liver parenchyma, image-
guided percutaneous approach is often feasible. However, for lesions that are near the periphery of the
liver where it comes within 1 cm of the visceral structures (e.g., stomach, duodenum, colon, gallbladder,
diaphragm), we prefer a laparoscopic approach to safely avoid injuries to such organs. In patients with
sub-diaphragmatic lesions (e.g., segment 7, 8) especially in the setting of multiple prior open abdominal
surgeries involving the right upper quadrant, we recommend a minimally invasive thorascopic approach.
Open ablations are reserved for patients who are undergoing laparotomies for other indications.

Trans-arterial therapies for HCC
For patients with multinodular tumors (> 3) and those larger than 5 cm (i.e., BCLC stage B), catheter-
[34]
based therapies are recommended if otherwise not a resection candidate . Options for catheter-based
therapies include transarterial bland embolization, chemoembolization (TACE), or radioembolization
(TARE) using yttrium-90 (Y90) glass beads. For these patients who have contraindications to undergo
resection or ablation, TACE has been demonstrated in RCTs to be superior in terms of survival compared
to supportive care [35,36] . For Y90 radioembolization, the SARAH trial in Europe did not demonstrate a
difference in OS with Y90 vs. sorafenib as first-line therapy, but did show better local tumor response and
improved quality of life, as indicated by lower total and median numbers of treatment-related adverse
events in the Y90 group . Similarly, SIRveNIB trial in Asia did not demonstrate an OS difference when
[37]
comparing Y90 radioembolization to sorafenib, but similarly showed increased tolerability to treatment
[38]
with radioembolization . Importantly, liver-directed Y90 treatment was not inferior to sorafenib as first-
line therapy for patients with advanced HCC confined to the liver, thus providing meaningful options for
these patients.

Comparing lobar TACE with TARE, both methods appear to have similar OS [39-44] . Patients undergoing
[45]
[43]
TARE benefit from longer time to progression and progression-free survival compared to TACE with
shorter hospitalization stays [41,42] . In a comparative effectiveness study of various transarterial strategies
based on network meta-analysis, chemo- and radio-embolization provide improved tumor objective
response over control (supportive care) and bland embolization, but did not show survival benefit over
[46]
bland embolization alone .
In recent years, there is a trend towards the use of selective, high-dose radioembolization, so-called
radiation segmentectomy, for HCCs that receive their arterial supply predominantly from one segmental
artery; these lesions tend to be located more peripherally rather than central tumors that often draw
blood supply from multiple segmental branches. In the appropriate patients, Y90 segmentectomy is
designed to deliver higher radiation dose to the target lesion while sparing more of the non-tumor liver.
In a retrospective experience of 178 patients undergoing segmental catheter-based treatments for HCC at
our institution, propensity score-matched analysis highlights 92% complete response of the index lesion
following Y90 segmentectomy compared with 74% in the TACE group . Progression-free survival was
[45]