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Spieler et al. Hepatoma Res 2019;5:4 I http://dx.doi.org/10.20517/2394-5079.2018.77 Page 7 of 13

[28]
Andolino et al. reported results of a phase I dose escalation study in which 36 patients with CP-A disease
received 48 Gy in 3 fractions while 24 patients with CP-B disease received 40 Gy in 5 fractions. Two-year
[28]
local control was 90%, 2-year OS was 67%, and median time to progression was 47.8 months .

SABR VS. TRANSARTERIAL RADIOEMBOLIZATION
While SABR is a minimally invasive, external beam radiation platform with precise dosimetry able to
reliably target subsegmental lesions, transarterial radioembolization (TARE), also known as selective internal
radiation therapy is often used to treat large multifocal disease impossible to address with SABR techniques.
TARE can deliver very high local doses of radiation to HCC involving entire segments of the liver with a
single invasive procedure. Published data support the use of both modalities, and no direct comparison has
been attempted through clinical trials. The decision to use TARE or SABR is institution specific, based on
disease distribution, co-morbidities and multidisciplinary tumor board consensus.

TARE is an ablative radiation technique that involves injection of radiolabeled yttrium-90 (Y-90)
microspheres into the hepatic artery by guided catheterization. Isotope-containing microspheres lodge in
arterioles feeding liver tumors, embolize the small vasculature and deliver very high, tumoricidal doses
[44]
(estimated to be 85-120 Gy and even higher in cases of TARE segmentectomy 300-400 Gy) . TARE
selectively targets disease by exploiting the liver’s dual blood supply: tumors greater than 3 cm in size are
fed primarily by the hepatic artery while the liver parenchyma’s main source of blood supply is through the
portal vein.

Y-90, a beta-emitting isotope with a half-life of 2.67 days, is packaged in glass (Theraspheres, BTG Canada)
or resin (SIR-Spheres, Sirtex Australia) particles. Spheres with diameters between 20 and 60 microns occlude
arteries feeding the tumor proximal to arteriovenous anastomoses, sparing central venules from toxic doses.
Central vein obliteration is characteristic of RILD, so precapillary entrapment combined with short-range
activity accounts for low rates of radioembolization induced liver disease (REILD) in TARE studies .
[45]
For HCC patients with CP-A liver function treated with TARE, multiple studies report OS greater than
15 months [46-48] . Many patients in these studies had significant tumor burdens, with multifocal disease, PVTT
and median tumor diameters greater than 5 cm. Table 2 summarizes prospective trials showing TARE as an
excellent option for tumor control in high-volume and multifocal HCC.

In the treatment of unresectable primary liver cancer, TARE’s clinical applications range from palliation to
[10]
transplant bridging . TARE can treat HCC in the setting of PVTT, whereas reduced main portal vein flow
is a contraindication to TACE [47,49] .

Mild TARE-related syndromes are commonly reported after treatment of HCC, such as fatigue, abdominal
pain, nausea, vomiting, and low-grade fever. Adverse events grade 3 or greater include 10% biliary
toxicity 2%-13% REILD and 5.8%-23% bilirubin elevation [50,51] . While randomized studies show that Y-90
radioembolization significantly prolongs time to HCC progression compared with TACE, grade 3 or higher
toxicity rates are comparable between TARE and TACE [46-49] .

Dosimetric software, providing accurate assessment of the dose delivered to tumor and adjacent normal
liver tissue during TARE procedures, has recently been FDA approved (Hermes Medical Solution). Better
assessment of dose delivered to tumor tissue and uninvolved liver may permit strategies combining both
SABR and TARE in selected situations or may allow for better comparisons and selection between the two
techniques for individual patients.