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Carr. Hepatoma Res 2019;5:3 I http://dx.doi.org/10.20517/2394-5079.2018.113 Page 3 of 10

Table 1. Comparison between glass (Therasphere) and resin microspheres (SIR-Spheres)
Therasphere SIR-Spheres
Half-life 64.2 h 64.2 h
Material Glass Resin
Size 20-30 μm 20-60 μm
Activity per sphere 2500 Bq 50 Bq
Number of sphere 1.2-8 milion 40-80 milion
Embolic effect Minimal Moderate

90
Yttrium-90 or Y SIRT has gained increased popularity in recent years as a safer alternative to TACE,
especially in the setting of PVT. Two non-identical products [Table 1] are available, namely Therasphere
and SIR-Spheres. Therasphere contains glass as the carrier and is much more radioactive, but almost not
embolic and is FDA-approved for HCC therapy under a humanitarian device exemption (requires individual
institutional review board approval). SIR-Spheres are made of resin carrier and are by contrast much less
radioactive per dose, but have many more particles per dose and are thus embolic (hence radioembolization).
Neither agent seems to induce much post-embolization syndrome, unlike TACE. Therasphere is thus really
a pure internal radiation treatment and not radioembolization. There have been few convincing randomized
trials with either agent for HCC survival, either against each other (although they are thought to have similar
[16]
results) or against TACE . However, several reports provide evidence for their effectiveness and safety [16-19] .
Unlike TACE, these radioactive agents need to be received by the institution and handled by radiation
safety staff and appropriately monitored. Thus, SIRT therapy requires a special team, including a radiation
pharmacy, radiation safety officer, nuclear medicine physician, as well as the interventional radiologist.
99m
Unlike for TACE, SIRT patients require a pre-treatment angiogram together with a Technetium Tc macro
99m
aggregated albumin ( Tc-MAA) scan to measure any significant lung shunting. More than 20% lung shunt
normally excludes SIRT, as does aberrant gastric or other feeder arteries than cannot be occluded, to prevent
gastrointestinal radiation toxicity.

The most remarkable benefit of SIRT is its safety in treating that 30%-40% of HCC patients that have PVT [20-22] .
However, overall survival (OS) did not differ significantly when SIRT was compared to sorafenib in a phase
[23]
III trial . Nevertheless, the combination of SIRT with sorafenib was associated in one study with enhanced
toxicity . In the SORAMIC randomized phase II trial, the addition of SIRT (SIR-Spheres) to sorafenib
[24]
did not add to survival compared with sorafenib alone. When TACE and SIRT were directly compared,
they were similar in safety, tumor responses and survival [25,26] . Studies are in progress on the uses of SIRT
in adjuvant and neo-adjuvant therapy for surgery of HCC, as well as in combinations with several newer
therapies.

Sorafenib (nexavar)
Sorafenib is a multikinase inhibitor that is antiangiogenic, inhibits HCC cell growth and induces apoptosis.
It is thought to target the Ras/Raf/methyl ethyl ketone (MEK)/extracellular signal-regulated kinase
signaling pathway via the vascular endothelial growth factor (VEGFR) and platelet-derived growth factor
receptor (PDGFR). For the last 10 years it has been the choice for first line of therapy for patients with HCC
metastases, PVT, or those who have failed TACE or SIRT, based on a multi-center, double-blind, placebo-
controlled phase III SHARP trial, which reported a 2.8 months increase in median OS with sorafenib (10.7
months) compared with placebo (7.9 months) [hazard ratio (HR) in sorafenib group, 0.69; 95% confidence
[27]
interval (CI) 0.55-0.87; P < 0.007] . However, in a similarly designed phase III trial from Asia, results were
much worse, with a median OS of 6.5 months (95% CI 5.56-7.56) in patients treated with sorafenib, compared
[28]
with 4.2 months (3.75-5.46) in those who received placebo (HR 0.68; 95% CI 0.50-0.93; P = 0.014) . The
reasons that the OS from Asia after sorafenib treatment was worse than the OS on placebo in the European
study are not clear, but point to the need for caution in comparing results of therapies in different ethnic
groups, or in patients with differing severity of tumor or cirrhosis. In addition to a significant but only