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Page 6 of 13 Spieler et al. Hepatoma Res 2019;5:4 I http://dx.doi.org/10.20517/2394-5079.2018.77

Intra-arterial embolizations such as TACE are primary treatments for HCC patients with unresectable
tumors and CP-A or B hepatic function who do not meet transplant criteria and cannot receive local
ablation. In bland transarterial embolization, micron-sized particles are delivered into the tumor vasculature
to decrease blood supply to the tumor and induce necrosis through hypoxia; in TACE, a chemotherapy
agent infused into the region of interest remains sequestered due to subsequent microparticle embolization,
[31]
potentiating cytotoxic effects . Absolute contraindications to TACE include tumor involving more than
half the liver, renal insufficiency, extrahepatic disease, reduced portal flow, or poor prognosis indicated by
[32]
hepatic encephalopathy and jaundice .

[33]
In 2017 Sapisochin et al. first compared SABR (n = 36) with TACE (n = 99) and RFA (n = 244) as bridges
to OLT in patient with HCC. The study found that SABR, while treating a greater tumor burden than RFA,
[33]
demonstrated similar post-transplant survival and recurrence rates as the other techniques .
In cases of borderline ineligibility for transplant, SABR is a logical option for downstaging HCC, as it is
less invasive than surgery, RFA or TACE and provides comparable survival outcomes [33-35] . A recent study
comparing SABR to resection in patients with CP-A disease and lesions ≤ 5 cm in greatest dimension
[34]
reported comparable OS with fewer complications in the SABR group . A 2015 University of California
San Francisco study recommended an individualized approach to the choice of locoregional therapy for
[36]
downstaging, determined case-by-case at a multidisciplinary tumor board . The multidisciplinary model
[37]
has been shown to improve HCC patient outcomes .

SABR FOR PATIENTS WHO ARE NOT SURGICAL CANDIDATES
Treatment algorithms corresponding to clinical stages of HCC continue to evolve. There is increasing
[38]
recognition that spatial cooperation with combination therapies can improve patient survival . Among
all treatments for HCC, only palliative systemic agents sorafenib and regorafenib are supported by category
1 evidence. Surgical, ablative, intra-arterial and external beam approaches rely on consensus support from
[10]
oncologists based on category 2 evidence .
The 2017 US NCCN guidelines emphasize the ability of SABR to treat HCC at any location in the
[10]
liver . NCCN considers SABR an appropriate alternative to ablation/embolization techniques. This
recommendation is supported by a bulk of published data including the retrospective studies comparing
[39]
SABR with RFA and TACE. A 2016 retrospective study by Wahl et al. compared SABR (63 patients treated
with 27-60 Gy in 3-5 fractions) to RFA (161 patients), showing these two modalities to be equally effective
for the treatment of inoperable HCC < 2 cm, with SABR providing better local control than RFA for lesions
≥ 2 cm. Another retrospective series that compared TACE and SABR reported that 2-year local control was
[40]
significantly better for SABR, 91.3%-22.9% with no significant difference in OS .
While SABR is most often used to treat tumors ≤ 5 cm and 1-3 liver lesions, it can ablate more extensive
disease provided radiation constraints and liver remnant limits are met. In Princess Margaret Hospital
[41]
(PMH) phase I and II trials, Bujold et al. reported the ability of SABR to accommodate an increased tumor
burden. While the PMH multivariate analysis revealed that gross tumor volume was unrelated to treatment
[41]
outcome , other studies report significantly better local control when using SABR on tumors < 5 cm [42,43] .
SABR also can serve as second-line therapy when alternatives are contraindicated or have already failed.
In the PMH trial, SABR was used to treat 102 patients with advanced HCC, ineligible for surgery, TACE
or RFA. Median tumor diameter was 7.2 cm, more than half the cohort had PVTT and 12% had distant
metastases. Despite this heavy disease burden, patients receiving a median dose of 36 Gy (range 30-54 Gy) in
6 fractions had a 17-month median OS and one year local control rate of 87%, superior to historical controls
[41]
for sorafenib (6.5-10.7 months OS) and supportive care (4.2-7.9 months OS) .