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Page 4 of 9 John et al. Hepatoma Res 2020;6:56 I http://dx.doi.org/10.20517/2394-5079.2020.37

Table 1. Outcomes of SBRT to liver metastases from selected recent studies
Dose/fractionation Median Followup 2 year LC 2 year OS
Authors Study design n Primary tumor
(#) in months (%) (%)
[7]
Scorsetti et al. 2015 Prospective (Phase 2) 42 CRC 75 Gy/3 # 24 91 65
[8]
Goodman et al. 2016 Retrospective 81 CRC 66.6% 32-60 Gy/3-5 # 33 90.5 68.6
Breast 7.4%
Lung 3.7%
Ovarian 3.7%
GI 13.6%
Others 4.9%
[9]
McPartlin et al. 2017 Prospective (Phase 1 & 2) 60 CRC 22.7-62.1 Gy/6 # 28.1 32 26
Joo et al. [10] 2017 Retrospective 70 CRC 45-60 Gy/3-4 # 34.2 73 75
Mahadevan et al. Retrospective 427 CRC 44.3% Median 45 (12-60) 14 72 49
[11]
2018 Lung 12.2% Gy/median 3 (1-5)
Breast 9.8% #
GI 7.7%
Gynae 5.9%
Pancreas 4.9%
Other 15.2%
SBRT: stereotactic body radiotherapy; LC: local control; OS: overall survival; CRC: colorectal cancer; GI: gastrointestinal
Outcomes
Local control of hepatic metastases with SBRT are generally encouraging with most studies achieving
approximately 80% at 2 years (range 32% to 91%) [Table 1]. This is mostly influenced by size of tumour,
prior treatment, and biologically equivalent dose delivered. Median overall survival after SBRT can vary
from 26% to 75% at 2 years [Table 1]. However, it is recognised that the patient’s overall prognosis may
be related to extra-hepatic metastases, thus reinforcing the need for multimodal treatment with effective
systemic therapy as opposed to monotherapy with either alone. In most studies concerning the outcomes
of SBRT for liver metastases, patients would have received systemic therapy (e.g., chemotherapy, targeted
therapy) before and/or after SBRT. This reinforces the need for both effective local and systemic therapy.

Toxicity
Radiation-induced liver disease (RILD) is a feared complication which can be hard to manage . RILD
[12]
typically presents 4-8 weeks after completion of radiotherapy (RT). The occurrence of RILD is related to
the volume of liver irradiated, pre-existing hepatic functional reserve, and patient co-morbidities. Classic
RILD symptoms include fatigue, abdominal pain, anicteric ascites and hepatomegaly. RILD however is
more common in whole liver RT (WLRT), although it can occur with SBRT . Collateral damage to nearby
[13]
structures is known to occur, including biliary obstruction and stricture formation (for lesions near the
porta hepatis), and gastro-intestinal injury (resulting in bleeding, perforation or strictures). With adherence
to known dose limits, the risks of these complications can be reduced to below 5%.

Comparison of SBRT with RFA
The most common technique of thermal ablation is radiofrequency ablation (RFA). RFA uses a high
frequency alternating electric current which produces ionic agitation and frictional heating, thereby
heating tumour tissue to over 60 degrees Celsius. Tumour heating causes extracellular and intracellular
dehydration, resulting in tissue destruction by coagulative necrosis. RFA can be performed percutaneously,
laparoscopically, or during open surgery . RFA is usually limited, however, by proximity to the biliary
[14]
[15]
tree as well as to blood vessels because of the “heat sink” effect. Stang et al. reported that local recurrence
rates were 5% to 42% after RFA and that the dominant factor affecting local failure rates were the size of the
[16]
lesion, particularly those larger than 3 cm. Jackson et al. . also reported similar efficacy of SBRT and RFA
for lesions smaller than 2 cm, however SBRT achieved better local control comparatively for lesions larger
[16]
than 2 cm . As such, RFA and SBRT are complementary modalities. SBRT is preferred for lesions near
blood vessels or the dome of the liver, and for larger lesions.