Page 45 - Read Online

Page 2 of 13 Spieler et al. Hepatoma Res 2019;5:4 I http://dx.doi.org/10.20517/2394-5079.2018.77

Patients with HCC often present with a large tumor burden on a background of cirrhosis and hepatic
[4,5]
decompensation, complicating treatment tolerance . Prognosis of HCC depends on stage at presentation as
[6]
well as overall liver function .
Surgical resection is considered the first-line treatment for non-cirrhotic patients. Preoperative criteria such
as Child-Pugh (CP) classification have been developed for risk stratification to minimize postoperative
[7]
hepatic decompensation and prevent futile interventions . Contraindications to resection include major
vascular invasion, portal hypertension, large multifocal lesions, extrahepatic disease, CP class B/C (CP-B/C)
or inadequate liver remnant. Predicted liver remnant must be in the range of 40% of preoperative total liver
[7]
3
volume or 700 cm for a patient to be considered eligible for resection .
More than 70% of HCC patients have portal hypertension and cirrhosis at diagnosis, making them ineligible
[8]
for liver resection . Orthotopic liver transplant (OLT) is an alternative for patients who meet the Milan
criteria (a single tumor < 5 cm or up to three tumors < 3 cm without vascular invasion or extrahepatic
[9]
manifestation) .

Patients who are not candidates for tumor resection or OLT may be candidates for liver-directed therapy.
Liver-directed therapies can be grouped into the following broad categories: intra-arterial treatments
(radioembolization, chemoembolization, bland embolization), percutaneous approaches [radiofrequency
ablation (RFA), microwave ablation, focused ultrasound, ethanol ablation, electroporation] and external
beam radiation therapy (EBRT). EBRT can use three-dimensional (3-D) conformal techniques for palliation
or more advanced strategies such as stereotactic ablative radiotherapy (SABR) or particle beam therapy for
[10]
definitive treatment .
Historically, EBRT (delivered mostly by 3-D conformal technique) had been considered ineffective in the
treatment of HCC since the dose required to cure HCC far exceeded liver tissue tolerance to radiation
therapy. Advances in EBRT techniques with SABR and particle beam therapy in the past two decades have
allowed clinicians to deliver much higher doses with significant sparing of uninvolved liver, increasing local
control while minimizing the risk of radiation induced liver disease (RILD). The major advantages of EBRT
are non-invasiveness and the ability to treat the majority of patients with localized liver disease who are
not candidates for surgery/transplant, arterial-directed therapy or ablative therapy. Multiple centers around
the world have reported long-term outcomes with excellent local control, survival and acceptable toxicity
profiles. Table 1 summarizes prospective trials showing that SABR is an excellent option for HCC tumor
control with limited toxicity. Recent National Comprehensive Cancer Network (NCCN) guidelines list EBRT
as a locoregional treatment option for patients who are not candidates for surgery/transplant or who are
[10]
waiting for transplantation (bridge to transplant) .

WHAT IS SABR?
SABR, also called stereotactic body radiation therapy, is an advanced form of EBRT that combines tumor/
organ motion management and multiple beams of high energy photons to deliver very high doses of
radiation precisely to a small target volume over a short treatment course. In US, SABR is delivered in one to
five fractions but can be more fractionated in other countries.

SABR effectively treats primary and secondary malignancies in the liver, lung, bone, spine, and pancreas.
When applied to malignant and benign disease of the central nervous system it is also referred to as
stereotactic radiosurgery.

Radiation treatment for liver cancer can be challenging because (1) tumors tend to be large and complex,
requiring high doses for control; (2) underlying liver is usually compromised from liver disease and