2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

SBRT FOR HEPATOCELLULAR CARCINOMA
Fig. 1. Axial slice of HCC SBRT plan showing a
conformal isodose distribution. The red and blue
solid lines represent the gross target volume (GTV)
and planning target volume (PTV) to be irradiated,
to account for uncertainties, respectively. The HCC
was treated with 42 Gy in six fractions (pink line),
which tightly surrounds the PTV, with a rapid
falloff in dose.
Abbreviations: HCC, hepatocellular carcinoma;
SBRT, stereotactic body radiotherapy.
disease included hepatitis B, 39%; hepatitis C, 40%; and
alcohol, 25%. Prior therapies were delivered in 50% of
patients. Baseline Barcelona Clinic Liver Cancer stage was
class C in 66%. Multiple lesions were present in 59% of
patients, and the median sum of liver lesion diameters was
10 cm (1.8–43 cm). Tumor vascular thrombosis was present
in 55% and extrahepatic disease in 14%. At one year, the
local control of irradiated HCC was 79% (CI 95%, 66–87%).
Median overall survival was 17.0 months (CI 95%, 10.6–21.8
months). 19
The Indiana University School of Medicine has also conducted
prospective studies of HCC SBRT. 20,21 In a phase I
study by Cardenes et al, in 17 patients with HCC with 25
lesions (median diameter 3.2 cm), dose was escalated in
patients with Child-Pugh A from 36 Gy in three fractions to
48 Gy in three fractions, without dose-limiting toxicity. In
patients with Child-Pugh B, two developed grade 3 hepatic
toxicity at 42 Gy in three fractions. Subsequently, five
patients with Child-Pugh B were treated with 40 Gy in five
fractions, and one patient developed liver failure. 21 Overall,
20% of patients experienced an increase in Child-Pugh class:
seven of 36 patients with Child-Pugh A experienced progression
to Child-Pugh B, and five of 24 patients with Child-
Pugh B progressed to Child-Pugh C, demonstrating an
increased risk of any toxicity in patients with worse Child-
Pugh class at baseline. After a median follow-up of 27
months, 2-year local control was 90%, progression-free survival
was 48%, and overall survival was 67%.
Retrospective series of SBRT have also been published.
22,23 Kwon et al treated 42 patients with HCC with 30
to 39 Gy in three fractions. With a median follow-up of 29
months, the response rate was 86% (60% complete response
and 26% partial response). 24 Seo et al treated 38 patients
with HCC with 33 to 57 Gy in three to four fractions, with a
61% 2-year survival and 79% local control rate. 25 Doses of
more than 42 Gy in three fractions were associated with
improved local control. Twenty-five European patients with
HCC have also been treated with SBRT (45 Gy in 3 fractions),
with a 1-year local control rate of 95%. 26
SBRT has been used to effectively treat HCC tumor
thrombi and has been used as a bridge to liver transplant.
21,27,28 In most series, following SBRT, the first site of
recurrence is in the liver outside the irradiated volume,
providing rationale for studies combining regional or systemic
therapies with SBRT.
Toxicity: SBRT
In addition to the potential for liver toxicity (including
classic and nonclassic RILD), as previously described, SBRT
is associated with the possibility for other late toxicity.
Gastric, duodenum, and small and large bowel late toxicity
(e.g., ulcer, fistula, bleed) are more likely to occur following
SBRT potent doses than conventional radiation fractionations.
Therefore, HCC tumors best suited for SBRT are
located at least 1 cm away from luminal gastrointestinal
structures. Proton pump inhibitors may reduce the risk of
luminal gastrointestinal toxicity, and strategies to move
gastrointestinal structures away from the tumor itself may
be beneficial to patients.
A potential toxicity that is unique to SBRT is chest pain
and rib fracture. This has not commonly been reported but is
a possible late sequelae from therapy for peripherally located
HCCs. The risk of toxicities can be reduced by ensuring
that radiation “hot spots” are within the target volume
and not near adjacent critical normal tissues.
Another potential toxicity is biliary. For caudate lesions
and HCC invading the biliary track, edema may occur
following SBRT, so care is required to stent the patient
before therapy and/or to premedicate patients with steroids
to reduce this risk. In the long term, there is a risk of late
biliary stenosis, which has been rarely reported following
proton therapy and not yet reported following SBRT. Nonetheless,
being cautious to reduce the dose per fraction and/or
overall maximal dose is reasonable for caudate lesions to
reduce the risk of this potential late toxicity.
Conclusion
Technical advances in radiation oncology have made it
possible for SBRT to be used safely for the treatment of
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