Page 48 - Read Online

Reyngold et al. Hepatoma Res 2018;4:49 I http://dx.doi.org/10.20517/2394-5079.2018.84 Page 3 of 10

compromise. Indeed, owing to the presence of underlying liver disease in many patients with primary liver
tumors such as HCC, the tolerance dose of the liver has been shown to be different for patients with primary
[3]
versus metastatic liver cancers . Thus, evaluation of liver reserve/function is an important aspect of planning
liver RT.

The most commonly used classification of liver function is the Child-Pugh score, which accounts for the
presence or absence of ascites and encephalopathy and measurements of bilirubin, albumin, and prothrom-
bin, the latter as an international normalized ratio. Although developed in a different context, Child-Pugh
score has been used to evaluate patients for RT. In general, patients with Child-Pugh Class A and B7 cirrho-
sis can safely receive radiation, but patients with Class B8 or above are not considered candidates. Medical
management of cirrhosis or other liver disease is always optimized before radiation therapy is begun.

In addition, several imaging modalities allow functional liver assessment. Indocyanin green (ICG) enables
assessment of overall hepatic metabolic function and Sulfur colloid Technetium 99m SPECT/CT can define
the spatial distribution of functional and cirrhotic liver parenchyma. ICG measurements correlate with de-
velopment of RILD and mortality [10-12] . Furthermore, subsequent effort showed that ICG measurements can
help guide RT: a 5-fraction RT regimen was risk adapted based on ICG measurements at baseline and after 3
[13]
initial fractions . Results for 90 patients with HCC and liver metastases showed 2-year local control of 95%,
[14]
with only an 8% risk of change in CP score > 2 . Further work will be needed in patients with larger tumors
and more advanced cirrhosis.

While cirrhosis is a major challenge to delivering radiation safely, surgical resection of the liver can reduce
hepatic reserve through the removal of functional healthy liver. Although hepatic regenerative capacity can
mitigate this problem, large resections can nonetheless substantially limit hepatic reserve. For example, 20%-
25% of patients with bilobar liver metastases with planned two-stage hepatectomy cannot undergo the sec-
ond stage owing to inadequate liver hypertrophy after portal vein embolization and a predicted inadequate
3
liver remnant [15,16] . The role of radiotherapy for patients with small liver remnants (< 1000 cm ) remains to be
defined.

Biliary obstruction often occurs in patients with HCC. Ursodiol is helpful for partial biliary obstruction with
stent placement reserved for complete obstruction.

Another aspect of HCC that can directly impact liver function is its predilection to vein invasion. Portal and
hepatic venous tumor thrombosis may complicate RT delivery due to liver decompensation caused by the
thrombus, the larger radiation volumes needed to cover the thrombus, and the presence of ascites resulting
from portal hypertension. Importantly such tumors may represent even a greater management challenge
[17]
for other local modalities . Studies of radiation alone or in combination with transarterial approaches for
tumors with portal vein tumor thrombosis have shown that efficacy of radiation in this setting is not influ-
enced by the location of the tumor thrombus in the same way that transarterial options are and suggested
that radiation should be considered in this setting [Figure 1] [18-20] .

FRACTIONATION
Development of stereotactic ablative radiotherapy (SABR) has revolutionized our approach to patients with
[23]
liver tumors. Studies of lung [21,22] and liver cancer have shown it to effectively ablate small tumors, defined
as local control rates of approximately 90% at 2 years or longer. For these organs consisting of parallel func-
tional subunits, overall organ function depends on preserving a minimum number of these subunits and
can otherwise tolerate destructive doses of radiation to small parts of its volume. However, SABR in 3 to 6
fractions is challenging or impossible when the tumors are near critical organs at risk (OARs) whose func-