NcXHF

ABOU-ALFA ET AL
tinuing liver injury should be triaged to maximally aggressive
surgical resection with salvage transplantation reserved for
therapeutic failures. Conversely, surgical resection has very
little effıcacy in all but the most minimal disease burden in
the presence of continuing liver injury. As these patients have
a low probability of maturing to salvage transplantation, they
will benefıt from early referral for OLT. 23
Ablation
Ablation techniques have evolved considerably over the past
20 years and are increasingly used to defınitively treat small
HCC tumors. Several methods for focal tumor destruction
have been developed and clinically tested. Although RFA has
been the most popular technique to date, several alternate
technologies—including thermal and nonthermal methods—have
recently been adopted, as they seem to overcome
some of the specifıc limitations of RFA. 24
Several studies have reported long-term outcomes of RFA
in patients with small, unresectable tumors and Child-Pugh
class A liver disease, and they demonstrate 5-year survival
rates as high as 50% to 70%. 25 The question remains whether
RFA can compete with surgical resection as a fırst-line treatment
for HCC. Randomized clinical trials of RFA and surgery
reported to date have failed to provide an unequivocal
answer to this question.
Recurrence after surgery or ablation remains a serious concern.
A randomized phase III study comparing adjuvant
sorafenib to placebo after curative resection or ablation
showed no difference in recurrence-free survival (33.4 for
sorafenib versus 33.8 months for placebo, hazard ratio [HR]
0.940; 95% CI, 0.780 to 1.134; p 0.26). 26
Although 18F-FDG PET-CT is not part of current routine
diagnostic work-up for patients with HCC, studies have suggested
that uptake of 18F-FDG is associated with poor tumor
differentiation and may be a predictor of recurrence and
worse outcomes following surgical or locoregional treatment.
27,28 These results will need to be validated in larger prospective
cohorts.
PALLIATIVE LOCAL THERAPIES
Interventional locoregional treatments play a key role in the
management of HCC. TACE is considered the standard of
care for patients with noninvasive multinodular tumors at
the intermediate stage. Bland embolization appears to have
similar virtues in some studies. Y90 radioembolization represents
a promising treatment option for patients unfıt or refractory
to TACE.
Transarterial Treatments
TACE is the most widely used treatment for patients with
HCC unsuitable for radical therapies worldwide. 29 The most
important advance in TACE therapy has been the drugeluting
beads for transarterial administration, which have
been shown to reduce liver toxicity and systemic drug exposure
compared to standard TACE. 30
Conventional TACE regimens are based on the administration
of an anticancer-in-oil emulsion followed by embolic
agents. The key component of this procedure is lipiodol,
which is used both as a vehicle to carry and localize the chemotherapeutic
agent inside the tumor and as an embolic
agent for tiny tumor vessels. Randomized, controlled trials
and meta-analyses have shown that TACE improves survival
with respect to best supportive care, extending the median
survival from 16 to 19–20 months.
However, such trials were performed more than a decade
ago. Distinct technical advances in the performance of TACE
and improved patient selection and management have taken
place since the completion of these studies. 31 In a randomized
phase II study comparing TACE using LC Bead loaded
with 150 mg of doxorubicin to bland transarterial embolization
(TAE) with Bead Block microspheres, there was no difference
in median progression-free survival (6.2 vs. 2.8
months; p 0.11) or overall survival (19.6 versus 20.8
months; p 0.40) for Bead Block and LC Bead, respectively.
32 Given a comparable safety profıle, and similar outcomes,
the advancement in technology and super selectivity
in arterial blockade place the role of added doxorubicin into
question.
An unsettled issue in the management of patients treated
with embolization is the assessment of tumor response and
the criteria for treatment discontinuation. Several recent investigations
conducted in the United States, Europe, and
Asia have shown that the assessment of tumor response by
modifıed Response Evaluation Criteria in Solid Tumors predicts
overall survival in patients with HCC treated with
TACE. 33 It has been suggested that TACE should be discontinued
in patients in whom an objective response in the
treated tumor has not been achieved after two treatment
cycles. 34
Radioembolization
Radioembolization is a form of intra-arterial radiation therapy
that was developed to capitalize on the arterial perfusion
of HCC, with the aim of delivering radiation tumoricidal
doses to liver tumors. 35 Radioembolization with Y90 is challenging
the current paradigm of HCC treatment. Multiple
centers around the world have provided compelling data that
suggest a clinical role in patients with portal vein thrombosis
as well as in downstaging to transplantation or conversion of
patients with surgically inoperable disease (because of small
liver remnant) to potential cure with resection. This approach,
however, still lacks randomized, controlled study
data.
Combination of Locoregional and Systemic Therapies
The key downside to locoregional treatment is the high rate
of tumor recurrence, which exceeds 70% at 5 years after local
ablation of early-stage HCC. 36 Several experimental studies
have suggested potential synergies between locoregional and
systemic therapies with antiangiogenic properties, such as
sorafenib. Unfortunately, the clinical trials completed so far
failed to provide evidence of a clinical benefıt. Such an ap-
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