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Page 10 of 18 Kouroumalis et al. Hepatoma Res 2018;4:34 I http://dx.doi.org/10.20517/2394-5079.2018.33

compared to patients who received palliative care only (2.9 months). Patients with BCLC stage A had also
higher survival (31.4 months) compared to palliative care (15.1 months) but this was not significant due to
small number of patients in this group .
[115]

In addition to these data there have been two case reports of HCC patients of viral etiology who responded
with complete regression of the tumor with either lanreotide or long-acting octreotide [116,117] . Recently a case
of HBV-associated HCC with SSTR2 overexpression and metastases in the lung and mediastinal lymph
nodes detected 17 months after left hepatectomy was described. Treatment with lanreotide 30 mg twice a
month resulted in a significant size reduction of the mediastinal nodes and complete disappearance of the
lung nodes. This objective response lasted for 42 months .
[118]
A randomized study of fairly advanced HCC compared treatment with either octreotide alone or in
combination with rofecoxib. Survival in both groups was significantly associated with baseline serum VEGF
and IGF1 levels .
[119]
Two large recent trials from China highlighted the significance of the presence of SSTR2 and SSTR5 for the
response to SSAs. Importantly these were studies on early-stage HCC and treatment was administered after
resection of the primary tumor. In the study by Li et al. , 76 patients with operable HBV-related HCC were
[120]
divided into two groups according to SSTR2 and 5 expression profiles. The mean survival time was longer in
the high SSTR2/5 expression group. Similar results were reported in another study of 99 HBV-related HCC.
Recurrence rate and survival were significantly higher in patients with high expression of SSTR2 . Both
[121]
studies concluded that the expression profile of SSTRs can be used as an independent prognostic factor.

There have been interesting results when SSAs were compared to transarterial chemoembolization (TACE)
or radiofrequency ablation (RAF) or were given in combination with TACE or sorafenib.

In an earlier report of a prospective non-randomized study from Germany, 41 patients were treated with
octreotide and compared for survival to another group of patients treated with TACE. A median survival
of 571 days was found in the octreotide group, similar to the TACE group . This was confirmed later in
[122]
a larger randomized trial where, octreotide treatment had a similar outcome compared to patients who
received TACE or multimodal therapy .
[115]
In an observational study, a combined approach of RAF followed by octreotide was adopted for treatment
of viral-associated HCCs, mostly Child A and Child B (60% and 34% respectively). All patients had multiple
liver HCC nodules; 14% had complete or partial tumor regression and a clinical benefit was evident in 80%.
Mean survival was 31.4 months. Serum VEGF was significantly correlated with response .
[123]

In a different setting, 147 patients diagnosed with HCC suitable for TACE received 2-4 TACE procedures; 84
patients received an additional heparin plus octreotide combination and 63 patients were given only heparin
and served as the controls without randomization. They reported a significant reduction in the incidence of
tumor metastasis within a year of follow-up post-TACE, in the combination treatment .
[124]
In a recent randomized study from China, 71 patients with mostly viral associated HCC, BCLC stages B and
C were assigned to either TACE (n = 35) or TACE plus celecoxib plus octreotide (n = 36) and were followed
up for 3 years. The median overall survival of the TACE + C + L group of 15.0 months was twice as much
compared to that of the TACE group (7.5 months) and the survival benefit was very significant for both
BCLC stage B or C. Equally significant was the improvement in the quality of life in favor of octreotide.
Post-embolization syndrome was also significantly lower in the octreotide group .
[125]