studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 449A
Disclosures:
Simona Bota - Speaking and Teaching: Janssen Pharmaceutica, Bristol-Myers
Squibb
Mattias Mandorfer - Consulting: Janssen; Speaking and Teaching: AbbVie, Gilead,
Janssen, Boehringer Ingelheim, Bristol-Myers Squibb, Roche
Thomas Reiberger - Consulting: Xtuit; Grant/Research Support: Roche, Gilead,
MSD, Phenex; Speaking and Teaching: Roche, Gilead, MSD
Michael Trauner - Advisory Committees or Review Panels: MSD, Janssen, Gilead,
Abbvie; Consulting: Phenex; Grant/Research Support: Intercept, Falk Pharma,
Albireo; Patent Held/Filed: Med Uni Graz (norUDCA); Speaking and Teaching:
Falk Foundation, Roche, Gilead
Wolfgang Sieghart - Grant/Research Support: Bayer Schering Pharma, Bayer
Schering Pharma, Bayer Schering Pharma, Bayer Schering Pharma; Speaking
and Teaching: Bayer Schering Pharma, Bayer Schering Pharma, Bayer Schering
Pharma, Bayer Schering Pharma
Markus Peck-Radosavljevic - Advisory Committees or Review Panels: Bayer, Gilead,
Janssen, BMS, AbbVie; Consulting: Bayer, Boehringer-Ingelheim, Jennerex,
Eli Lilly, AbbVie; Grant/Research Support: Bayer, Roche, Gilead, MSD, AbbVie;
Speaking and Teaching: Bayer, Roche, Gilead, MSD, Eli Lilly, AbbVie, Bayer
The following authors have nothing to disclose: Florian Hucke, Remy Schwarzer,
Philipp Schwabl, Arnulf Ferlitsch
476
Pro-angiogenic Tie2-expressing monocytes/TEMs as a
biomarker of the response to sorafenib in patients with
advanced hepatocellular carcinoma
Hirotaka Shoji 1,2 , Sachiyo Yoshio 1 , Yohei Mano 1 , Masaya Sugiyama
1 , Yoshihiko Aoki 1 , Norio Itokawa 3 , Masanori Atsukawa 3 ,
Yosuke Osawa 4 , Kiminori Kimura 4 , Akinobu Taketomi 2 , Masashi
Mizokami 1 , Tatsuya Kanto 1 ; 1 The Research Center for Hepatitis &
Immunology, National Center for Global Health and Medicine,
Ichikawa, Japan; 2 Department of Gastroenterological Surgery
1, Hokkaido University Graduate School of Medicine, Sapporo,
Japan; 3 Division of Gastroenterology, Department of Internal Medicine,
Nippon Medical School Chiba Hokusoh Hospital, Inzai,
Japan; 4 Division of Hepatology, Tokyo Metropolitan Cancer and
Infectious Diseases Center Komagome Hospital, Tokyo, Japan
Background Sorafenib is a multi-kinase inhibitor that has been
used for the patients with advanced stages of HCC. The survival
benefit of sorafenib has been clinically proven, however,
majority of patients are forced to discontinue the therapy due to
severe adverse effects. It is anticipated to discover the biomarkers
for the prediction of sorafenib response, in order to establish
the tailored therapy by selecting patients promising for the
outcome. We reported that Tie2-expressing monocytes (TEMs)
were increased in patients with HCC, the frequency of which
was correlated with the degree of angiogenesis in the liver.
We sought to examine the possibility of TEMs as the biomarker
for the drug response in patients with HCC. Furthermore, in
order to discover more feasible markers reflecting the response
to sorafenib, we explore the factors involving in the development
of Tie2 expression on myeloid lineage cells. Method We
enrolled 25 patients with advanced HCC treated with sorafenib
in this study (13 Child-Pugh A and 12 CP-B). The anti-tumor
effect of sorafenib was evaluated after a month and thereafter
by dynamic CT and MRI with the criteria of modified RECIST.
We analyzed the frequency of TEMs (CD14+CD16+TIE2+
cells) in the periphery of the patients and its correlation with
clinical and radiological response to sorafenib. We examined
41 serum factors by multiplexed analysis in 71 HCC patients
and healthy donors. Finally, we examined the impact of such
factors on the differentiation of TEMs from monocytes in vitro.
Results Among the subjects, 9 patients tolerated the continuation
of sorafenib therapy. They were categorized into the
responder group (one partial response and 4 stable disease)
and non-responder group (4 progressive disease) judged by
the modified RECIST. In the responders, the pre-treatment frequency
of TEMs tended to be higher than those in the non-responders
(6.1±2.2% vs. 3.5±0.9%, P=0.06). Furthermore, the
frequency of TEMs in the responders was dropped from 6.1%
to 3.5% after one month. In contrast, TEMs in the non-responders
did not change after the therapy. In patients with high TEMs
frequency (>2.75% cut-off), the levels of M-CSF, HGF, Osteopontin,
and Follistatin were significantly higher than those in
patients with lesser TEMs (p