studies

404A AASLD ABSTRACTS HEPATOLOGY, October, 2015
10 years of 100%, 96.0%, 81.2% in group A, 95.3%, 77.6%
and 45.5% in group B, 70.1%, 41.7% and 8.7% in group C,
and 50.4%, 22.2% and 0% in group D, respectively (P < 0.01
by the log-rank test). Adjusting for significant factors in univariate
analysis, multivariate analysis indicated that frequency of
receiving RFA (HR: 0.60 pre 1 time, P < 0.01), frequency of
receiving TACE or TAI (HR: 0.88 per 1 time, P < 0.01) and
LFT rate over 1.0 (HR: 29.4, P < 0.01) as independent factors
which affected on OS. First recurrence, tumor sizes, and tumor
numbers were not significant risk factors in the univariate analysis.
Conclusion: Appropriate treatment at the time of each HCC
recurrence remarkably prolonged OS even if HCC patients had
multiple relapse. Repeat RFA and TACE or TAI were promising
strategy to achieve a long term survival. However, LFT rate
over 1.0 which indicated high rate of HCC recurrence was an
independent factor of poor prognosis suggesting the malignant
potential of HCC.
Disclosures:
Takamasa Ohki - Speaking and Teaching: Otsuka Pharmaceutical Co. Ltd.
The following authors have nothing to disclose: Yuki Hayata, Satoshi Kawamura,
Daisaku Ito, Koki Kawanishi, Kentaro Kojima, Michiharu Seki, Nobuo Toda,
Kazumi Tagawa
383
Efficacy and safety of miriplatin versus epirubicin in
transcatheter arterial chemoembolization therapy for
advanced hepatocellular carcinoma: a randomized controlled
trial
Tatehiro Kagawa 1 , Shunji Hirose 1 , Yoshitaka Arase 1 , Kota
Tsuruya 1 , Kazuya Anzai 1 , Sei-ichiro Kojima 1 , Koichi Shiraishi 1 ,
Masako Shomura 3 , Jun Koizumi 2 , Tetsuya Mine 1 ; 1 Gastroenterology,
Tokai University, Isehara, Japan; 2 Radiology, Tokai University
School of Medicine, Isehara, Japan; 3 Nursing, Tokai University
School of Medicine, Isehara, Japan
Purpose: Miriplatin, a hydrophobic platinum-based anticancer
agent, is used for transcatheter arterial chemoembolization
(TACE), but its efficacy and safety are still unclear. To clarify
the efficacy and safety of TACE with miriplatin in the treatment
of patients with advanced hepatocellular carcinoma (HCC),
we performed a randomized trial to compare miriplatin with
epirubicin. Patients and Methods: We randomly assigned
patients with advanced HCC to receive TACE with miriplatin
or TACE with epirubicin after stratification by the tumor
diameter (3 cm). Enrollment criteria were (1) presence of HCC
with contrast-enhancement in the arterial phase of dynamic CT
scan, (2) no indication of surgical resection or local therapy
including radiofrequency ablation and percutaneous ethanol
injection, (3) no previous treatment for the target HCC, (4) no
extrahepatic metastasis, (5) no tumor thrombus in the portal
or hepatic veins, (6) Child-Pugh class A or B, (7) ECOG PS
score of 2 or less, and (8) serum bilirubin < 3 mg/dl, creatinine
< 1.5 mg/dl, white blood cell count ≥ 3000/mm 3 ,
platelet count ≥ 50000/mm 3 , and hemoglobin concentration
≥ 9.5 g/dl. Dynamic CT was performed within 3 months after
TACE and the efficacy was blindly evaluated by two radiologists
according to the modified Response Evaluation Criteria in
Solid Tumors (mRECIST). Overall survival and recurrence-free
survival were compared by log-rank test. The treatment modality
for the recurrence was decided by the primary doctors.
This study was approved by the institutional ethics committee
(UMIN000003987) and written informed consent was
obtained from each patient. Results: 23 and 24 patients were
allocated to the miriplatin (M) group and the epirubicin (E)
group, respectively. No significant difference was observed in
age gender, etiology, tumor size, Child-Pugh sore, and clinical
stage between two groups. The rate of complete response in
the M group was significantly lower than in the E group (33%
vs 79%, P < 0.01). Recurrence-free survival was significantly
shorter in the M group than in the E group (P < 0.05); 1-yr
recurrence-free survival rate was 18% in the M group and 33%
in the E group. OS was not significantly different between two
groups; 1-yr and 3-yr OS were 95% and 58%, respectively, in
the M group and 88% and 79%, respectively, in the E group.
As adverse effects grade 2 fever was observed with similar
frequency; 19% in the M group and 32% in the E group. Conclusions:
This randomized trial demonstrated that the efficacy
of the miriplatin-TACE was inferior to the conventional epirubicin-TACE,
although miriplatin was as safe as epirubicin.
Disclosures:
The following authors have nothing to disclose: Tatehiro Kagawa, Shunji Hirose,
Yoshitaka Arase, Kota Tsuruya, Kazuya Anzai, Sei-ichiro Kojima, Koichi Shiraishi,
Masako Shomura, Jun Koizumi, Tetsuya Mine
384
Identification of candidate extracellular non-coding RNA
biomarkers for Hepatocellular Carcinoma
Irene K. Yan, Tushar Patel; Mayo Clinic, Jacksonville, FL
Hepatocellular carcinoma (HCC) has a poor prognosis. Early
detection may improve outcomes by detecting the cancer at a
stage when curative procedures may be possible. Our overall
goals are to evaluate the utility of extracellular non-coding
RNA as biomarkers for the early detection of HCC. Towards
this goal, we sought to identify non-coding extracellular RNA
(exRNA) that are associated with HCC cells, and to develop
assays for their detection. METHODS: A systematic profiling
approach evaluated non-coding RNA that are (1) associated
with malignant HCC cells and (2) expressed within extracellular
vesicles (EV) released from these cells. qPCR, Nanostring
and droplet digital PCR were used for the detection of
exRNA from culture supernatants or from serum of patients with
HCC. Profiling was performed on RNA from cells and exRNA
released by these cells for non-malignant (HH and THLE-2), and
malignant HCC cells (Hep3B, HepG2, PLC/PRF/5, SNU-182,
SNU-398). MicroRNA expression was assessed using qPCR
panels from Exiqon to screen 752 miRNAs, and expression of
90 selected lncRNAs was assessed using lncRNA qPCR assays.
The expression of 800 miRNAs and 33 lncRNAs was analyzed
in selected samples using Nanostring. Assay precision
and reproducibility were individually determined for selected
exRNA candidate biomarkers. RESULTS: HCC cells released
a larger amount of extracellular RNA compared to normal
hepatocytes (average of 1.23% vs. 0.55% of total donor cell
RNA). Compared to exRNA from normal hepatocytes, qPCR
analyses identified 14 lncRNAs and 33 miRNAs that were
increased in exRNA from HCC cells. In addition, Nanostring
analysis identified three miRNAs (miR-25, miR-302d, and miR-
612) in exRNA preparations from all HCC cells, and from
serum obtained from patients with HCC. These three microR-
NAs were also detected using droplet digital PCR but not using
qPCR. Droplet digital PCR assays for long non-coding RNA
GAS5 and H19 in exRNA had a CV of 10.6% and 7.1% for
precision, and a CV of 11% and 3% for reproducibility respectively.
Digital PCR assays and nanostring were more sensitive
than qPCR assays for the detection of low abundance exRNA
in serum. SUMMARY and CONCLUSIONS: Non-coding RNAs
that are selectively enriched within exRNA from HCC cells can
be detected in the circulation. Using a novel biomarker discovery
platform based on exRNA release, we have identified
several candidate microRNA and long non-coding RNA biomarkers
for HCC. Sensitive assay platforms have been devel-