Annals of Oncology

abstracts
Results: Of 105 received articles, 6 were deemed suitable for review, with a total
population of 283 patients underwent statistical meta-analysis.
Immuno-histochemically detected hENT1 expression is found to be significantly
associated with both univariate PFS (0.43[95% CI 0.31-0.69]; I 2 0%; Z Score= 5.16; p=
0.00001) and univariate OS (0.50[95%CI 0.38-0.67]; I 2 0%; Z score= 4.75; p= 0.00001).
Conclusions: This meta-analysis demonstrates empirical evidence that hENT1
expression is a valid predictor of survival for patients undergoing gemcitabine-based
chemotherapy. The hENT1 biomarker should be used to stratify patients into
appropriate adjuvant chemotherapeutic regimens to improve outcomes and reduce
un-necessary exposure to inefficacious treatments for patients determined to be
hENT1-ve.
Legal entity responsible for the study: Liverpool University and University Hospital
Aintree
Funding: Liverpool University Translational Medicine Department
Disclosure: All authors have declared no conflicts of interest.
128P
Modulation of specificity protein 1 (SP1) is a novel therapeutic
strategy for pancreatic cancer
J.S. Park, Y.S. Lee, D.S. Yoon
Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine,
Seoul, Republic of Korea
Background: Pancreatic cancer is one of the most aggressive and lethal malignancies.
Specificity Protein 1 (SP1) is a transcription factor regulates and promotes tumor
progression. Some studies have reported SP1 promotes epithelial-mesenchymal
transition (EMT) and is associated with aggressive and poor patient prognosis.
However, there is a paucity of clinical evidence regarding the role of SP1 in pancreatic
cancer. In this study, we aimed to confirm the function of SP1 in invasiveness of
pancreatic cancer cells and to evaluate the clinical impact in patients with pancreatic
cancer.
Methods: Between June 2002 and December 2012, 81 patients underwent radical
curative resection for pancreatic cancer at Gangnam Severance Hospital, Seoul, Korea.
Pancreatic cancer cell lines MIA PaCa-2, PANC-1, AsPC-1, and BxPC-3 were used for
in vitro study. To evaluate the endogenous expression level of SP1, we purified the
whole RNA and protein to perform the qPCR, RT-PCR and Western blot. si-SP1 was
used for specifically inhibit the function of SP1. The invasive potential of pancreatic
cancer cells were assessed in matrigel coated chambers.
Results: Among the 81 patients, 32 (39.5%) were positive for SP1. On univariate and
multivariate analyses, poor differentiation tumor and SP1-positive status were
identified as independent prognostic factors for DFS. High expression of SP1 was
observed and correlated with the expression of mesenchymal markers (Snail, L1CAM,
Vimentin) unlike epithelial markers (CDH1). Importantly, silencing of SP1 showed
markedly decrease in motility and the invasiveness of cancer cells (p < 0.001) as
determined from transwell invasion and transendothelial migration assays, respectively.
Conclusions: Our results demonstrated that SP1 is an independent marker for
metastatic disease and death in patients with pancreatic cancer. Additionally, our in
vitro study demonstrated that SP1 expression promotes EMT and the invasiveness of
pancreatic cancer cell lines, a finding compatible with the results of previous in vitro
studies. These findings suggest that SP1 can potentially be a valuable target for the
improvement of survival rates in patients with pancreatic cancer.
Legal entity responsible for the study: J. Park
Funding: Gangnam Severance Hospital
Disclosure: All authors have declared no conflicts of interest.
patients in stage I and II from 890 healthy individuals controls with 96% accuracy*.
Furthermore, when analyzing all stages of pancreatic cancer in retrospective studies
covering more than 3000 blood samples, the test accuracy is as high as 98%.
*Manuscript in preparation
Conclusions: IMMray PanCan-d can detect asymptomatic pancreatic cancer patients
stage 1 and 2 with 96% accuracy and stage 1 to 4 with 98% accuracy.
Legal entity responsible for the study: Lund University, Create Health, Dept. of
Immunotechnology
Funding: Lund University, Create Health, Dept. of Immunotechnology
Disclosure: L. Dexlin Mellby, A. Holmér: Employee at Immunovia AB. All authors
have declared no conflicts of interest.
130P
Annals of Oncology
Novel genetic marker of diarrhea in renal cell carcinoma
patients treated with sorafenib
F. Innocenti 1 , A. Karabinos 1 , A. Etheridge 1 , C. Pena 2 , D. Crona 1
1 Eshelman School of Pharmacy, University of North Carolina - Chapel Hill, Chapel
Hill, NC, USA, 2 Clinical Pharmacology, Oncology, Bayer Healthcare
Pharmaceuticals, Whippany, NJ, USA
Background: Sorafenib, the first oral anti-angiogenic multikinase inhibitor, is
primarily used in the treatment of advanced renal cell carcinoma (RCC), hepatocellular
carcinoma, and thyroid cancer. Common toxicities experienced by patients treated
with sorafenib limit its use and affect adherence to treatment, reducing sorafenib
efficacy. No biomarkers are currently available to identify patients at risk of toxicity.
Methods: Metastatic RCC (mRCC) patients (n = 153) treated with sorafenib, as part of
the TARGET study (Escudier B, N Engl J Med. 2007), were genotyped for common
germline DNA variants in 56 candidate genes. Associations between 5846 variants and
grade 2-4 toxicities were analyzed. Patients treated for ≤28 days were excluded.
Toxicities included diarrhea, hypertension, hand-foot skin reaction, and/or rash or
desquamation. For each toxicity, the worst grade event for each patient was used. After
linkage disequilibrium-based pruning, 685 variants were utilized for analysis via a
chi-squared test.
Results: Out of 153 patients, 28 (18%) experienced grade ≥2 diarrhea. The A allele of
rs917881 (G > A) in the epidermal growth factor receptor (EGFR) gene was associated
with an increased risk of grade ≥2 diarrhea (p = 0.00006, p = 0.04 after Bonferroni’s
correction, odds ratio 3.6). The frequency of grade ≥2 diarrhea was 50% (3/6) in AA,
33% (15/45) in GA, and 10% (10/102) in GG patients. The frequency of grade 3
diarrhea was 8% (4/51) in patients with the A allele (AA + GA) versus 2% (2/102) in
patients with the GG genotype. No other variants were significantly associated with
sorafenib toxicity after Bonferroni correction.
Conclusions: To our knowledge, this is the first reported study of a genetic basis of
sorafenib toxicity. rs917881 is a common intronic variant (17% allele frequency) in
EGFR. RAF kinase, a critical component of the EGFR signaling pathway, is a known
target of sorafenib. Patients with the rs917881 A allele treated with sorafenib may be at
an increased risk for diarrhea as a result of decreased EGFR expression potentiated by
sorafenib-induced inhibition of the RAF/MEK/Erk pathway, which regulates chloride
secretion (Keely SJ, J Biol Chem. 1998). Replication analyses in additional patient
cohorts and functional studies are ongoing.
Clinical trial identification: NCT00073307
Legal entity responsible for the study: University of North Carolina at Chapel Hill
Funding: National Institutes of Health
Disclosure: C. Pena: Employee of and owns stock in Bayer Healthcare
Pharmaceuticals. All other authors have declared no conflicts of interest.
129P
Early-stage diagnosis of pancreatic cancer offers opportunity
to improve overall patient survival
L. Dexlin Mellby 1 , A. Holmér 1 , C. Wingren 2 , J. Johansen 3 , S.E. Bojesen 4 ,B.
G. Nordestgaards 4 , C.A. Borrebaeck 2
1 Immunovia AB, Lund, Sweden, 2 Immunotechnology, Lund University, Lund,
Sweden, 3 Department of Oncology, Herlev and Gentofte Hospital, Herlev,
Denmark, 4 Health and Medical Sciences, University of Copenhagen, Copenhagen,
Denmark
Background: Pancreatic ductal adenocarcinoma (PDAC) has one of the worst survival
rates with only 5% five years survival. By providing physicians with actionable
information when the tumour is still resectable, the overall 5 year PDAC patient
survival rate could increase from 5 % to 50- 60%. We present a summary of
retrospective studies performed on IMMray PanCan-d, a blood test developed for
early stage diagnosis of pancreatic cancer.
Methods: IMMray PanCan-d creates a biological snapshot of an individual’s
immune response by analysing serum proteins that change as a sign of disease. The
process to derive unique biomarker immunosignatures from an antibody microarray
platform, through state of the art bioinformatics algorithms, is also presented.
Results: Based on recent results from the largest retrospective study on pancreas cancer
covering 1400 blood samples, we have been able to differentiate 148 asymptomatic
131P
Molecular pathology of the 10q23.3-26.3 chromosome region
in glioblastoma
E. Alekseeva 1 , A. Tanas 1 , E. Prozorenko 2 , A. Zaytsev 3 , O. Kirsanova 3 ,
V. Strelnikov 1 , D. Zaletayev 4
1 Federal Agency for Scientific Organizations, Federal State Budgetary Institution
"Research Centre for Medical Genetics", Moscow, Russian Federation,
2 N. N. Blokhin Russian Cancer Research Center, Moscow, Russian Federation,
3 Moscow Oncology Research Institute, Moscow, Russian Federation, 4 IM
Sechenov First Moscow State Medical University, Moscow, Russian Federation
Background: Glioblastoma is the most common and aggressive primary brain tumor
in adults. The most common genetic alteration in glioblastoma is the loss of
heterozygosity (LOH) of the chromosome 10q. However LOH merely reflects allelic
imbalance in the area without detailed information on the gene copy number.
Methods: We have been the first to conduct a targeted analysis of LOH at the
10q23.3-26.3 chromosome region which contains candidate genes PTEN, FGFR2,
MKI67 and MGMT in glioblastoma. A panel of microsatellite markers to detect LOH
in the area under study, which includes 20 microsatellite polymorphisms, has been
developed and characterized. In order to assess copy number alterations at the
10q23.3-26.3 region in glioblastoma samples with identified LOH, we have developed a
system for quantitative microsatellite analysis (QuMA). QuMA is based on
vi38 | abstracts Volume 27 | Supplement 6 | 2016