Results: As single agents, CsnB and BYL719 reduced cell viability in allcell lines in a dose-dependent manner. Cell lines with activated PI3Kwere most sensitive to BYL719-mediated inhibition of cell viability andphospho-AKT. When CsnB and BYL719 were combined, there was asignificant decrease in viability and increase in apoptosis markers in allcell lines compared to each drug alone. Augmented apoptosis bycombination treatment involved upregulated TR3 expression, withcorresponding increases in association of TR3 with mitochondrialHsp60 and cytochrome C release, and TR3 DNA binding.Conclusions: These studies highlight the potential of combinationactivation of TR3 and PI3K inhibition as a novel therapeutic strategyin cisplatin-resistant ovarian cancer.

doi:10.1016/j.ygyno.2014.03.239

220 - Poster Session AForkhead box M1 (FOXM1) gene expression inversely correlateswith survival and targeting FOXM1 improves cytotoxicity ofpaclitaxel and cisplatinum in platinum-resistant ovarian cancerascites cells ex vivoG.L. Westhoff1, Y. Chen2, M. Bieber2, N.N.H. Teng2. 1Stanford Hospitaland Clinics, Stanford, CA, USA, 2Stanford University Medical Center,Stanford, CA, USA.

Objectives: Aberrantly activated FOXM1 leads to uncontrolled cellproliferation, and dysregulation of the FOXM1 transcription networkoccurs in 87% of ovarian cancer cases. We have previouslydemonstrated that thiostrepton, a thiazole antibiotic, decreasesFOXM1 expression, and adding thiopstrepton to standard paclitaxel/cisplatin chemotherapy showed a synergistic cytotoxicity in ovariancancer cell lines. We sought to determine if FOXM1 expressioncorrelates to survival in platinum-resistant patients and if targetingthis pathway can improve the efficacy of paclitaxel and cisplatinumin human ovarian cancer ascites cells ex vivo.Methods: A Cox regression analysis was performed on FOXM1 mRNAexpression data from a subgroup of 151 patients from The CancerGenome Atlas (progression-free survival b12 months). Human ovariancancer ascites cells from five patients were treated with paclitaxel/cisplatinum/thiostrepton or a combination for 48 h and cytotoxicity wasassessed by flow cytometry. Drug combination effects were determinedby calculating the combination index (CI) values using the Chouand Talalay method (CI b0.9 = synergy, CI 0.9–1.10= additive, and CIN1.10 = antagonism). Quantitative reverse transcriptase polymerasechain reaction was performed to determine changes in FOXM1expression and its downstream targets.Results: In a subgroup of platinum-resistant patients from The CancerGenome Atlas, high FOXM1 mRNA expression correlated with worseoverall survival (24 months vs 33 months, P=0.017). In ascites cellsfrom three patients with platinum-resistant tumors and one tumor ofunknownplatinum response, FOXM1mRNA expressionwas upregulatedcompared to normal ovarian tissue. Treatment with thiostreptondecreased FOXM1mRNA expression and the downstream targets CCNB1and CDC25B in all five patients. Combination therapy with paclitaxel,cisplatinum, and thiostrepton showed synergy in three of the fourpatients with platinum-resistant disease (CI 0.40–0.83).Conclusions: Aberrantly activated FOXM1 correlates with worsesurvival in patients with platinum-resistant tumors. Thiostreptonimproves the cytotoxic effect of paclitaxel and cisplatinum in ascitescells from platinum-resistant patients. FOXM1 expression may be auseful marker for prognosis, and targeting this pathway may lead tonovel therapeutics for epithelial ovarian cancer.

doi:10.1016/j.ygyno.2014.03.240

221 - Poster Session AA mycobacterial heat shock protein 70-based fusion proteintargeting mesothelin induces dendritic cell maturation andcross-presentation in a murine model of ovarian carcinomaN. Hashim Arrifin1,2, J. Yuan2, S. Kashiwagi2, M. Nguyen2, G. Jean-Mary2,J. Nezivar2, Y. Yang2, P. Leblanc2, T. Brauns2, M. Poznansky2. 1ImperialCollege London, London, United Kingdom, 2Massachusetts GeneralHospital, Charlestown, MA, USA.

Objectives: Failure of current ovarian cancer immunotherapy is believedto result from poor induction of dendritic cell (DC) maturation andantigen presentation. We developed a novel immunotherapeutic agentlinking a single-chain antibody variable fragment (scFv) targetingmesothelin (MSLN), a surface glycoprotein expressed at high levels inovarian cancer, to Mycobacterium tuberculosis (MTB) heat shock protein70 (Hsp70), which is a potent immune activator known to bind to CD40on DCs. We evaluated its ability to induce DC maturation and cross-presentation of tumor-associated antigens.Methods: To investigate DC maturation, unsorted and low-CD40 bonemarrow-derived dendritic cells (BMDCs) isolated by cell sorting werestimulated with scFvMTBHsp70 fusion protein and then assessed forexpression of DCmaturationmarkers by flow cytometry. To study cross-presentation, FVB mice were immunized intradermally withscFvMTBHsp70. Lymphocytes from harvested skin-draining lymphnodes were restimulated ex vivo with tumor-associated antigens beforeassessment of CD4+ and CD8+ T-cell Granzyme B production.Results: In vitro, the scFvMTBHsp70 fusion protein significantly(P b 0.05) induced BMDC expression of maturation markers. Inter-action of the MTBHsp70 portion with CD40 is a likely but notexclusive mechanism of signaling. Tumor-specific Granzyme Bproduction by CD4+ and CD8+ T-cells from mice immunized withthe fusion protein was significantly enhanced (P b 0.05), but high-dose immunization induced immunosuppression and decreasedsubsequent Granzyme B production (P b 0.05).Conclusions: The ability of scFvMTBHsp70 to induce DCmaturation andpotent tumor-specific CD4+ and CD8+ T-cell responses is crucial toovercoming tumor-mediated immune latency in ovarian cancer andrescue DCmaturation and function from tumor-induced defects in caseswhere many other immunotherapies have failed. This new cancerimmunotherapy bypasses complex ex vivo manipulation of patient cellsand has the potential to be a cost-effective and powerful tool at optimaldoses, especially when used in combination with other agents thatmodulate the inhibitory tumor microenvironment.

doi:10.1016/j.ygyno.2014.03.241

222 - Poster Session APelvic magnetic resonance imaging diagnosis correlates withpathology of adnexal massesA.F. Haggerty1, A.R. Hagemann2, C. Chu1, E. Siegelman3, S.C. Rubin1.1University of Pennsylvania, Philadelphia, PA, USA, 2Washington UniversitySchool of Medicine, St. Louis, MO, USA, 3University of Pennsylvania HealthSystem, Philadelphia, PA, USA.

Objectives: Given the frequent use of pelvic magnetic resonanceimaging (MRI) at our institution to further characterize indetermi-nate pelvic masses, we sought to evaluate the accuracy of MRI inwomen with subsequent surgical resection of a complex adnexalmass. The primary objective of our study was to determine theaccuracy of pelvic MRI in differentiating benign and malignantadnexal pathology compared to the final surgical pathology in acohort of women who underwent both a pelvic MRI for an adnexalmass and subsequent surgical management. Our secondary aim wasto determine the accuracy with which MRI can detect type-specific

Abstracts / Gynecologic Oncology 133 (2014) 2–20790

ovarian histopathology compared to the final histopathology subtypeand determine the frequency of discrepancy.Methods: We performed a retrospective cohort study of women whounderwent pelvicMRIwith a diagnosis of an adnexalmass between June2008 and 2010 at our tertiary care institution. The radiologic interpre-tations (benign ormalignant) and the favored specific histologic subtypeonMRI reports were abstracted from themedical records. The radiologicdiagnoses were then compared to the diagnoses by surgical pathology.Results: Data from 237 patients who underwent pelvic MRI wereincluded, of whom 41.35% underwent surgical intervention for theadnexal mass. Pelvic MRI had a sensitivity of 95.0% and specificity of94.1% for diagnosis of malignancy when compared to availablepathology (n = 88). The predicted specific histologic subtype by MRI(n= 84) was accurate in 56/57 women (98.25%) with an anticipatedbenign diagnosis and in 23/27 women (85.19%) with an anticipatedmalignancy. The correlation between a benign diagnosis from MRIand benign final surgical pathology was 0.74 (P b 0.001).Conclusions: In our tertiary care center, MRI is used to furthercharacterize indeterminate adnexal masses and can accurately differen-tiate benign vs malignant adnexal masses. The specific diagnosis on MRIwas also highly correlative with the final histopathology. Themajority ofthe cohort (59%) was managed expectantly based on reassuring resultsof the MRI. MRI offered diagnostic value, more detailed patientcounseling, appropriate subspecialty referral and surgical planning, andreassurance to pursue conservative management of benign masses byMRI, such as when patients are poor surgical candidates.

doi:10.1016/j.ygyno.2014.03.242

223 - Poster Session AThe presence of endometriosis is associated with improvedsurvival in epithelial ovarian cancerH.E. Dinkelspiel, C. Matrai, S. Pauk, Y.L. Chiu, D. Gupta, T.A. Caputo, L.Ellenson, K.M. Holcomb.Weill Cornell Medical Center, New York, NY, USA.

Objectives:To characterize ovarian cancers associatedwith endometriosisand to evaluate the prognostic impact of the presence of endometriosis.Methods: Ovarian cancer cases from a single institution diagnosedbetween 2000 and 2013 were examined and specimens reviewed bytwo pathologists for the presence of endometriosis. Ovarian cancercases with and without endometriosis were compared to determinethe clinical factors associated with endometriosis and the prognosticsignificance of the presence of endometriosis. Two-sample T-tests,chi-square tests, multivariable logistic regression, and Cox propor-tional hazards models were used for statistical analysis.Results: Among 139 epithelial ovarian cancers diagnosed between 2000and 2013, there were 49 (35%) with endometriosis and 90 (65%) withoutendometriosis. The distribution of histologies of ovarian cancers withendometriosis was 43% endometrioid, 23% clear cell, 20% mixed, 8%mucinous, and 6% serous. Ovarian cancer cases with endometriosis weremore likely to be confined to the pelvis (89% vs 41%, P b 0.0001) anddiagnosedwith lower-grade tumors (41% vs 21%, P=0.014). Younger ageand earlier stage independently predicted the presence of endometriosis(P=0.0011 and P b 0.0001, respectively). Ovarian cancer patients withendometriosis had improved progression-free survival (HR= 0.20,P b 0.0001) and overall survival (HR= 0.18, P=0.025) compared topatients without endometriosis. After controlling for tumor stage and ageat diagnosis, however, endometriosis was not an independent predictor ofsurvival.Conclusions: Patients with ovarian cancer and endometriosis haveyounger age at diagnosis, earlier-stage and lower-grade disease,and disease distribution limited to the pelvis compared to patientswithout endometriosis. Ovarian cancers with endometriosis have amore favorable prognosis with improved progression-free survival

and overall survival due to these clinical factors, but endometriosishad no independent prognostic significance in our study population.

doi:10.1016/j.ygyno.2014.03.243

224 - Poster Session ACharacterization of primary platinum resistance in an era ofbiologic agents and novel chemotherapeutic designE.D. Thomas1, K.N. Slaughter2, C.C. Gunderson2, L. Perry2, R. Farrell2,J.K. Lauer1, K. Ding2, D.S. McMeekin2, K.N. Moore2. 1Stephenson CancerCenter, The University of Oklahoma, Oklahoma City, OK, USA, 2TheUniversity of Oklahoma, Oklahoma City, OK, USA.

Objectives: Primary platinum resistance (PPR) confers a poorprognosis for patients with epithelial ovarian carcinoma (EOC).Median overall survival (OS) is 12 months. Given the increased useof biologic agents, we sought to examine the characteristics andoutcomes of patients with PPR EOC in the modern treatment era.Methods: Patients with EOC from 2000–2010 were retrospectivelyreviewed. PPR was defined as not achieving complete response (CR)with primary therapy or documented recurrence b6 months from theend of therapy. Medical records were abstracted for clinicopathologicvariables, treatment, and outcomes. Data were abstracted using SAS 9.2.Results: A total of 538 patients were identified, 186 (34%) of whom hadPPR and 156 (84%) of whom had high-grade serous carcinoma (HGSC).The median age of patients who had PPR was 63 years, 3.7% receivedprimary chemotherapy, 11.3% received neoadjuvant chemotherapy(NACT), and 84.9% underwent primary debulking. Optimal debulkingwas achieved in 76%. Median progression-free survival was 4.3 months.Onmultivariate analysis, neither residual disease, histology, age, primarytreatment nor clinical trial was associatedwith PPR. The use of NACTwasassociated with PPR (HR 5.53; 95% CI 1.02, 30.04; P=0.048). Followingdevelopment of PPR, the median number of treatment regimens wasthree. The Median number of cytotoxic agents was three and biologicagents were 1.5. Use of biologic agents differed by histology. Patientswith acquired platinum resistance had a median overall survival (OS) of18.3 months vs 13.8 months for those who had PPR. Platinum-sensitivepatients had an OS of 115.9 months. Patients with PPR and HGSC hadnearly twice themedianOS as thosewith non-HGSC (15.1 vs 8.7 months,P=0003). Use of maintenance therapy following primary chemother-apy was associated with increased OS in HGSC (32.3 vs 13.8 months,P=0.036) but not for non-serous histologies (4.3 vs 6.0 months,P=0.37). Among all patients with PPR, 37.7% had an OS probabilityN24 months and 15.9% had an OS probability N48 months.Conclusions: PPR in the modern treatment era still confers a poorprognosis. Maintenance therapy was associated with an improvedOS, which needs to be further elucidated. Although some patientswith PPR survive well beyond the reported median, efforts aimed ateliminating any modifiable risk factors for PPR are important as isfurther development of effective salvage strategies to convert morepatients to survival beyond the 12-month mark.

doi:10.1016/j.ygyno.2014.03.244

225 - Poster Session APrimary debulking surgery in stage IIIC and IV ovarian cancerresults in improved survival compared to those undergoingneoadjuvant chemotherapy with interval cytoreductionR.M. Clark1, J.T. Clemmer1, A.Melamed2, J.A. Rauh-Hain1, N. Joseph1, D.M.Boruta1, M.G. Del Carmen1, A. Goodman1, W.B. Growdon3, J.O. Schorge1.1Massachusetts General Hospital/Harvard University, Boston, MA, USA,2Brigham and Women's Hospital/Massachusetts General Hospital, Boston,MA, USA, 3Massachusetts General Hospital, Boston, MA, USA.

Abstracts / Gynecologic Oncology 133 (2014) 2–207 91