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(34%) (p-value 0.008) and DM-non metformin (29%) (p-value0.009). In Kaplan-Meier analyses, DM-Metformin group had a longerOS and PFS compared to DM non-metformin patients (p-values0.0217 and 0.0252 respectively). In Cox proportional hazardsanalyses that included adjustment for demographic and clinicalcovariates there was a trend for a longer OS and PFS but it did notreach statistical significance.Conclusions: Metformin use is associated with earlier stage diseaseat diagnosis compared to DM non-metformin patients and non-diabetic ovarian cancer patients. Although metformin use is associ-ated with longer OS and PFS compared to non-metformin DM andcontrol in univariate analyses, it did not reach statistical significancein the multivariate analyses.
doi:10.1016/j.ygyno.2014.03.489
470 - Poster Session BOvarian high grade serous cancer xenografts as pre-clinicalmodels of response to chemotherapyP. Cybulska1,2, J.M. Stewart2, B.A. Clarke2, B.G. Neel3, M.Q. Bernardini4.1Institute of Medical Science, Toronto, ON, Canada, 2University of Toronto,Toronto, ON, Canada, 3Ontario Cancer Institute, Princess Margaret Hospital,Toronto, ON, Canada, 4University Health Network Princess MargaretHospital, Toronto, ON, Canada.
Objectives: Primary treatment for high-grade serous cancer (HGSC)patients consists of surgical debulking and platinum/taxol chemo-therapy. This uniform approach to treating a highly heterogeneousdisease is largely to blame for the virtually unchanged overallsurvival in the last 30 years. For successful new treatment strategies,pre-clinical in vivo models must be predictive of similar activity inhumans. To date, no models of HGSC exist that recapitulate bothinter- and intra-patient heterogeneity. HGSC patient-derived xeno-grafts (PDX) could potentially resolve some of these issues, as thesetumors have been shown to recapitulate the biological characteristicsof the primary tumor. In this study, we tested the ability of a PDXmodel of HGSC to predict response to standard of care chemother-apeutics and thus examined its utility as a pre-clinical model.Methods: We have established conditions to generate PDX from freshtumor and ascites samples. The mammary fat pads of NOD/SCID/Il2rg-/-
mice were injected with 106 cancer cells from platinum sensitive(n= 3), platinum resistant/refractory (n= 13) and prospectivelyidentified (n= 2) patients. Once tumors were palpable (~200 mm3),mice were treated with carboplatin (75 mg/kg IP q week x 2 doses) orvehicle (saline IP q week x 2 doses). Tumor size was assessed every72 hours. At the end of treatment, tumor histology was assessed.Results: PDX derived from sensitive patients showed a 77-90% reductionin tumor volumewith platinum therapy. Platinum resistant PDX showedat most a 30% reduction in tumor volume or grew in spite of platinumtherapy. Two samples obtained prospectively showed a 60-90%reduction in tumor volume and correspond to platinum sensitivepatients. All PDX histology was confirmed to be HGSC.Conclusions:Our results suggest that PDX recapitulate patient responseto chemotherapy. Specifically, the xenografts derived from chemo-sensitive patients show a nearly complete response to platinum therapy;conversely, xenografts derived from chemoresistant patients show aminimal response. Impressively, we were able to prospectively identifychemosensitive patients. These data suggest that the PDX model allowsfor accurate identification of platinum sensitivity and resistance andmayallow for assessment of the efficacy of novel chemotherapies.
doi:10.1016/j.ygyno.2014.03.490
471 - Poster Session BPractice intentions: cervical cancer screening amongHPV-vaccinated womenN. Nair1, Z. Berkowitz2, M. Saraiya2. 1Emory University, Atlanta, GA,2Centers for Disease Control and Prevention, Atlanta, GA.
Objectives: The Centers for Disease Control Advisory Committee onImmunization Practices recommends HPV vaccination of all femalesaged 9 to 26 years. Current recommendations for cervical cancerscreening do not vary by HPV vaccination status. The objective of thisstudy is to investigate whether physicians intend to change theirscreening practices and beliefs based on HPV vaccination status andwhether they use criteria to vaccinate.Methods: A nationally representative sample of 2,101 U.S. physicianswho perform cervical cancer screening from the 2007 to 2010Cervical Cancer Screening Supplement to the National AmbulatoryMedical Care Survey (NAMCS) and National Hospital AmbulatoryMedical Care Survey (NHAMCS) was used. Data representedapproximately 100,000 providers and were stratified by specialty:obstetrician/gynecologist (ob/gyn) vs other specialties (internalmedicine, family/general medicine and midlevel providers) and bysurvey type.Results: Over 92% of providers did not intend to change their cervicalcancer screening practices and management for HPV vaccinatedwomen. The majority believed that HPV vaccination will result infewer abnormal Papanicolaou (Pap) tests and fewer referrals tocolposcopy, with percentages ranging from 58.6% to 66.8% for thedifferent physician and surveys types.
NAMCS office-based ob/gyn’s were more likely than otherspecialties to rarely or never use number of sexual partners todetermine who gets the HPV vaccine (66.7% vs 55.1%, P b 0.05), morelikely to recommend the vaccine to females with history of abnormalPap result (77.3% vs 62%, P b 0.05) and to females with a history ofHPV positive test result (73.9% vs 56.1, P b 0.05).Conclusions: Although the majority of providers believe that HPVvaccination will result in fewer abnormal Pap tests and colposcopies,they do not intend to change cervical cancer screening practicesbased on vaccination status. Ob/gyn’s are more likely to recommendvaccination to females with abnormal test results who may benefitless from it than those with normal results while other specialties aremore likely to use number of sexual partners to determine whoshould receive the vaccine, which is not recommended. Improvingphysician understanding of the HPV vaccine and appropriate vaccinetargeting may lead to more efficient cervical cancer screening andprevention.
doi:10.1016/j.ygyno.2014.03.491
472 - Poster Session BTreatment of low-risk GTN with biweekly actinomycin-DC.J.M. Reade1, U. Habiba1, L.R. Eiriksson2, M. Cesari1, R.J. Osborne1.1University of Toronto, Toronto, ON, Canada, 2Juravinski Hospital andCancer Centre, Hamilton Health Sciences, Hamilton, ON, Canada.
Objectives: Biweekly “pulsed” actinomycin-D (act-D) for the treat-ment of low-risk gestational trophoblastic neoplasia (GTN) has beenshown to be superior to weekly methotrexate in terms of achieving acomplete response in a randomized controlled trial (RCT). However,results from RCTs do not always translate into the ‘real-world’setting. We endeavored to evaluate the performance of act-D in ourinstitution, and to document the rate of complete response inpatients with WHO scores of 5-6 and in those with high pre-treatment bHCG levels.
Abstracts / Gynecologic Oncology 133 (2014) 2–207 185