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BACKGROUND Hemorrhage is a leading cause of maternal death worldwide, with increased risk in women with abnormal placentation. Aortic balloon occlusion (ABO), including resuscitative endovascular balloon occlusion (REBOA), has been used for obstetrical hemorrhage for 20 years, and is associated with decreased operative blood loss, fewer transfusions, and lower rates of hysterectomy. However, the effect of aortic occlusion on fetal/neonatal outcomes is not well known. METHODS A literature review on ABO for obstetrical or traumatic hemorrhage was performed. Cases were included if fetal/neonatal outcomes were reported. Data was collected on timing of balloon inflation (pre or post-delivery), fetal/neonatal mortality, and Apgar scores. Secondary maternal outcomes included blood loss, need for hysterectomy, ABO-related complications, and mortality. RESULTS Twenty-one reports of aortic balloon occlusion in 825 cases of obstetrical hemorrhage were reviewed (nine case reports/series and twelve comparative studies). 13.5% (111/825) had aortic occlusion prior to delivery of the fetus. Comparative cohorts included 448 patients who underwent iliac artery balloon occlusion (n = 219) or no vascular balloon occlusion (n = 229). The most common neonatal outcome reported was Apgar scores, with no difference in fetal/neonatal outcomes between ABO and non-ABO patients in any study. One neonatal mortality occurred in the sole reported case of ABO use in a pregnant trauma patient at 24 weeks gestation. One maternal mortality occurred due to aortic dissection. Five comparative studies reported significantly decreased blood loss in ABO patients compared to non-ABO patients and fourstudies reported significantly lower rates of hysterectomy in ABO patients. ABO-related complications were reported in 1.6% of patients (13/825). CONCLUSION Obstetrical hemorrhage is a devastating complication, and aortic balloon occlusion may potentially decrease blood loss and reduce the hysterectomy rate without compromising fetal and neonatal outcomes. Further research is needed to determine the safety of pre-delivery aortic occlusion as this occurred in 14% of cases. TYPE OF STUDY Review. LEVEL OF EVIDENCE IV.

Objective To assess the efficacy and safety of stereotactic body radiation therapy (SBRT) for oligometastatic gynecologic malignancies. Method A comprehensive search of the PubMed, Medline, and EMBASE databases was conducted using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. “Oligometastatic” was defined as a limited number of uncontrolled/untreated metastatic lesions (typically ≤ 5), including regional nodal metastases. Primary outcomes were response rate (complete response or partial response), local control of oligometastatic lesions, and toxicity. Results Of 716 screened records, 17 studies (13 full length articles, 4 conference abstracts) were selected and analyzed as 16 unique studies. A total of 667 patients were treated with ~1071 metastatic lesions identified. Primary sites included ovarian (57.6%), cervical (27.1%), uterine (11.1%), vaginal (0.4%), vulvar (0.3%), and other/unspecified (3.4%). Most patients (65.4%) presented with a single metastatic lesion. Metastatic lesion sites included the abdomen (44.2%), pelvis (18.8%), thorax (15.5%), neck (4.6%), central nervous system (4.3%), bone (1.6%), and other/unspecified (11%). Of the lesions, 64% were nodal. Response rate (among 8 studies) ranged from 49% to 97%, with 7/8 studies reporting > 75% response rate. Local control ranged from 71% to 100%, with 14/16 studies reporting ≥ 80% local control. No grade ≥ 3 toxicities were observed in 9/16 (56%) studies. Median progression-free survival (PFS) (among 10 studies) ranged from 3.3 months to 21.7 months. Disease progression most commonly occurred outside of the SBRT radiation field (79% to 100% of failures). Conclusions SBRT for oligometastatic gynecologic malignancies is associated with favorable response and local control rates but a high rate of out-of-field progression and heterogeneous PFS. Additional study into rational combinations of SBRT and systemic therapy appears warranted to further improve patient outcomes.

ObjectiveWe prospectively evaluated patients with completely resected uterine serous carcinoma (USC) treated with radiation “sandwiched” between carboplatin/paclitaxel (C/T). The primary objective was to determine the safety profile, and the secondary outcome was to evaluate progression-free and overall survival.MethodsSurgically staged patients with completely resected USC were enrolled to receive 3 cycles of paclitaxel 175 mg/m2 and carboplatin (area under the curve, 6–7.5) every 21 days, followed by radiotherapy and an additional 3 cycles of T/C at area under the curve of 5–6 (6 cycles + radiotherapy). Toxicity was graded according to National Cancer Institute Common Toxicity Criteria, version 4.03. Kaplan-Meier and log-rank tests were used to compare survival probabilities.ResultsOne hundred forty patients were enrolled, of which 132 were evaluable, completed at least 3 cycles of chemotherapy and radiation. One hundred seven (81%) completed 6 cycles of chemotherapy and radiation. Patients with early-stage (I/II) disease have survival probabilities of 0.96 and 0.81 at 2 and 5 years. Patients with stage I USC and lymphovascular invasion have considerably worse overall survival, with 2.7 times’ higher risk of death than those without lymphovascular invasion. Patients with late-stage (III/IV) disease had overall survival probabilities of 0.64 and 0.18 at 2 and 5 years, which is far higher survival than what has been reported in single-modality trials. Interestingly, and different than what is reported in other studies, there is no difference in survival in African Americans versus whites/other races who were evaluable. Of the 779 cycles administered, 22% and 14% of cycles were associated with grades 3 and 4 hematologic toxicities, respectively. Grades 3 and 4 nonhematologic toxicities occurred in 6.9% of cycles.ConclusionsThe long-term follow-up in this study demonstrates that “sandwich” therapy is an efficacious, well-tolerated treatment approach with acceptable toxicities. Lymphovascular invasion (LVSI) is a significantly poor prognostic factor in stage I USC. Multimodal “sandwich” therapy should be considered in all USC patients who have undergone complete surgical resection and staging.

To evaluate risk factors for 30-day unplanned readmission and increased length of stay (LOS) following minimally invasive surgery (MIS) for endometrial cancer.This was a retrospective, case-control study using the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP). Multivariable logistic regression was used to assess perioperative variables associated with readmission and increased LOS after MIS for endometrial cancer.The study population included 10,840 patients who met the criteria of having undergone MIS with a resultant endometrial malignancy confirmed on postoperative pathology. Common reasons for readmission included organ/space surgical site infection (65 cases), sepsis/septic shock (19 cases), and venous thromboembolism (20 cases). Notable risk factors for readmission included (Odds Ratio, Confidence Interval, p-value): dialysis dependence (6.77, 2.51-17.80,0.01), increased length of stay (3.00, 2.10-4.10,0.01), and preoperative weight loss (2.80, 1.06-7.17, 0.03); notable risk factors for increased LOS: ascites (8.51, 2.00-36.33,0.01), operation duration5 h (6.93, 5.29-9.25,0.01), and preoperative blood transfusion (5.37, 2.05-14.04,0.01).Identification of risk factors for adverse postoperative outcomes is necessary to inform and improve standards of care in MIS for endometrial cancer. Using nationally reported data from the ACS NSQIP, this study identifies independent risk factors for unplanned readmission and prolonged LOS, and in doing so, highlights potential avenues for quality improvement.

Objectives: The purpose of this retrospective study is to determine racial and social determinants associated with use of genetic testing for heritable cancer mutations in a high risk, low community resource academic institution population. Methods: Women with a personal or family history of heritable cancer (ovarian, fallopian tube, primary peritoneal, breast, colorectal, and endometrial) were identified through the electronic medical record database from August 2015 through August 2019. Demographics (age, sex, race, ethnicity), insurance, and clinical parameters including medical, surgical, social determinants, prior cancer, and family cancer history were evaluated. Patients without a heritable cancer history were excluded.Summary statistics and exact binomial testing were used for comparisons of the rate of genetic testing at the study hospital versus that of reported normative data. To examine whether the internal rates of testing are associated with either demographic or clinical factors, both bivariate and multivariate analyses were performed. For bivariate analyses, chi-square or fisher exact tests for categorical measures and either t-tests or Wilcoxon rank sum tests for continuous measures were used. The effect of the integration of panel testing, which was instituted in August 2017, was determined using a bivariate analysis comparing the groups of patients that were seen before or after August 2017. Results: Of the 344 patients analyzed, only 54 (16%) underwent genetic testing, which is significantly lower than the national average (p Conclusions: The findings of this study highlight a lower rate of genetic testing among African American women diagnosed with heritable cancers relative to national recommendations. Our results indicate that despite inclusion of panel testing, racial disparities in rates of testing persist in our vulnerable, high risk population. Interventions to overcome implicit bias and patient education should be further developed.

Objectives: Advanced vulvar carcinoma typically affects the elderly and treatment options are limited. Moderate antitumor activity of pembrolizumab (ORR, 6%) was noted in a small population of patients (pts) with PD-L1-positive vulvar cancer in the phase 1b KEYNOTE-028 study. KEYNOTE-158 ( ClinicalTrials.gov , NCT02628067) is a larger, nonrandomized, multicohort, open-label, phase 2 study that evaluates pembrolizumab in pts with previously treated advanced cancers irrespective of tumor PD-L1 expression. We report results for pts in the vulvar carcinoma cohort receiving pembrolizumab monotherapy. Methods: Enrolled pts were aged ≥18 y with histologically/cytologically documented advanced vulvar squamous cell carcinoma with prior treatment failure; measurable disease per RECIST v1.1; ECOG performance status ≤1; and tumor samples available for biomarker analysis, including PD-L1. PD-L1 positivity was defined as combined positive score ≥1 with expression evaluated using the PD-L1 IHC 22C3 pharmDx assay (Agilent Technologies, Carpinteria, CA, USA). Pts received pembrolizumab 200 mg Q3W until disease progression, unacceptable toxicity, or completion of 35 treatment cycles. Tumor imaging was performed every 9 weeks for 1 y and every 12 weeks thereafter. Response was assessed per RECIST v1.1 by independent central radiologic review. The primary endpoint was ORR. Secondary endpoints included duration of response (DOR), PFS, OS, and safety. Results: A total of 101 pts were enrolled. As of October 5, 2020, median time from start of treatment to data cutoff was 36.0 (range, 15.4–55.2) months. Median age was 64.0 (range, 31–87) y; 9 (8.9%) pts had no prior therapy, 57 (56.4%) had 1, 23 (22.8%) had 2, and 11 (10.9%) had 3 or more lines of prior therapy. Tumors were PD-L1–positive in 84 pts (83.2%), PD-L1–negative in 7 pts (6.9%), and non-evaluable/not assessed in 10 pts (9.9%). Overall, ORR was 10.9% (95% CI, 5.6–18.7); 1 pt had a CR and 10 pts had PR. Among pts with PD-L1–positive tumors, 8 of 84 (9.5%; 95% CI, 4.2–17.9) had CR or PR; among pts with PD-L1–negative tumors, 2 of 7 (28.6%; 95% CI, 3.7–71.0) had CR or PR. Among pts with a response, median DOR was 20.4 months (range, 2.1+ to 28.0). Among all enrolled pts (n=101), median PFS was 2.1 months (95% CI, 2.0–2.1) and median OS was 6.2 months (95% CI, 4.9–9.4 months). Treatment-related AEs occurred in 51 pts (50.5%), including 12 pts (11.9%) who had grade 3–5 events (no event occurred in >1 pt). There were 2 deaths (2.0%) considered related to treatment (hepatitis, n=1; fulminant hepatitis, n=1). Neither pt had comorbidities or pre-existing liver disease to contribute to these events; no other contributing factors were identified. A total of 5 pts (5.0%) discontinued because of treatment-related AEs. Immune-mediated AEs occurred in 18 pts (17.8%). Conclusions: Pembrolizumab monotherapy was associated with durable responses in a subset of pts with vulvar carcinoma (ORR, 10.9%; median DOR, 20.4 months). Responses occurred in both PD-L1-positive and PD-L1-negative pts.

5580 Background: HER2 is an emerging prognostic and therapeutic target in uterine serous carcinoma (USC). Testing algorithms and platforms in breast and gastric cancers are well studied and validated, but optimal HER2 testing in uterine cancer is not yet established. We aimed to assess the concordance of chromogenic in situ hybridization (CISH), immunohistochemistry (IHC), and next generation sequencing (NGS) platforms to aid in the development of USC specific testing guidelines. We also evaluated the rate of downstream mutations that may affect response to HER2 directed therapy. Methods: A total of 2,192 USC tumors were analyzed using NGS (NextSeq, 592 Genes and WES, NovaSEQ), a subset of 1,423 tumors were also tested by IHC and CISH (Caris Life Sciences, Phoenix, AZ). HER2 positivity through IHC (4B5, Ventana) and CISH (INFORM DUAL HER2 ISH Assay, Ventana) was determined based on 2007 and 2018 ASCO/CAP HER2 breast cancer guidelines. PD-L1 expression was tested by IHC using SP142 (Spring Biosciences) (positive cut-off >1%). Microsatellite instability (MSI) was tested by fragment analysis (FA), IHC and NGS. Tumor mutational burden (TMB) was measured by totaling somatic mutations per tumor (TMB-high cut-off > 10 mutations per Mb). Statistical significance was determined using chi-square. Results: Rates of HER2 positivity were comparable using the 2018 and 2007 breast cancer guidelines (19.5% vs 17.5%; p=0.25). Based on 2018 guidelines, the concordance between IHC and CISH was 98.9%. Specifically, 229/1423 patients (16%) were IHC+/CISH+, 5 patients (0.4%) were IHC+/CISH- and 11 patients (0.8%) were IHC-/CISH+ (Table). Common pathway alterations in HER2+ USC include TP53, RTK RAS, PI3K, NOTCH, chromatin remodeling and cell cycle genes. Single gene alterations in HER2+ tumors that may implicate HER2 therapy resistance (based on pathway analyses in other tumor types) included PI3K (36%), KRAS (2.6%), and PTEN (2.1%). HER2+ tumors had low immunotherapy biomarker profiles (0.3% MSI-H, 0.8% TMB, 17.1% PD-L1). Conclusions: High concordance rates were observed between CISH and IHC. Ultimately these testing platforms need to be validated by response to HER2 targeted therapies in order to develop USC specific HER2 testing guidelines.[Table: see text]

Highlights • There are no documented case of an ICPi therapy causing vaginal mucositis. • This is a presentation of a patient on ICPi therapy with grade 3 mucositis. • Providers need to correctly identify and treat appropriately and expediently. • The 1st reported case of vaginal mucositis from PD-1 inhibitor therapy in a patient with gyn cancer., Immunotherapy, specifically immune checkpoint inhibitors (ICPi), has revolutionized our approach to treating all solid tumors, including gynecologic malignancies. Compared to standard chemotherapy, the adverse events associated with immunotherapies, are often mild and localized, although more severe systemic responses can also occur. While dermatitisdermatitis is a most commonly reported side effect of ICPi therapy, cutaneous toxicities have a range of clinical manifestations and can provide a challenge in an otherwise favorable treatment protocol. There have been few documented cases of mucositis caused by ICPi therapy and to our knowledge, no documented case of an ICPi therapy causing vaginal mucositis. As such, we present a case of a patient with metastatic uterine serous carcinoma (USC) treated with immunotherapy, who developed grade 3 vaginal mucositis. This is a case presentation of a 67-year-old woman with a history of stage I metastatic uterine serous carcinoma who was initially treated with a hysterectomy, bilateral salpingo-oophorectomy, and lymphadenectomy. Eight months after surgery, patient was found to have a vaginal recurrence treated with external beam radiation therapy and vaginal brachytherapy, as well as port site recurrence treated with resection and 6 cycles of systemic chemotherapy with Carboplatin and Paclitaxel. The patient was found to have progression of her disease and was treated with a combinatorial therapy using PD-L1 inhibitor and TK inhibitor. Patient tolerated first two cycles of treatment without severe side effects. Nine days after administration of the second cycle, the patient reported new onset of severe non-radiating vaginal and perineal pain, that worsened with sitting down, and was refractory to pain medications. Pelvic examination revealed multiple, deep, erythematous ulcerations on the vaginal mucosa involving the left and anterior vaginal introitus, distal vagina and necrosis around the periurethral area, consistent with grade 3 mucositis. The treatment was immediately discontinued, and the patient was started on prednisone 100 mg by mouth daily for 7 days, which was tapered over the course of 10 days and Gabapentin and Oxycodone were given for pain control. The patient started to report improvement in symptoms after 3 weeks and re-examination in 1 month showed decreased amount of fibrinous material involving 50% of the lesions, indicating that the initial grade 3 mucositis had improved to grade 1. As immunotherapy is becoming more widely used in gynecologic and other malignancies, providers need to be aware of rare but significant complications associated with these therapies. Such toxicities should be correctly identified and treated appropriately and expediently. Most patients will continue to benefit from administered immunotherapy and often times can be restarted once the toxicities are alleviated. To our knowledge, this is a first reported case of vaginal mucositis associated with immunotherapy treatment with ICPi in a patient with gynecologic malignancy.

ONC201 is a small molecule DRD2 antagonist and ClpP agonist that has prolonged antitumor efficacy and immunomodulatory properties in preclinical models. The enhanced immune modulatory nature of ONC201 was observed in a Phase I study that revealed increased infiltration of granzyme B+ and CD56+ cells, corroborating preclinical reports of NK cell intratumoral infiltration in response to ONC201. A broad induction of immune cytokines and effector molecules was observed in patients treated with ONC201, in particular among patients who experienced at least stable disease by RECIST for 12 or more weeks. Patients who had a > 50% induction in serum perforin, a cytolytic protein found in the granules of cytotoxic T lymphocytes (CTLs) and NK cells, upon ONC201 administration had better outcomes. Regressions in individual metastatic lesions were noted in a small number of EC patients. A multi-center Phase 2 study to explore the efficacy of weekly ONC201 in recurrent or metastatic Type II EC enrolled 5 patients with recurrent EC who underwent paired tumor biopsies before and 9 days after ONC201 initiation. Four of the 5 patients exhibited a 2-5-fold increase in CD4+ Thelper cells in their tumors and the majority of these patients also had CD4+FoxP3+ cells, indicating a significant population of Tregulatory cells (Treg). One patient exhibited an 80% increase in CD8+ T-cells in their tumor 8 days after initiating ONC201. Two of the patients had >2 fold induction of intratumoral granzyme B expression that was surprisingly not accompanied by NK cell infiltration, as assessed by CD56 staining. These results may be consistent with innate immune system activation by ONC201 that results in T-cell modulation. The multi-fold increase in Treg expression could be suppressing tumor cell death. As such, ONC201 dose intensification or combination with immunotherapy are being evaluated for ONC201 in the context of endometrial cancer. Citation Format: Rohinton S. Tarapore, Varun V. Prabhu, Samuel C. Mok, Chilam Au Yeung, Lorna Rodriguez, Eugenia Girda, Gina Mantia-Smaldone, Victoria Bae-Jump, Guangrong Lu, Wolfgang Oster, Joshua E. Allen. Immunomodulatory activity of selective DRD2 antagonist ONC201, an imipridone, in metastatic endometrial cancer (mEC) [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-145.

e18040 Background: Therapeutic options for patients with recurrent platinum resistant ovarian cancer are scarce and represent an unmet need in ovarian cancer. Chemotherapy resistance has been linked to many CD44 pathways including P-glycoprotein mediated efflux of chemotherapeutic agents. Our working hypothesis was that chemotherapy resistant ovarian tumors that expressed CD44 would revert drug resistance by using a CD44 inhibitor SPL-108, that had proven safe as a single agent. Methods: Patients with platinum refractory or resistant CD44+ ovarian tumors were eligible. We used a standard 3+3 phase I design, open-label, 2-arm trial of the combination of SPL-108 and IV paclitaxel (PTX): Arm 1 (2 cohorts) Safety Phase: Cohort 1: SPL-108 150 mg SQ Daily +80 mg PTX weekly Cohort 2: SPL-108 300mg daily +80 mg PTX weekly Arm 2 (1 cohort) Exploratory Phase: Cohort 3: SPL-108 daily dose 300 mg +80 mg PTX weekly Days 1-15 in 28 day cycles Primary end points were safety and tolerability. Secondary endpoints included determining molecular signatures of response using NGS. Tumors were sequenced at the time of recurrence or initial diagnosis. Results: Fourteen patients were enrolled in the study. Prior number of treatments ranged from 2-6, except for one patient with platinum refractory disease that progressed during first line of therapy. There was no DLT and all cohorts were completed as designed. The treatment was well tolerated. There was one instance of a bowel micro-perforation that was treated medically. This patient had platinum refractory disease and eventually underwent an interval cytoreduction. There was one patient with grade 3 neurotoxicity. Sixty-two% of the patients had clinical benefit with 36% having a PR. Forty-three % of patient had a PFS of more than 6 months. Two patients enjoyed a PR of 12 months. Molecular profiling of the tumors revealed that all tumors had TP53 alterations and the 4 patients that did not have a response had tumors with TP53 truncations or a lack of function alteration. Conclusions: Daily SPL-108 300mg SQ in combination with weekly PTX is safe and feasible. The promising clinical activity on drug resistant ovarian tumors warrants further investigation. Resistance to SPL-108 are characterized by lack of function of TP53, mostly early truncations. It is possible that SPL-108 may be reactivating TP53 by promoting its active conformation. Once TP53 is active CD44 expression is abrogated at the promoter. Therefore SPL-108 is effectively acting on CD44 through 2 different mechanisms to promote chemotherapy sensitivity. Clinical trial information: NCT03078400.

6010 Background: The efficacy of treatment for recurrent endometrial cancer (EC) remains limited. Vascular endothelial growth factor and inflammatory chemokines are proangiogenic factors and immune modulators involved in immune suppression. Reprogramming the tumor microenvironment by combining antiangiogenic and immunotherapy (IO) could enhance antitumor responses. Methods: A 2:1 randomized phase 2 trial compared the combination of cabozantinib and nivolumab (Arm A) versus nivolumab (Arm B) in recurrent EC. Primary endpoint was progression free survival (PFS) assessed by RECIST 1.1 (NCT03367741). Women with recurrent measurable EC were eligible. There were no limits on prior therapy, but at least one prior platinum-based chemotherapy was required. Patients (pts) were stratified according to MSI status and assessed by CT every 8 weeks. Cabozantinib was given at 40 mg daily (Arm A) and nivolumab at 240 mg, on D1 and D15 of a 28-day cycle for 4 cycles, followed by 480 mg every 4 weeks (Arms A & B). Pts with carcinosarcoma or prior IO were enrolled in an exploratory cohort and received combination treatment (Arm C). A baseline biopsy was required for all pts. CyTOF analysis was performed on fresh biopsies. Results: 76 evaluable pts were enrolled (Arm A: 36, Arm B: 18, Arm C: 9 carcinosarcoma, and 20 post IO including 7 pts crossed over from Arm B). 55% of pts had received ≥3 prior lines of therapy. Two pts were MSI high in Arm A and none in Arm B. The Kaplan-Meier estimated median PFS was 5.3 (95% CI: 3.5-9.5) months in Arm A and 1.9 (95% CI: 1.6-3.8) months in Arm B, with a log-rank p = 0.07, which met the significance level of 0.1 used for sample size calculation. Objective response rate (ORR) was 25% for Arm A and 16.7% for Arm B; stable disease (SD) was seen in 44.4% vs 11.1%, respectively. Clinical benefit (ORR+SD) was significantly higher in arm A vs B (p < 0.001). In Arm C-carcinosarcoma, one patient had a partial response (11.9 months duration) and four SD. In Arm C-prior IO, six pts responded and eight had SD. The most common related AEs in Arm A were diarrhea (47.2%), elevated liver enzymes (44.4%), fatigue (38.9%), anorexia, hypertension, and nausea (30.6%), mainly grade 1/2. Preliminary CyTOF analysis across treatment arms identified multiple immune subsets for further interrogation including activated CD8+ and CD4+ T cells. Conclusions: Cabozantinib plus nivolumab demonstrates improved PFS compared to nivolumab in heavily pre-treated women with recurrent EC. In-depth CyTOF analysis of the tumor microenvironment to identify predictive immune biomarkers of response is ongoing. Clinical trial information: NCT03367741.

OBJECTIVE: To evaluate the association of 3 hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitor (statin) use and concordant polypharmacy with disease-specific survival from endometrial cancer. METHODS: A retrospective cohort study was conducted of 985 endometrial cancer cases treated from January 1999 through December 2009 at a single institution. Disease-specific survival was estimated by Kaplan-Meier analyses. A Cox proportional hazards model was used to study factors associated with survival. All statistical tests were two-sided and performed using Stata. RESULTS: At the time of analysis, 230 patients (22% of evaluable patients) died of disease and median follow-up was 3.28 years. Disease-specific survival was greater (179/220 [81%]) for women with endometrial cancer taking statin therapy at the time of diagnosis and staging compared with women not using statins (423/570 [74%]) (log rank test, P=.03). This association persisted for the subgroup of patients with nonendometrioid endometrial tumors who were statin users (59/87 [68%]) compared with nonusers (93/193 [43%]) (log rank test, P=.02). The relationship remained significant (hazard ratio 0.63, 95% confidence interval [CI] 0.40-0.99) after adjusting for age, clinical stage, radiation, and other factors. Further evaluation of polypharmacy showed an association between concurrent statin and aspirin use with an especially low disease-specific mortality (hazard ratio 0.25, 95% CI 0.09-0.70) relative to those who used neither. CONCLUSION: Statin and aspirin use was associated with improved survival from nonendometrioid endometrial cancer.

Supplemental digital content is available in the text., Objective Patient-derived organoids (PDOs), used in multiple tumor types, have allowed evaluation of tumor characteristics from individual patients. This study aimed to assess the feasibility of applying PDO in vitro culture for endocrine-based and drug sensitivity testing in endometrial cancer. Methods Endometrial cancer cells were enzymatically dissociated from tumors retrieved from fresh hysterectomy specimens and cultured within basement membrane extract in serum-free medium. An organoid growth assay was developed to assess the inhibitory effects of a variety of drugs including endocrine treatments. Organoid cultures were also prepared for histological and immunohistochemical comparison to the tumors of origin. Results Fifteen endometrial cancer specimens were successfully cultured as PDOs. Small spherical structures formed within 24 hours, and many continued to grow to larger, denser organoids, providing the basis for an organoid growth assay. The STAT3 transcription factor inhibitor, BBI608 (Napabucasin), strongly inhibited growth in almost all PDO cultures, suggesting that stemness programing is involved in organoid formation and/or growth. Inhibition by different growth factor receptor tyrosine kinase inhibitors was observed in several PDO specimens. Four cultures were inhibited by fulvestrant, implying the importance of estrogen-receptor signaling in some PDO cultures. Organoids closely resembled their tumors of origin in both histomorphology and immunohistochemical expression. Conclusions The use of endometrial cancer PDO cultures for development of drug sensitivity testing for individual patient tumors is feasible. The potential value of the PDO model for clinical decision making will require clinical trial evaluation.

79 Background: The Metabotropic Glutamate Receptor 1 (GRM1) is overexpressed in many solid tumors. It activates MAPK and PI3K/AKT pathways and promotes an immune-suppressive tumor microenvironment. In an immunocompetent melanoma mouse model, GRM1 blockade using riluzole or its pro-drug troriluzole (BHV-4157) and PD-1 blockade inhibit tumor growth in an additive manner. We conducted a phase Ib trial of troriluzole and the PD-1 antibody nivolumab. Methods: Patients with advanced or refractory solid tumors were treated with increasing doses of troriluzole. Troriluzole monotherapy was given for a 14-day lead-in period and then patients received troriluzole in combination with nivolumab 240 mg IV every 2 weeks. Results: We enrolled 14 patients with advanced solid tumors (melanoma=3, NSCLC=3, renal cell cancer=2, NSCLC=2, head and neck cancer=2). Eleven patients had prior therapy with anti-PD-(L)1. PK sampling demonstrated that the prodrug was cleaved efficiently without regard to food (Table). The most common TEAEs (all grades) occurring in >40% of patients were transaminitis, increased lipase and nausea. DLT occurred in 3 patients: 1) grade 3 anorexia, 2) grade 3 fatigue and, 3) atrial fibrillation. The MTD was determined to be troriluzole 140 mg QAM + 280 mg PO QHS. The response rate was 7 % (1/14); this occurred in a PD-L1 treated patient. The 6-month PFS rate was 21%. Correlative studies will be presented. Conclusions: The combination of troriluzole and nivolumab was safe and well-tolerated in this highly PD-1 refractory population. Clinical trial information: NCT03229278. [Table: see text]

OBJECTIVE Obesity is an established risk factor for development of endometrial cancer. We hypothesized that obesity might also be associated with an earlier age at endometrial cancer diagnosis, because mechanisms that drive the obesity-endometrial cancer association might also accelerate tumorigenesis. METHODS A retrospective chart review was conducted of all cases of endometrial cancer diagnosed from 1999 to 2009 at a large medical center in New York City. The association of body mass index (BMI) with age at endometrial cancer diagnosis, comorbidities, stage, grade, and radiation treatment was examined using analysis of variance and linear regression. Overall survival by BMI category was assessed using Kaplan-Meier method and the log-rank test. RESULTS A total of 985 cases of endometrial cancer were identified. The mean age at endometrial cancer diagnosis was 67.1 years (±11.9 standard deviation) in women with a normal BMI, whereas it was 56.3 years (±10.3 standard deviation) in women with a BMI greater than 50. Age at diagnosis of endometrioid-type cancer decreased linearly with increasing BMI (y=67.89-1.86x, R=0.049, P

e17040 Background: HIPEC showed a progression free survival when incorporated into interval cytoreductive surgery for ovarian cancer patients in a recent phase lll trial. This has led to a paradigm shift at many institutions and the consideration of HIPEC. The goal of this study is to report on the initiation of this program and change in practice at a high volume cancer center over a period of 1 year. Methods: Reviewed surgical cases from 1/2018 through 1/2019 where patients were thought to have a primary ovarian or fallopian tube cancer. Variables included age, stage, histology, primary or interval debulking surgery, number of neoadjuvant (NAJ) chemotherapy cycles. HIPEC patients were selected out and variables examined included intraoperative procedures, optimal cytoreduction, type of chemotherapy administered, postoperative complications, and ability to receive consolidation chemotherapy. Results: 35 cases where ovarian cancer known or suspected preoperatively. 23 patients had primary surgery consisting of tah/bso/surgical staging/tumor debulking. 0/23 of these patients were offered HIPEC chemotherapy as an upfront strategy. 12 patients received neoadjuvant chemotherapy for recurrent (2) or advanced (10) disease. 11/12 of these patients proceeded to an interval surgery. 6/11 (54%) were planned for HIPEC. This was aborted in 1/6 because of thrombocytopenia. 5/6 patients went on to receive HIPEC. They received 3-6 cycles of NAJ chemotherapy, platinum and taxane. 3/5 also received preoperative Avastin. All had R0 resection. 1 patient had a bowel resection. Either carboplatin or cisplatin was used for HIPEC over 90 minutes. 2/5 patients had postoperative G2-3 cytopenias. 3/5 patients were able to receive consolidation chemotherapy, 2 of them within six weeks of surgery and with Avastin containing regimens. Conclusions: In a large volume center initiating a HIPEC ovarian cancer program in less than one years’ time, HIPEC was offered to 50% of patients undergoing interval debulking for Stage III or IV serous ovarian cancer after NAJ chemotherapy and in rare cases for patients with recurrent cancer planned for cytoreduction. Patients may go on to receive postoperative chemotherapy but may have prolonged cytopenias and consolidation therapy delays. HIPEC was not incorporated into an upfront surgical strategy.[Table: see text]

Objective: The objective of this study is to assess the outcome of port-a-cath (PAC) maintenance every three months in patients with gynecologic malignancies with the goal of standardizing a safe and appropriate interval that would maintain patency and minimize side effects. Methods: We performed a retrospective medical record review and evaluation of all patients with a Bard? PAC who were noted to have no evidence of disease (NED) during the years 2003 to 2010. The interval between accessions and any complications related to the presence of the PAC were recorded. Relevant complications included skin infections, bacteremia, thrombosis, and occlusions. Statistical analysis was done using the Fisher’s exact test. Results: A total of 201 patients had PAC placed and 43 patients underwent PAC accessions to maintain patency. The total number of accessions was 150 with a median number per patient of 2.0 (range 1 - 10). The mean time between flushes was 112 days (SD = 57). When comparing women in maintenance who had flushes within 90 days versus those who had flushes over 90 days apart, there was no difference in infection or occlusion rates between these groups (p = 0.515). In the Conclusion: Infections and occlusions are rare in women with gynecologic malignancies undergoing maintenance of their PAC. Longer intervals between PAC flushes do not appear to affect the outcome in our patients. Our ongoing data and follow-up confirm that extending the interval of PAC accession to every 3 months, rather than monthly, is safe, effective and convenient in the patient population with gynecologic malignancies.

TPS5608Background: Ovarian cancer often presents in advanced stages and is treated with platinum-based chemotherapy. However, many patients develop platinum-resistant disease with either failing to...

Objective To report a case of pelvic actinomycosis presenting as large, multiloculated abscesses after an in vitro fertilization (IVF) cycle for male factor infertility. Design A case report and literature review. Setting University hospital. Patient(s) A 31-year-old nulligravid woman presenting with urinary retention, pelvic pain, and fever 6 days after transvaginal oocyte retrieval and an embryo transfer for male factor infertility. Intervention(s) Intravenous and oral antimicrobial therapy, and computed tomography (CT)-guided drainage of pelvic abscesses. Main Outcome Measure(s) Clinical and radiologic resolution of symptoms and infection. Result(s) The CT scan revealed several large, multiloculated pelvic and tuboovarian abscesses. The patient defervesced after 6 days of intravenous antibiotics, but the pelvic pain did not improve. After CT-guided drainage of the pelvic abscesses, the patient's symptoms improved. The drained material was cultured, and the patient was diagnosed with pelvic actinomycosis tuboovarian abscesses, an infrequent cause of tuboovarian abscess and a rare complication of assisted reproductive technology (ART). The patient was switched from intravenous to oral antibiotics and discharged home. Conclusion(s) Pelvic Actinomyces israelii presenting as pelvic abscesses may occur as a rare complication of ART. Physicians should consider a diagnosis of tuboovarian abscess in a patient reporting fever and pelvic pain after IVF and embryo transfer.

Background/Aim. The aim of this study was to determine the effect of propofol on acid reflux as measured with the Bravo pH monitoring system. Methods. 48-hour pH tracings of 88 children were retrospectively evaluated after placement of the Bravo capsule under propofol. Comparisons between day 1 and day 2, as well as 6-hour corresponding segments from day 1 and day 2, were made. Results. The number of reflux episodes was significantly increased during the first six-hour period on day one as compared to day 2 . The fraction of time the pH was Conclusion. Our data suggest an increase in gastroesophageal reflux during the postanesthesia period. This could be a direct effect of propofol, or related to other factors. Regardless of the cause, monitoring of pH for the first 6 hours following propofol administration may not be reliable when assessing these patients. Monitoring pH over a prolonged 48-hour time period can overcome this obstacle.

5592 Background: Statins, or 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors, are commonly used to manage hyperlipidemia. Epidemiologic studies have recently linked statins to improved cancer survival. Molecular pathways that explain this effect are not well defined, but may involve cell death and angiogenesis. Our aim was to determine the association between statin use and overall survival in a cohort of women with uterine malignancies. Methods: After IRB approval, a retrospective review of consecutive patients with uterine malignancies diagnosed between 01/2005 and 12/2009 at a single institution was performed. Age, race, diagnosis of hyperlipidemia, diabetes, hypertension, medication use including statins, beta-blockers, aspirin, pathology, and exposure to chemotherapy or radiation were abstracted from the time of initial diagnosis and treatment. Kaplan-Meier analysis, univariate, and multivariate Cox Proportional Hazard Regression were performed to assess the association between statin use, aspirin use, and survival. Results: Of 554 patients identified, 333 (60%) were not hyperlipidemic (NH), 165 (30%) were hyperlipidemic on statins (HS), and 56 (10%) were hyperlipidemic and not on statin therapy (HNS). The HS cohort was older, diabetic, hypertensive, used beta-blockers and aspirin. Stage, grade, and chemotherapy use were similar, but HS and HNS received more radiation (p