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The study provides insights in HGSOC by identifying that ascitic CAFs selectively recruit ITGA5high ascitic tumor cells to form heterotypic spheroids named metastatic units (MUs), which actively engage in peritoneal metastasis, discriminates HGSOC from LGSOC, and act as therapeutic targets in hampering OC metastasis., High-grade serous ovarian cancer (HGSOC) is hallmarked by early onset of peritoneal dissemination, which distinguishes it from low-grade serous ovarian cancer (LGSOC). Here, we describe the aggressive nature of HGSOC ascitic tumor cells (ATCs) characterized by integrin α5high (ITGA5high) ATCs, which are prone to forming heterotypic spheroids with fibroblasts. We term these aggregates as metastatic units (MUs) in HGSOC for their advantageous metastatic capacity and active involvement in early peritoneal dissemination. Intriguingly, fibroblasts inside MUs support ATC survival and guide their peritoneal invasion before becoming essential components of the tumor stroma in newly formed metastases. Cancer-associated fibroblasts (CAFs) recruit ITGA5high ATCs to form MUs, which further sustain ATC ITGA5 expression by EGF secretion. Notably, LGSOC is largely devoid of CAFs and the resultant MUs, which might explain its metastatic delay. These findings identify a specialized MU architecture that amplifies the tumor–stroma interaction and promotes transcoelomic metastasis in HGSOC, providing the basis for stromal fibroblast-oriented interventions in hampering OC peritoneal propagation., Graphical Abstract

e13062 Background: To confirm data from older studies reporting reduced risks of breast cancer (BC) in BRCA mutated (BRCA+) ovarian cancer (OC) patients and to re-evaluate BC surveillance and/or prophylactic mastectomy in OC patients. Methods: Data on 430 BRCA+ mutation carriers diagnosed with OC between 2000 and 2017 in 6 medical centers (one in the USA and five in Israel) were analyzed. Data included demographics, breast surveillance type, family history, BRCA mutation types, timing of BC diagnosis (before or after OC diagnosis) and family history of cancer. Results: Median age at diagnosis of OC was 55.4 years (range, 31.3-90) and median follow-up was 4.6 years. Most patients were BRCA1 (66.6%), and 35.7% had 185delAG. Most patients (68.4%) were Ashkenazi Jews, 27.4% had a family history of BC and 16.5% were diagnosed with BC before OC. Five percent developed BC following OC diagnosis with a median time to BC diagnosis of 68 months (range, 11-210). Of those diagnosed with BC, 50% had triple-negative BC, 40% had luminal B ER+, PR-, Her2-neg and 10% had luminal A -ER+, PR+, her2-neg. There was a non-significant increase in BC after OC, and in BC prior to OC diagnosis; there was no correlation of BC with family history. No definite deaths from BC were recorded. Conclusions: The incidence of BC after OC diagnosis in the BRCA+ population at a median follow-up of 4.6 years is consistent with prior series. Prophylactic bilateral Surveillance measures should be re-evaluated in this population and may only be needed in long-term disease-free survivors and/or subpopulations to be identified. Clinical trial information: 07-146.

5569 Background: For patients with ovarian cancer undergoing neoadjuvant chemotherapy, the effectiveness of treatment is not evaluable by conventional methods until all or much of the treatment has been given. The purpose of this study is to investigate the performance of FDG PET, dynamic contrast-enhanced (DCE) and intra-voxel incoherent motion (IVIM) MR as early predictors of treatment response. Methods: Subjects with a new diagnosis of epithelial ovarian cancer underwent 3 cycles of standardized chemotherapy followed by cytoreduction. FDG PET/MR including DCE and IVIM was performed at baseline (T0), after cycle 1 (T1) and after cycle 3 (T2) of chemotherapy. Final responses were categorized at T2 by RECIST 1.1. Image volumes at T1 were analyzed as predictors of final response. Parametric images of molecular diffusion restriction (D), tissue perfusion (D*), vascular volume fraction (F), blood- > interstitium constant of transfer (Ktrans), interstitum- > plasma constant of transfer (Kep), extravascular/extracellular volume % (Ve) and plasma volume % (Ve) were investigated along with routine measures of SUV and ADC. Results: Nine subjects were enrolled, 8 were responders by RECIST at T2 and one had stable disease. At T0 the mean, min, and max SUVmax of dominant tumor deposits was 11.5, 6.3, 19.0, respectively. Mean, min, and max values were 1.0, 0.75 and 1.63 for ADCmean and 0.62, 0.30, 0.96 for ADCmin. At T1, ADCmean increased in 8 subjects by +0.22% (s.d. +/- 13%) and decreased by -3% in one subject. ADCmin increased in 8 subjects by +21% (s.d. +/-11%) and decreased by -23% in one subject. D increased for 8 subjects (average +29% s.d. +/- 13%) and decreased by -10% in one. D*, F, Kep, Ktrans, Ve and Vp had no recognizable pattern. At T2, SUVmax, SUVmin, and ADCmean maintained their change direction across all subjects with measurable lesions. The only subject with a complete response at T2 had the highest ADCmin and ADCmean change at +45% after one cycle of chemotherapy (T1). The subject with stable disease at T2 had no significant difference in changes amongst all metrics. Conclusions: FDG PET/MR SUVmax and ADCmean values obtained after one cycle of neoadjuvant chemotherapy were consistently associated with partial anatomical treatment responses after three cycles. Molecular diffusion restriction also was reliably associated with treatment response. Future studies evaluating FDG PET/MR in platinum-resistant patients may allow for early discontinuation of ineffective and toxic treatment.

e17018 Background: In the US, cervical cancer (CC) disproportionately impacts minorities and women with insufficient access to care. In our department, patients (pts) with advanced CC referred from a public hospital (PbH) and a private hospital (PrH) are treated with the same integrated team of physicians. We sought to determine whether referral source affects outcome post definitive chemoradiation (CRT) and brachytherapy (BT) for CC pts. Methods: An IRB approved retrospective review was conducted for pts diagnosed with CC and treated with definitive CRT. All pts were treated with external beam RT and chemotherapy followed by intracavitary BT boost (median 7 Gy x 4 fractions) delivered via two insertions of intracavitary BT two weeks apart with image-guided CT/MR delineation. Disease free survival (DFS) and overall survival (OS) were analyzed with the Kaplan-Meier method. Multivariate Cox hazards analysis was run to identify the effects of covariates, using R v3.5.1. Results: Between 7/2009 and 9/2017, 106 pts were diagnosed with FIGO stage IA(1), IB(22), IIA(10), IIB(46), IIIA(3), IIIB(24) and IVA(2) CC. 81 (76.4%) pts were diagnosed and received chemotherapy and operative insertion at PbH, 25 (23.6%) at PrH. Median age was 54 years (y), range (28-83). At median follow-up of 32.2 months (3.8-110.2), local control was 82%. 5-y DFS and OS was 62.4% and 84.2%. 19.8% pts were diagnosed at age 65 or greater. PbH pts were diagnosed at a younger median age of 52.4y (28.1-77.7) compared to 59.8y (30-83) at PrH (P = 0.03). PbH vs PrH pts were more likely to present at earlier stages I/II (79% vs 56%), than stages III/IV (21% vs 44%), p = 0.04 and have better outcomes; PbH vs PrH DFS was 65.0% vs 54.5% (P = 0.1), while OS was 89.3% vs 54.9% (P = 0.01). In Cox multivariate analysis, only stage at diagnosis was a significant independent predictor of survival (P = 0.006). Conclusions: Our data suggests that patients referred from a public hospital do not have worse outcomes when treated by a centralized multidisciplinary team. PrH pts presented at older age, more advanced stage and had worse OS than PbH pts. Twenty percent of pts diagnosed with advanced CC were above age 65, highlighting the need for continued screening.

BackgroundPhase 2 trials suggest that prolonged intravenous (IV) infusion of the topoisomerase 1 inhibitor topotecan may be less toxic than when given by standard IV bolus 5-day administration. Oxaliplatin exhibits efficacy in platinum-pretreated disease and shows preclinical synergy with topoisomerase 1 inhibitors. We sought to determine the efficacy and safety of oxaliplatin plus infusion topotecan in recurrent platinum-pretreated ovarian cancer.MethodsPatients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancers previously treated with 1 to 2 prior regimens including platinum and taxane received oxaliplatin (85 mg/m2day 1 and day 15) and topotecan (0.4 mg/m2per day) by continuous IV infusion over 14 days every 4 weeks. The primary objective of the trial was to estimate the objective response rate in platinum-resistant disease (stratum 1) and in platinum-sensitive disease (stratum 2). Toxicities were assessed in all patients.ResultsThirty-eight patients received 144 cycles of therapy (median, 4; range, 1–6). The most common grade 3 and grade 4 toxicities included thrombocytopenia (grade 3, 37%; and grade 4, 19%), neutropenia (grade 3, 37%; grade 4, 11%), and anemia (grade 3, 15%). Response occurred in 4 of 19 patients in stratum I (21%; 95% confidence intervals, 6%–46%) and 9 of 19 patients in stratum 2 (47%; 95% CI, 24%–71%). Three in each stratum had lengthy complete responses.ConclusionsBiweekly oxaliplatin plus a 14-day continuous IV infusion of topotecan, given monthly, is an active regimen in platinum-pretreated ovarian cancer and merits additional evaluation.

CME Learning Objectives Describe the range of palliative procedures utilized in gynecologic cancers. Evaluate the indications for palliative bowel surgery in ovarian cancer. Assess the clinical scenario for which palliative pelvic exenteration would be considered. Compare the morbidities associated with palliative gynecologic surgeries to the potential benefits gained. The decision to undergo major palliative surgery in end-stage gynecologic cancer is made when severe disease symptoms significantly hinder quality of life. Malignant bowel obstruction, unremitting pelvic pain, fistula formation, tumor necrosis, pelvic sepsis, and chronic hemorrhage are among the reasons patients undergo palliative surgeries. This review discusses and summarizes the literature on surgical management of malignant bowel obstruction and palliative pelvic exenteration in gynecologic oncology.

Until recently our knowledge of a genetic contribution to ovarian cancer focused almost exclusively on mutations in the BRCA1/2 genes. However, through germline and tumor sequencing an understanding of the larger phenomenon of homologous recombination deficiency (HRD) has emerged. HRD impairs normal DNA damage repair which results in loss or duplication of chromosomal regions, termed genomic loss of heterozygosity (LOH). The list of inherited mutations associated with ovarian cancer continues to grow with the literature currently suggesting that up to one in four cases will have germline mutations, the majority of which result in HRD. Furthermore, an additional 5–7% of ovarian cancer cases will have somatic HRD. In the near future, patients with germline or somatic HRD will likely be candidates for a growing list of targeted therapies in addition to poly (ADP-ribose) polymerase (PARP) inhibitors, and, as a result, establishing an infrastructure for widespread HRD testing is imperative. The objective of this review article is to focus on the current germline and somatic contributors to ovarian cancer and the state of both germline and somatic HRD testing. For now, germline and somatic tumor testing provide important and non-overlapping clinical information. We will explore a proposed testing strategy using somatic tumor testing as an initial triage whereby those patients found with somatic testing to have HRD gene mutations are referred to genetics to determine if the mutation is germline. This strategy allows for rapid access to genomic information that can guide targeted treatment decisions and reduce the burden on genetic counselors, an often limited resource, who will only see patients with a positive somatic triage test.

Occult endometrial cancer is occasionally discovered in women with Lynch syndrome undergoing risk-reducing hysterectomy. The case presented here demonstrates that preoperative endometrial sampling can help detect these occult cancers; however, there are currently no recommendations for this preoperative intervention. A 50-year-old woman with Lynch syndrome underwent endometrial sampling prior to planned risk-reducing hysterectomy and bilateral salpingo-oophorectomy. The endometrial biopsy demonstrated a serous endometrial cancer. The patient was counselled regarding the diagnosis and revised operative plan, which now included staging, prior to surgery. Although the prevalence of occult endometrial cancer at the time of risk-reducing surgery in women with Lynch syndrome remains unknown, preoperative endometrial sampling may allow for improved patient counselling and surgical planning in this population, and can help avoid a subsequent surgery for staging.

Background Suppression of neoangiogenesis and pegylated liposomal doxorubicin (PLD) each contribute to the management of platinum-resistant/refractory ovarian cancer. The aim of this study is to test the combination of bevacizumab and PLD in women with resistant or refractory ovarian cancer. Methods Eligibility criteria were no more than two prior treatments with platinum-containing regimens and one additional regimen, without anthracyclines. Treatment was administered every 3 weeks (bevacizumab 15 mg/kg beginning on cycle 2 and PLD 30 mg/m2). The primary end point was progression-free survival (PFS) at 6 months; the secondary end points included side-effects, overall response rates (ORR) and survival (OS). Results Forty-six patients were enrolled. The average number of courses administered was 7. The median PFS was 6.6 months (range 1–24.6 months) according to Gynecologic Cancer Intergroup Committee (GCIC) criteria and 7.8 months (range 2–13.3 months) according to Response Evaluation Criteria in Solid Tumors (RECIST). The median OS was 33.2 months (range 3–37.5+ months). The ORR was 30.2% [95% confidence interval (CI) 17.2–46.1] and the clinical benefit rate (CBR) was 86.1% (95% CI 72.1–94.7). Adverse events included mucosal and dermal erosions (30% grade 3) and asymptomatic cardiac dysfunction. Additional toxic effects included hypertension, headache, renal dysfunction and proteinuria, wound healing delay, and one episode each of central nervous system (CNS) ischemia and hemolytic uremic syndrome. Conclusion PLD with bevacizumab has improved activity in recurrent ovarian cancer with increased toxicity.

1544Background: The NCCN guidelines recommend risk-reducing bilateral salpingo-oophorectomy (RRBSO) for patients with BRCA mutations by age 35-40 or upon completion of childbearing. We previously r...

5564Background: The NCCN recommends risk-reducing salpingo-oophorectomy (RRSO) for women with BRCA mutations by age 35-40 or upon completion of childbearing. We previously reported that RRSO was be...

1537Background: Lynch syndrome (LS) accounts for most inherited endometrial cancers (EC). The identification of probands presents a chance to prevent other cancers and enable cascade testing. Profe...

e13619Background: Identification of a BRCA mutation can profoundly impact family planning for women of reproductive age. Assisted reproductive technology (ART), including pre-implantation genetic d...

Cervical cancer (CC) is the second most common cancer in women. Currently no tractable molecular based therapeutic targets exist for patients with invasive CC and no predictive markers of risk assessment for progression of precancerous lesions are identified. New molecular insights into CC pathogenesis are urgently needed. Towards this goal, we first determined the copy number alterations of chromosome 4 and then examined the role of PCDH10 mapped to 4q28 as a candidate tumor suppressor gene. We identified monosomy 4 in 47% of 81 invasive CC studied by SNP array and found that 91% of 130 invasive CC harboring methylation in the promoter region of the PCDH10 gene. We then showed that aberrant promoter hypermethylation of PCDH10 is associated with down-regulation of gene expression and cell lines exposed to demethylating agent resulted in profound reactivated gene expression. We also showed that the promoter methylation in the PCDH10 gene occurs at an earliest identifiable stage of low-grade squamous intraepithelial lesion (LSIL). Our studies demonstrate that inactivation of PCDH10 may be a critical event in CC progression and form a potentially useful therapeutic target for CC.

Multiple chromosomal regions are affected by deletions in cervical cancer (CC) genomes, but their consequence and target gene involvement remains unknown. Our single nucleotide polymorphism (SNP) array identified 8p copy number losses localized to an 8.4 Mb minimal deleted region (MDR) in 36% of CC. The 8p MDR was associated with tumor size, treatment outcome, and with multiple HPV infections. Genetic, epigenetic, and expression analyses of candidate genes at MDR identified promoter hypermethylation and/or inactivation of decoy receptors TNFRSF10C and TNFRSF10D in the majority of CC patients. TNFRSF10C methylation was also detected in precancerous lesions suggesting that this change is an early event in cervical tumorigenesis. We further demonstrate here that CC cell lines exhibiting downregulated expression of TNFRSF10C and/or TNFRSF10D effectively respond to TRAIL-induced apoptosis and this affect was synergistic in combination with DNA damaging chemotherapeutic drugs. We show that the CC cell lines harboring epigenetic inactivation of TRAIL decoy receptors effectively activate downstream caspases suggesting a critical role of inactivation of these genes in efficient execution of extrinsic apoptotic pathway and therapy response. Therefore, these findings shed new light on the role of genetic/epigenetic defects in TRAIL decoy receptor genes in the pathogenesis of CC and provide an opportunity to explore strategies to test decoy receptor gene inactivation as a biomarker of response to Apo2L/TRAIL-combination therapy.

ObjectiveWe aimed to compare access to gynecologic oncology care at a private and a city hospital, both of which closed for a period of time because of Hurricane Sandy.MethodsThis was a cross-sectional study of gynecologic oncology chemotherapy, radiotherapy, and surgical patients from October 29, 2012 (the eve of the storm), to February 7, 2013 (the reopening of the city hospital). New referrals during this time were excluded. Delays in chemotherapy, radiotherapy, and surgery were compared.ResultsAnalysis included 113 patients: 59 private patients (52.2%) and 54 city patients (47.8%). Of the private patients, 33/59 received chemotherapy (55.9%), 1/59 received radiotherapy (1.7%), and 28/59 had planned surgery (47.5%). Of the city patients, 40/54 received chemotherapy (74.1%), 7/54 received radiotherapy (12.3%), and 18/54 had planned surgery (33.3%). The mean delay in chemotherapy was 7.6 days at the private hospital and 21.7 days at the city hospital (P=0.0004). The mean delay in scheduled surgery was 14.2 days at the private hospital and 22.7 days at the city hospital (P=0.3979). The mean delay in radiotherapy was 0.0 days at the private hospital and 25.0 days at the city hospital (P=0.0046). Loss to follow-up rates were 3/59 of the private patients (5.1%) and 3/54 of the city patients (5.6%).ConclusionsGynecologic oncology care was maintained during a natural disaster despite temporary closure and relocation of services. Disparity in care was in access to chemotherapy. (Disaster Med Public Health Preparedness. 2015;9:605–608)

Percutaneous gastrostomy tube placement is a technically feasible and safe procedure for palliation in patients with small bowel obstruction (SBO) caused by advanced gynecologic malignancies. It is used commonly in patients who are poor surgical candidates, those who elect to not undergo surgery, and in patients with a limited lifespan because of end-stage cancer. Percutaneous gastrostomy tube placement is even technically possible in patients with tumor encasing the stomach, diffuse carcinomatosis, and ascites. Percutaneous endoscopic gastrostomy (PEG) tubes provide symptomatic relief of nausea and vomiting in most patients with advanced gynecologic cancer and SBO. PEG tube placement allows most patients to have end- of-life care at home or in an inpatient hospice. It is a cost effective procedure and is associated with low morbidity and mortality. Placement of PEG tubes should be highly considered in patients who present with recurrent bowel obstruction and who have undergone a prior operation for SBO in the setting of advanced gynecologic malignancy.

Introduction: Fertility sparing therapy for epithelial ovarian cancer has been suggested for well-selected patients with early stage disease. The overall recurrence rate of 10% and 5-year disease free survival greater than 90% is similar in conservative and traditional surgical management of epithelial ovarian cancer. Thus, conservative approaches may be considered in young women diagnosed with FIGO stage I cancer who wish to preserve reproductive function. Subsequent use of assisted reproductive technologies (ART) may facilitate production of biologic offspring in these cancer survivors. However, each candidate requires unique consideration by subspecialists to avoid potentially fatal management errors. Case report: We present two cases in which fertility sparing therapy for early stage epithelial ovarian cancer was considered. The first case delineates the comprehensive work-up required to identify candidates for this therapy, while the second case illustrates the successful application of a fertility sparing approach. Discussion: The conservative management of early epithelial ovarian cancer and use of ART to obtain offspring are reviewed.

Objective Acute large-bowel obstruction (LBO) is considered a surgical emergency. In gynecologic oncology patients with LBO due to recurrent tumor, surgery has been the standard treatment. However, operative intervention has significant associated morbidity and mortality. Recent reports have addressed the use of colorectal stents for the treatment of colonic malignancies. We are reporting our experience with colorectal stents in gynecologic oncology patients. Methods We reviewed the records of all patients who underwent colorectal stent placement for palliation of LBO due to recurrent gynecologic malignancy from August 2001 to January 2003. Results Six patients were identified; five patients had recurrent ovarian cancer and one had recurrent endometrial cancer. The mean age of the six patients at the time of stent placement was 51.5 years (range, 22–83 years).The length of LBO ranged from 2 to 10 cm. Two patients had a lumen of 1 to 2 mm before stent placement, while the other four had a complete obstruction and needed balloon dilatation before the deployment of the stent. Four (67%) of six patients had immediate relief, with passage of stool and flatus noted at the time of the colorectal stent placement. Stent placement failed to relieve the LBO in two patients (33%); these patients went on to receive colostomies. Of the four patients who had successful stent placement, the mean survival after stent placement was 120 days. One patient had a contained sigmoid bowel perforation noted 12 days after stent placement, which resolved with conservative measures. Conclusion Colonic stents appear to be a useful option in the management of patients with LBO due to recurrent gynecologic malignancy.

Patients with advanced stage invasive cervical cancer (CC) exhibit highly complex genomic alterations and respond poorly to conventional treatment protocols. In our efforts to understand the molecular genetic basis of CC, we examined the role of Fanconi Anemia (FA)-BRCA pathway. Here, we show that FANCF gene is disrupted by either promoter hypermethylation and/or deregulated gene expression in a majority of CC. Inhibition of DNA methylation and histone deacetylases induces FANCF gene re-expression in CC cell lines. FANCF-deregulated CC cell lines also exhibit a chromosomal hypersensitivity phenotype after exposure to an alkylating agent, a characteristic of FA patients. We also show the involvement of BRCA1 gene by promoter hypermethylation or down-regulated expression in a small subset of CC patients. Thus, we have found inactivation of genes in the FA-BRCA pathway by epigenetic alterations in a high proportion of CC patients, suggesting a major role for this pathway in the development of cervical cancer. Thus, these results have important implications in understanding the molecular basis of CC tumorigenesis and clinical management in designing targeted experimental therapeutic protocols.

Objective Intestinal obstruction is a frequent sequela of recurrent ovarian cancer. Previous series report median survivals of 3–6 months in patients undergoing surgery for obstruction due to recurrent disease. We analyze a contemporary series of patients to determine if outcomes have changed in patients undergoing palliative surgery. Methods We retrospectively reviewed all patients undergoing surgery for intestinal obstruction due to recurrent ovarian cancer from 1994 to 1999. Results During the study period, 68 operations were performed on 64 patients. Mean age at the time of obstruction was 57.3 years. Mean time from original diagnosis of ovarian cancer to obstruction was 2.8 years. Surgical correction (intestinal surgery performed for relief of obstruction) was attained in 57 of 68 (84%) cases. Successful palliation (the ability to tolerate a regular or low-residue diet at least 60 days postoperatively) was achieved in 71% of cases where surgical correction was possible. The rate of major surgical morbidity was 22%. There was one death from pulmonary embolus and one from peritonitis. Two other deaths occurred due to progression of disease, for an overall perioperative mortality rate of 6%. Postoperative chemotherapy was administered in 45 of 57 (79%) cases where surgical correction was possible. The median survival of the entire cohort was 8 months. If surgery resulted in successful palliation, median survival was 11.6 months, versus 3.9 months for all other patients ( P Conclusions The majority of our patients undergoing surgery had successful palliation, and were able to receive further chemotherapy. They were discharged home, and could tolerate solid food.

Background. Although central nervous system (CNS) metastases from epithelial ovarian carcinoma are rare, recent studies indicate that the incidence may be increasing. Numerous series have reported various modalities for treatment with median survivals of 3 to 5 months, but the role of craniotomy has not been specifically addressed. Methods. We conducted a retrospective review of all patients who underwent craniotomy between 1989 and 2001 for pathologically confirmed recurrent epithelial ovarian cancer metastatic to the CNS. Results. We identified 14 patients who had a mean age at diagnosis of 59.3 years (range, 45 to 70). Distribution by stage and grade was as follows: Stage I, 0; II, 1; III, 12; and IV, 1; and grade 1,0; 2,4; and 3,10. Histologic distribution was as follows: papillary serous, 9; endometrioid, 2; mixed papillary serous and endometrioid, 1; carcinosarcoma, 1; and poorly differentiated adenocarcinoma, 1. Six patients had optimal primary cytoreduction, while 7 had suboptimal primary cytoreduction. All patients received initial platinum-based chemotherapy. Ten of 14 patients underwent second-look evaluation, and in 8 patients the findings were negative. The median time from initial diagnosis of ovarian carcinoma to CNS relapse was 3.5 years (range, 1.3 to 8.2). In 7 patients (50%), the CNS recurrence was the first site of relapse. Eight patients (57%) had extracranial disease at the time of craniotomy. Distribution of CNS lesions were as follows: supratentorial, 12; and cerebellar, 2. The mean operative time for craniotomy was 178 min (range, 70 to 305). The average blood loss was 125 mL (range, 20 to 250). The only major operative complications were deep vein thromboses that developed in two patients. No patient developed a neurologic deficit as a result of craniotomy. One patient died of progressive disease 37 days after surgery. Postoperative treatment included whole-brain radiation in 11 patients, chemotherapy in 4, and hormonal therapy in 4. Four patients (29%) had a CNS relapse after craniotomy. The median survival of patients after craniotomy was 18 months, and the 1- and 2-year survival rates were 66% (95% confidence interval (CI): 43–100) and 39% (95% CI: 17–90), respectively. Conclusions. Despite optimal cytoreduction, platinum-based chemotherapy, and negative second-look surgical assessment, patients with ovarian cancer can fail distantly with CNS metastases. Craniotomy with adjuvant radiation therapy can provide control of brain metastases in the majority of these patients and may result in improved survival over radiation therapy alone in selected patients.

The most common indication for palliative surgery in recurrent ovary cancer is malignant bowel obstruction. After careful diagnosis of bowel obstruction, conservative management should be employed. If resolution of obstruction does not occur, the decision to perform surgery must be made. Several authors have reported on outcomes in patients undergoing surgery. Operative morbidity and mortality is 7–64% and 4–32%, respectively, and median survival is 5–33 weeks in these reports. Surgery should be considered in select patients after a thorough discussion with the patient regarding the likely outcome following the procedure, including the potential for morbidity and mortality. The surgery should be aimed at relieving the symptoms and improving quality of life.

To determine the accuracy of spiral computed tomography (CT) in the depiction of peritoneal metastases by using surgical findings in patients with ovarian cancer as the standard of reference.Three independent readers reviewed the preoperative CT scans obtained in 64 patients who underwent primary surgery for ovarian cancer. Readers rated the likelihood of peritoneal metastases on a five-point scale and recorded the presence or absence of ascites, parietal peritoneal thickening or enhancement, and small-bowel wall thickening or distortion. Peritoneal metastases were identified as nodular, plaquelike, or infiltrative soft-tissue lesions in the peritoneal fat or on the peritoneal surface. Area under the receiver operating characteristic curve was calculated for each reader. Interreader agreement was evaluated with the kappa statistic. Descriptive statistical data were determined with dichotomized ratings (1-3 = absent; 4-5 = present).Areas under the receiver operating characteristic curves for the three readers were 0.95, 0.93, and 0.89. Paired kappa values ranged from 0.75 to 0.91. Reader sensitivity for metastases 1 cm or smaller in maximum diameter (25%-50%) was significantly (P.05) lower than overall sensitivity (85%-93%). Ascites, parietal peritoneal thickening or enhancement, and small-bowel wall thickening or distortion demonstrated positive predictive values of 72%-93%, with kappa values of 0.12-0.80.Spiral CT is accurate in the depiction of peritoneal metastases from ovarian cancer, although sensitivity is reduced in patients with tumor implants 1 cm or smaller. Ancillary signs of peritoneal malignancy are limited by low interobserver agreement.

A minimally invasive surgical approach has proven to decrease peri- and postoperative complications and shorten duration of hospital stay; however, there are limited data evaluating the safety of robotic-assisted surgery and early hospital discharge in the elderly population. Because age is a well-known, independent risk factor for perioperative morbidity and gynecologists treat many elderly patients, this is an important area of study.The objective of the study was to evaluate discharge timing and surgical outcomes in elderly compared with younger patients undergoing robotic-assisted gynecologic surgery.This was a retrospective cohort study of all patients who underwent robotic-assisted gynecologic surgery at a high-volume, single institution from January 2013 through May 2016. Demographic information, discharge timing, and peri- and postoperative outcomes were compared for patients65 years with those ≥65 years using univariate and multivariate analyses.There were 2757 patients included, with 252165 years and 236 ≥65 years. Median age of the younger group was 42 years, while the median age of the elderly group was 69 years. Elderly patients had a higher body mass index (kilograms per square meter) (28 vs 26, P.001) and higher American Society of Anesthesia classification (P.001). Elderly were more likely to have malignancy as the indication for surgery (68% vs 11%, P.001) and to undergo hysterectomy (81% vs 38%, P.001) or surgery with lymph node dissection (44.5% vs 7.1%, P.001). Elderly patients had a higher incidence of intraoperative complications (9% vs 4.6%, P = .002) and longer median hospital stay (17 vs 7 hours, P .001) compared with younger patients. Same-day discharge was more common in younger patients (76% vs 45%, P.001), and elderly patients were more likely to have admissions lasting23 hours (13% vs 3%, P.001) on univariate and multivariate analysis. Analysis of postoperative outcomes included 2023 patients with available postoperative data (80% of total population) (179465 years, 229 ≥ 65 years). There were no differences between elderly and younger patients in overall postoperative complications, reoperations, intensive care unit admissions, emergency room visits, or hospital readmission within 6 weeks of surgery.Despite having more preoperative risk factors and more surgically complex procedures, elderly patients undergoing robotic-assisted gynecologic surgery had similar postoperative complication rates, and almost half of elderly patients were safely discharged the day of surgery. Our data suggest that robotic-assisted gynecologic surgery and early hospital discharge are safe in elderly patients.

PURPOSE: To evaluate the outcomes of intraperitoneal (IP) chemotherapy compared with those of intravenous (IV) chemotherapy in patients with advanced ovarian cancer treated either with neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS) or with primary debulking surgery (PDS). METHODS: Patients diagnosed with FIGO stage III or IV epithelial ovarian, fallopian tube or primary peritoneal carcinoma treated at our institutions with PDS or NACT and IDS from 2006-2014 were identified. Covariates were compared using chi-square analyses, t-tests and Mann-Whitney tests. Survival rates were calculated using the Kaplan-Meier method and compared with log rank tests and Cox multivariate regression models. RESULTS: Sixty one patients received NACT and underwent IDS with residual disease of ≤ 1 cm; 40 patients (65.6%) received IP chemotherapy and 21 patients (34.4%) were given IV chemotherapy after IDS. The median number of chemotherapy cycles was three (range 3-8), and 34 patients (85.0%) completed the prescribed dose of IP chemotherapy. The median progression free survival was 16.5 months in the IP group and 15.0 months in the IV group (p = 0.88). The estimated median overall survival was 64.0 months in the IP group and 42.0 months in the IV group (p = 0.12). During the same study period, 148 patients underwent optimal PDS after which 93 patients (83.6%) received IP chemotherapy and 55 patients (37.2%) were given IV chemotherapy. Patients after IP chemotherapy had improved survival outcomes when compared to patients after IV chemotherapy. The median progression free survival was 29.0 months after IP chemotherapy and 16.0 months after IV chemotherapy (p < 0.0001) and the median overall survival was 93.0 months after IP chemotherapy and 43.0 months after IV chemotherapy (p < 0.0001). CONCLUSIONS: Although IP chemotherapy after PDS showed improved survival, IP chemotherapy after NACT and IDS, while tolerable with high rates of completion, did not demonstrate a survival advantage over IV chemotherapy in our patients. Citation Format: Jessica Lee MD, John P Curtin MD, Franco M Muggia MD, Bhavana Pothuri MD, Leslie R. Boyd MD, Jing-Yi Chern MD, Melissa K Frey MD, Stephanie V Blank MD. INTRAPERITONEAL CHEMOTHERAPY AFTER PRIMARY OR INTERVAL DEBULKING SURGERY FOR ADVANCED EPITHELIAL OVARIAN CANCER [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr NTOC-096.

e13024 Background: Genetic assessment (GA) is recommended for all women with ovarian cancer however little is known about the psychological implications of this intervention. We sought to evaluate the psychological response to GA in newly diagnosed ovarian cancer patients as part of our facilitated genetics referral pathway. Methods: English-speaking patients with ovarian cancer undergoing GA at the time of cancer diagnosis completed three validated anxiety, stress and depression survey instruments immediately prior to and following GA and again 6-9 months after GA. Results: Forty-eight English-speaking patients underwent GA; 43 (90%) completed the pre-GA survey, 32 (67%) post-GA survey and 11 (23%) 6-9 months follow-up survey. Eight patients (17%) had documented psychiatric diagnoses (5 anxiety, 2 depression, 1 anxiety+depression) prior to cancer diagnosis. Overall, patients demonstrated mild to moderate stress, clinically significant anxiety and borderline depression (Table 1). There was no change in depression, anxiety or stress scores when comparing pre- to post-GA surveys. Age, stage, method of treatment, performance status at enrollment and history of psychiatric disorders were not associated with anxiety, stress or depression. Conclusions: A genetic testing pathway whereby GA is encouraged and facilitated at the time of diagnosis has not increased patient depression, anxiety or stress in our cohort. Concern about causing additional emotional distress should not deter clinicians from early genetics referral. [Table: see text]

1503 Background: Lynch syndrome accounts for the majority of inherited endometrial cancers and the identification of probands presents a unique opportunity to treat and prevent multiple cancers. This is now even more relevant with the potential of novel immunotherapy agents for women with germline mutations. The diagnosis of endometrial cancer (EC) can provide the indication for women with specific risk factors to undergo genetic testing (GT). We sought to evaluate genetic counseling referrals (GCR) and subsequent GT rates. Methods: All women with EC between 2012 and 2015 were identified. Statistical analyses were performed to evaluate risk factors including age, body mass index (BMI), positive family history defined as two or more family members with Lynch-related cancers, and tumor mismatch repair (MMR) protein expression loss. Results: A total of 447 women were diagnosed with EC and of these, 107 (24%) were given GCR by their gynecologic oncologist based on their discretion. Compared to non-GCR, GCR women were significantly younger (median 54 vs 65, p < 0.0001) and had lower BMI (median 28.2 vs 30.8, p= 0.007). Of the 107 GCR women, 71 (66%) underwent GT. Of the 71 GT women, 8 (11%) were found to have a germline mutation in one of the MMR genes. Table 1 lists GCR, GT and positive germline mutations among specific high-risk cohorts. Of these cohorts, 56% under 50 years of age, 28% with family history, and 61% with loss of tumor MMR proteins had GCR. Conclusions: Many young, thin EC women with a family history or a tumor MMR deficiency are not given GCR. Among GCR women, 66% underwent GT, despite there being a high rate of germline mutations among these women. It is imperative that high-risk women receive GCR with subsequent GT to capture the maximum number with Lynch syndrome to screen and prevent additional cancers as well as enable cascade testing in family members. Facilitated pathways may be helpful in increasing GCR, as well as GT in EC women. [Table: see text]

5588 Background: Lynch syndrome (LS) accounts for 2-6% of all endometrial cancers (EC), and women with a germline mutation in the mismatch repair (MMR) genes ( MLH1, MSH2, MSH6, and PMS2) have an average lifetime risk of EC of 40%. As with breast and ovarian cancer syndromes, there are likely other genes implicated in the development of EC outside of the MMR genes. Multi-gene panel testing (MGPT) with next generation sequencing (NGS) allows for simultaneous analysis of numerous genes.We sought to evaluate the characteristics and incidence of gene mutations in women with newly diagnosed EC. Methods: We conducted a review of EC patients diagnosed from 6/2013 to 12/2016 who had MGPT at our institution. Demographics, family history, genetic testing results, and tumor characteristics were collected and analyzed using χ2 tests. Results: Of the 129 patients who had MGPT, 13 (10%) had a mutation and only 5 (38%) were in patients < 50 years old. The median age of EC diagnosis is 55 (31-100) years and median BMI = 27.5 (21-59). Majority were stage 1, 76 (59%) and grade 1, 50 (39%). Patients with additional primary cancers, breast or colon were not more likely to have a mutation. However, patients with a family history of gynecologic cancer were more likely to have a mutation identified, 10 (77%) mutation vs no mutation 34 (29%), p = 0.003. Among all patients tested, 8 (6%) had a mutation in LS genes, and 6 (5%) had mutations in other genes ( BRCA1, BRCA2, RAD51C, MUTYH, CHEK2); 1 (0.8%) had both MSH2 and CHEK2 mutation. Three patients had prior testing for breast cancer; 2 were found to have a BRCA1/ 2 mutation and the other was on Tamoxifen and BRCA negative. IHC was performed on 7 of 13 patients, and 5 (71%) had a loss of MMR protein expression. Variants of uncertain significance were noted in 35/129 (27%) of patients tested. Conclusions: Majority of EC patients with a mutation detected with NGS were > age 50. We identified additional new mutations in non-LS genes including, CHEK2, RAD51C, and MUYTH with MGPT. These accounted for 29% of the mutations and would have not been not detected using classic LS gene testing. These genes are implicated in breast, ovary or colon cancer. MGPT testing is feasible and useful in identifying additional actionable gene mutations.

e13022 Background: Obesity and Lynch syndrome are well-known risk factors for the development of endometrial cancer. However, there is a paucity of data comparing patients across multiple ethnicities. Methods: All patients diagnosed with endometrial cancer or complex atypical hyperplasia between 2012 and 2015 were retrospectively identified and evaluated. Comparative statistical analyses were performed and stratified by ethnicity with appropriate two-sided statistical tests. Results: A total of 506 patients were diagnosed with endometrial cancer (n = 447) or complex atypical hyperplasia (n = 59) and of these, 31 were East Asian (EA, 6.3%). The remaining 475 patients (93.9%) were of Caucasian, black, Latino, South Asian, Southeast Asian or other unspecified ethnicity. Compared to other patients, EA were diagnosed at a younger age (median age 53 vs 62, p = 0.0003) and had lower body mass indices (BMI) (median BMI 23.0 vs 30.7, p < 0.0001). There were no differences in stage, tumor grade or histology. Differences in age and BMI remained significant despite controlling for these factors on multivariate analysis. Of the EA group, 10 of 31 patients (32.3%) underwent genetic testing and of these, three (30.0%) were found to have a germline mutation in a mismatch repair (MMR) gene. All three patients were of Chinese ancestry, and two had mutations in MLH1 and one in MSH2. In comparison, 69 (14.5%) of the remaining 475 had genetic testing, and six (8.7%) were diagnosed with Lynch syndrome. Chinese patients were more likely to have Lynch syndrome (42.9% vs 8.7%, p= 0.04). There were no differences found in family history of Lynch-related cancers between Chinese and other patients. There was no correlation between germline mutations and MMR testing on tumor immunohistochemistry. All three Chinese patients with Lynch syndrome had negative MMR tumor testing. Conclusions: EA patients with endometrial cancer are diagnosed at younger ages and with lower BMIs compared to patients of other ethnic backgrounds. Chinese patients have a high rate of germline Lynch mutations despite negative tumor MMR testing. EA, particularly Chinese patients, may represent a high-risk cohort, and referral for genetic counseling regardless of tumor MMR testing should be considered.

Objective. While initial surgical treatment for palliation of malignant bowel obstruction is well described, data on reoperation for palliation of recurrent obstruction in ovarian carcinoma are limited. The purpose of this study was to analyze the outcome of patients undergoing reoperation for repeat bowel obstruction. Methods. We reviewed the records of all patients with ovarian cancer who underwent repeat surgery for recurrent, malignant bowel obstruction at our institution between 1994 and 2002. Results. Ten patients were identified. All patients had bowel obstruction caused by recurrent ovarian carcinoma and had a previous corrective surgical procedure for malignant bowel obstruction. The mean age at diagnosis of repeat obstruction was 54.1 years (range, 34–74 years). All patients had initial stage III or IV disease with moderately to poorly differentiated cancers. No patient received prior radiation therapy. The sites of obstruction in patients were as follows: small bowel, 3; large bowel, 3; both small and large bowel, 4. The mean number of prior laparotomies was 2.7 (range, 2–5). The mean interval from previous surgery for bowel obstruction to recurrent bowel obstruction was 8.3 months (range, 1–22 months). Surgical correction was possible in 5 (50%) of 10 patients, with 3 (60%) of these 5 patients obtaining successful palliation. Successful palliation is defined as the ability to tolerate a regular or low-residue diet at least 60 days postoperatively. Complications included enterocutaneous fistulas in three patients (two had enterotomies at time of surgery) and wound infection in one patient. There were no postoperative mortalities. The mean postoperative stay was 15.8 days (range, 8–29 days). Two of the three patients successfully palliated presented with a subsequent obstruction at 3 and 5 months postoperatively and were treated with gastrostomy tubes. The median length of survival for the entire cohort from the date of surgery for repeat obstruction was 4.5 months (range, 3–17 months). Conclusions. Patients undergoing repeat surgery for recurrent bowel obstruction have a low likelihood of successful palliation (30%). The surgery is associated with significant complications after surgery, rapid development of subsequent bowel obstructions, and limited survival rates. Alternative management approaches such as percutaneous endoscopic gastrostomy (PEG) tube placement should be considered in this group of patients.

TPS5606Background: Niraparib is a highly selective PARP1/2 inhibitor that induces synthetic lethality in tumor cells with homologous recombination DNA repair deficiencies (HRD). Niraparib is admini...