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No prospective data have been described to inform guidelines on antibiotic prophylaxis for partial vulvectomies. Thus, we conducted a single-center, pilot, double-blind randomized controlled trial to assess the effectiveness of prophylactic antibiotics to prevent wound complications after partial vulvectomies. Patients were randomly assigned 1:1 to preoperative antibiotics or no preoperative antibiotics. The primary outcome of 30-day postoperative wound complications occurred in 31 (62 %) of all patients, with no differences between groups. The most common wound complications were superficial separation (54.2 % antibiotic prophylaxis vs. 65.3 % no prophylaxis, p = 0.37) and surgical site infection (0 % antibiotic prophylaxis vs 7.7 % no prophylaxis, p = 0.49). However, this study was limited by differences in patient characteristics between the groups. This study provides data to perform power calculations for a trial examining the effect of preoperative antibiotics on surgical site infection., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Inc.)

Objectives: Tissue banking procedures have evolved to keep pace with precision medicine, technology, emerging understanding of racial disparities, and regulatory requirements. However, there is little published guidance regarding strategies to create and maintain a successful biorepository. Our objective is to describe the infrastructure and protocols used by our Gynecologic Oncology Tissue Bank., Methods: Our Tissue Bank was founded in 1992. In August 2022, internal funding was used to modernize the Tissue Bank. We hired three full-time employees, implemented universal screening of patients treated by gynecologic oncology faculty, updated consenting protocols, and standardized communication with providers. Tumor tissue, blood derivatives, ascites, and pleural fluid were collected from eligible, consenting patients and processed. Patient-derived cell lines and organoids were generated. For quality control purposes, one formalin-fixed, paraffin-embedded (FFPE) sample per tissue site was analyzed by a board-certified pathologist. All samples were labeled and tracked in an OpenSpecimen collection protocol and clinically annotated in a secure database., Results: From August 2022 to October 2023, 227 patients (83% white, 15% Black, 1% Asian) were enrolled and 4249 specimens were collected. Adherent cell lines were generated from 15 patients with ovarian cancer and cell suspensions for organoid generation were collected from 46 patients with ovarian cancer. A recharge center was established to self-sustain the Tissue Bank. Samples have been shared with academic and commercial collaborators., Conclusions: Our Tissue Bank has enrolled a large number of diverse patients, collected numerous specimen types, and collaborated widely. The procedures described here provide guidance for other institutions establishing similar resources., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To assess the impact of photoacoustic imaging (PAI) on the assessment of ovarian/adnexal lesion(s) of different risk categories using the sonographic ovarian-adnexal imaging-reporting-data system (O-RADS) in women undergoing planned oophorectomy., Method: This prospective study enrolled women with ovarian/adnexal lesion(s) suggestive of malignancy referred for oophorectomy. Participants underwent clinical ultrasound (US) examination followed by coregistered US and PAI prior to oophorectomy. Each ovarian/adnexal lesion was graded by two radiologists using the US O-RADS scale. PAI was used to compute relative total hemoglobin concentration (rHbT) and blood oxygenation saturation (%sO 2 ) colormaps in the region of interest. Lesions were categorized by histopathology into malignant ovarian/adnexal lesion, malignant Fallopian tube only and several benign categories, in order to assess the impact of incorporating PAI in the assessment of risk of malignancy with O-RADS. Malignant and benign histologic groups were compared with respect to rHbT and %sO 2 and logistic regression models were developed based on tumor marker CA125 alone, US-based O-RADS alone, PAI-based rHbT with %sO 2 , and the combination of CA125, O-RADS, rHbT and %sO 2. Areas under the receiver-operating-characteristics curve (AUC) were used to compare the diagnostic performance of the models., Results: There were 93 lesions identified on imaging among 68 women (mean age, 52 (range, 21-79) years). Surgical pathology revealed 14 patients with malignant ovarian/adnexal lesion, two with malignant Fallopian tube only and 52 with benign findings. rHbT was significantly higher in malignant compared with benign lesions. %sO 2 was lower in malignant lesions, but the difference was not statistically significant for all benign categories. Feature analysis revealed that rHbT, CA125, O-RADS and %sO 2 were the most important predictors of malignancy. Logistic regression models revealed an AUC of 0.789 (95% CI, 0.626-0.953) for CA125 alone, AUC of 0.857 (95% CI, 0.733-0.981) for O-RADS only, AUC of 0.883 (95% CI, 0.760-1) for CA125 and O-RADS and an AUC of 0.900 (95% CI, 0.815-0.985) for rHbT and %sO 2 in the prediction of malignancy. A model utilizing all four predictors (CA125, O-RADS, rHbT and %sO 2 ) achieved superior performance, with an AUC of 0.970 (95% CI, 0.932-1), sensitivity of 100% and specificity of 82%., Conclusions: Incorporating the additional information provided by PAI-derived rHbT and %sO 2 improves significantly the performance of US-based O-RADS in the diagnosis of adnexal lesions. © 2023 International Society of Ultrasound in Obstetrics and Gynecology., (© 2023 International Society of Ultrasound in Obstetrics and Gynecology.)

Ovarian cancer is the leading cause of gynecologic cancer-related deaths. The propensity for metastasis within the peritoneal cavity is a driving factor for the poor outcomes associated with this disease, but there is currently no effective therapy targeting metastasis. In this study, we investigate the contribution of stromal cells to ovarian cancer metastasis and identify normal stromal cell expression of the collagen receptor, discoidin domain receptor 2 (DDR2), that acts to facilitate ovarian cancer metastasis. In vivo, global genetic inactivation of Ddr2 impairs the ability of Ddr2-expressing syngeneic ovarian cancer cells to spread throughout the peritoneal cavity. Specifically, DDR2 expression in mesothelial cells lining the peritoneal cavity facilitates tumor cell attachment and clearance. Subsequently, omentum fibroblast expression of DDR2 promotes tumor cell invasion. Mechanistically, we find DDR2-expressing fibroblasts are more energetically active, such that DDR2 regulates glycolysis through AKT/SNAI1 leading to suppressed fructose-1,6-bisphosphatase and increased hexokinase activity, a key glycolytic enzyme. Upon inhibition of DDR2, we find decreased protein synthesis and secretion. Consequently, when DDR2 is inhibited, there is reduction in secreted extracellular matrix proteins important for metastasis. Specifically, we find that fibroblast DDR2 inhibition leads to decreased secretion of the collagen crosslinker, LOXL2. Adding back LOXL2 to DDR2 deficient fibroblasts rescues the ability of tumor cells to invade. Overall, our results suggest that stromal cell expression of DDR2 is an important mediator of ovarian cancer metastasis., Implications: DDR2 is highly expressed by stromal cells in ovarian cancer that can mediate metastasis and is a potential therapeutic target in ovarian cancer., (©2023 American Association for Cancer Research.)

Purpose: To determine the ability of RAD51 foci to predict platinum chemotherapy response in high-grade serous ovarian cancer (HGSOC) patient-derived samples., Experimental Design: RAD51 and γH2AX nuclear foci were evaluated by immunofluorescence in HGSOC patient-derived cell lines (n = 5), organoids (n = 11), and formalin-fixed, paraffin-embedded tumor samples (discovery n = 31, validation n = 148). Samples were defined as RAD51-High if >10% of geminin-positive cells had ≥5 RAD51 foci. Associations between RAD51 scores, platinum chemotherapy response, and survival were evaluated., Results: RAD51 scores correlated with in vitro response to platinum chemotherapy in established and primary ovarian cancer cell lines (Pearson r = 0.96, P = 0.01). Organoids from platinum-nonresponsive tumors had significantly higher RAD51 scores than those from platinum-responsive tumors (P < 0.001). In a discovery cohort, RAD51-Low tumors were more likely to have a pathologic complete response (RR, 5.28; P < 0.001) and to be platinum-sensitive (RR, ∞; P = 0.05). The RAD51 score was predictive of chemotherapy response score [AUC, 0.90; 95% confidence interval (CI), 0.78-1.0; P < 0.001). A novel automatic quantification system accurately reflected the manual assay (92%). In a validation cohort, RAD51-Low tumors were more likely to be platinum-sensitive (RR, ∞; P < 0.001) than RAD51-High tumors. Moreover, RAD51-Low status predicted platinum sensitivity with 100% positive predictive value and was associated with better progression-free (HR, 0.53; 95% CI, 0.33-0.85; P < 0.001) and overall survival (HR, 0.43; 95% CI, 0.25-0.75; P = 0.003) than RAD51-High status., Conclusions: RAD51 foci are a robust marker of platinum chemotherapy response and survival in ovarian cancer. The utility of RAD51 foci as a predictive biomarker for HGSOC should be tested in clinical trials., (©2023 The Authors; Published by the American Association for Cancer Research.)

High-grade serous ovarian cancer (HGSC) is the most lethal histotype of ovarian cancer and the majority of cases present with metastasis and late-stage disease. Over the last few decades, the overall survival for patients has not significantly improved, and there are limited targeted treatment options. We aimed to better characterize the distinctions between primary and metastatic tumors based on short- or long-term survival. We characterized 39 matched primary and metastatic tumors by whole exome and RNA sequencing. Of these, 23 were short-term (ST) survivors (overall survival (OS) < 3.5 years) and 16 were long-term (LT) survivors (OS > 5 years). We compared somatic mutations, copy number alterations, mutational burden, differential gene expression, immune cell infiltration, and gene fusion predictions between the primary and metastatic tumors and between ST and LT survivor cohorts. There were few differences in RNA expression between paired primary and metastatic tumors, but significant differences between the transcriptomes of LT and ST survivors in both their primary and metastatic tumors. These findings will improve the understanding of the genetic variation in HGSC that exist between patients with different prognoses and better inform treatments by identifying new targets for drug development., (© 2023. The Author(s).)

Objectives: Visceral adiposity has been established as a predictor of outcomes in various cancers. We aimed to determine the association of radiographic measurements of visceral fat with clinical outcomes in patients with endometrial cancer., Methods: A retrospective review of patients with stage III-IV endometrial cancer who underwent surgery between 2004 and 2014 was performed. Visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and total adipose tissue (TAT;VAT+SAT) were assessed on preoperative computed tomography (CT) scans. Exploratory analysis was performed to establish the optimal cut-off values for VAT, SAT, and TAT to identify patients with poor prognostic body composition. Survival rates were analyzed using Kaplan-Meier analysis, log-rank tests, and cox-regression., Results: Eighty-three patients were included. Forty-two (51%) patients had a low VAT/SAT ratio (<0.45) and 41 (49.4%) had a high VAT/SAT ratio (>0.45). There were no significant differences in demographics between the groups. The mean VAT, SAT, and TAT were 176.3 cm 2 , 379.3 cm 2 , and 555.3 cm 2 respectively. Compared to patients with low VAT/SAT ratios, patients with high VAT/SAT ratios had a shorter recurrence-free survival (median 29.6 vs 32.3 months, P = 0.01) and shorter overall survival (median 56 vs 93.7 months, P = 0.03)., Conclusions: Visceral fat measurements are predictive of outcomes in patients with advanced stage endometrial cancer. Specifically, VAT to SAT ratios are predictive of overall survival. Future studies should be pursued to identify potential therapeutic targets and biological mechanisms that underlie obesity's relationship with endometrial cancer., Competing Interests: Declaration of Competing Interest The authors have no relevant conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: Given the importance of understanding neighborhood context and geographic access to care on individual health outcomes, we sought to investigate the association of community primary care (PC) access on postoperative outcomes and survival in ovarian cancer patients., Methods: This was a retrospective cohort study of Stage III-IV ovarian cancer patients who underwent surgery at a single academic, tertiary care hospital between 2012 and 2015. PC access was determined using a Health Resources and Services Administration designation. Outcomes included 30-day surgical and medical complications, extended hospital stay, ICU admission, hospital readmission, progression-free and overall survival. Descriptive statistics and chi-squared analyses were used to analyze differences between patients from PC-shortage vs not PC-shortage areas., Results: Among 217 ovarian cancer patients, 54.4 % lived in PC-shortage areas. They were more likely to have Medicaid or no insurance and live in rural areas with higher poverty rates, significantly further from the treating cancer center and its affiliated hospital. Nevertheless, 49.2 % of patients from PC-shortage areas lived in urban communities. Residing in a PC-shortage area was not associated with increased surgical or medical complications, ICU admission, or hospital readmission, but was linked to more frequent prolonged hospitalization (26.3 % vs 14.1 %, p = 0.04). PC-shortage did not impact progression-free or overall survival., Conclusions: Patients from PC-shortage areas may require longer inpatient perioperative care in order to achieve the same 30-day postoperative outcomes as patients who live in non-PC shortage areas. Community access to PC is a critical factor to better understanding and reducing disparities among ovarian cancer patients., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

The heterogeneity in the pathological and clinical manifestations of ovarian cancer is a major hurdle impeding early and accurate diagnosis. A host of imaging modalities, including Doppler ultrasound, MRI, and CT, have been investigated to improve the assessment of ovarian lesions. We hypothesized that pathologic conditions might affect the ovarian vasculature and that these changes might be detectable by optical-resolution photoacoustic microscopy (OR-PAM). In our previous work, we developed a benchtop OR-PAM and demonstrated it on a limited set of ovarian and fallopian tube specimens. In this study, we collected data from over 50 patients, supporting a more robust statistical analysis. We then developed an efficient custom analysis pipeline for characterizing the vascular features of the samples, including the mean vessel diameter, vascular density, global vascular directionality, local vascular definition, and local vascular tortuosity/branchedness. Phantom studies using carbon fibers showed that our algorithm was accurate within an acceptable error range. Between normal ovaries and normal fallopian tubes, we observed significant differences in five of six extracted vascular features. Further, we showed that distinct subsets of vascular features could distinguish normal ovaries from cystic, fibrous, and malignant ovarian lesions. In addition, a statistically significant difference was found in the mean vascular tortuosity/branchedness values of normal and abnormal tubes. The findings support the proposition that OR-PAM can help distinguish the severity of tubal and ovarian pathologies., (© 2022. The Author(s).)

Objectives: Assess and improve advance care planning (ACP) awareness and uptake among gynecologic oncology patients., Methods: Using a quality improvement Plan-Do-Check-Act framework, we completed a single institution needs assessment and intervention. The needs assessment was a 26-question survey assessing baseline ACP knowledge and preferences of gynecologic oncology patients. We used this survey to implement an outpatient intervention in which patients were offered ACP resources (pamphlet, discussion with their gynecologic oncologist, and/or social work referral). We conducted a post-intervention survey among patients who had and had not received ACP resource(s) to assess whether our intervention increased ACP knowledge, discussions, or uptake., Results: Among 106 patients surveyed in the needs assessment, 33 % had ACP documents, 26 % had discussed ACP with a physician, and 82 % thought discussing ACP was important. The majority preferred these conversations in the outpatient setting (52 %) with their gynecologic oncologist (80 %) instead of nurses or trainees. In the intervention, 526 patients were offered ACP resources. Compared to women who did not receive resources (n = 324), patients who received ACP resource(s) (n = 202) were more likely to have ACP discussions with their gynecologic oncologist (38 % vs 68 %, P  = 0.001) and had greater proficiency regarding how to create ACP documents (median score 5/10 vs 8/10, P  = 0.048), although they were no more likely to have ACP documented in their electronic medical record (27 % vs 9 %, p = 0.08)., Conclusions: ACP uptake among gynecologic oncology patients is low, but ACP discussions with an oncologist during outpatient visits are important to patients and improve their knowledge regarding completing ACP documents., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Fuh reports participation on advisory boards for Aravive and Myriad, grants from Merck, and patents/royalties from Stanford University, outside the submitted work. Dr. Kuroki reports grants from National Center for Advancing Translational Sciences of the NIH (KL2TR002346) and Doris Duke Fund to Retain Clinical Scientists, a patent from the GOG Foundation, and a leadership role as a Junior Board Member of the ASSCP, outside the submitted work. Dr. Powell reports advisory board participation for Merck, GSK/Tesaro, AstraZeneca, Eisai, SeaGen, and Clovis Oncology, outside the submitted work. Dr. Mutch reports leadership roles in the Foundation for Women’s Cancer, NCI Gynecologic Cancer Steering committee, and NCCN Committee for Cervix and Corpus, outside the submitted work. Dr. McCourt reports royalties from UpToDate, outside the submitted work. Dr. Palisoul reports consulting fees from Medtronic, outside the submitted work. There were no other reported conflicts of interest., (© 2022 The Authors.)

Chemotherapy is often ineffective in advanced-stage and aggressive histologic subtypes of endometrial cancer. Overexpression of the receptor tyrosine kinase AXL has been found to be associated with therapeutic resistance, metastasis, and poor prognosis. However, the mechanism of how inhibition of AXL improves response to chemotherapy is still largely unknown. Thus, we aimed to determine whether treatment with AVB-500, a selective inhibitor of GAS6-AXL, improves endometrial cancer cell sensitivity to chemotherapy particularly through metabolic changes. We found that both GAS6 and AXL expression were higher by immunohistochemistry in patient tumors with a poor response to chemotherapy compared with tumors with a good response to chemotherapy. We showed that chemotherapy-resistant endometrial cancer cells (ARK1, uterine serous carcinoma and PUC198, grade 3 endometrioid adenocarcinoma) had improved sensitivity and synergy with paclitaxel and carboplatin when treated in combination with AVB-500. We also found that in vivo intraperitoneal models with ARK1 and PUC198 cells had decreased tumor burden when treated with AVB-500 + paclitaxel compared with paclitaxel alone. Treatment with AVB-500 + paclitaxel decreased AKT signaling, which resulted in a decrease in basal glycolysis. Finally, multiple glycolytic metabolites were lower in the tumors treated with AVB-500 + paclitaxel than in tumors treated with paclitaxel alone. Our study provides strong preclinical rationale for combining AVB-500 with paclitaxel in aggressive endometrial cancer models., (©2022 American Association for Cancer Research.)

Objective: To evaluate the impact of the COVID-19 pandemic on referral to and delivery of gynecologic oncology care at a National Cancer Institute-designated Comprehensive Cancer Center., Methods: We conducted a retrospective cohort study of patients referred for evaluation by a gynecologic oncologist at Washington University in St. Louis from October 2019 - February 2020 (pre-COVID-19), and April - August 2020 (COVID-19). The primary outcome, time from referral to evaluation by a gynecologic oncologist, was compared between the two time periods. Secondary outcomes included time from initial evaluation to treatment and delays/interruptions in care due to the pandemic. Sub-group analyses were performed on patients with a cancer diagnosis to evaluate the impact of COVID-19 on treatment decision making., Results: 884 patients were referred during the study period. Total referrals fell by 32% (526 to 358 patients, p  < 0.001) and referrals for cancer fell by 18% (228 to 188 patients, p  = 0.049). The pandemic did not impact time from referral to initial gynecologic oncology appointment overall (pre-COVID-19: 19.1 vs. COVID-19: 17.4 days, p  = 0.315) or among patients with cancer (14.4 vs. 13.9 days, p  = 0.662). Time from initial appointment to cancer treatment decreased by 9 days (34 days to 25 days, p  = 0.001)., Conclusion: Referrals to gynecologic oncology decreased significantly during the early months of COVID-19. Though time from referral to evaluation was not impacted by the pandemic, time to treatment initiation decreased despite institutional changes related to COVID-19., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Over 80% of women with high-grade serous ovarian cancer (HGSOC) develop tumor resistance to chemotherapy and die of their disease. There are currently no FDA-approved agents to improve sensitivity to first-line platinum- and taxane-based chemotherapy or to PARP inhibitors. Here, we tested the hypothesis that expression of growth arrest-specific 6 (GAS6), the ligand of receptor tyrosine kinase AXL, is associated with chemotherapy response and that sequestration of GAS6 with AVB-S6-500 (AVB-500) could improve tumor response to chemotherapy and PARP inhibitors. We found that GAS6 levels in patient tumor and serum samples collected before chemotherapy correlated with ovarian cancer chemoresponse and patient survival. Compared with chemotherapy alone, AVB-500 plus carboplatin and/or paclitaxel led to decreased ovarian cancer-cell survival in vitro and tumor burden in vivo . Cells treated with AVB-500 plus carboplatin had more DNA damage, slower DNA replication fork progression, and fewer RAD51 foci than cells treated with carboplatin alone, indicating AVB-500 impaired homologous recombination (HR). Finally, treatment with the PARP inhibitor olaparib plus AVB-500 led to decreased ovarian cancer-cell survival in vitro and less tumor burden in vivo . Importantly, this effect was seen in HR-proficient and HR-deficient ovarian cancer cells. Collectively, our findings suggest that GAS6 levels could be used to predict response to carboplatin and AVB-500 could be used to treat platinum-resistant, HR-proficient HGSOC. IMPLICATIONS: GAS6/AXL is a novel target to sensitize ovarian cancers to carboplatin and olaparib. Additionally, GAS6 levels can be associated with response to carboplatin treatment., (©2021 American Association for Cancer Research.)

Endometrial cancer remains the most prevalent gynecologic cancer with continued rising incidence. A less common form of this cancer is uterine serous cancer, which represents 10% of endometrial cancer cases. However, this is the most aggressive cancer. The objective was to assess whether inhibiting the receptor tyrosine kinase AXL with AVB-500 in combination with bevacizumab would improve response in uterine serous cancer. To prove this, we conducted multiple angiogenesis assays including tube formation assays and angiogenesis invasion assays. In addition, we utilized mouse models with multiple cells lines and subsequently analyzed harvested tissue through immunohistochemistry CD31 staining to assess microvessel density. The combination treatment arms demonstrated decreased angiogenic potential in each assay. In addition, intraperitoneal mouse models demonstrated a significant decrease in tumor burden in two cell lines. The combination of AVB-500 and bevacizumab reduced tumor burden in vivo and reduced morphogenesis and migration in vitro which are vital to the process of angiogenesis.

Objective: To evaluate the ability of a personalized text-message-based intervention to increase weight loss among endometrial cancer survivors with obesity., Methods: In this randomized, controlled trial, endometrial cancer survivors with obesity (BMI ≥30 kg/m 2 ) were randomized to a personalized SMS text-message-based weight loss intervention or enhanced usual care. Primary outcome was weight loss at 6 months; secondary outcomes were weight loss at 12 months and changes in psychosocial measures. We also compared clinical characteristics and weight change between trial participants and non-participants., Results: Between May 18 and December 31, 2017, 80 endometrial cancer survivors with obesity consented to participate in the randomized trial. There were no differences in clinical characteristics between the two arms. Weight changes were similar in the two arms (P = 0.08). At 6 months, no differences in quality of life, physical activity, or body image were noted. Of 358 eligible patients, 80 became trial participants and 278, non-participants. Trial participants were younger (59.3 vs. 63.4 years, P < 0.001), more likely non-white (P = 0.02), on fewer medications (4 vs. 7, P < 0.001), and had a higher median BMI (38.7 vs. 37.6 kg/m 2 , P = 0.01) than non-participants. Weight change was similar between participants and non-participants (P = 0.85). At 6 months, similar percentages of participants and non-participants (47.7% vs. 44.4%) had gained weight, and similar percentages (9.2% vs. 11.2%) had lost at least 5% of their body weight., Conclusions: This text-message-based intervention did not increase weight loss among endometrial cancer survivors with obesity, nor did participation in the trial. Other weight management interventions should be promoted to increase weight loss., Clinical Trial Registration: ClinicalTrials.gov, www.clinicaltrials.gov, NCT03169023., Competing Interests: Declaration of Competing Interest There are no additional conflicts of interest to disclose by any author., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: To determine the association between scores from a 25-item patient-reported Rockwood Accumulation of Deficits Frailty Index (DAFI) and survival outcomes in gynecologic cancer patients., Methods: A frailty index was constructed from the SEER-MHOS database. The DAFI was applied to women age ≥ 65 diagnosed with all types of gynecologic cancers between 1998 and 2015. The impact of frailty status at cancer diagnosis on overall survival (OS) was analyzed using Kaplan-Meier curves and Cox proportional hazards regression., Results: In this cohort (n = 1336) the median age at diagnosis was 74 (range 65-97). Nine hundred sixty-two (72%) women were Caucasian and 132 (10%) were African-American. Overall, 651(49%) of patients were considered frail. On multivariate analysis, frail patients had a 48% increased risk for death (aHR 1.48; 95% CI 1.29-1.69; P < 0.0001). Each 10% increase in frailty index was associated with a 16% increased risk of death (aHR, 1.16; 95% CI, 1.11 to 1.21; P < 0.0001). In subgroup analyses of the varying cancer types, the association of frailty status with prognosis was fairly consistent (aHR 1.15-2.24). The DAFI was more prognostic in endometrial (aHR 1.76; 95% CI 1.41-2.18, P < 0.0001) and vaginal/vulvar (aHR 1.94; 95% CI 1.34-2.81, P = 0.0005) cancers as well as patients with loco-regional disease (aHR 1.94; 95% CI 1.62-2.33, P < 0.0001)., Conclusions: Frailty appears to be a significant predictor of mortality in gynecologic cancer patients regardless of chronological age. This measure of functional age may be of particular utility in women with loco-regional disease only who otherwise would have a favorable prognosis., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interests pertaining to this manuscript., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: To evaluate how women with epithelial ovarian cancer (EOC), dichotomized by BRCA status, tolerate intravenous (IV) or intraperitoneal (IP) chemotherapy given with veliparib and bevacizumab (bev) on a GOG phase I study (GOG 9923, NCT00989651)., Methods: This is an unplanned, post hoc analysis of an IRB approved, multi-institutional, prospective study (GOG 9923). Clinical characteristics and toxicity data based on BRCA status were evaluated and descriptive statistics were used to summarize baseline patient characteristics and toxicities. The Kaplan Meier method was used to generate survival estimates., Results: Four hundred twenty-four patients were evaluable. Patients were treated with IV carboplatin, paclitaxel, and bev every 21 days (regimen 1), weekly IV paclitaxel with carboplatin and bev (regimen 2) or IV paclitaxel and bev with IP cisplatin (regimen 3). Bev was continued as maintenance in all arms. Within each of these regimens, veliparib was given either twice daily for the entirety of each cycle (continuous) or on days -2 to 5 (intermittent). Ten percent of patients treated on regimen 1, 12% on regimen 2, and 19.8% on regimen 3 had BRCA-associated tumors. Patients with BRCA-associated tumors, when compared to wild type, experienced similar rates of anemia, febrile neutropenia (, abdominal pain, colonic perforation, nausea, vomiting, and peripheral sensory neuropathy. Median progression free survival (PFS) was not significantly different between BRCA-associated and wild type cancers (HR 0.96, CI 0.65-1.42), though this study's primary aim was not to evaluate outcomes., Conclusions: Germline BRCA mutations positively affect chemosensitivity in EOC, but whether differences in toxicities among BRCA-associated and BRCA wild type tumors existed was previously not reported. In this population with newly diagnosed ovarian cancer no differences in reported toxicity between the two groups was observed., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: To study associations among employment, insurance status, and distress in gynecologic oncology patients; and to evaluate the impact of being unemployed or having no/Medicaid insurance on different distress problem areas., Methods: In this single institution, cross-sectional analysis of gynecologic oncology patients, we screened for distress and problem areas using the National Comprehensive Cancer Network distress thermometer and problem list at outpatient appointments between 6/2017-9/2017. Primary outcome was self-reported high distress (score ≥ 5). The distress problem list included 5 categories-practical, family, emotional, physical, and other. Employment status included employed, unemployed, homemaker, and retired. Logistic regression was used to predict high distress from employment and insurance statuses, adjusting for relevant covariates., Results: Of 885 women, 101 (11.4%) were unemployed, and 53 (6.0%) uninsured or had Medicaid coverage. One in five patients (n = 191, 21.6%) indicated high distress. Unemployed patients were more likely than employed to endorse high distress [adjusted odds ratio (aOR) = 3.5, 95% confidence interval (CI) 2.2-5.7, p < 0.001]. Compared to employed patients, a greater proportion of unemployed patients endorsed distress related to practical (p < 0.05), emotional (p < 0.001), physical (p < 0.01), and other (p < 0.05) problems. Uninsured/Medicaid patients were more likely to endorse high distress (aOR = 2.8, 95% CI 1.5-5.1, p < 0.001) and report family (p < 0.001), emotional (p < 0.001), and other (p < 0.01) problems than patients who had Medicare/commercial insurance., Conclusions: Gynecologic oncology patients who are unemployed or have no/Medicaid insurance face high distress that appears to arise from issues beyond practical problems, including financial and/or insurance insecurities., Competing Interests: Declaration of Competing Interest The following stated conflicts of interest are all outside of the submitted work. Dr. Kuroki reports grants from Washington University Institute of Clinical and Translational Sciences, KL2TR002346, GOG Foundation. Dr. Thaker reports personal fees from Stryker, AstraZeneca, Iovance, Novocure, Celsion, Aravive; and grants and personal fees from Glaxo Smith Kline and Merck. Dr. Fuh reports grants from Merck, and personal fees from Myriad, Genentech, Aravive, GSK, and Immunogen. Dr. Powell reports personal fees from Tesaro, Merck, Roche/ Genentech, Clovis Oncology, AstraZeneca, Johnson & Johnson, and Eisai. Dr. Khabele reports grants and other from NIH/NCI, grants from Deciphera Pharmaceuticals, and personal fees from AstraZeneca., (Copyright © 2021 Elsevier Inc. All rights reserved.)

We aimed to evaluate obese endometrial cancer (EC) survivors' perceptions of weight loss barriers and previously attempted weight loss methods and to identify characteristics that predicted willingness to enroll in a behavioral intervention trial. We administered a 27-question baseline survey at an academic institution to EC survivors with body mass index ≥ 30 kg/m 2 . Survivors were asked about their lifestyles, previous weight loss attempts, perceived barriers, and were offered enrollment into an intervention trial. Data was analyzed using Fisher's Exact, Kruskal-Wallis, and univariate and multivariate regressions. 155 of 358 (43%) eligible obese EC survivors were surveyed. Nearly all (n = 148, 96%) had considered losing weight, and 77% (n = 120) had tried two or more strategies. Few had undergone bariatric surgery (n = 5, 3%), psychologic counseling (n = 2, 1%), or met with physical therapists (n = 9, 6%). Lower income was associated with difficulty in accessing interventions. Survivors commented that negative self-perceptions and difficulties with follow-through were barriers to weight loss, and fear of complications and self-perceived lack of qualification were deterrents to bariatric surgery. 80 (52%) of those surveyed enrolled in the trial. In a multivariate model, adjusting for race and stage, survivors without recurrence were 4.3 times more likely to enroll than those with recurrence. Most obese EC survivors have tried multiple strategies to lose weight, but remain interested in weight loss interventions, especially women who have never experienced recurrence. Providers should encourage weight loss interventions early, at the time of initial diagnosis, and promote underutilized strategies such as psychological counseling, physical therapy, and bariatric surgery., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. McCourt reports fees from UpToDate outside the submitted work; Dr. Fuh reports grants from Merck, personal fees from Myriad, personal fees from Aravive, personal fees from Immunogen, personal fees from GSK, personal fees from Genentech all outside the submitted work; Dr. Powell reports personal fees from Tesaro, personal fees from Merck, personal fees from Roche/ Genentech, personal fees from Clovis Oncology, personal fees from AstraZeneca, personal fees from Johnson & Johnson, and personal fees from Eisai all outside the submitted work. Dr. Thaker reports personal fees from Stryker, grants and personal fees from Merck, personal fees from Astra Zeneca, personal fees from Aravive, grants and personal fees from Glaxo Smith Kline, personal fees from Celsion, and personal fees from Iovance all outside the submitted work. Ms. Leon and Drs. Wilson, Zamorano, Liu, Morris, Mutch, Colditz and Hagemann have nothing to disclose., (© 2021 The Authors.)

Objectives: Fellow involvement in patient care is important for education, but effect on patient care is unclear. Our aim was to compare patient outcomes in gynecologic oncology attending clinics versus a fellow training clinic at a large academic medical center., Methods: A retrospective review of consecutive gynecologic oncology patients from six attending clinics and one faculty-supervised fellow clinic was used to analyze differences based on patient demographics, cancer characteristics, and practice patterns. Primary outcome was overall survival (OS); secondary outcomes included recurrence-free survival (RFS), postoperative complications and chemotherapy within the last 30 days of life. Survival analyses were performed using Kaplan-Meier curves with log-rank tests., Results: Of 159 patients, 76 received care in the attending clinic and 83 in the fellow clinic. Patients in the fellow clinic were younger, less likely to be Caucasian, and more overweight, but cancer site and proportion of advanced stage disease were similar. Both clinics had similar rates of moderate to severe adverse events related to surgery (15% vs. 8%, p = .76), chemotherapy (21% vs. 23%, p = .40), and radiation (14% vs. 17%, p = .73). There was no difference in median RFS in the fellow compared to attending clinic (38 vs. 47 months, p = .78). OS on both univariate (49 months-fellow clinic, 60 months-attending clinic vs. p = .40) and multivariate analysis [hazard ratio 1.3 (0.57, 2.75), P = .58] was not significantly different between groups., Conclusions: A fellow-run gynecologic oncology clinic designed to provide learning opportunities does not compromise patient outcomes and is a safe and feasible option for fellow education., Competing Interests: Declaration of Competing Interest Dr. Thaker reports personal fees from Celsion, personal fees from Stryker, grants and personal fees from Glaxo-Smith Kline, grants and personal fees from Merck, personal fees from Abbvie, and personal fees from Astra Zeneca, outside the submitted work. Dr. Powell reports personal fees from Merck, personal fees from Tesaro, personal fees from Clovis Oncology, personal fees from AstraZeneca, personal fees from Roche/Genentech, and personal fees from GOG Foundation, outside the submitted work. Dr. Kuroki reports a career development grant (KL2) from Washington University Institute of Clinical and Translational Sciences (KL2TR002346) during the conduct of the study. All other authors declare no potential conflict of interest., (Published by Elsevier Inc.)

Purpose: Single-agent PD-1 blockade exhibits limited efficacy in epithelial ovarian cancer (EOC). We evaluated ipilimumab plus nivolumab compared with nivolumab alone in women with persistent or recurrent EOC., Methods: Eligibility criteria included measurable disease, 1-3 prior regimens, and platinum-free interval (PFI) < 12 months. Participants were randomly allocated to intravenous nivolumab (every 2 weeks) or induction with nivolumab plus ipilimumab for 4 doses (every 3 weeks), followed by every-2-week maintenance nivolumab for a maximum of 42 doses. The primary null hypothesis was equal probability of objective response within 6 months of random allocation in each arm., Results: One hundred patients were allocated to receive either nivolumab (n = 49), or nivolumab plus ipilimumab (n = 51), with PFI of < 6 months in 62%. Six (12.2%) responses occurred within 6 months in the nivolumab group and 16 (31.4%) in the nivolumab plus ipilimumab group (odds ratio, 3.28; 85% CI, 1.54 to infinity; P = .034). The median progression-free survival (PFS) was 2 and 3.9 months in the nivolumab and nivolumab plus ipilimumab groups, respectively, with a PFI-stratified hazard ratio of 0.53 (95% CI, 0.34 to 0.82); the respective hazard ratio for death was 0.79 (95% CI, 0.44 to 1.42). Grade ≥ 3 related adverse events occurred in 33% of patients in the nivolumab group and 49% in the combination group, with no treatment-related deaths. PD-L1 expression was not significantly associated with response in either treatment group., Conclusion: Compared with nivolumab alone, the combination of nivolumab and ipilimumab in EOC resulted in superior response rate and longer, albeit limited, PFS, with toxicity of the combination regimen comparable to prior reports. Additional combination studies to enhance durability of the dual regimen are warranted.

Objective: Cascade genetic testing (CGT) of hereditary breast and ovarian cancer (HBOC) or Lynch Syndrome (LS) patients' relatives offers opportunities to prevent cancer, but CGT rates are not well described. We aimed to measure reported disclosure of genetic testing results and CGT rates in these families and evaluate patients' views of educational media., Methods: Patients with HBOC or LS identified from germline genetic testing at an academic institution between 2011 and 2016 were surveyed regarding disclosure, testing among relatives, and perceptions of educational materials. Medical records and pedigrees provided numbers of total and first-degree relatives., Results: Of 103 mutation carriers consented, 64 (63%) completed the survey an average of 38 months after receiving genetic testing results. Participants' mean age was 53 years, and thirty-one (48%) had a cancer diagnosis. The majority (86%) felt extremely or very comfortable sharing health information. Participants disclosed results to 87% of first-degree relatives, but reported that only 40% of first-degree relatives underwent testing. First-degree female relatives had significantly higher CGT rates than first-degree male relatives (59% versus 21%, P < 0.001). Participants with HBOC reported higher CGT rates than those with LS (49% versus 33%, P = 0.02). Participants did not identify any one educational medium as more helpful than the others for disclosing results., Conclusion: Disclosure rates are high among HBOC and LS mutation carriers, but reported CGT rates are low. Gender- and mutation-specific barriers prevent patients' family members from undergoing CGT. Future studies should implement materials to address these barriers and improve CGT rates., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Improvements in disease free survival for epithelial ovarian, peritoneal or fallopian tube cancer (EOC) will only come with improved primary therapy. Incorporation of poly-ADP-ribose inhibitors (PARPi) in the frontline setting may represent one strategy. This study sought to determine the maximum tolerated and feasible doses of the PARPi veliparib in combination with chemotherapy for EOC., Methods: A phase I, 3 + 3 dose escalation evaluated dose-limiting toxicities (DLTs) in cycles 1-2. Once <2/6 patients experienced a DLT, that dose level expanded to evaluate feasibility over 4 cycles. This study opened 10/2009 and closed 8/2016. Eligible patients had untreated, stage II-IV EOC. Veliparib was added either continuous (day 1-21) or intermittent (day - 2 to 5) during 6 cycles of chemotherapy. Three chemotherapy backbones were evaluated (2 intravenous (q3week and weekly) and 1 intraperitoneal (IP)) all inclusive of bevacizumab with and as maintenance to 22 cycles., Findings: Dose evaluations for 424 treated patients were available. Regimen 1 (q3 week), continuous (Reg1c) the maximum tolerated dose (MTD) was 250 mg veliparib BID and feasible dose was 150 mg BID. For regimen 1, intermittent (Reg1i) the MTD and feasible dose were 400 and 250 mg BID. For Reg2c (weekly paclitaxel) the MTD and feasible dose were 150 mg BID. For Reg2i the MTD and feasible dose were 250 and 150 mg BID. For Reg3c (IP) the MTD and feasible dose were 150 mg BID and for Reg3i (IP), the MTD and feasible dose were 400 mg and 300 mg BID., Interpretation: The feasible dose for Reg1c, 2c, 2i and 3c was 150 mg po BID. For Reg1i and 3i the dose was pushed to 250 and 300 mg po BID respectively. There is no apparent difference in efficacy between continuous and intermittent dosing indicating that the higher doses achieved in intermittent dosing may not be needed. (NCT00989651)., Funding: National Cancer Institute., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Data are limited regarding the use of poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitors, such as veliparib, in combination with chemotherapy followed by maintenance as initial treatment in patients with high-grade serous ovarian carcinoma., Methods: In an international, phase 3, placebo-controlled trial, we assessed the efficacy of veliparib added to first-line induction chemotherapy with carboplatin and paclitaxel and continued as maintenance monotherapy in patients with previously untreated stage III or IV high-grade serous ovarian carcinoma. Patients were randomly assigned in a 1:1:1 ratio to receive chemotherapy plus placebo followed by placebo maintenance (control), chemotherapy plus veliparib followed by placebo maintenance (veliparib combination only), or chemotherapy plus veliparib followed by veliparib maintenance (veliparib throughout). Cytoreductive surgery could be performed before initiation or after 3 cycles of trial treatment. Combination chemotherapy was 6 cycles, and maintenance therapy was 30 additional cycles. The primary end point was investigator-assessed progression-free survival in the veliparib-throughout group as compared with the control group, analyzed sequentially in the BRCA -mutation cohort, the cohort with homologous-recombination deficiency (HRD) (which included the BRCA -mutation cohort), and the intention-to-treat population., Results: A total of 1140 patients underwent randomization. In the BRCA -mutation cohort, the median progression-free survival was 34.7 months in the veliparib-throughout group and 22.0 months in the control group (hazard ratio for progression or death, 0.44; 95% confidence interval [CI], 0.28 to 0.68; P<0.001); in the HRD cohort, it was 31.9 months and 20.5 months, respectively (hazard ratio, 0.57; 95 CI, 0.43 to 0.76; P<0.001); and in the intention-to-treat population, it was 23.5 months and 17.3 months (hazard ratio, 0.68; 95% CI, 0.56 to 0.83; P<0.001). Veliparib led to a higher incidence of anemia and thrombocytopenia when combined with chemotherapy as well as of nausea and fatigue overall., Conclusions: Across all trial populations, a regimen of carboplatin, paclitaxel, and veliparib induction therapy followed by veliparib maintenance therapy led to significantly longer progression-free survival than carboplatin plus paclitaxel induction therapy alone. The independent value of adding veliparib during induction therapy without veliparib maintenance was less clear. (Funded by AbbVie; VELIA/GOG-3005 ClinicalTrials.gov number, NCT02470585.)., (Copyright © 2019 Massachusetts Medical Society.)

Ovarian cancer is a heterogeneous disease at the molecular and histologic level. Optical coherence tomography (OCT) is able to map ovarian tissue optical properties and heterogeneity, which has been proposed as a feature to aid in diagnosis of ovarian cancer. In this manuscript, depth-resolved en face scattering maps of malignant ovaries, benign ovaries, and benign fallopian tubes obtained from 20 patients are provided to visualize the heterogeneity of ovarian tissues. Six features are extracted from histograms of scattering maps. All features are able to statistically distinguish benign from malignant ovaries. Two prediction models were constructed based on these features: a logistic regression model (LR) and a support vector machine (SVM). The optimal set of features is mean scattering coefficient and scattering map entropy. The LR achieved a sensitivity and specificity of 97.0% and 97.8%, and SVM demonstrated a sensitivity and specificity of 99.6% and 96.4%. Our initial results demonstrate the feasibility of using OCT as an "optical biopsy tool" for detecting the microscopic scattering changes associated with neoplasia in human ovarian tissue., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Ovarian cancer is the leading cause of death among gynecological cancers, but is poorly amenable to preoperative diagnosis. In this study, we investigate the feasibility of "optical biopsy," using high-optical-resolution photoacoustic microscopy (OR-PAM) to quantify the microvasculature of ovarian and fallopian tube tissue. The technique is demonstrated using excised human ovary and fallopian tube specimens imaged immediately after surgery. Quantitative parameters are derived using Amira software. The parameters include three-dimensional vascular segment count, total volume and length, which are associated with tumor angiogenesis. Qualitative results of OR-PAM demonstrate that malignant ovarian tissue has larger and more tortuous blood vessels as well as smaller vessels of different sizes, while benign and normal ovarian tissue has smaller vessels of uniform size. Quantitative analysis shows that malignant ovaries have greater tumor vessel volume, length and number of segments, as compared with benign and normal ovaries. The vascular pattern of benign fallopian tube is different than that of benign ovarian tissue. Our initial results demonstrate the potential of OR-PAM as an imaging tool for fast assessment of ovarian tissue and fallopian tube and could avoid unnecessary surgery if the risk of the examined ovary is extremely low.

Background: Ovarian cancer is the deadliest gynecologic malignancy, yet the effects on survival of modifiable pre-diagnosis lifestyle factors, such as obesity and physical activity, remain largely unexplored. Our objective was to evaluate the effect of pre-diagnosis BMI and physical activity on ovarian cancer mortality using prospectively collected data., Methods: Data on women who developed ovarian cancer after enrollment into the NIH-AARP Diet and Health Study were analyzed. Cancer incidence was ascertained through linkage state cancer registries and consisted of 741 cases of epithelial ovarian cancer., Results: Higher pre-diagnosis BMI was associated with increased overall and ovarian cancer-specific mortality. Comparing women with BMI 25-29.9, 30-34.9 and ≥ 35 to normal weight women, the HRs of overall mortality were 1.18 (95%CI 0.96-1.45), 1.05 (0.82-1.36) and 1.59 (1.14-2.18, p-trend = 0.02). The findings were similar for ovarian cancer-specific mortality comparing women with BMI ≥ 35 to normal weight women (BMI <25) with a HR of 1.47 (95%CI 1.03-2.09, p-trend 0.08). Pre-diagnosis physical activity was not associated with mortality, with HRs for overall mortality of 1.06 (95%CI 0.79-1.43), 0.94 (0.72-1.23), 0.98 (0.76-1.25), and 0.98 (0.75-1.28, p-trend = 0.91), comparing women who engaged in vigorous physical activity 1-3 times/month, 1-2 times/week, 3-4 times/week and 5 times/week, respectively, with those who never/rarely engaged in such activity., Conclusions: Women who were obese before developing ovarian cancer had increased mortality than those who were normal weight, but physical activity before diagnosis was not associated with mortality in this study population. These results suggest that maintaining a healthy weight is a powerful preventative tool., (Copyright © 2019 Elsevier Inc. All rights reserved.)

It is unclear if endometrial cancer (EC) patients are aware of their modifiable risk factors. We administered a 33-item questionnaire to EC patients at a university-based cancer center to assess their understanding of how comorbidities and lifestyle/sexual behaviors impact their cancer risk. We also inquired about their access to a primary care physician (PCP). Pearson's χ 2 test or Fisher's exact test were used to assess differences in understanding based on a dichotomized Charlson comorbidity score, <7 vs ≥7. Of the 50 surveyed women (81% response rate), 39 reported hypertension (80%) and 36 (72%) diabetes. All had a PCP. Most were aware that obesity contributes to diabetes (43/48, 90%), hypertension (42/48, 88%), and heart attack (42, 88%), but only 19/49 (39%) knew that EC is more common in overweight/obese women. More than half lacked understanding of the following risks including modifiable risk factors-unhealthy diet (31, 62%), hormone replacement therapy (38, 76%), alcohol (30, 60%), and the protective effects of cigarette smoking (38, 76%). Most also incorrectly identified the following sexual health factors as risks for EC: early coitarche (30, 60%), or having an abortion (27, 54%), a sexually transmitted infection (35, 70%) or human immunodeficiency virus (34, 68%). Although EC patients recognize that obesity is linked to comorbidities, less than half are aware that it contributes to their cancer risk. Furthermore, responses to lifestyle/sexual health behaviors suggest women may lack understanding of global differences between endometrial and cervical cancer risk factors., Competing Interests: Dr. McCourt reports UpToDate Ad Hoc section editor for EC. Dr. Thaker reports personal fees from Celsion, personal fees from Stryker, grants and personal fees from Tesaro, grants and personal fees from Merck, personal fees from Abbvie, personal fees from Clovis, personal fees from AstraZeneca outside the submitted work. Dr. Powell reports personal fees from Merck, personal fees from Tesaro, personal fees from Clovis Oncology, personal fees from AstraZeneca, personal fees from Roche/Genentech, personal fees from GOG Foundation, outside the submitted work. Dr. Kuroki reports grants from Washington University Institute of Clinical and Translational Sciences (R25 STRENGTH and KL2) during the conduct of the study. All other authors declare no potential conflict of interest.

Objective: To assess the rate of wound complications and evaluate the effectiveness of antibiotic prophylaxis in vulvar wide local excision procedures., Methods: We performed a single-institution, retrospective cohort study of women undergoing vulvar surgery for premalignant lesions between January 2007 and January 2017. The primary outcome was a composite wound complication rate that included breakdown or infection within 8 weeks postoperatively. Data were analyzed using Fisher exact or χ test, Student t-test, and Poisson regression., Results: Wound complications occurred in 154 (28.7%) of the 537 patients. Mean age was 52 years; most patients were white (83.1%), cigarette smokers (65.2%), had no prior vulvar treatment (54.4%), and had a preoperative diagnosis of high-grade squamous intraepithelial lesion (vulvar HSIL) (70.0%). The presence of other predisposing factors was similar between groups. In multivariate analysis, smoking (odds ratio [OR] 1.64, 95% CI 1.14-2.38) and primary rather than repeat vulvar surgery (OR 1.99, 95% CI 1.31-3.01) were associated with increased risk for wound complications. There was no significant difference in wound complications between women who received preoperative antibiotics and those who did not (30.4% vs 27.4%, P=.45), although the mean length of wound separation in the antibiotic group was shorter (1 vs 2 cm, P=.03)., Conclusion: Wound complications are common among women undergoing surgery for vulvar HSIL, and interventional trials are warranted to evaluate the role of smoking cessation and prophylactic antibiotics to reduce postoperative morbidity.

Objectives: Premenopausal women may undergo surgical menopause after staging for their endometrial cancer. Our aim was to determine the association between body mass index (BMI) and surgical menopausal symptoms., Methods: We report a retrospective review of endometrial cancer patients whom underwent menopause secondary to their surgical staging procedure. Symptoms were classified as severe if treatment was prescribed, or mild if treatment was offered, but declined. Univariate analysis was performed with ANOVA and Chi-square tests as appropriate. Relative risks (RR) were generated from Poisson regression models., Results: We identified 166 patients in whom the BMI (kg/m 2 ) distribution was as follows: 33 (19.9%) had BMI <30, 49 (29.5%) had BMI 30-39.9, 50 (30.1%) had BMI 40-49.9, and 34 (20.5%) had BMI ≥50. There were no differences in race, age, or adjuvant treatment among the groups. Overall, 65 (39.2%) women reported symptoms of surgical menopause, including 19 (11.4%) mild and 46 (27.7%) severe. Symptom type did not differ by BMI; however, the prevalence of severe menopausal symptoms decreased with increasing BMI: <30 (45.5%), 30-39.9 (30.6%), 40-49.9 (22%), and ≥ 50 (14.7%); P = 0.002. Multivariate analysis confirmed that symptom prevalence decreased with increasing BMI. Compared to women with a BMI of <30, those with a BMI 40-49.9 (RR = 0.39, 95% CI: 0.17-0.87) or ≥ 50 (RR = 0.24, 95% CI: 0.08-0.70) were significantly less likely to experience menopausal symptoms., Conclusions: Women younger than 50 with BMI >40 and stage I endometrial cancer are significantly less likely than women with BMI <30 to experience menopausal symptoms after oophorectomy. This information may assist in peri-operative counseling., (Copyright © 2019. Published by Elsevier Inc.)

Ovarian cancer, one of the deadliest malignancies in female cancer patients, is characterized by recurrence and poor response to cytotoxic chemotherapies. Fewer than 30% of patients with resistant disease will respond to additional chemotherapy treatments. This study aims to determine whether and how inhibition of the receptor tyrosine kinase AXL can restore sensitivity to first-line platinum and taxane therapy in ovarian cancer. AXL staining was quantified in a patient tissue microarray and correlated with chemoresponse of patients. We used small hairpin RNAs to knock down AXL expression and the small-molecule inhibitor BGB324 to inhibit AXL and assessed sensitivity of cell lines and primary patient-derived cells to chemotherapy. We quantified platinum accumulation by inductivity-coupled plasma phase mass spectrometry. Finally, we treated chemoresistant patient-derived xenografts with chemotherapy, BGB324, or chemotherapy plus BGB324 and monitored tumor burden. AXL expression was higher in chemoresistant patient tumors and cell lines than in chemosensitive tumors and cell lines. AXL staining significantly predicted chemoresponse. Knockdown and inhibition of AXL dose-dependently improved response to paclitaxel and carboplatin in both cell lines and primary cells. AXL inhibition increased platinum accumulation by 2-fold ( *, P < 0.05). In vivo studies indicated that AXL inhibition enhanced the ability of chemotherapy to prevent tumor growth (****, P < 0.0001). AXL contributes to platinum and taxane resistance in ovarian cancer, and inhibition of AXL improves chemoresponse and accumulation of chemotherapy drugs. This study supports continued investigation into AXL as a clinical target., (©2018 American Association for Cancer Research.)

Objectives: Gynecologic oncologists frequently care for patients at the end of life with the aid of palliative care (PC) specialists. Our primary objectives were to identify perceived barriers to integrating specialty PC into gynecologic cancer care., Materials and Methods: Members of the Society of Gynecologic Oncology (SGO) were invited to participate in an anonymous online survey. A Likert scale captured perceptions regarding primary and specialty PC, frequent barriers to use of PC, and potential interventions., Results: A total of 174 (16%) gynecologic oncologists completed the survey. The majority (75%) agreed or strongly agreed that PC should be integrated into cancer care at diagnosis of advanced or metastatic cancer. The most frequently perceived PC barriers included patients' unrealistic expectations (54%), limited access to specialty PC (25%), poor reimbursement (25%), time constraints (22%), and concern of reducing hope or trust (21%). The most agreed upon potential intervention was increased access to outpatient PC (80%)., Conclusions: According to this cohort of SGO members, families' or patients' unrealistic expectations are the most frequent barriers to specialty PC. Understanding this communication breakdown is critically important., (© 2018 S. Karger AG, Basel.)

To determine how obstetricians and gynecologists (OB/GYNs) perceive the gynecologic health effects of obesity and to identify perceived obstacles to counseling. OB/GYNs with 3 St. Louis health systems were emailed a 46-question survey regarding physicians' role in counseling women on the health risks of obesity and barriers faced in achieving this counseling. Differences between respondents' gender, age, practice type, years in practice, and body mass index were assessed using Chi-square or Fisher's exact tests as appropriate. Of 318 OB/GYNs emailed, 134 completed surveys, including 82 generalists and 52 subspecialists. 93% of respondents believed it was necessary to educate patients on health risks of obesity. 90% and 75%, respectively, cited diagnoses of endometrial hyperplasia and cancer as teachable moments for counseling. The most frequently cited barriers to successful counseling were lack of time, referral services, and patient tools/information. Most did not believe they had adequate reimbursement (65%), training (53%) or educational resources (50%) to counsel patients. Survey answers differed by practice setting, gender, and provider age. Although most OB/GYN providers consider obesity counseling important, execution is hindered by perceived barriers that differ by provider gender, age, and practice type. For OB/GYNs, more effective weight management counseling will require better training and practice-specific strategies. Based on survey responses, better reimbursement combined with increased resources for appropriate referrals and cancer prevention counseling are needed in order to improve weight management implementation in OB/GYN. •The majority of OB/GYNs believe obesity counseling is important•Perceptions of obesity counseling differ based on provider/practice characteristics.•Lack of time, referral services, and patient tools are the biggest cited barriers to counseling.•Improved obesity counseling could improve downstream OB/GYN morbidities.

Objective: Paclitaxel, a microtubule inhibitor, is subject to tumor resistance while treating high-grade serous ovarian and uterine cancer. This study aims to directly compare the effects of SQ1274, a novel microtubule inhibitor that binds to the colchicine-binding site on tubulin, and paclitaxel in high-grade serous ovarian and uterine cancer cell lines both in vitro and in vivo., Methods: We assessed the sensitivity of ovarian (OVCAR8) and uterine (ARK1) cancer cell lines to SQ1274 and paclitaxel using XTT assays. We used western blot and quantitative real-time PCR to analyze changes in AXL RNA and protein expression by SQ1274 and paclitaxel. Differences in cell-cycle arrest and apoptosis were investigated using flow cytometry. Finally, we treated ovarian and uterine xenograft models with vehicle, paclitaxel, or SQ1274., Results: First, we demonstrate that SQ1274 has a much lower IC 50 than paclitaxel in both ARK1 (1.26 nM vs. 15.34 nM, respectively) and OVCAR8 (1.34 nM vs. 10.29 nM, respectively) cancer cell lines. Second, we show SQ1274 decreases both RNA and protein expression of AXL. Third, we show that SQ1274 causes increased cell-cycle arrest and apoptosis compared to paclitaxel. Finally, we report that SQ1274 more effectively inhibits tumor growth in vivo compared to paclitaxel., Conclusions: SQ1274 presents as a viable alternative to paclitaxel for treating ovarian and uterine cancer. This study supports the development of SQ1274 as a chemotherapeutic to treat ovarian and uterine cancer., (Copyright © 2018. Published by Elsevier Inc.)

The incidence of endometrial cancer (EC) is steadily increasing due in large part to an aging world population and rise in rates of obesity. Patients with obesity and advancing age can be seen as vulnerable populations, as they are both often subject to physician bias regarding surgical choices and assumptions regarding long-term outcomes. As we operate on an older and/or obese patient population, it is increasingly important that we adopt peri-operative management strategies and surgical techniques to best serve this complex patient population. Careful orchestration pre-, intra- and postoperatively is key to successful outcomes in robotic and laparoscopic surgery. Here, we review existing literature regarding EC in women with older age and/or obesity, outline recommendations for peri-operative management and common intra-operative issues-specifically common anesthetic issues surrounding cardiovascular, respiratory and neuromuscular systems-that are of heightened importance in women with older age and/or obesity. The goal of this review is to help define and mitigate common complications for these vulnerable patients with an EC diagnosis who, in accordance with carefully assessed health risks, can and should be offered standard of care surgery and treatment., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Aims: The study aimed to do the following: (1) describe progression free survival (PFS) and overall survival (OS) of women with cervical cancer presenting with occult supraclavicular lymph node (SCLN) metastases, identified by positron emission tomography CT (PET-CT) and (2) compare OS of patients with isolated SCLN metastases to that of patients with SCLN and extranodal metastatic disease., Methods: Patients were identified retrospectively. Treatment intent was abstracted. PFS and OS in the high-dose chemo-radiotherapy (RT), palliative RT, and supportive treatment groups, as well as OS of patients with SCLN metastases only vs. SCLN and extranodal metastases were calculated., Results: Fourteen patients received high-dose chemo-RT, 32 received palliative RT, and 6 received supportive care (n = 52). Median PFS was 3 months in high-dose chemo-RT group and 1 month in palliative RT (p = ns). Median OS was 12 months in high-dose chemo-RT group, 7 months in palliative RT group, and 2 months in palliative care group (p = 0.05). OS was significantly different between patients with isolated SCLN disease vs. SCLN and extranodal disease, that is, 10.5 vs. 3 months (p = 0.009, χ2 = 6.9)., Conclusions: In this limited analysis, median OS of cervical cancer patients with PET/CT-positive SCLN metastases was the longest when treated with high-dose chemo-RT. Patients with SCLN and extranodal metastases experienced significantly shorter OS, as compared to patients with SCLN only disease., (© 2017 S. Karger AG, Basel.)

Uterine serous cancer (USC) is aggressive, and the majority of recurrent cases are chemoresistant. Because the receptor tyrosine kinase AXL promotes invasion and metastasis of USC and is implicated in chemoresistance in other cancers, we assessed the role of AXL in paclitaxel resistance in USC, determined the mechanism of action, and sought to restore chemosensitivity by inhibiting AXL in vitro and in vivo We used short hairpin RNAs and BGB324 to knock down and inhibit AXL. We assessed sensitivity of USC cell lines to paclitaxel and measured paclitaxel intracellular accumulation in vitro in the presence or absence of AXL. We also examined the role of the epithelial-mesenchymal transition (EMT) in AXL-mediated paclitaxel resistance. Finally, we treated USC xenografts with paclitaxel, BGB324, or paclitaxel plus BGB324 and monitored tumor burden. AXL expression was higher in chemoresistant USC patient tumors and cell lines than in chemosensitive tumors and cell lines. Knockdown or inhibition of AXL increased sensitivity of USC cell lines to paclitaxel in vitro and increased cellular accumulation of paclitaxel. AXL promoted chemoresistance even in cells that underwent the EMT in vitro Finally, in vivo studies of combination treatment with BGB324 and paclitaxel showed a greater than 51% decrease in tumor volume after 2 weeks of treatment when compared with no treatment or single-agent treatments ( P < 0.001). Our results show that AXL expression mediates chemoresistance independent of EMT and prevents accumulation of paclitaxel. This study supports the continued investigation of AXL as a clinical target, particularly in chemoresistant USC. Mol Cancer Ther; 16(12); 2881-91. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Objectives: To evaluate the effect of palliative care (PC) consultation on hospice enrollment and end-of-life care in gynecologic oncology patients., Methods: A retrospective chart review of gynecologic oncology patients who died 1year before and after 2014 implementation of a PC initiative for patients at a single NCI-designated comprehensive cancer center. Patient demographics, admission and procedural history, anti-cancer therapy, and end-of- life care were collected retrospectively. Data was analyzed using Student's t-test, Mann-Whitney U test, Chi-Square test, or Fisher's exact test., Results: We identified 308 patients. Median age at death was 63years (range 17 to 91). Most patients were white (78.2%), married (47.4%), and had ovarian (35.7%) or uterine cancers (35.4%). Introduction of the PC initiative was associated with increased PC consultations (40%, 53%, p=0.02), increased hospice enrollment (57%, 61%, p=0.29), and fewer procedures in the last 30days of life (44%, 31%, p=0.01). The rate of enrollment to inpatient hospice doubled from 12.5% to 25.7% (p=0.02) while time from inpatient hospice enrollment to death increased from 1.9 to 6.0days (p=0.02). Time from outpatient hospice enrollment to death increased from 26.2 to 35.4days (p=0.18). PC consultation was associated with a doubling of outpatient (40%) and inpatient (80%) hospice enrollment., Conclusions: The PC quality improvement initiative was associated with more palliative care consults, increased rates of inpatient and outpatient hospice utilization, increased time on hospice, and fewer procedures in the last 30days of life, although most women were not enrolled until the last days of life., (Copyright © 2017. Published by Elsevier Inc.)

Objective: The optimal strategy for adjuvant therapy in stage IIIC endometrial cancer has not been determined. Our aim was to evaluate survival benefit of different treatments and to investigate if benefit varied by histologic grade., Methods: We identified 199 patients with stage IIIC endometrial cancer from 2000 to 2012 through the Siteman Cancer Center registry. All patients underwent surgical staging followed by no adjuvant therapy (NAT), radiation (RT), chemotherapy (CT) or chemoradiation (CRT). The association between adjuvant treatment and overall survival was explored using Kaplan-Meier plots and multivariable Cox regression analysis. Multivariable analysis was stratified by low- or high-grade to explore the interaction between grade and treatment., Results: Most patients received CRT (50.3%) followed by CT (23.1%), RT (16.1%) and NAT (10.5%). Survival after CRT was superior to NAT (p<0.001), RT (p=0.010) and CT (p<0.001). After adjusting for covariates, treatment with RT, CT and CRT led to a 57% (p=0.024), 62% (p=0.003) and 83% (p<0.001) reduction in risk of death compared to NAT, respectively. With CRT as the reference, the adjusted hazard of death was higher with NAT (5.94, p<0.001), RT (2.56, p=0.009) and CT (2.24, p=0.004). Stratifying by grade, RT and CRT led to a 67% (p=0.039) and 85% (p<0.001) reduction in death, compared to NAT in low-grade patients. CT and CRT led to a 72% (p=0.003) and 83% (p<0.001) reduction in death, compared to NAT in high-grade patients., Conclusions: Our findings suggest that CRT should be the preferred adjuvant treatment strategy for patients with stage IIIC endometrial cancer., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To compare wound complication rates after skin closure with staples and subcuticular suture in obese gynecology patients undergoing laparotomy through a midline vertical incision., Methods: In this randomized controlled trial, women with body mass indexes (BMIs) of 30 or greater undergoing surgery by a gynecologic oncologist through a midline vertical incision were randomized to skin closure with staples or subcuticular 4-0 monofilament suture. The primary outcome was the rate of wound complication, defined as the presence of a wound breakdown, or infection, within 8 weeks postoperatively. Secondary outcomes included operative time, Stony Brook scar cosmetic score, and patient satisfaction. A sample size of 162 was planned to detect a 50% reduction in wound complications. At planned interim review (n=82), there was no significant difference in primary outcome., Results: Between 2013 and 2016, 163 women were analyzed, including 84 who received staples and 79 suture. Women who received staples were older (mean age 59 compared with 57 years), had lower mean BMI (37.3 compared with 38.9), and fewer benign indications for surgery (22 compared with 27). There were no differences in wound complication rates between staple compared with suture skin closure (28 [33%] compared with 25 [32%], relative risk 1.05, 95% confidence interval [CI] 0.68-1.64). Women with staples reported worse median cosmetic scores (four of five compared with five of five, P<.001), darker scar color (37 [49%] compared with 13 [18%], relative risk 2.69, 95% CI 1.57-4.63), and more skin marks (30 [40%] compared with three [4%], relative risk 9.47, 95% CI 3.02-29.65) compared with women with suture closure. There was no group difference regarding satisfaction with their scar. Stepwise multivariate analysis revealed BMI (odds ratio [OR] 1.13, 95% CI 1.07-1.20), maximum postoperative glucose (OR 1.01, 95% CI 1.00-1.01), and cigarette smoking (OR 4.96, 95% CI 1.32-18.71) were correlates of wound complication., Conclusion: Closure of midline vertical skin incisions with subcuticular suture does not reduce surgical site wound complications compared with staples in obese gynecology patients., Clinical Trial Registration: ClinicalTrials.gov, NCT01977612.

Purpose: Intraperitoneal (IP) therapy improves survival compared to intravenous (IV) treatment for women with newly diagnosed, optimally cytoreduced, ovarian cancer. However, the role of IP therapy in recurrent disease is unknown. Preclinical data demonstrated IP administration of the proteasome inhibitor, bortezomib prior to IP carboplatin increased tumor platinum accumulation resulting in synergistic cytotoxicity. We conducted this phase I trial of IP bortezomib and carboplatin in women with recurrent disease., Methods: Women with recurrent ovarian cancer were treated with escalating doses of IP bortezomib - in combination with IP carboplatin (AUC 4 or 5) every 21days for 6cycles. Pharmacokinetics of both agents were evaluated in cycle 1., Results: Thirty-three women participated; 32 were evaluable for safety. Two patients experienced dose-limiting toxicity (DLT) at the first dose level (carboplatin AUC 5, bortezomib 0.5mg/m 2 ), prompting carboplatin reduction to AUC 4 for subsequent dose levels. With carboplatin dose fixed at AUC 4, bortezomib was escalated from 0.5 to 2.5mg/m 2 without DLT. Grade 3/4 related toxicities included abdominal pain, nausea, vomiting, and diarrhea which were infrequent. The overall response rate in patients with measurable disease (n=21) was 19% (1 complete, 3 partial). C max and AUC in peritoneal fluid and plasma increased linearly with dose, with a favorable exposure ratio of the peritoneal cavity relative to peripheral blood plasma., Conclusion: IP administration of this novel combination was feasible and showed promising activity in this phase I trial of heavily pre-treated women with ovarian cancer. Further evaluation of this IP combination should be conducted., (Copyright © 2017. Published by Elsevier Inc.)

The receptor tyrosine kinase AXL promotes migration, invasion, and metastasis. Here, we evaluated the role of AXL in endometrial cancer. High immunohistochemical expression of AXL was found in 76% (63/83) of advanced-stage, and 77% (82/107) of high-grade specimens and correlated with worse survival in uterine serous cancer patients. In vitro, genetic silencing of AXL inhibited migration and invasion but had no effect on proliferation of ARK1 endometrial cancer cells. AXL-deficient cells showed significantly decreased expression of phospho-AKT as well as uPA, MMP-1, MMP-2, MMP-3, and MMP-9. In a xenograft model of human uterine serous carcinoma with AXL-deficient ARK1 cells, there was significantly less tumor burden than xenografts with control ARK1 cells. Together, these findings underscore the therapeutic potentials of AXL as a candidate target for treatment of metastatic endometrial cancer.