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Background: A study was undertaken to determine recurrence patterns and survival outcomes of stage I uterine papillary serous carcinoma (UPSC) patients. Methods: A retrospective, multi-institutional study of stage I UPSC patients diagnosed from 1993 to 2006 was performed. Patients underwent comprehensive surgical staging; postoperative treatment included observation (OBS); radiotherapy alone (RT); or platinum/taxane-based chemotherapy (CT) +/- RT. Results: The authors identified 142 patients with a median follow-up of 37 months (range, 7-144 months). Thirty-three patients were observed, 20 received RT alone, and 89 received CT +/- RT. Twenty-five recurrences (17.6%) were diagnosed, and 60% were extrapelvic. Chemotherapy-treated patients experienced significantly fewer recurrences than those treated without chemotherapy (P = .013). Specifically, CT +/- RT patients had a lower risk of recurrence (11.2%) compared with patients who received RT alone (25%, P = .146) or OBS (30.3%, P = .016). This effect was most pronounced in stage IB/IC (P = .007). CT- and CT + RT-treated patients experienced similar recurrence. After multivariate analysis, treatment with chemotherapy was associated with a decreased risk of recurrence (P = .047). The majority of recurrences (88%) were not salvageable. Progression-free survival (PFS) and cause-specific survival (CSS) for chemotherapy-treated patients were more favorable than for those who did not receive chemotherapy (P = .013 and .081). Five-year PFS and CSS rates were 81.5% and 87.6% in CT +/- RT, 64.1% and 59.5% in RT alone, and 64.7% and 70.2% for OBS. Conclusions: Stage I UPSC patients have significant risk for extrapelvic recurrence and poor survival. Recurrence and survival outcomes are improved in well-staged patients treated with platinum/taxane-based chemotherapy. This multi-institutional study is the largest to support systemic therapy for early stage UPSC patients. [ABSTRACT FROM AUTHOR]

•Ruptured dermoids can present with chronic peritonitis which can mimic malignant disease.•Surgical washout is mainstay of treatment for chronic peritonitis with ruptured dermoids.•Corticosteroids can be considered as second line for chronic peritonitis when surgical washout alone is insufficient., 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.)

Objective: Women are experiencing growing rates of incarceration at twice the pace of that for men. Additionally, one-third will be older than 55 years of age by the end of the decade. Women who are incarcerated experience a higher prevalence of gynecologic malignancies and present with higher stage disease, which may be contributing to the greater mortality from cancer than the age-adjusted US population. Limited access to guideline-recommended screening and prevention and resource limitations across correctional facilities may result in gynecologic cancer disparities. Reasons for delayed gynecologic cancer care in prisons remain underexplored. Therefore, we sought to identify contributors to delayed gynecologic cancer care among women experiencing incarceration., Methods: Women at a single tertiary center in the Southeastern U.S. who were incarcerated and were diagnosed with a gynecologic cancer during 2014-2021 were identified in the electronic medical record. Note text was extracted and contributors to delay were identified and categorized using the RADaR method. Descriptive statistics were used to assess quantitative data., Results: 14 patients were identified with a total of 14,879 text excerpts. Data reduction was performed to identify excerpts that were relevant to the central research question resulting in 175 relevant note excerpts. Delays prior to the tertiary care visit included patient and institutional contributors. Delays during transition from the tertiary center to prison included discharge planning and loss to follow-up during/after incarceration. Transportation, authorization, and restraints were concrete contributors. Abstract contributors included communication, and the patient's emotional experience., Conclusions: We identify myriad contributors to delayed or fractured gynecologic cancer care in women experiencing incarceration. The impact of these issues warrants further study and intervention to improve care., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: With the results of several recently published clinical trials, this guideline informs on the use of adjuvant radiation therapy (RT) and systemic therapy in the treatment of endometrial cancer. Updated evidence-based recommendations provide indications for adjuvant RT and the associated techniques, the utilization and sequencing of adjuvant systemic therapies, and the effect of surgical staging techniques and molecular tumor profiling., Methods: The American Society for Radiation Oncology convened a multidisciplinary task force to address 6 key questions that focused on the adjuvant management of patients with endometrial cancer. The key questions emphasized the (1) indications for adjuvant RT, (2) RT techniques, target volumes, dose fractionation, and treatment planning aims, (3) indications for systemic therapy, (4) sequencing of systemic therapy with RT, (5) effect of lymph node assessment on utilization of adjuvant therapy, and (6) effect of molecular tumor profiling on utilization of adjuvant therapy. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for quality of evidence grading and strength of recommendation., Results: The task force recommends RT (either vaginal brachytherapy or external beam RT) be given based on the patient's clinical-pathologic risk factors to reduce risk of vaginal and/or pelvic recurrence. When external beam RT is delivered, intensity modulated RT with daily image guided RT is recommended to reduce acute and late toxicity. Chemotherapy is recommended for patients with International Federation of Gynecology and Obstetrics (FIGO) stage I to II with high-risk histologies and those with FIGO stage III to IVA with any histology. When sequencing chemotherapy and RT, there is no prospective data to support an optimal sequence. Sentinel lymph node mapping is recommended over pelvic lymphadenectomy for surgical nodal staging. Data on sentinel lymph node pathologic ultrastaging status supports that patients with isolated tumor cells be treated as node negative and adjuvant therapy based on uterine risk factors and patients with micrometastases be treated as node positive. The available data on molecular characterization of endometrial cancer are compelling and should be increasingly considered when making recommendations for adjuvant therapy., Conclusions: These recommendations guide evidence-based best clinical practices on the use of adjuvant therapy for endometrial cancer., (Copyright © 2022 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Objective: To determine the utility of a clinical calculator to redefine prognosis and need for chemotherapy among patients with early-stage high-risk epithelial ovarian cancer., Methods: Data were abstracted for stage I-II, high-risk ovarian cancer from the National Cancer Database from years 2005 to 2015. Based on demographic, pathologic, surgical, and laboratory characteristics, a clinical score was developed using Cox regression. Propensity score weighting was used to adjust for differences between patients who did and did not receive chemotherapy., Results: Of 8188 patients with early-stage high-risk ovarian cancer, 6915 (84%) did and 1273 (16%) did not receive chemotherapy. A clinical calculator was created utilizing age, stage, histology, grade, tumor size, number of pelvic and paraaortic lymph nodes examined, the presence of malignant ascites, and CA125. The calculator divided patients into low, moderate, and high-risk groups with 5-year OS (overall survival) of 92%, 82%, and 66%, and 10-year OS of 85%, 67%, and 44%, respectively. Chemotherapy improved 5-year OS and 10-year OS in the high-risk group (56% to 73%; p < 0.001, 34% to 48%; p < 0.001). The moderate risk group had improved 5-year OS (80% to 85%; p = 0.01) but not 10-year OS (66% to 66%; p = 0.13). Chemotherapy did not improve 5-year or 10-year OS in low-risk patients (93% to 92%, p = 1.0, 86% to 84%, p = 0.99)., Conclusions: The prognosis among high-risk early-stage ovarian cancer patients is heterogeneous. This calculator may aid in patient-centered counseling regarding potential treatment benefits., Competing Interests: Declaration of Competing Interest None of the authors have conflicts of interest as it relates to the submitted work. Outside of the submitted work, Dr. Ghamande has received compensation from GlaxoSmithKline for consulting and from Merck as part of their speaker bureau. Dr. Chan has received compensation from Astra Zeneca, Aravive, Clovis, Eisai, GlaxoSmithKline Merck, Myriad, Roche/GenentechSeagen., (Published by Elsevier Inc.)

Objectives: A patient's understanding of surgery is often limited, especially in the setting of complex oncologic procedures. The use of supplemental materials can improve patients' knowledge of their procedure and satisfaction with decision making. We sought to determine if a multimedia-supplemented approach in patients undergoing robotic endometrial cancer staging improves satisfaction with preoperative counseling. Secondary objectives were patient comprehension, physician satisfaction, and visit length., Methods: From 2018 to 2019, patients were randomized to standard physician education (SPE) or multimedia-based education (MBE), which included watching two novel videos followed by focused physician counseling. Basic demographic information was collected. Patient satisfaction was assessed using the Client Satisfaction Questionnaire-8 (CSQ-8, a validated satisfaction survey, scored 8-32) and a global satisfaction score (GGS, 10-point scale). Physician satisfaction was assessed using a GGS. Comprehension was assessed with a study-specific 9-question survey at three time points. t-tests and linear mixed models were used to compare groups., Results: Of the 75 patients included in the analysis, the majority were white (70%), 50-70 years old (72%), and had at least some college education (74%). The MBE group reported higher satisfaction on the CSQ-8 (31.69 vs 30.69, p < 0.01) and global satisfaction score (9.95 vs 9.74, p = 0.04). There was no difference in comprehension scores over time (p = 0.84) or between groups (p = 0.23). Visit lengths were significantly longer in the MBE group (90.36 vs 80.46 min, p = 0.04)., Conclusions: Patients had high satisfaction and comprehension with both SPE and MBE. Multimedia education may be implemented in preoperative counseling based on provider preference and consideration should be made for further study of satisfaction, both patient and physician, and visit length after the initial implementation period., Competing Interests: Declaration of Competing Interest There are no COI disclosures among the included authors., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to investigate survival differences between equivalent residual disease [complete gross resection (CGR), minimal residual disease (MRD), suboptimal] at the time of primary debulking surgery (PDS) and interval debulking surgery (IDS)., Methods: The National Cancer Database was used to identify patients from 2010 to 2015 with stage IIIC/IV primary peritoneal or ovarian cancer who had residual disease recorded. Propensity score matching (PSM) was used to correct for differences in characteristics between the PDS and IDS groups., Results: Of 8683 patients with advanced ovarian cancer, 4493 (52%), 2546 (29%), and 1644 (19%) had CGR, MRD, or suboptimal resection, respectively. From 2010 to 2015, the number of patients undergoing IDS increased 27% (p trend  < 0.001), and there was an 18% increase in CGRs (p trend  = 0.005). The increased use of IDS from 2010 to 2015 was associated with increased CGRs (p trend  = 0.02) and decreased MRD (p trend  = 0.001), but not with decreased suboptimal resections (p trend  = 0.18). IDS, even after PSM, was associated with inferior overall survival [OS; hazard ratio (HR) 1.12, 95% confidence interval (CI) 1.03-1.22, p = 0.008]. A CGR at PDS had prolonged median OS compared with a CGR at IDS (51 vs. 44 months, p < 0.001). Additionally, MRD at PDS had worse median OS compared with a CGR at IDS (41 vs. 44 months, p = 0.03), but improved median OS compared with MRD at IDS (median OS 35 months, p = 0.05)., Conclusion: The use of IDS continues to rise in the US, and is associated with improved surgical outcomes but not necessarily similar oncologic outcomes. There should be continued efforts to improve cytoreductive outcomes in women with advanced ovarian and peritoneal malignancies.

A 37-yr-old woman presented to the gynecology clinic with abnormal uterine bleeding in the setting of known, large uterine fibroids. Preoperative endometrial biopsy identified atypical melanocytic cells concerning for uterine melanoma. Care was transferred to the gynecologic oncology service for hysterectomy. Intraoperative findings included macular, blue-black pigmentation of the peritoneum of the bladder and cervix, which was resected and sent for frozen section, confirming melanocytic neoplasia. The hysterectomy revealed multiple tan leiomyomas up to 12 cm, and a distinct 3 cm black, incompletely circumscribed mass in the endomyometrium composed of bland spindled cells with delicate melanin granules. The tumor cells were positive for Sox-10, BAP1, and Mart-1 (Melan-A) and negative for PRAME, PD-L1, and BRAFV600E by immunostains. Microscopic elements of similar melanocytes and melanophages were found in the cervix and bladder peritoneum. Molecular analysis of the uterine tumor identified a GNA11 mutation but no TERT or BAP1 mutation. The uterine melanocytic tumor has characteristic findings of a cellular blue nevus arising in association with dendritic melanocytosis of Mullerian and pelvic tissues, a rarely seen benign phenomenon that should be distinguished from malignant melanoma of the upper genital tract., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 by the International Society of Gynecological Pathologists.)

Introduction: In 2014, the Society of Gynecologic Oncology's Clinical Practice Committee published a clinical update reviewing the treatment of women with endometrial cancer. At that time, there had been significant advances in the diagnosis, work-up, surgical management, and available treatment options allowing for more optimal care of affected women. Despite these advances, the incidence of endometrial cancer as well as the deaths attributable to the disease have continued to rise; from 1987 to 2014 there has been a 75% increase in cases and almost 300% increase in endometrial cancer deaths. Fortunately, since then, there has been progress in the treatment of patients with endometrial cancer with increased utilization of molecular pathology, greater understanding of genetic predisposition, enhanced methods for lymph node assessment, a broader understanding of the efficacy of radiation and chemotherapy, and a more efficient approach to survivorship and surveillance. The purpose of this document is to present a comprehensive review of this progress., Manuscript Development Process: The authors reviewed the available evidence, contributed to the development of this manuscript, provided critical review of the guidelines, and finalized the manuscript recommendations. The review was also presented to and approved by the Society of Gynecologic Oncology (SGO) Clinical Practice Committee, SGO Publications Committee, and the SGO board members prior to submission for publication. The recommendations for this manuscript were developed by a panel of gynecologic oncologists who were members of the SGO Clinical Practice and Education Committees. Panelists reviewed and considered evidence from current uterine cancer literature. The terminology used in these guidelines was adopted from the ASCCP management guidelines [1] using a two-part rating system to grade the strength of recommendation and quality of evidence (Table 1). The rating for each recommendation is given in parentheses., Competing Interests: Declaration of Competing Interest The authors of this paper report that they have no conflicts of interest related to any of the content of this manuscript., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: We aim to describe the false negative (FN) and false positive (FP) rates of preoperative cross-sectional imaging (PCI) prior to radical surgery for cervical cancer., Methods: A retrospective cohort study of patients who underwent radical hysterectomy for early-stage cervical cancer from January 2010 until December 2017 at a single tertiary care center was performed. Patients were included if they underwent preoperative PCI and radical surgery. Patient demographics and clinicopathologic information were recorded from medical record review. Descriptive statistics were used., Results: Overall, 106 patients met inclusion criteria. Eighty-four percent (89/106) of patients had no suspicion for metastatic disease on PCI, while 16% (17/106) had suspicion for metastatic disease. Of the 89 without suspicion for metastatic disease on PCI, 16% (14/89) had a false negative study with metastatic disease identified on final surgical pathology. False negative rates by modality were 16% (11/70) for PET/CT and 6% (2/33) for diagnostic CT. Of the 17 cases with suspicion for metastatic disease on imaging, 53% (9/17) were false positive studies with no metastatic disease identified histologically. False positive rates by modality were 7% (5/70) for PET/CT and 12% (4/33) for diagnostic CT., Conclusion: PCI is a tool to help identify patients who are optimal candidates for radical surgery. In this sample, the false negative rate was 16%, and false positive rate was 53% for PCI among women who underwent primary radical surgery. Further study is needed to explore preoperative testing that may more accurately identify optimal surgical candidates., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Adjuvant therapy in early-stage endometrial cancer has not shown a clear overall survival benefit, and hence, patient selection remains crucial., Objective: To determine whether women with high-intermediate risk, early-stage endometrial cancer with lymphovascular space invasion particularly benefit from adjuvant treatment in improving oncologic outcomes., Methods: A multi-center retrospective study was conducted in women with stage IA, IB, and II endometrial cancer with lymphovascular space invasion who met criteria for high-intermediate risk by Gynecologic Oncology Group (GOG) 99. Patients were stratified by the type of adjuvant treatment received. Clinical and pathologic features were abstracted. Progression-free and overall survival were evaluated using multivariable analysis., Results: 405 patients were included with the median age of 67 years (range 27-92, IQR 59-73). 75.0% of the patients had full staging with lymphadenectomy, and 8.6% had sentinel lymph node biopsy (total 83.6%). After surgery, 24.9% of the patients underwent observation and 75.1% received adjuvant therapy, which included external beam radiation therapy (15.1%), vaginal brachytherapy (45.4%), and combined brachytherapy + chemotherapy (19.1%). Overall, adjuvant treatment resulted in improved oncologic outcomes for both 5-year progression-free survival (77.2% vs 69.6%, HR 0.55, p=0.01) and overall survival (81.5% vs 60.2%, HR 0.42, p<0.001). After adjusting for stage, grade 2/3, and age, improved progression-free survival and overall survival were observed for the following adjuvant subgroups compared with observation: external beam radiation (overall survival HR 0.47, p=0.047, progression-free survival not significant), vaginal brachytherapy (overall survival HR 0.35, p<0.001; progression-free survival HR 0.42, p=0.003), and brachytherapy + chemotherapy (overall survival HR 0.30 p=0.002; progression-free survival HR 0.35, p=0.006). Compared with vaginal brachytherapy alone, external beam radiation or the addition of chemotherapy did not further improve progression-free survival (p=0.80, p=0.65, respectively) or overall survival (p=0.47, p=0.74, respectively)., Conclusion: Adjuvant therapy improves both progression-free survival and overall survival in women with early-stage endometrial cancer meeting high-intermediate risk criteria with lymphovascular space invasion. External beam radiation or adding chemotherapy did not confer additional survival advantage compared with vaginal brachytherapy alone., Competing Interests: Competing interests: All authors reported their potential conflict of interest and there were none directly relating to this study., (© IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The objective of this study was to assess the rate of discordance between clinical and pathologic tumor size for women with stage IB1 cervical cancer (FIGO 2009 criteria), assess risk factors for discordance, and determine the impact of discordance on oncologic outcomes., Methods: This was a secondary analysis of a prior multi-institutional retrospective review of patients diagnosed with stage IB1 (FIGO 2009 staging) cervical cancer undergoing radical hysterectomy between 2010 and 2017. Demographic, clinicopathologic, and oncologic data were collected. Pathologic upstaging was defined as having a preoperative diagnosis of stage IB1 cervical cancer with pathology demonstrating a tumor size >4 cm. Demographic and clinicopathologic data was compared using chi-square, fisher exact or 2-sided t-test. Survival was estimated using the Kaplan-Meier method., Results: Of the 630 patients, 77 (12%) were upstaged. Patients who were upstaged had lower rates of preoperative conization (p < .001) or preoperative tumor sizes ≤2 cm (p < .001). Upstaged patients had increased odds of deep stromal invasion, lymphovascular space invasion, positive margins and positive lymph nodes. Almost 88% of upstaged patients received adjuvant therapy compared to 29% of patients with tumors ≤4 cm (odds 18.49, 95% CI 8.99-37.94). Finally, pathologic upstaging was associated with an increased hazard of recurrence (hazard ratio [HR] 1.95, 95% CI 1.03-3.67) and all-cause death (HR 2.31, 95% CI 1.04-5.11)., Conclusions: Pathologic upstaging in stage IB1 cervical cancer is relatively common. Upstaging is associated with an 18-fold increased risk of receipt of adjuvant therapy. Patients undergoing preoperative conization and those with tumors <2 cm had lower risks of upstaging. Improvement in preoperative assessment of tumor size may better inform primary treatment decisions., Competing Interests: Declaration of Competing Interest The authors of this manuscript have no conflicts of interest to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: To compare the disease-free survival (DFS) between open and minimally invasive radical hysterectomies (RH) performed in academic medical institutions., Methods: Retrospective multi-institutional review of patients undergoing RH for stage IA1 (with lymphovascular invasion), IA2, and IB1 squamous, adenocarcinoma, or adenosquamous carcinoma between January 1, 2010 and December 31, 2017., Results: Of 815 patients, open RH was performed in 255 cases (29.1%) and minimally invasive RH in 560 cases (70.9%). There were 19 (7.5%) recurrences in the open RH and 51 (9.1%) recurrences in the minimally invasive group ( P = .43). Risk-adjusted analysis revealed that minimally invasive RH was independently associated with an increased hazard of recurrence (aHR, 1.88; 95% CI, 1.04 to 3.25). Other factors independently associated with an increased hazard of recurrence included tumor size, grade, and adjuvant radiation. Conization before surgery was associated with lower recurrence risk (aHR, 0.4; 95% CI, 0.23 to 0.71). There was no difference in OS in the unadjusted analysis (HR, 1.14; 95% CI, 0.61 to 2.11) or after risk adjustment (aHR, 1.01; 95% CI, 0.5 to 2.2). Of 264 patients with tumors ≤ 2 cm on final pathology (excluding those with no residual tumor on final pathology), 2/82 (2.4%) recurred in the open RH group and 16/182 (8.8%) in the minimally invasive RH group ( P = .058). In propensity score matching analysis, 7/159 (4.4%) recurrences were noted in the open RH group and 18/156 (11.5%) in the minimally invasive RH group ( P = .019). Survival analysis revealed an increased risk of recurrence in the minimally invasive group in propensity-matched cohort (HR, 2.83; 95% CI, 1.1 to 7.18)., Conclusion: In this retrospective series, patients undergoing minimally invasive radical hysterectomy, including those with tumor size ≤ 2 cm on final pathology, had inferior DFS but not overall survival in the entire cohort.

Objectives: Severe skeletal muscle loss (sarcopenia) is associated with poor cancer outcomes, including reduced survival and increased treatment toxicity. Our goal was to evaluate if sarcopenia was associated with worse survival outcomes and chemotoxicity in EOC patients undergoing primary platinum and taxane-based chemotherapy., Methods: EOC patients diagnosed between 06/2000 and 02/2017 who received treatment with platinum and taxane-based chemotherapy were included. CT abdominal images closest to the time of diagnosis were retrospectively evaluated for skeletal muscle area at the 3rd lumbar vertebrae. Measurements were obtained with use of TomoVision® radiological software (SliceOmatic - version 5.0, Quebec, Canada). Sarcopenia was defined as Skeletal Muscle Index (SMI) ≤ 41. Data analysis included Kaplan-Meier plots to assess survival, and unpaired t-tests were used to compare the means by groups., Results: 201 EOC patients were evaluated. Sixty-four percent (128/201) met criteria for sarcopenia (SMI ≤ 41) at time of diagnosis. The mean overall survival did not differ between patients with SMI > 41 and SMI ≤ 41 (36.5 vs 40.8 months, p = 0.4, respectively). No difference in frequency of dose reduction, dose delay, hospital admissions, changes in regimen, blood transfusion, or toxicity was noted. There was no difference in distribution of toxicity grade., Conclusion: Sarcopenia was not associated with worse survival outcomes or chemotoxcity in EOC patients receiving first-line platinum and taxane-based chemotherapy in this cohort. Future prospective studies should focus on interventions to prevent or reverse sarcopenia and possibly increase ovarian cancer survival, performance status, and quality of life., Competing Interests: Declaration of competing interest None of the authors have any financial or personal conflicts of interest. The authors declare that they have no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: Lymphovascular space invasion (LVSI) is an independent risk factor for recurrence and poor survival in early-stage endometrioid endometrial cancer (EEC), but optimal adjuvant treatment is unknown. We aimed to compare the survival of women with early-stage EEC with LVSI treated postoperatively with observation (OBS), radiation (RAD, external beam and/or vaginal brachytherapy), or chemotherapy (CHEMO)+/-RAD., Methods: This was a multi-institutional, retrospective cohort study of women with stage I or II EEC with LVSI who underwent hysterectomy+/-lymphadenectomy from 2005 to 2015 and received OBS, RAD, or CHEMO+/-RAD postoperatively. Progression-free survival and overall survival were evaluated using Kaplan-Meier estimates and Cox proportional hazards models., Results: In total, 478 women were included; median age was 64 years, median follow-up was 50.3 months. After surgery, 143 (30%) underwent OBS, 232 (48.5%) received RAD, and 103(21.5%) received CHEMO+/-RAD (95% of whom received RAD). Demographics were similar among groups, but those undergoing OBS had lower stage and grade. A total of 101 (21%) women recurred. Progression-free survival (PFS) was improved in both CHEMO+/-RAD (HR = 0.18, 95% CI: 0.09-0.39) and RAD (HR = 0.31, 95% CI: 0.18-0.54) groups compared to OBS, though neither adjuvant therapy was superior to the other. However, in grade 3 tumors, the CHEMO+/-RAD group had superior PFS compared to both RAD (HR 0.25; 95% CI: 0.12-0.52) and OBS cohorts (HR = 0.10, 95% CI: 0.03-0.32). Overall survival did not differ by treatment., Conclusions: In early-stage EEC with LVSI, adjuvant therapy improved PFS compared to observation alone. In those with grade 3 EEC, adjuvant chemotherapy with or without radiation improved PFS compared to observation or radiation alone., Competing Interests: Declaration of competing interest All authors reported their potential conflicts of interest, and there were not relevant conflicts of interest disclosed., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Sentinel lymph node (SLN) biopsy is increasingly used in endometrial cancer staging; however, success of the technique is variable, and the learning curve needs to be better understood. Success is defined as identification of a SLN specimen containing nodal tissue in bilateral hemi-pelvises., Objective: To assess the learning curve of surgeons at an academic institution in performing successful SLN mapping and biopsy during robotic staging for endometrial cancer., Methods: After institutional review board approval, patients who underwent staging with robotic SLN mapping using indocyanine green at a single academic program between July 2012 and December 2017 were identified. Demographic, pathologic, and surgical data were retrospectively collected from the medical records. Descriptive and comparative statistics were performed. Surgeon rates of successful bilateral SLN mapping and removal of lymphoid-containing SLN specimens were compared. A logistic model was used to analyze the probability of successful SLN mapping and removal of lymph node-containing tissue with increasing number of procedures performed., Results: Three hundred and seventeen patients met the eligibility criteria. Most had early-stage, low-grade endometrial cancer. A total of 194 (61%) patients had successful bilateral mapping. Among seven surgeons, a plateau in rates of successful bilateral mapping was achieved after 40 cases. No linear correlation was seen between the number of surgeries performed and the rate of removal of lymph node-containing tissue among surgeons. Each additional 10 procedures performed was associated with a 5% and an 11% increase in the odds of successful SLN mapping and removal of lymph node-containing tissue, respectively., Discussion: The successful removal of lymph node-containing specimens appears to be a surgeon-specific phenomenon. The plateau of the learning curve for successful bilateral mapping seems to be reached at around 40 cases. These first 40 cases offer a time for auditing of individual rates of SLN mapping and removal to identify surgeons who may benefit from procedure-specific remediation., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Determine the utility of a clinical calculator to predict the benefit of chemotherapy in stage IA uterine papillary serous cancer (UPSC)., Patients and Methods: Data were collected from NCDB from years 2010-2014. Based on demographic and surgical characteristics, a clinical score was developed using the random survival forest machine learning algorithm., Results: Of 1,751 patients with stage IA UPSC, 1,012 (58%) received chemotherapy and 739 (42%) did not. Older age (HR 1.06), comorbidities (HR 1.31), larger tumor size (HR 1.27), lymphovascular invasion (HR 1.86), positive peritoneal cytology (HR 2.62), no pelvic lymph node dissection (HR 1.51), and no chemotherapy (HR 2.16) were associated with poorer prognosis. Compared to no chemotherapy, patients who underwent chemotherapy had a 5-year overall survival of 80% vs. 67%. To better delineate those who may derive more benefit from chemotherapy, we designed a clinical calculator capable of dividing patients into low, moderate, and high-risk groups with associated 5-year OS of 86%, 73%, and 53%, respectively. Using the calculator to assess the relative benefit of chemotherapy in each risk group, chemotherapy improved the 5-year OS in the high (42% to 64%; p < 0.001) and moderate risk group (66% to 79%; p < 0.001) but did not benefit the low risk group (84% to 87%; p = 0.29)., Conclusion: Our results suggest a clinical calculator is useful for counseling and personalizing chemotherapy for stage IA UPSC., (Published by Elsevier Inc.)

Background: The Multinational Association of Supportive Care of Cancer (MASCC) risk-index score has been validated as a stratification tool for febrile neutropenia (FN) risk in a heterogeneous group of cancer patients; recently, it has been deemed a suitable tool in gynecologic oncology patients in a retrospective study. This is a prospective multi-institutional study wherein we sought to validate MASCC score for stratifying FN morbidity in gynecologic oncology patients., Methods: IRB approval was obtained at 4 institutions for prospective data collection of gynecologic cancer patients admitted with FN from 3/1/2013 to 9/1/2014. Participating institutions have a policy of inpatient management of FN patients receiving chemotherapy. Deidentified data was compiled and processed at the leading institution., Results: In total, 31 patients met inclusion criteria. Most had advanced stage disease (67%). 100% of patients were receiving chemotherapy (57% for primary, 43% for recurrent disease). 55% had a positive culture. Median MASCC score was 21 (range, 10 to 26); 58% of patients were considered low risk. High risk patients more often had one (11% vs. 38%, P=0.09) or multiple (6% vs. 23%, P=0.28) severe complications, ICU admission (0% vs. 15%, P=0.17), and delay in next chemotherapy cycle (33% vs. 54%, P=0.25). No patients died from FN during the study period., Conclusions: This pilot data suggests that MASCC score may be a promising tool for determining suitability of outpatient management of FN in gynecologic oncology patients. Larger studies are warranted to achieve statistically significant results, which may enable us to effectively utilize this risk stratification tool for cost containment and avoidance of nosocomial infections.

With the spread of positron emission tomography/magnetic resonance (PET/MR), the question of comparability of studies becomes important. We aim to determine whether PET/MR and PET/computed tomography (PET/CT) are comparable for the case of cervical cancer. Fifteen cervical cancer patients identified by either a radiation oncologist or an oncologic surgeon had both PET/MR and PET/CT performed for initial staging within 3 weeks. We then compared the results both quantitatively (measuring standardized uptake values [SUVs] on visible lesions) as well as qualitatively (having radiologists and nuclear medicine physicians interprets the results). While interpretations between PET/MR and PET/CT varied in many cases, SUVs of primary lesions were similar to within 25% in all but one case, and correlation coefficient was 0.92. Maximum SUV ranged between 4.9 and 25.2 for PET-MR and between 5.8 and 30.4 for PET-CT for primary tumors and between 1.5 and 18.8 for PET-MR and between 1.8 and 20.8 for PET-CT for nodes. However, clinical reads often varied significantly between PET/MR and PET/CT. This suggests that SUV is similar on PET/MR and PET/CT although the differing anatomic modalities available for correlation may make the difference in terms of qualitative interpretation., Competing Interests: There are no conflicts of interest.

Objective: Advanced stage epithelial ovarian cancer (AEOC) can be treated with either neoadjuvant chemotherapy (NACT) or primary cytoreductive surgery (PCS). Although randomized controlled trials show that NACT is non-inferior in overall survival compared to PCS, there may be improvement in short-term morbidity. We sought to investigate the cost-effectiveness of NACT relative to PCS for AEOC from the US Medicare perspective., Methods: A cost-effectiveness analysis using a Markov model with a 7-month time horizon comparing (1) 3cycles of NACT with carboplatin and paclitaxel (CT), followed by interval cytoreductive surgery, then 3 additional cycles of CT, or (2) PCS followed by 6cycles of CT. Input parameters included probability of chemotherapy complications, surgical complications, treatment completion, treatment costs, and utilities. Model outcomes included costs, life-years gained, quality-adjusted life-years (QALYs) gained, and incremental cost-effectiveness ratios (ICER), in terms of cost per life-year gained and cost per QALY gained. We accounted for differences in surgical complexity by incorporating the cost of additional procedures and the probability of undergoing those procedures. Probabilistic sensitivity analysis (PSA) was performed via Monte Carlo simulations., Results: NACT resulted in a savings of $7034 per patient with a 0.035 QALY increase compared to PCS; therefore, NACT dominated PCS in the base case analysis. With PSA, NACT was the dominant strategy more than 99% of the time., Conclusions: In the short-term, NACT is a cost-effective alternative compared to PCS in women with AEOC. These results may translate to longer term cost-effectiveness; however, data from randomized control trials continues to mature., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: Sexual health in survivors of gynecologic cancer has been studied; however, sexual health in these women before treatment has not been thoroughly evaluated. The objective of our study was to describe the pretreatment characteristics of sexual health of women with suspected gynecologic cancer before cancer treatment., Materials and Methods: We performed a cross-sectional analysis of women with a suspected gynecologic cancer, who were prospectively enrolled in a hospital-based cancer survivorship cohort from August 2012 to June 2013. Subjects completed the validated Patient-Reported Outcomes Measurement Information System Sexual Function and Satisfaction Questionnaire. Pretreatment sexual health was assessed in terms of sexual interest, desire, lubrication, discomfort, orgasm, enjoyment, and satisfaction., Results: Of 186 eligible women with suspected gynecologic cancer, 154 (82%) completed the questionnaire pretreatment. Mean age was 58.1 ± 13.3 years. Sexual health was poor: 68.3% reported no sexual activity, and 54.7% had no interest in sexual activity. When comparing our study population to the general U.S. population, the mean pretreatment scores for the subdomains of lubrication and vaginal discomfort were similar, while sexual interest was significantly lower and global satisfaction was higher. In a linear regression model, controlling for cancer site, age remained significantly associated with sexual function while cancer site did not., Conclusions: Problems with sexual health are prevalent in women with suspected gynecologic malignancies before cancer treatment. Increasing awareness of the importance of sexual health in this population will improve quality of life for these women.

Objectives: To determine the association between treatment with neoadjuvant chemotherapy (NACT) or primary debulking surgery (PDS) and readmission after surgical hospitalization as well as overall survival among women with stage IIIC epithelial ovarian cancer (EOC)., Methods: We identified incident cases of stage IIIC EOC treated with both chemotherapy and surgery in the National Cancer Database (NCDB) from 2006 to 2012. 30-day readmissions were categorized as planned or unplanned. Log binomial models were used to estimate risk ratios and 95% confidence intervals. Survival analysis was performed using cox proportional hazards models., Results: We identified 20,853 women with stage IIIC EOC. 15.6% (n=3242) were treated with NACT and 11.6% (n=2427) were readmitted within 30days of surgery, 59% (n=1421) were unplanned. NACT was associated with a 48% reduction in the risk of any readmission (aRR 0.52 95%CI 0.45-0.60) compared to PDS with adjustment for age, race, insurance, histology, year of diagnosis, and Charlson co-morbidity index score. However, in the same population, receipt of neoadjuvant chemotherapy was also associated with a 33% increase in the rate of death (HR 1.33 95%CI 1.29-1.40) with adjustment for the same factors., Conclusions: Among women with stage IIIC EOC, NACT is associated with both decreased rates of readmission and decreased survival compared to PDS. While selection bias may account for some of the observed differences in survival, the current focus on short-term hospital-wide quality metrics, such as postoperative readmission, in the ovarian cancer population, may be creating incentives inconsistent with long-term goals., (Copyright © 2017. Published by Elsevier Inc.)

Objectives: Readmission after surgery is a quality metric hypothesized to reflect the quality of care in the index hospitalization. We examined the link between readmissions and a surrogate of surgical quality - major postoperative complication - among ovarian cancer patients., Methods: Patients who underwent surgery for ovarian cancer between 2012 and 2013 were identified from the National Surgical Quality Improvement Project (NSQIP). Major complications were defined as grade 3 or ≥complications on the validated Claviden-Dindo scale and included both NSQIP and non-NSQIP defined complications based on readmission ICD-9 code. Readmissions and complications within 30-days of surgery were analyzed using rate ratios and modified Poisson regression., Results: We identified 2806 ovarian cancer patients of whom 9.1% (n=259) experienced an unplanned readmission. Overall major complication rate was 10.9% (n=307). Major complications in the index hospitalization were not associated with subsequent readmission (RR 1.2, 95% CI 0.7-1.9). Overall, 41.4% of readmissions were not attributable to any major postoperative complication. Of the unplanned readmissions, 55.2% (n=143) never experienced a NSQIP-defined major complication. Of these 143 patients, the reason for readmission was known for 107 patients and was: 28.0% non-NSQIP-defined major complications; 16.8% cancer or other medical factors; 22.4% minor complications; and 32.7% symptoms without a diagnosis of complication., Conclusions: Forty percent of unplanned readmissions after ovarian cancer surgery occur among patients who have not experienced a major postoperative complication. Quality metric benchmarks and efforts to decrease readmissions should account for this high percentage of readmissions not associated with a major complication., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To assess the endometrial response rates to treatment with the levonorgestrel intrauterine device in post-menopausal women with atypical hyperplasia/endometrial intraepithelial neoplasia and grade 1 endometrioid (AH/EC) endometrial carcinoma who are not surgical candidates., Methods: Chart review was undertaken of patients with AH/EC who underwent levonorgestrel intrauterine device insertion by a gynecologic oncologist within two academic health systems between 2002 and 2013. When available, tissue blocks were evaluated with immunohistochemical staining for progesterone receptor expression., Results: A total of 41 patients received treatment for AH/EC with the levonorgestrel intrauterine device. Follow up sufficient to assess response occurred in 36 women (88%). Complete response was documented in 18 of 36 women (50%), no response in 8 patients (22%), partial response in 3 women (8%) and progression of disease in 7 patients (19%). Four of 18 patients with complete response (22%) later experienced relapse of hyperplasia or cancer. Four patients (10%) died during the study period: none had evidence of metastatic disease and 1 of the 4 woman died of perioperative complications following hysterectomy for stage I disease. Patients responding to treatment had significantly lower progesterone receptor expression on post-treatment biopsies., Conclusions: Intrauterine levonorgestrel is a viable treatment option for post-menopausal women with AH/EC who are poor candidates for standard surgical management. The response rate in this series is similar to published reports in premenopausal patients and includes cases of disease recurrence following conversion to benign endometrium., (Copyright © 2017 Elsevier Inc. All rights reserved.)

There is evidence that systems-based factors influence surgical outcomes of intraoperative and postoperative morbidity. The goal of this study was to provide an exploratory analysis of systems-based variables and their associations with surgical outcomes in gynecologic oncology patients. We merged electronic records from operating room software with billing claims from major surgeries performed from 2011 to 2013, at a tertiary care academic medical center. Univariate and bivariate analyses were performed to evaluate the relationship between baseline demographic and clinical covariates (age, comorbidity, procedure type, and surgeon volume), the main exposure variables (case start time, case order, and personnel handoffs), and the primary outcome of 30-day postoperative complications. Multiple logistic regression models were created to analyze the contributing effect of each systemic variable on postoperative complications. The overall rate of postoperative complications among patients was 31.4% (n = 182). Although traditional risk factors of comorbidity, procedure type, and case length were the strongest primary drivers of complication risk, there was a significant relationship between handoffs among surgical scrub technicians and postoperative complications (odds ratio: 2.12; 95% CI: 1.00-4.47). As a novel finding in surgical quality and safety research, this supports greater efforts into integrating key staffing information into studies of systemic variables and surgical outcomes.

Objectives: For women with gynecologic cancer, the impact of surgery on sexual interest and desire in the immediate and later postoperative period is not well characterized. The objective of this study was to report the perioperative trends of changing sexual interest and desire in a cohort of women undergoing surgery for suspected gynecologic malignancies., Methods: This is an ancillary analysis of a cohort study analyzing health-related outcomes in women who underwent primary surgical management of a suspected gynecologic malignancy between 10/2013 and 10/2014. Subjects completed the Patient-Reported Outcomes Measurement Information System Sexual Function and Satisfaction Questionnaire (PROMIS-SFQ) preoperatively and questions on sexual interest and desire at one, three, and six months postoperatively. Bivariate tests and multiple linear regression were used to analyze data., Results: Of 231 women who completed a baseline PROMIS-SFQ, 187 (81%) completed one-month, 170 (74%) three-month, and 174 (75%) six-month follow-up interviews. Following surgery, 71% of enrolled subjects were diagnosed with a malignancy. Women age <55 had a greater decrease in sexual interest from baseline to one month than women age >55 (-5.5±1.0 vs -2.3±0.9, p=0.02). In a multivariable analysis, age <55 remained associated with a larger decrease in sexual interest at one month postoperatively (-4.6, 95% CI: -1.8, -7.4), as did having cancer vs benign disease for women of all ages (-5.6, 95% CI: -9.6, -1.5)., Conclusions: This study provides new data regarding the timing and magnitude of changes in sexual interest following gynecologic oncology procedures., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Study Objective: To confirm the safety and feasibility outcomes of robotic radical parametrectomy and pelvic lymphadenectomy and compare the clinicopathological features of women requiring adjuvant treatment with the historical literature., Design: Retrospective cohort study and review of literature (Canadian Task Force classification II-2)., Setting: Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill., Patients: All patients who underwent robotic radical parametrectomy with upper vaginectomy (RRPV), and pelvic lymphadenectomy for occult cervical cancer discovered after an extrafascial hysterectomy at our institution between January 2007 and December 2015., Interventions: RRPV and pelvic lymphadenectomy for occult cervical cancer discovered after an extrafascial hysterectomy. We also performed a literature review of the literature on radical parametrectomy after occult cervical carcinoma., Measurements and Main Results: Seventeen patients with invasive carcinoma of the cervix discovered after extrafascial hysterectomy underwent RRPV with bilateral pelvic lymphadenectomy. There were 2 intraoperative complications, including 1 bowel injury and 1 bladder injury. One patient required a blood transfusion of 2 units. Three patients underwent adjuvant treatment with chemoradiation with radiation-sensitizing cisplatin. One of these patients had residual carcinoma on the upper vagina, 1 patient had positive parametria and pelvic nodes, and 1 patient had positive pelvic lymph nodes. No patients experienced recurrence, and 1 patient died from unknown causes at 59.4 months after surgery. We analyzed 15 studies reported in the literature and found 238 women who underwent radical parametrectomy; however, no specific preoperative pathological features predicted outcomes, the need for adjuvant treatment, or parametrial involvement., Conclusion: RRPV is a feasible and safe treatment option. As reflected in the literature, RRPV can help avoid empiric adjuvant chemoradiation; however, no pathological features predict the need for adjuvant treatment after surgery., (Copyright © 2017 AAGL. Published by Elsevier Inc. All rights reserved.)

Objective: To estimate variation in the use of neoadjuvant chemotherapy by high volume hospitals and to determine the association between hospital utilization of neoadjuvant chemotherapy and survival., Methods: We identified incident cases of stage IIIC or IV epithelial ovarian cancer in the National Cancer Database from 2006 to 2012. Inclusion criteria were treatment at a high volume hospital (>20 cases/year) and treatment with both chemotherapy and surgery. A logistic regression model was used to predict receipt of neoadjuvant chemotherapy based on case-mix predictors (age, comorbidities, stage etc). Hospitals were categorized by the observed-to-expected ratio for neoadjuvant chemotherapy use as low, average, or high utilization hospitals. Survival analysis was performed., Results: We identified 11,574 patients treated at 55 high volume hospitals. Neoadjuvant chemotherapy was used for 21.6% (n=2494) of patients and use varied widely by hospital, from 5%-55%. High utilization hospitals (n=1910, 10 hospitals) had a median neoadjuvant chemotherapy rate of 39% (range 23-55%), while low utilization hospitals (n=2671, 14 hospitals) had a median rate of 10% (range 5-17%). For all ovarian cancer patients adjusting for clinical and socio-demographic factors, treatment at a hospital with average or high neoadjuvant chemotherapy utilization was associated with a decreased rate of death compared to treatment at a low utilization hospital (HR 0.90 95% CI 0.83-0.97 and HR 0.85 95% CI 0.75-0.95)., Conclusions: Wide variation exists in the utilization of neoadjuvant chemotherapy to treat stage IIIC and IV epithelial ovarian cancer even among high volume hospitals. Patients treated at hospitals with low rates of neoadjuvant chemotherapy utilization experience decreased survival., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: To evaluate progression-free survival (PFS) and overall survival (OS) outcomes in women diagnosed with uterine papillary serous carcinoma (UPSC) who have had (UPSCBR+) or have not had (UPSCBR-) an antecedent history of breast cancer and to correlate their outcomes to prior tamoxifen exposure., Methods: Data were collected for women diagnosed with UPSC at two academic institutions between January 1997 and July 2012. Patient demographics, tumor histology, stage, and treatments were recorded. Patients were divided into two groups: those with and without a personal history of breast cancer. Within the UPSCBR+ cohort, we identified those with a history of tamoxifen use. Cox regression modeling was used to explore associations between selected covariates of interest and the time-to-event outcomes of PFS and OS., Results: Of 323 patients with UPSC, 46 (14%) were UPSCBR+. Of these, 15 (33%) had a history of tamoxifen use. UPSCBR+ patients were older than UPSCBR- (median years, 72 vs. 68, p=0.004). UPSCBR+ women showed no significant difference in PFS or OS compared to UPSCBR- (p=0.64 and p=0.73 respectively), even after controlling for age (p=0.15 and p=0.48 respectively). Within the UPSCBR+ cohort, there was no difference in PFS or OS with or without tamoxifen exposure (p=0.98 and p=0.94 respectively)., Conclusions: There was no difference in PFS or OS between the UPSCBR+ and UPSCBR- cohorts. We did not demonstrate significant OS or PFS differences in women who took tamoxifen prior to their endometrial cancer diagnosis. These findings have implications for counseling, and should be encouraging to women who are facing their second cancer diagnosis., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Circulating tumor cells consist of phenotypically distinct subpopulations that originate from the tumor microenvironment. We report a circulating tumor cell dual selection assay that uses discrete microfluidics to select circulating tumor cell subpopulations from a single blood sample; circulating tumor cells expressing the established marker epithelial cell adhesion molecule and a new marker, fibroblast activation protein alpha, were evaluated. Both circulating tumor cell subpopulations were detected in metastatic ovarian, colorectal, prostate, breast, and pancreatic cancer patients and 90% of the isolated circulating tumor cells did not co-express both antigens. Clinical sensitivities of 100% showed substantial improvement compared to epithelial cell adhesion molecule selection alone. Owing to high purity (>80%) of the selected circulating tumor cells, molecular analysis of both circulating tumor cell subpopulations was carried out in bulk, including next generation sequencing, mutation analysis, and gene expression. Results suggested fibroblast activation protein alpha and epithelial cell adhesion molecule circulating tumor cells are distinct subpopulations and the use of these in concert can provide information needed to navigate through cancer disease management challenges., Competing Interests: Competing interests: The presented CTC isolation technology is being commercialized by Biofluidica, Inc. S.A.S. and M.L.H. hold equity shares in BioFluidica, Inc. M.A.W. declares conflict of interest as spouse of M.L.H. The remaining authors declare that they have no competing financial interests.

Objective: Fatty acid synthase (FAS) is a key lipogenic enzyme that is highly expressed in endometrial cancer. Orlistat is a weight loss medication that has been shown to be a potent inhibitor of FAS. The goal of this study was to evaluate the anti-tumorigenic potential of orlistat in endometrial cancer cell lines., Methods: The endometrial cancer cell lines ECC-1 and KLE were used. Cell proliferation was assessed by MTT assay after treatment with orlistat. Cell cycle progression was evaluated by Cellometer and apoptosis was assessed using the Annexin V assay. Reactive oxygen species (ROS) was measured using the DCFH-DA assay. Western immunoblotting was performed to determine changes in FAS, cellular stress, cell cycle progression, and the AMPK/mTOR pathways., Results: Orlistat inhibited cell proliferation by 61 % in ECC-1 cells and 57 % in KLE cells at a dose of 500 μM. Treatment with orlistat at this concentration resulted in G1 arrest (p < 0.05) but did not affect apoptosis. Orlistat increased ROS and induced the expression of BIP (1.28-fold in ECC-1 compared to control, p < 0.05; 1.92-fold in KLE, p < 0.05) and PERK (2.25-fold in ECC-1, 1.4-fold in KLE, p < 0.05). Western immunoblot analysis demonstrated that orlistat decreased expression of important proteins in fatty acid metabolism including FAS (67 % in ECC-1, 15 % in KLE), acetyl-CoA carboxylase (40 % in ECC-1, 35 % in KLE), and carnitine palmitoyltransferase 1A (CPT1A) (65 % in ECC-1, 25 % in KLE) in a dose-dependent manner. In addition, orlistat at a dose of 500 μM increased expression of phosphorylated-AMPK (1.9-fold in ECC-1, p < 0.01; 1.5-fold in KLE, p < 0.05) and decreased expression of phosphorylated-Akt (25 % in ECC-1, p < 0.05; 37 % in KLE, p < 0.05) and phosphorylated-S6 (68 % in ECC-1, 56 % in KLE)., Conclusions: Orlistat inhibits cell growth in endometrial cancer cell lines through inhibition of fatty acid metabolism, induction of cell cycle G1 arrest, activation of AMPK and inhibition of the mTOR pathway. Given that patients with endometrial cancer have high rates of obesity, orlistat should be further investigated as a novel strategy for endometrial cancer treatment.

Objective: Our overall goal was to investigate the anti-tumor activity of the glutaminase 1 (GLS1) Inhibitor compound 968 in ovarian cancer cells. The human ovarian cancer cell lines, HEY, SKOV3 and IGROV-1 were used. Cell proliferation was assessed by MTT assay after treatment with compound 968. Cell cycle progression and Annexin V expression were evaluated using Cellometer. Western blotting was performed to determine changes in GLS1, cellular stress and cell cycle checkpoints. Reactive oxygen species (ROS) and glutamate dehydrogenase (GDH) activity were assessed by ELISA assay. Compound 968 significantly inhibited cell proliferation and the expression of GLS1 in a dose-dependent manner in all three ovarian cancer cell lines. Compound 968 induced G1 phase cell cycle arrest and apoptosis. Treatment with compound 968 increased ROS levels and induced the protein expression of calnexin, binding immunoglobulin protein (BiP) and protein kinase RNA-like endoplasmic reticulum kinase (PERK). Deprivation of glutamine increased the sensitivity of cells to paclitaxel, and compound 968 sensitized cells to the anti-proliferative effects of paclitaxel. Compound 968 inhibited cell growth in ovarian cancer cells through induction of G1 phase cell cycle arrest, apoptosis and cellular stress, suggesting that targeting GLS1 provide a novel therapeutic strategy for ovarian cancer.

Overexpression of c-Myc is associated with worse outcomes in endometrial cancer, indicating that c-Myc may be a promising target for endometrial cancer therapy. A novel small molecule, JQ1, has been shown to block BRD4 resulting in inhibition of c-Myc expression and tumor growth. Thus, we investigated whether JQ1 can inhibit endometrial cancer growth in cell culture and xenograft models. In PTEN-positive endometrial cancer cells, JQ1 significantly suppressed cell proliferation via induction of G1 phase arrest and apoptosis in a dose-dependent manner, accompanied by a sharp decline in cyclin D1 and CDK4 protein expression. However, PTEN-negative endometrial cancer cells exhibited intrinsic resistance to JQ1, despite significant c-Myc inhibition. Moreover, we found that PTEN and its downstream PI3K/AKT signaling targets were modulated by JQ1, as evidenced by microarray analysis. Silencing of PTEN in PTEN-positive endometrial cancer cells resulted in resistance to JQ1, while upregulation of PTEN in PTEN-negative endometrial cancer cells increased sensitivity to JQ1. In xenografts models of PTEN-positive and PTEN-knock-in endometrial cancer, JQ1 significantly upregulated the expression of PTEN, blocked the PI3K/AKT signaling pathway and suppressed tumor growth. These effects were attenuated in PTEN-negative and PTEN-knockdown xenograft models. Thus, JQ1 resistance appears to be highly associated with the status of PTEN expression in endometrial cancer. Our findings suggest that targeting BRD4 using JQ1 might serve as a novel therapeutic strategy in PTEN-positive endometrial cancers.

Background: There are currently no assessments of the impact of surgical complications on health-related quality of life in gynecology and gynecologic oncology. This is despite complications being a central focus of surgical outcome measurement, and an increasing awareness of the need for patient-reported data when measuring surgical quality., Objective: We sought to measure the impact of surgical complications on health-related quality of life at 1 month postoperatively, in women undergoing gynecologic and gynecologic oncology procedures., Study Design: This is a prospective cohort study of women undergoing surgery by gynecologic oncologists at a tertiary care academic center from October 2013 through October 2014. Patients were enrolled preoperatively and interviewed at baseline and 1, 3, and 6 months postoperatively. Health-related quality of life measures included validated general and disease-specific instruments, measuring multiple aspects of health-related quality of life, including anxiety and depression. The medical record was abstracted for clinical data and surgical complications were graded using validated Clavien-Dindo criteria, and women grouped into those with and without postoperative complications. Bivariate statistics, analysis of covariance, responder analysis, and multivariate modeling was used to analyze the relationship of postoperative complications to change health-related quality of life from baseline to 1 month. Plots of mean scores and change over time were constructed., Results: Of 281 women enrolled, response rates were 80% (n = 231/281) at baseline, and from that cohort, 81% (n = 187/231), 74% (n = 170/231), and 75% (n = 174/231) at 1, 3, and 6 months, respectively. The primary analytic cohort comprised 185 women with completed baseline and 1-month interviews, and abstracted clinical data. Uterine (n = 84, 45%), ovarian (n = 23, 12%), cervical (n = 17, 9%), vulvar (n = 3, 2%), and other (n = 4, 2%) cancers were represented, along with 53 (30%) cases of benign disease. There were 42 (24%) racial/ethnic minority women. Minimally invasive (n = 115, 63%) and laparotomy (n = 60, 32%) procedures were performed. Postoperative complications occurred in 47 (26%) of patients who experienced grade 1 (n = 12), grade 2 (n = 29), and grade 3 (n = 6) complications. At 1 month, physical (20.6 vs 22.5, P = .04) and functional (15.4 vs 18.3, P = .02) well-being, global physical health (43.1 vs 46.3, P = .02), and work ability (3 vs 7.2, P = .001) were lower in postoperative complication vs non-postoperative complication women. Relative change, however, in most health-related quality of life domains from baseline to 1 month did not differ between postoperative complication and nonpostoperative complication groups. Postoperative complication patients did have increased odds of sustained or worsened anxiety at 1 month vs baseline (odds ratio, 2.5; 95% confidence interval, 1.2-5.0) compared to nonpostoperative complication patients., Conclusion: Collectively, women who experienced postoperative complications after gynecologic and gynecologic oncology procedures did not appear to have differences in most health-related quality of life trends over time compared to those who did not. An exception was anxiety, where postoperative complications were associated with sustained or worsened levels of high anxiety after surgery., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: High-volume center surgery and gynecologic oncology care are associated with improved outcomes for women with uterine cancer. Referral patterns, from biopsy through to chemotherapy, may have patients interacting with high-volume centers for all, a portion, or none of their care. The relative frequency, the underlying factors that contribute to referral, and the potential impact of these referral patterns on treatment outcomes are unknown., Objective: We sought to analyze the referral patterns and subsequent impact of care sites on treatment for women with high- and low-risk uterine cancer., Study Design: This is a population-based retrospective cohort study of uterine cancer cases from 2004 through 2009 in North Carolina. Using state cancer registry files linked to Medicare, Medicaid, and private payer insurance claims, we analyzed referral and treatment patterns by annual surgical volume (high ≥12/y). We examined clinical and demographic factors associated with referral and used modified Poisson regression to evaluate risk of referral, lymphadenectomy, and chemotherapy. Stratified Kaplan-Meier plots and Cox proportional hazard models were used to examine survival., Results: A total of 2053 women were analyzed, including 34% (n = 677) with grade 3 histology. Of 1630 (80%) women with preoperative biopsies, referral patterns (biopsy to surgery) were: low volume to high volume (n = 652, 40%), followed by high volume to high volume (n = 605, 37%), then low volume to low volume (n = 318, 20%), and the rare high volume to low volume (n = 50, 3%). Women retained in low-volume centers after biopsy were older, were less likely to have private insurance, and had more comorbidities. High-risk histology (aRR, 1.14; 95% confidence interval, 1.04-1.25) was positively associated with referral, while Medicaid insurance was negatively associated with referral (aRR, 0.64; 95% confidence interval, 0.42-0.96). Most women (74%, n = 1557) had surgery at high-volume centers. Lymphadenectomy was less likely at low-volume centers (aRR, 0.71; 95% confidence interval, 0.64-0.77). Similarly, for high-risk patients, the relationship between low-volume center surgery and subsequent chemotherapy was aRR, 0.71 (95% confidence interval, 0.48-1.02). Of 290 women who received chemotherapy, the referral patterns (surgery to chemotherapy) were: high volume-all (high volume to high volume), high volume-hybrid (high volume to low volume, or low volume to high volume), and high volume-none (low volume to low volume). In all, 36% (n = 104/290) received chemotherapy at a low-volume center, the majority (68%, n = 71/104) of whom were referred from high-volume centers after surgery. Crude, unadjusted mortality risk of chemotherapy recipients differed by referral pattern (surgery to chemotherapy): high volume-all patients (hazard ratio, 1.0; referent), followed by high volume-hybrid (hazard ratio, 1.33; 95% confidence interval, 0.93-1.91) then high volume-none patients (RR, 1.95; 95% confidence interval, 1.24-3.08)., Conclusion: Most women with uterine cancer treated at high-volume centers arrive through referral, which is affected by age and type of insurance, in addition to histology. For high-risk women who require chemotherapy, survival may be related to the extent of treatment received at high-volume centers., Competing Interests: statement: The authors report no conflict of interest., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: Open radical hysterectomy followed by adjuvant radiation for cervical cancer has been associated with significant rates of morbidity. Radical hysterectomy is now often performed robotically. We sought to examine if the robotic platform decreased the morbidity associated with radical hysterectomy followed by adjuvant radiation., Materials/methods: A retrospective cohort of patients with cervical cancer undergoing radical hysterectomy from 1995 to 2013 was evaluated. Complications were assessed using electronic record review and graded. χ tests and Student t tests were used for analysis., Results: Overall, 243 patients underwent radical hysterectomy for cervical cancer. Surgical approach was 43% open and 57% robotic. Eighty-three patients (34.2%) required adjuvant radiation. Overall, radical hysterectomy plus adjuvant radiation was associated with increased risk of complication (29%) compared to radical hysterectomy alone (7%) (P < 0.001). Complications included lymphedema (n = 18), bowel-associated complications (n = 10), and urinary complications (n = 7). There was no difference in time to initiation of radiation between open and robotic surgery (43 vs 47 days; P = 0.33). There was no difference in grade 2/3 complications in patients receiving adjuvant radiation between open and robotic surgery (27.5% vs 27.9%; P = 0.97). Patients undergoing open surgery followed by radiation experienced a trend toward increased adhesion-related complications, such as bowel obstruction and ureteral stricture (10% vs 2.3%; P = 0.19); whereas patients undergoing robotic surgery followed by radiation experienced a trend toward increased lymphedema (19% vs 8%; P = 0.20)., Conclusions: We found no difference in long-term complications between patients who underwent robotic surgery compared to open radical hysterectomy with adjuvant radiation. There may be fewer adhesion-related complications with robotic surgery. However, as many radiation-related complications occur at later time points, continued follow-up to evaluate for potential differences between the 2 groups is necessary.