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Homologous recombination deficiency is a critical biologic feature of ovarian cancer. This weakness in DNA damage repair relies on functional poly(ADP-ribose) polymerase. Niraparib is a poly(ADP-ribose) polymerase inhibitor, orally available and initially approved for maintenance therapy in women with ovarian cancer by the US FDA in 2017 and by the EMA in 2017 for the same indication. Ovarian cancer represents the most lethal of gynecologic malignancies. The efficacy of niraparib has changed the landscape of ovarian cancer treatment, but overall survival data is still to come. This review summarizes the data regarding niraparib mechanism of action, toxicities, single agent efficacy and novel combinations in ovarian cancer. [ABSTRACT FROM AUTHOR]

PURPOSE: Inefficiencies in the clinical trial infrastructure result in protracted trial completion timelines, physician-investigator turnover, and a shrinking skilled labor force and present obstacles to research participation. Taken together, these barriers hinder scientific progress. Technological solutions to improve clinical trial efficiency have emerged, yet adoption remains slow because of concerns with cost, regulatory compliance, and implementation. METHODS: A prospective pilot study that compared regulatory-compliant digital and traditional wet ink paper signatures was conducted over a 6.5-month period in a hospital-based health system. Staff time and effort, error rate, costs, and time to completion were measured. Wilcoxon rank sum tests were used to compare staff time and time to completion. A value analysis was conducted. A survey was administered to measure user satisfaction. RESULTS: There where 96 participants (47 digital, 49 paper), 132 studies included (31 digital, 101 paper), and 265 documents processed (156 digital, 109 paper). A moderate reduction in staff time required to prepare documents for signature was observed (P <.0001). Error rates were reported in 5.1% of digital and 2.8% of paper documents, but this difference was not significant. Discrepancies requiring revisions included incomplete mandatory fields, inaccurate information submitted, and technical issues. A value analysis demonstrated a 19% labor savings with the use of digital signatures. Survey response rate was 57.4% (n = 27). Most participants (85.2%) preferred digital signatures. The time to complete documents was faster with digital signatures compared with paper (P =.0241). CONCLUSION: The use of digital signatures resulted in a decrease in document completion time and regulatory burden as represented by staff hours. Additional cost and time savings and information liquidity could be realized by integrating digital signatures and electronic document management systems. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the utility of liquid-based cytology in detecting recurrent cervical cancer among treated cervical cancer patients.Methods: A retrospective multi-institution study identified patients treated for cervical cancer from January 1, 2000, to November 1, 2009, through local cancer registries and patient databases. Patients were excluded if they lacked follow-up or treatment data.Results: In all, 4,167 cytology results from 929 women were identified. Of these, 626 (15%) Pap test results from 312 (34%) women were abnormal, including 296 atypical squamous cells of undetermined significance (ASC-US; 47%); 179 low-grade squamous intraepithelial lesions (LSIL; 29%), 59 atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesions (ASC-H; 9%); 55 high-grade squamous intraepithelial lesions (HSIL; 9%); 14 atypical glandular cells (2%), and 23 favor neoplasia (4%). Abnormal Pap test results led to 201 colposcopies in 135 women. Only 45 women had cervical intraepithelial neoplasia (CIN) 2 or worse, 25 had CIN 3, and 12 had cancer. Only 5 of 475 (1%) women with ASC-US or LSIL had CIN 3. Cancer recurred in 147 women, with 12 (8.1%) detected by Pap test; all but one had Pap test results of ASC-H or worse. One patient with ASC-US and human papillomavirus had a visible lesion on return for assessment 2 months after Pap testing. Colposcopy for cytology less than HSIL without a visible lesion on examination did not detect any recurrence or CIN 3. When stratified by stage and institution, patients treated with radiation had a higher risk of abnormal Pap test results (P<.001).Conclusion: A third of cervical cancer survivors will have abnormal cytology during follow-up, but in the absence of a visible lesion, those with ASC-US or LSIL can be followed without colposcopy unless abnormalities persist. Women with ASC-H, HSIL, and similar abnormalities deserve colposcopy.Level Of Evidence: II. [ABSTRACT FROM AUTHOR]

Background: Patients may use crowdfunding to solicit donations, typically from multiple small donors using internet-based means, to offset the financial toxicity of cancer care., Objective: To describe crowdfunding campaigns by gynecologic cancer patients and to compare campaign characteristics and needs expressed between patients with cervical, uterine, and ovarian cancer., Study Design: We queried the public crowdfunding forum GoFundMe.com for "cervical cancer," "uterine cancer," and "ovarian cancer." The first 200 consecutive posts for each cancer type fundraising within the United States were analyzed. Data on campaign goals and needs expressed were manually extracted. Descriptive statistics and bivariate analyses were performed., Results: Among the 600 fundraising pages, the median campaign goal was $10,000 [IQR $5000-$23,000]. Campaigns raised a median of 28.6% of their goal with only 8.7% of campaigns reaching their goal after a median of 54 days online. On average, ovarian cancer campaigns had higher monetary goals, more donors, and larger donation amounts than cervical cancer campaigns and raised more money than both cervical and uterine cancer campaigns. Campaigns were fundraising to support medical costs (80-85%) followed by lost wages (36-56%) or living expenses (27-41%). Cervical cancer campaigns reported need for non-medical costs more frequently than uterine or ovarian cancer campaigns. States without Medicaid expansions (31% of the national population) were over-represented among cervical cancer and uterine cancer, but not ovarian cancer campaigns., Conclusions: Crowdfunding pages reveal patients fundraising for out-of-pocket costs in the thousands of dollars and a wide range of unmet financial needs based on cancer type., Competing Interests: Declaration of competing interest 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. The author is an Editorial Board Member/Editor-in-Chief/Associate Editor/Guest Editor for [Journal name] and was not involved in the editorial review or the decision to publish this article. The authors have no conflicts of interest related to this work. This paper was presented as an oral presentation at the Western Association of Gynecologic Oncology in June 2023 in Monterey, CA., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: This paper reports the efficacy of the poly (ADP-ribose) polymerase inhibitor olaparib alone and in combination with the antiangiogenesis agent cediranib compared with cediranib alone in patients with advanced endometrial cancer., Methods: This was open-label, randomized, phase 2 trial (NCT03660826). Eligible patients had recurrent endometrial cancer, received at least one (<3) prior lines of chemotherapy, and were Eastern Cooperative Oncology Group performance status 0 to 2. Patients were randomly assigned (1:1:1), stratified by histology (serous vs. other) to receive cediranib alone (reference arm), olaparib, or olaparib and cediranib for 28-day cycles until progression or unacceptable toxicity. The primary end point was progression-free survival in the intention-to-treat population. Homologous repair deficiency was explored using the BROCA-GO sequencing panel., Results: A total of 120 patients were enrolled and all were included in the intention-to-treat analysis. Median age was 66 (range, 41-86) years and 47 (39.2%) had serous histology. Median progression-free survival for cediranib was 3.8 months compared with 2.0 months for olaparib (hazard ratio, 1.45 [95% CI, 0.91-2.3] p = .935) and 5.5 months for olaparib/cediranib (hazard ratio, 0.7 [95% CI, 0.43-1.14] p = .064). Four patients receiving the combination had a durable response lasting more than 20 months. The most common grade 3/4 toxicities were hypertension in the cediranib (36%) and olaparib/cediranib (33%) arms, fatigue (20.5% olaparib/cediranib), and diarrhea (17.9% cediranib). The BROCA-GO panel results were not associated with response., Conclusion: The combination of cediranib and olaparib demonstrated modest clinical efficacy; however, the primary end point of the study was not met. The combination was safe without unexpected toxicity., (© 2023 American Cancer Society.)

Poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitors (PARPi) are metabolized either via carboxylesterase (niraparib) or cytochrome P450 (CYP) enzymes (olaparib and rucaparib). Patients with advanced epithelial ovarian cancer (aOC) who receive concomitant medication metabolized by the CYP system may be at risk of drug-drug interactions impacting PARPi efficacy and tolerability. This study investigated CYP inhibitor/inducer treatment patterns in the first-line maintenance (1Lm) setting for patients with aOC. This retrospective cohort study used de-identified databases of US patients with aOC. Eligible patients were aged ≥18 years, diagnosed with aOC between January 2015-March 2021, and received CYP inhibitors/inducers during 1Lm PARPi initiation or the eligibility window (90 days before to 120 days after first-line platinum-based therapy ended [index]). Patients were either prescribed 1Lm PARPi monotherapy (PARPi cohort) or were not prescribed any 1Lm therapy within 120 days post-index (PARPi-eligible cohort). Strong/moderate CYP inhibitors/inducers were defined as area under the plasma concentration-time curve ratio (AUCR) ≥2 or clearance ratio (CL) ≤0.5 (inhibitors), and AUCR ≤0.5 or CL ratio ≥2 (inducers). Of 1411 patients (median age 63), 158 were prescribed PARPis and 1253 were PARPi-eligible. Among the PARPi cohort, 46.2%, 48.7%, and 5.1% were prescribed niraparib, olaparib, and rucaparib, respectively. For patients prescribed olaparib or rucaparib, 42.4% also received strong and/or moderate CYP inhibitors/inducers. This real-world study indicated a considerable proportion of patients received strong and/or moderate CYP inhibitors/inducers and were prescribed PARPis metabolized by the CYP system. Understanding potential impacts of concomitant CYP inhibitors/inducers on PARPi efficacy and safety is warranted., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: BJR has received consulting or advisory fees from Deep6AI, AstraZeneca, and Tesaro, a GSK company; DMC declares advisory/consultancy for AstraZeneca, GSK, Clovis Oncology; speaker bureaus for AstraZeneca, GSK; and travel/accommodation/expenses from AstraZeneca, GSK; JP is an employee of GSK and holds stock/shares at GSK and Boston Scientific; AKG, JAH, and LK are employees of GSK; AAG is a former GSK employee; EXD, TW, and JS are employees of Analysis Group, which received consulting fees from GSK; RS reports honoraria from Arcus, Clovis, Genentech, GSK, Immunogen, Instil Bio, Merck, and Seagen; and advisory fees from Genentech; BJM reports consulting fees from Amgen, Aravive AstraZeneca, Clovis, GOG Foundation, Gradalis ImmunoGen Laekna Health Care, Merck, Mersana Myriad, Nucana Oncomed Oncoquest Pfizer, Roche/Genentech, GSK), speakers’ bureau fees (Clovis, Merck, Roche/Genentech, GSK), honoraria (Amgen, Aravive AstraZeneca, Clovis, GOG Foundation, Gradalis ImmunoGen Laekna Health Care, Merck, Mersana Myriad, Nucana Oncomed Oncoquest Pfizer, Roche/Genentech, GSK)., (© 2024 GSK.)

Objective: To identify correlations between disease recurrence and adherence to NCCN posttreatment surveillance guidelines in patients who develop recurrent uterine cancer., Methods: Retrospective analysis identified patients (n = 60) with recurrent uterine cancer and at least one surveillance visit with a gynecologic oncologist between 2011 and 2020. Adherence to NCCN guidelines and details of recurrence were recorded., Results: Recurrent uterine cancer was identified in 60 patients with an average time to recurrence (TTR) of 25 months. Of those, 39 (65%) were adherent to NCCN surveillance guidelines and 36 (60%) were symptomatic at the time of recurrence diagnosis. Asymptomatic recurrence was diagnosed by imaging in 11 (46%), physical exam in 7 (29%), and blood work in 6 (25%) patients. Patients who were adherent to NCCN guidelines were diagnosed with recurrence on average 11 months earlier (p = 0.0336). Adherence was an independent predictor of TTR for all patients regardless of symptoms. There was no significant effect of age, race, primary language, or stage of disease on adherence., Conclusion: Adherence to NCCN posttreatment surveillance guidelines for uterine cancer is independently associated with an earlier diagnosis of recurrence., Competing Interests: Declaration of Competing Interest Christopher M. Mayer, Reed M. O'Connor, Anthony T. Do, Victoria R. Cerda, Stephanie M. Wang, Marla E. Scott, Andrew J. Li, BJ Rimel, Michael R. Manuel, Kristin N. Taylor, and Kenneth H. Kim report no conflict of interest. BJ Rimel reports being a consultant for Deep6AI as well as participation on a Data Safety Monitoring Board or Advisor Board for Merck, GSK, AstraZeneca, and Immunogen., (Copyright © 2023. Published by Elsevier Inc.)

Study Objective: To compare rates of vaginal cuff dehiscence (VCD) in transgender patients with cisgender patients after minimally invasive hysterectomy (MIH)., Design: We performed a single-surgeon, retrospective cohort analysis comparing the rates of VCD in patients undergoing MIH for gender affirmation with other indications (benign, malignant, prophylactic) with our study surgeon between January, 2015, and December, 2021., Setting: Major, urban, academic tertiary care hospital in the United States., Patients: 166 patients met inclusion criteria with 49 of those patients undergoing MIH (29.5%) for gender affirmation. Of the remaining 117 patients, 92 (78.6%) underwent MIH for cancer, 15 (12.8%) for prophylaxis, and 10 (8.5%) for benign indications., Interventions: Not applicable., Measurements: We assessed included patients for baseline demographics, presence of risk factors for VCD, details of index hysterectomy, and details of cuff dehiscence events., Main Results: Transgender patients tended to be younger at the time of surgery, but demographics were otherwise similar between both groups. Most transgender patients (n = 36, 73.5%) had both ovaries removed at the time of hysterectomy, 100% were on testosterone therapy pre- and postoperatively, and none used supplementary estrogen. Three of the 49 transgender patients (6.1%) experienced postoperative dehiscence of the vaginal cuff compared with 2 of the 117 cisgender patients (1.7%). This failed to reach statistical significance; however, our descriptive analysis showed that all cases of dehiscence in the cisgender group had identifiable precipitating factors (i.e., trauma). By comparison, all cases of dehiscence in the transgender group were spontaneous with few identifiable risk factors., Conclusion: Transgender patients undergoing MIH may be at increased risk of VCD, although the rarity of this surgical complication precluded determination of statistical significance in our data set. We propose testosterone exposure as a possible risk factor for VCD, although we cannot exclude other factors, such as young age, as drivers of VCD in this population. Future studies of biospecimens are needed to evaluate for cellular differences in these patients., (Copyright © 2023 AAGL. Published by Elsevier Inc. All rights reserved.)

Most high-grade serous ovarian cancers (HGSCs) likely initiate from fallopian tube (FT) epithelia. While epithelial subtypes have been characterized using single-cell RNA-sequencing (scRNA-Seq), heterogeneity of other compartments and their involvement in tumor progression are poorly defined. Integrated analysis of human FT scRNA-Seq and HGSC-related tissues, including tumors, revealed greater immune and stromal transcriptional diversity than previously reported. We identified abundant monocytes in FTs across two independent cohorts. The ratio of macrophages to monocytes is similar between benign FTs, ovaries, and adjacent normal tissues but significantly greater in tumors. FT-defined monocyte and macrophage signatures, cell-cell communication, and gene set enrichment analyses identified monocyte- and macrophage-specific interactions and functional pathways in paired tumors and adjacent normal tissues. Further reanalysis of HGSC scRNA-Seq identified monocyte and macrophage subsets associated with neoadjuvant chemotherapy. Taken together, our work provides data that an altered FT myeloid cell composition could inform the discovery of early detection markers for HGSC., Competing Interests: The authors declare no competing interests., (© 2024 The Authors.)

Background: In the United States, inequities in preventive health behaviors such as cervical cancer screening have been documented. Sexual orientation, gender identity, and race/ethnicity all individually contribute to such disparities. However, little work has investigated their joint impact on screening behavior., Methods: Using sampling weighted data from the 2016 and 2018 Behavioral Risk Factor Surveillance System, we assessed differences in two metrics via chi-square statistics: 1) lifetime uptake, and 2) up-to-date cervical cancer screening by sexual orientation and gender identity, within and across racial/ethnic classifications., Results: Within all races, individuals who identify as members of sexual and gender minority (SGM) communities reported higher rates of never being screened (except for Black transgender men) than straight or cisgender individuals (p < 0.0001). [*START* Across all races, the Asian/Pacific Islander transgender population (32.4%; weighted n (w.n.) = 1,313) had the lowest proportion of lifetime screening, followed by the Asian/Pacific Islander gay/lesbian (53.0%, w.n. = 21,771), Hispanic transgender (58.7%; w.n. = 24,780), Asian/Pacific Islander bisexual (61.8%, w.n. = 54,524), and Hispanic gay/lesbian (69.6%, w.n. = 125,781) populations. *END*] Straight or cisgender Non-Hispanic White (w.n. = 40,664,476) individuals had the highest proportion of lifetime screening (97.7% and 97.5%, respectively). However, among individuals who had been screened at least once in their lifetime, identifying as SGM was not associated with a decreased proportion of up-to-date screening within or between races., Conclusions: Due to small sample sizes, especially among Asian/Pacific Islander and Hispanic populations, confidence intervals were wide. Heterogeneity in screening participation by SGM status within and across racial/ethnic groups were observed., Impact: These screening disparities reveal the need to disaggregate data to account for intersecting identities and for studies with larger sample sizes to increase estimate reliability., (© 2023. The Author(s).)

Objective: To investigate the joint impact of sexual orientation, gender identity, and race/ethnicity on colorectal and breast cancer screening disparities in the United States., Methods: Utilizing sampling weighted data from the 2016 and 2018 Behavioral Risk Factor Surveillance System, we assessed differences in two metrics via chi-square statistics: 1) lifetime uptake, and 2) up-to-date colorectal and breast cancer screening by sexual orientation and gender identity, within and across racial/ethnic classifications., Results: Within specific races/ethnicities, lifetime CRC screening was higher among gay/lesbian (within NH-White, Hispanic, and Asian/Pacific Islander) and bisexual individuals (Hispanic) compared to straight individuals, and lowest overall among transgender women and transgender nonconforming populations ( p  < 0.05). Asian transgender women had the lowest lifetime CRC screening (13.0%; w.n.  = 1,428). Lifetime breast cancer screening was lowest among the Hispanic bisexual population (86.6%; w.n.  = 26,940) and Hispanic transgender nonconforming population (71.8%; w.n.  = 739); within all races, SGM individuals (except NH-White, Hispanic, and Black bisexual populations, and NH-White transgender men) had greater breast cancer screening adherence compared to straight individuals., Conclusions: Due to small, unweighted sample sizes, results should be interpreted with caution. Heterogeneity in screening participation by SGM status within and across racial/ethnic groups were observed, revealing the need to disaggregate data to account for intersecting identities and for studies with larger sample sizes to increase estimate reliability., Competing Interests: All authors of this article declare they have no relevant conflicts of interest., (© 2023 The Authors.)

Objective: To determine whether Black race is associated with treatment and survival among women with low-risk endometrial cancer., Methods: Black and White women with Stage IA grade 1-2 endometrioid endometrial carcinoma diagnosed from 2010 to 2016 in the SEER 18 dataset were identified (n = 23,431), and clinical and socioeconomic attributes obtained. Five-year cancer-specific survival (CSS) and relative survival (RS) were calculated using SEER*Stat 8.3.9. Cox proportional hazards model was used to determine predictors of overall survival (OS) and CSS., Results: There was a significantly higher proportion of Black women who did not have surgery compared to White women (3% vs 1%, respectively; p < 0.0001). Residing in the South, being insured with Medicaid, and residing in a county with low median income were also associated with non-receipt of surgery. Black women remained less likely to undergo hysterectomy on multivariable analysis (OR 0.44, 95% CI 0.32-0.60). Non-receipt of hysterectomy was predictive of decreased CSS (HR 0.14, 95% CI 0.09-0.21) and OS (HR 0.18, 95% 0.14-0.23) on adjusted analysis. Black race was also an independent predictor of increased cancer-specific death (HR 2.07, 95% CI 1.50-2.86) as well as death from any cause (HR 1.74, 95% CI 1.44-2.09) on adjusted analysis., Conclusions: Black women with low-risk endometrial cancer were less likely to undergo hysterectomy and experienced decreased survival relative to White women. Further investigation is warranted to better understand the socioeconomic, geographic, and biologic factors that influence this disparity., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: Oral tyrosine kinase inhibitors (TKIs) have new indications for treatment in gynecologic malignancies. These targeted drugs have both unique and overlapping toxicities, which require careful attention and management. New combination therapies with immune-oncology agents have demonstrated promise in endometrial cancer. This review examines common adverse events associated with TKIs and provides readers with an evidence-based review on current uses and strategies for the management of these medications., Methods: A comprehensive review of the medical literature on TKI use in gynecologic cancer was undertaken by a committee approach. Details of each drug, its molecular target, and relevant data on both clinical efficacy and side effects were compiled and organized for clinical use. Information on drug-related secondary effects and management strategies for specific toxicities, including dose reduction and concomitant medications, were gathered., Results: TKIs can potentially offer improved response rates and durable responses for a group of patients who were previously without an effective standard second-line therapy. The combination of lenvatinib and pembrolizumab represents a more targeted approach to the drivers of endometrial cancer; however, there remains significant drug-related toxicity, and thus dose reduction and dose delay are frequently required. Toxicity management requires frequent check-ins and management strategies to help patients find the highest tolerable dose. TKIs are expensive and patient financial toxicity is as critical a measure of a drug's utility as any drug side effect. Many of these drugs have patient assistance programs, which should be fully utilized to minimize cost., Conclusions: Future studies are needed to expand the role of TKIs into new molecularly driven groups. Attention to cost, durability of response, and long-term toxicity management is needed to ensure all eligible patients have access to treatment., Competing Interests: Declaration of Competing Interest, (Copyright © 2023 Elsevier Inc. All rights reserved.)

Niraparib is a poly (ADP-ribose) polymerase inhibitor that has shown a significant improvement in progression-free survival irrespective of biomarker status in patients with advanced epithelial ovarian cancer. This review focuses on the adverse events associated with niraparib and their management to maintain efficacy of niraparib treatment and improve quality of life for patients. In five trials assessing efficacy of niraparib in patients with advanced epithelial ovarian cancer (PRIMA, NOVA, NORA, QUADRA, and PRIME), treatment-emergent adverse events of any grade were reported in nearly all patients (≥99%) receiving niraparib; the events were grade ≥3 in 51-74% of patients. Across all lines of therapy, treatment-emergent adverse events led to dose interruptions in 62-80% of patients receiving niraparib and dose reductions in 47-71%. Hematologic events were most frequently reported, including thrombocytopenia, anemia, and neutropenia. Common non-hematologic events included gastrointestinal events, which were generally low grade (<5% were grade ≥3). Clinical strategies to manage these and other events, such as fatigue and insomnia, cognitive behavioral therapy and pharmacologic agents, are summarized. Once-daily niraparib dosing may be advantageous for some patients for many reasons, including night-time dosing which may help alleviate gastrointestinal symptoms. An individualized starting dose (determined by baseline body weight and platelet count) of niraparib demonstrated an improved safety profile while maintaining efficacy. Patients receiving the niraparib individualized starting dose had fewer grade ≥3 adverse events, dose interruptions, and dose reductions than patients receiving a fixed starting dose. The safety profile of niraparib across five pivotal studies in advanced epithelial ovarian cancer was consistent across multiple lines of treatment, including as maintenance therapy in first-line and recurrent settings and as treatment in heavily pre-treated patients. Long-term safety data from the NOVA trial confirmed that, with appropriate and early dose modifications, niraparib is well tolerated., Competing Interests: Competing interests: BJM reports consulting fees from AbbVie, Amgen, Aravive, AstraZeneca, Clovis, GSK, GOG Foundation, Gradalis, ImmunoGen, Laekna Health Care, Merck, Mersana, Myriad, Nucana, Oncomed, Oncoquest, Pfizer, and Roche/Genentech; speakers’ bureau fees from AstraZeneca, Clovis, GSK, Merck, and Roche/Genentech; and honoraria from AbbVie, Amgen, Aravive, AstraZeneca, Clovis, GSK, GOG Foundation, Gradalis, ImmunoGen, Laekna Health Care, Merck, Mersana, Myriad, Nucana, Oncomed, Oncoquest, Pfizer, and Roche/Genentech. AGM received consulting/advisory fees from Alkermes, Amgen, AstraZeneca, Clovis, Genmab, GSK, HederaDx, Immunogen, Illumina, Macrogenics, Mersana, MSD, Novartis, Novocure, Oncoinvent, PharmaMar, Roche, SOTIO, SUTRO, Seagen, and Takeda; speakers’ bureau fees from AstraZeneca, Clovis, GSK, MSD, and Roche; institutional research funding from GSK and Roche; travel support from AstraZeneca, GSK, and Roche. LB received consulting/advisory fees from GSK, AstraZeneca, and Clovis. UM received consulting/advisory fees from Merck, NextCure, Novartis, Immunogen, 2X Oncology, AstraZeneca, Blueprint Medicines, Trillium, Agenus, GSK, and Boehringer Ingelheim; DSMB fees from Advaxis, Symphogen, and Alkermes; SAB for Rivkin Foundation, Ovarian Cancer Research Alliance, and Clearity Foundation. BJR received consulting/advisory fees from AstraZeneca, GSK, Merck, Immunogen, and Deep6AI. XW was an investigator for the NORA trial and has no conflicts of interest to declare. KNM reports consulting fees from Aravive, AstraZeneca, Alkemeres, Addi, Blueprint Pharma, Clovis, Elevar, Eisai, Genentech/Roche, GSK/Tesaro, Hengrui, ImmunoGen, Imab, Merck, Mersana, Myriad, Novartis, Lilly, Mereo, OncXerna, OncoNova, Verastem, Sorrento, and VBL Therapeutics; research funding from Lilly, Merck, Verastem, and PTC Therapeutics; and serves on Board of Directors for Gynecologic Oncology Group F and is Associate Director for Gynecologic Oncology Group Partners. MRM reports personal fees and other from Karyopharm Therapeutics, Roche, and Sera Prognostics; institutional grants and personal fees from AstraZeneca, BioCad, Boehringer Ingelheim, Clovis Oncology, Geneos Therapeutics, GenMab, GSK, Merck, Oncology Venture, Pfizer, Seattle Genetics, Sera Prognostics, Sotio, Takeda Pharmaceutical Company Ltd, and Zai Lab., (© IGCS and ESGO 2023. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Objectives: Guidelines recommend risk-reducing bilateral salpingo-oophorectomy (RRSO) for women with pathogenic variants of non-BRCA and Lynch syndrome-associated ovarian cancer susceptibility genes. Optimal timing and findings at the time of RRSO for these women remains unclear. We sought to characterize practice patterns and frequency of occult gynecologic cancers for these women at our two institutions., Methods: Women with germline ovarian cancer susceptibility gene pathogenic variants who underwent RRSO between 1/2000-9/2019 were reviewed in an IRB-approved study. All patients were asymptomatic with no suspicion for malignancy at time of RRSO. Clinico-pathologic characteristics were extracted from the medical records., Results: 26 Non-BRCA (9 BRIP1, 9 RAD51C, and 8 RAD51D) and 75 Lynch (36 MLH1, 18 MSH2, 21 MSH6) pathogenic variants carriers were identified. Median age at time of RRSO was 47. There were no occurrences of occult ovarian or fallopian tube cancer in either group. Two patients (3%) in the Lynch group had occult endometrial cancer. Median follow up was 18 and 35 months for non-BRCA and Lynch patients, respectively. No patient developed primary peritoneal cancer upon follow up. Post-surgical complications occurred in 9/101 (9%) of patients. Hormone replacement therapy (HRT) was rarely used despite reported post-menopausal symptoms in 6/25 (23%) and 7/75 (37%) patients, respectively., Conclusions: No occult ovarian or tubal cancers were observed in either group. No recurrent or primary gynecologic-related cancers occurred upon follow-up. Despite frequent menopausal symptoms, HRT use was rare. Both groups experienced surgical complications when hysterectomy and/or concurrent colon surgery was performed suggesting concurrent surgeries should only be performed when indicated., Competing Interests: Declaration of Competing Interest There were no true conflicts of interest, financial or otherwise, for any on the authors of this study. Dr. B.J. Rimel consults for Deep6AI and has served on the advisory boards for GlaxoSmithKline, Immunogen, and AstraZeneca. Dr. Christine S. Walsh has grants or contracts through Merck, consults for Immunogen and Genentech, and participates in educational events through OncLive. Dr. Ilana Cass is a board member of the Society of Gynecologic Oncology., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The original vision of the field of gynecologic oncology was to establish a multidisciplinary approach to the management of patients with gynecologic cancers. Fifty years later, scientific advances have markedly changed the overall practice of gynecologic oncology, but the profession continues to struggle to define its value-financial and otherwise. These issues were examined in full at the Society of Gynecologic Oncology (SGO) Future of the Profession Summit and the purpose of this document is to summarize the discussion, share the group's perceived strengths, weaknesses, opportunities, and threats (SWOT) for gynecologic oncologists, further educate members and others within the patient care team about the unique role of gynecologic oncologists, and plan future steps in the short- and long- term to preserve the subspecialty's critical mission of providing comprehensive, longitudinal care for people with gynecologic cancers., Competing Interests: Declaration of Competing Interest Dr. Huh reports personal fees from AstraZeneca, Roche, SeaGen and Inovio outside the submitted work. Dr. Hardesty reports personal fees from Immunogen, Axiom, GSK, Takeda, AZ-Mereck, and Intuitive outside the submitted work. Dr. Prendergast reports personal fees from Heron Therapeutics and AstraZeneca outside the submitted work. Dr. Rimel reports being an Advisory Board Participant for GSK, Merck, and Immunogen and a consultant for Deep 6AI. Dr. Shahin reports grants and personal fees from GSK, AstraZeneca, and Merck, personal fees from Eisai, Immunogen, and GenMab during the conduct of the study. All other authors have nothing to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

In their fiscal year 2021 reports, the US House and Senate Appropriations Committees requested that the National Institutes of Health (NIH) evaluate current research related to women's health and topics that include stagnant cervical cancer survival. In response, the NIH Office of Research on Women's Health, with input from women's health experts; members of the public; representatives from NIH institutes, centers, and offices; and members of the NIH Advisory Committee on Research on Women's Health, reviewed the public health needs and current NIH activities on cervical cancer. The Advancing NIH Research on the Health of Women: A 2021 Conference held in October 2021 reviewed these findings and allowed the identification of opportunities to strengthen research. In this review, the authors summarize public health needs related to cervical cancer and NIH activities in this realm. Cervical cancer has become a rare disease in the United States, yet significant portions of the US population remain under screened or unscreened for cervical cancer, human papillomavirus vaccination rates remain low, access to high-quality treatment remains a challenge for many, and large inequities by race and ethnicity persist. Novel, inclusive, and intentional research is needed to produce improvements in cervical cancer survival within the United States., (© 2022 American Cancer Society.)

In this analysis, we examined the relationship between progression-free survival (PFS) and mutation status of 18 homologous recombination repair (HRR) genes in patients in the non-germline BRCA -mutated (non-g BRCA m) cohort of the ENGOT-OV16/NOVA trial (NCT01847274), which evaluated niraparib maintenance therapy for patients with recurrent ovarian cancer. This post hoc exploratory biomarker analysis was performed using tumor samples collected from 331 patients enrolled in the phase III ENGOT-OV16/NOVA trial's non-g BRCA m cohort. Niraparib demonstrated PFS benefit in patients with either somatic BRCA- mutated (s BRCA m; HR, 0.27; 95% confidence interval, CI, 0.08-0.88) or BRCA wild-type ( BRCA wt; HR, 0.47; 95% CI, 0.34-0.64) tumors. Patients with BRCA wt tumors with other non- BRCA HRR mutations also derived benefit from niraparib (HR, 0.31; 95% CI, 0.13-0.77), as did patients with BRCA wt/HRRwt (HRR wild-type) tumors (HR, 0.49; 95% CI, 0.35-0.70). When patients with BRCA wt/HRRwt tumors were further categorized by genomic instability score (GIS), clinical benefit was observed in patients with homologous recombination-deficient (GIS ≥ 42; HR, 0.33; 95% CI, 0.18-0.61) and in patients with homologous recombination-proficient (HRp; GIS < 42; HR, 0.60; 95% CI, 0.36-0.99) disease. Although patients with s BRCA m, other non- BRCA HRR mutations, or GIS ≥ 42 benefited the most from niraparib treatment, PFS benefit was also seen in HRp (GIS < 42) patients without HRR mutations. These results support the use of niraparib in patients with recurrent ovarian cancer regardless of BRCA /HRR mutation status or myChoice CDx GIS., Significance: We retrospectively evaluated the mutational profile of HRR genes in tumor samples from 331 patients from the non-germline BRCA -mutated cohort of the phase III NOVA trial of patients with platinum-sensitive high-grade serous ovarian cancer. Patients with non- BRCA HRR mutations generally benefited from second-line maintenance treatment with niraparib compared with placebo., Competing Interests: G. Lindahl reports personal fees from Honoraria for lectures outside the submitted work. S. Mahner reports grants, personal fees, and other from AbbVie, AstraZeneca, Clovis, Eisai, GSK, Hubro, Medac, MSD, Novartis, Nykode, Olympus, PharmaMar, Pfizer, Roche, Sensor Kinesis, Teva, and Tesaro outside the submitted work. A. Redondo reports personal fees from GSK, MSD; personal fees and other from AstraZeneca; other from Clovis; grants and personal fees from Pharmamar; and grants from Eisai outside the submitted work. M. Fabbro reports personal fees from GSK and AstraZeneca outside the submitted work. B.J. Rimel reports other from GSK, Merck, Immunogen, and personal fees from Deep6AI outside the submitted work. A.M. Oza reports PI and Steering Committees with AstraZeneca, GSK, and Clovis; advisory Board member with AstraZeneca and Morphosys. U. Canzler reports personal fees from AstraZeneca, Lilly, and Roche outside the submitted work. J.S. Berek reports grants from Tesaro during the conduct of the study. A. González-Martín reports personal fees from Alkermes, Amgen, AstraZeneca, Clovis Oncology, Genmab, GSK, ImmunoGen, Merck Sharp & Dohme, MacroGenics, Novartis, Oncoinvent, Pfizer/Merck, PharmaMar, Roche, Sotio, Sutro and grants from GSK and Roche outside the submitted work. P. Follana reports personal fees from GSK, AstraZeneca, and Clovis outside the submitted work. R. Lord reports personal fees from GSK outside the submitted work. Z. Wang reports other from GSK during the conduct of the study; other from GSK outside the submitted work. D. Gupta reports other from GSK during the conduct of the study; other from GSK outside the submitted work; and D. Gupta is an employee of GSK which sponsored the NOVA trial. U. Matulonis reports personal fees from GSK, AstraZeneca, Merck, Novartis, Next Cure, Agenus, 2X oncology, Symphogen, Alkermes, and Morphosys during the conduct of the study; personal fees from Clearity Foundation and Ovarian Cancer Research Alliance outside the submitted work. B. Feng is an employee of GSK. No disclosures were reported by the other authors., (© 2022 The Authors; Published by the American Association for Cancer Research.)

Background: Little is known about the role of global DNA methylation in recurrence and chemoresistance of high grade serous ovarian cancer (HGSOC)., Methods: We performed whole genome bisulfite sequencing and transcriptome sequencing in 62 primary and recurrent tumors from 28 patients with stage III/IV HGSOC, of which 11 patients carried germline, pathogenic BRCA1 and/or BRCA2 mutations., Results: Landscapes of genome-wide methylation (on average 24.2 million CpGs per tumor) and transcriptomes in primary and recurrent tumors showed extensive heterogeneity between patients but were highly preserved in tumors from the same patient. We identified significant differences in the burden of differentially methylated regions (DMRs) in tumors from BRCA1/2 compared to non-BRCA1/2 carriers (mean 659 DMRs and 388 DMRs in paired comparisons respectively). We identified overexpression of immune pathways in BRCA1/2 carriers compared to non-carriers, implicating an increased immune response in improved survival (P = 0.006) in these BRCA1/2 carriers., Conclusion: These findings indicate methylome and gene expression programs established in the primary tumor are conserved throughout disease progression, even after extensive chemotherapy treatment, and that changes in methylation and gene expression are unlikely to serve as drivers for chemoresistance in HGSOC., (© 2022. The Author(s).)

Endometriosis is associated with increased risk of epithelial ovarian cancers (EOCs). Using data from large endometriosis and EOC genome-wide association meta-analyses, we estimate the genetic correlation and evaluate the causal relationship between genetic liability to endometriosis and EOC histotypes, and identify shared susceptibility loci. We estimate a significant genetic correlation (r g ) between endometriosis and clear cell (r g  = 0.71), endometrioid (r g  = 0.48), and high-grade serous (r g  = 0.19) ovarian cancer, associations supported by Mendelian randomization analyses. Bivariate meta-analysis identified 28 loci associated with both endometriosis and EOC, including 19 with evidence for a shared underlying association signal. Differences in the shared risk suggest different underlying pathways may contribute to the relationship between endometriosis and the different histotypes. Functional annotation using transcriptomic and epigenomic profiles of relevant tissues/cells highlights several target genes. This comprehensive analysis reveals profound genetic overlap between endometriosis and EOC histotypes with valuable genomic targets for understanding the biological mechanisms linking the diseases., Competing Interests: M.L.F. reports other support from Nuscan Diagnostics outside the scope of the submitted work. C.W. reports research funding support from Merck, is a member of the Immunogen advisory board (1/2022), and has been a member of the Genentech advisory board (8/2020). The remaining authors declare no competing interests., (© 2022 The Authors.)

Introduction: Despite improvement in progression-free survival with poly (ADP-ribose) polymerase inhibitors (PARPi) as maintenance therapy for ovarian cancer, many patients will eventually progress on therapy. Oligoprogression is uniquely suited to considerations of local consolidation therapy in this setting, but not commonly used in ovarian cancer. In this study we evaluated the proportion of patients on PARPi maintenance who developed limited sites of disease, the location of progression, and their natural history., Methods: From January 2006 to December 2020, natural language processing software (DEEP6AI) was used to identify 58 patients with ovarian cancer treated with PARPi maintenance after complete or partial response after surgery and platinum-based chemotherapy at our institution. Patients were assessed for presence and location of recurrence based on radiologic findings., Results: The median patient age was 65 (IQR 57-71) years. Patients had a median of two lines of chemotherapy prior to starting PARPi. With a median follow-up of 48 (range 12-149) months, 32 (55%) patients had a recurrence on maintenance olaparib and 11 (34%) patients developed oligoprogression (≤3 sites). For the 11 patients with oligoprogression, three patients developed recurrence in one site, five in two sites, and three in three sites. The sites of oligoprogression were pelvic/periaortic nodal (27%), peritoneal (27%), liver (27%), lung/mediastinal (14%), and brain (5%). The median progression-free survival for the entire cohort was 6.0 months (95% CI 4.2 to 7.8); median overall survival was not met. There were no significant differences in overall survival (p=0.81) or progression-free survival (p=0.95) between patients with and without oligoprogression., Conclusions: One-third of patients on PARPi maintenance experienced oligoprogression defined as limited to ≤3 sites. These patients may benefit from local consolidation therapy. A larger dataset is needed to validate these findings to assess if trials investigating local therapy for these patients is of value., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: BRCA 1 or 2 mutation carriers have increased risk of developing breast cancer (BC) and serous epithelial ovarian cancer (EOC). The incidence of BC over time after EOC is unknown. Optimal BC surveillance for BRCA mutation carriers following EOC has not been defined., Methods: A multi-institutional retrospective chart review was performed. Patients with BRCA -associated EOC diagnosed between 1996 and 2016 were followed for an average of 80 months. Women with previous bilateral mastectomy were excluded; women with prior BC and an intact breast were included. Descriptive statistics, Chi Square, and univariate survival analysis were performed., Results: 184 patients with BRCA -associated EOC were identified. Eighteen (10%) were diagnosed with BC a median of 48 months following EOC. Two (1%) with prior BC developed contralateral BC and 16 (9%) developed primary BC. The majority of BC (55%) was diagnosed 3 years following EOC. The 3-, 5- and 10-year incidence of BC was 5.6%, 9.5% and 33.3%. Annual mammography was performed in 43% and MRI in 34%. Twenty-eight (15%) women underwent risk-reducing mastectomy (RRM). There was no statistically significant difference in BC screening between women with, and without, a prior BC. BC was most commonly detected on mammogram. Three (17%) women had occult BC at the time of RRM. Nine (50%) had DCIS, and 8 (44%) had stage I/II BC. Median 5- and 10-year survival was 68% and 43% and was comparable between groups., Conclusions: Ten percent of women developed BC after EOC. The incidence of BC following EOC in BRCA carriers increases over time, and surveillance is recommended given their enhanced survival of EOC. Timely genetic testing for women with EOC is imperative to better triage BC screening resources and treatment., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: There is a paucity of data analyzing the anatomic locations and dose volume metrics achieved for surgically transposed ovaries in patients desiring fertility or hormonal preservation receiving pelvic radiation therapy (RT), which were examined herein., Methods and Materials: This is a retrospective study including women who underwent ovarian transposition before pelvic RT between 2010 to 2020. The craniocaudal (CC) distance of the ovary centroid to the (1) plane of the sacral promontory, (2) iliac crest, and (3) the nearest distance between the ovary edge and RT planning target volume (PTV) were measured (cm). The area under the receiver operating characteristic curve and cut-point analysis estimating ovary location outside the PTV was performed., Results: Thirty-one ovaries were analyzed from 18 patients. Thirteen (72.2%) were treated with intensity modulated RT, and 5 (27.8%) were treated with 3-dimensional conformal radiation therapy. Most ovaries were located above the sacral promontory (64.5%, n = 20), below the iliac crest (96.8%, n = 30), and outside the PTV (64.5%, n = 20). The median distance from the ovaries to the sacral promontory, iliac crest, and PTV was 0.8 cm (interquartile range [IQR], -0.83 to 1.59 cm), -3.22 cm (IQR, -5.12 to -1.84 cm), and 0.9 cm (IQR, -1.0 to 1.9 cm), respectively. The area under the receiver operating characteristic curve and cut-point analysis demonstrated that distance from the iliac crest predicted an ovary to be outside the PTV with an optimal cut-point of -3.0 cm (C-index = 0.82). The median mean and maximum (Dmax) ovary doses were 15.5 Gy (IQR, 9.6-20.2 Gy) and 32.2 Gy (IQR 24.8-46.5 Gy), respectively., Conclusions: Despite most transposed ovaries being located outside the PTV, nearly all remained below the iliac crest and received RT doses associated with a high risk of ovarian failure. These findings deepen our understanding of the spatial relationship between transposed ovaries and dose to inform surgical and pre-RT planning and suggest that more aggressive ovary-sparing strategies are warranted., (© 2021 The Authors.)

Objective: To evaluate the combination of pembrolizumab, cisplatin and gemcitabine in recurrent platinum-resistant ovarian cancer., Methods: Patients received six cycles of chemotherapy with gemcitabine and cisplatin on day 1 and day 8 of a 21-day treatment cycle. Pembrolizumab was administered on day 1 of cycles 3-6 and as maintenance monotherapy in cycles 7-34. Palliative radiation to a non-target symptomatic lesion was allowed. The primary objective was overall response rate by RECIST 1.1 criteria. Secondary objectives included safety, progression-free survival, time to progression, duration of response and overall survival., Results: An interim analysis for futility was performed at 18 evaluable patients. Overall response rate was 60%, duration of response was 4.9 months and time to progression was 5.2 months. Progression-free survival at 6 and 12 months was 43% and 5%. Median progression-free survival was 6.2 months and median overall survival was 11.3 months. In all patients, CA125 levels reflected response and progression. There were no pseudoprogression events. After receiving palliative radiation during pembrolizumab maintenance, a patient with recurrent ovarian clear cell carcinoma had an exceptional and durable response that is ongoing for greater than 2 years. After consultation with the sponsor, based on the modest duration of response observed at the interim analysis for futility, the decision was made to close the trial to further accrual., Conclusions: The addition of pembrolizumab to cisplatin and gemcitabine did not appear to provide benefit beyond chemotherapy alone in patients with recurrent platinum-resistant ovarian cancer., Competing Interests: This study was funded by the Merck Investigator Studies Program (MISP #52261) (CW). URL: http://engagezone.msd.com/oncology.php. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

The human fallopian tube harbors the cell of origin for the majority of high-grade serous "ovarian" cancers (HGSCs), but its cellular composition, particularly the epithelial component, is poorly characterized. We perform single-cell transcriptomic profiling of around 53,000 individual cells from 12 primary fallopian specimens to map their major cell types. We identify 10 epithelial subpopulations with diverse transcriptional programs. Based on transcriptional signatures, we reconstruct a trajectory whereby secretory cells differentiate into ciliated cells via a RUNX3 high intermediate. Computational deconvolution of advanced HGSCs identifies the "early secretory" population as a likely precursor state for the majority of HGSCs. Its signature comprises both epithelial and mesenchymal features and is enriched in mesenchymal-type HGSCs (p = 6.7 × 10 -27 ), a group known to have particularly poor prognoses. This cellular and molecular compendium of the human fallopian tube in cancer-free women is expected to advance our understanding of the earliest stages of fallopian epithelial neoplasia., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Niraparib is a poly(ADP-ribose) polymerase (PARP) inhibitor approved for use in heavily pretreated patients and as maintenance treatment in patients with newly-diagnosed or recurrent ovarian cancer following a response to platinum-based chemotherapy. We present long-term safety data for niraparib from the ENGOT-OV16/NOVA trial., Methods: This multicenter, double-blind, randomized, controlled phase III trial evaluated the efficacy and safety of niraparib for the treatment of recurrent ovarian cancer. Patients were randomly assigned 2:1 to receive either once-daily niraparib 300 mg or placebo. Two independent cohorts were enrolled based on germline BRCA mutation status. The primary endpoint was progression-free survival, reported previously. Long-term safety data were from the most recent data cutoff (September 2017)., Results: Overall, 367 patients received niraparib 300 mg once daily. Dose reductions due to TEAEs were highest in month 1 (34%) and declined every month thereafter. Incidence of any-grade and grade ≥ 3 hematologic and symptomatic TEAEs was also highest in month 1 and subsequently declined. Incidence of grade ≥ 3 thrombocytopenia decreased from 28% (month 1) to 9% and 5% (months 2 and 3, respectively), with protocol-directed dose interruptions and/or reductions. Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) were reported in 2 and 6 niraparib-treated patients, respectively, and in 1 placebo patient each. Treatment discontinuations due to TEAEs were <5% in each month and time interval measured., Conclusion: These data demonstrate the importance of appropriate dose reduction according to toxicity criteria and support the safe long-term use of niraparib for maintenance treatment in patients with recurrent ovarian cancer., Trial Registration: ClinicalTrials.gov identifier: NCT01847274., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

BRCA 1 or 2 mutations result in higher cancer risk for breast cancer (BC) and epithelial ovarian cancer (EOC) for carriers than exists in the general population. Optimal breast imaging surveillance in these patients has not been well defined. An Institutional Review Board-approved, multi-institutional retrospective chart review was performed. Patients diagnosed with BRCA-associated EOC between 1990-2015 were identified; demographic and clinical data were collected and analyzed. 192 BRCA mutation-positive patients with EOC were identified. 16/192 (8.3%) women were diagnosed with BC following EOC, at a median of 50 (range 5-327) months following EOC diagnosis and median age 59.5 (45-84) years. Breast cancer was most commonly detected on mammogram 7/16 (44%) or clinical exam 7/16 (44%). 2/16 (12.5%) had occult BC found during risk-reducing mastectomy. 14 (88%) had early-stage (0-2) disease. At mean follow-up of 8.1 years, 6 (37.5%) patients with BC following EOC had died due to EOC. The risk of BC diagnosis following EOC in BRCA mutation carriers is low; most of these BCs are early stage and diagnosed with mammography or physical exam. Overall, survival in BRCA mutation carriers is dominated by EOC-related mortality. Breast cancer surveillance in BRCA mutation carriers following EOC should prioritize nonsurgical strategies.

Objective: Gynecologic oncology includes increasing percentages of women. This study characterizes representation of faculty by gender and subspecialty in academic department leadership roles relevant to the specialty., Methods: The American Association of Medical Colleges accredited schools of medicine were identified. Observational data was obtained through institutional websites in 2019., Results: 144 accredited medical schools contained a department of obstetrics and gynecology with a chair; 101 a gynecologic oncology division with a director; 98 a clinical cancer center with a director. Women were overrepresented in academic faculty roles compared to the US workforce (66 vs 57%, p < 0.01) but underrepresented in all leadership roles (p < 0.01). Departments with women chairs were more likely to have >50% women faculty (90.2 vs 9.8%, p < 0.01); and have larger faculties (80.4 vs 19.6% >20 faculty, p = 0.02). The cancer center director gender did not correlate to departmental characteristics. A surgically focused chair was also associated with >50% women faculty (85.7 vs 68.3%, p = 0.03); faculty size >20 (85.7 vs 61.4%, p < 0.01); and a woman gynecologic oncology division director (57.6 vs 29.4%, p < 0.01; 68.4 vs 31.7%, p < 0.01) and gynecologic oncology fellowship (50 vs 30.4%, p < 0.01; 59.1 vs 32%, p < 0.01). Gynecologic oncology leadership within cancer centers was below expected when incidence and mortality to leadership ratios were examined (p < 0.01, p < 0.01)., Conclusion: Within academic medical schools, women remain under-represented in obstetrics and gynecology departmental and cancer center leadership. Potential benefits to gynecologic oncology divisions of inclusion women and surgically focused leadership were identified., Competing Interests: Declaration of competing interest None of the authors have financial conflicts to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: Listing more than one option for treatment, termed "option-listing" (OL) is one way to facilitate shared decision-making. We seek to evaluate how oncologists do option-listing in clinical encounters across disease contexts., Method: We coded and transcribed 90 video-recorded interactions between 5 oncologist participants and a convenience sample of 82 patients at 2 large clinics in the western U.S. We used conversation analytic (CA) methods to examine patterns of behavior when oncologists provided more than one treatment option to patients., Results: In early-stage disease, OL provides patients with options while at the same time constraining those options through expression of physician bias. This effect disappears when cancer is at an advanced stage. In this context, OL is presented without physician preference and demonstrates recission of medical authority., Conclusion: In early-stage contexts, OL functions as a way for physicians to array available options to patients while also communicating their expertise. In advanced-stage contexts, OL functions as a way to minimize treatment options and highlight dwindling possibilities., Practice Implications: OL is one way to implement shared decision-making, but it can also be used to facilitate a realization that treatment choices are diminishing and disease is progressing beyond a cure., (Copyright © 2019 Elsevier B.V. All rights reserved.)

PARP (poly(ADP-ribose) polymerase) inhibitors represent a novel class of anti-cancer therapy; they take advantage of synthetic lethality and induce cell death by exploiting a defect in DNA repair. This class of medication was initially evaluated in patients with BRCA-associated tumors, but efficacy was also demonstrated in other populations. Since 2014, four PARP inhibitors have been approved in various indications: olaparib, niraparib, and rucaparib in high-grade serous ovarian cancer, and olaparib and talazoparib in metastatic breast cancer. The exact indications and study populations vary slightly between the different approvals in both disease states but there is significant overlap. PARP inhibitors continue to be investigated in ongoing clinical trials. In line with other targeted therapies, benefit appears to be strongest in a distinct population of patients with BRCA mutations or other defects in homologous recombination repair. Combination therapies, which include anti-angiogenesis agents and immunotherapy, show promise as a strategy to broaden efficacy for unselected patients. Initial studies of PARP inhibitors in combination with chemotherapy were limited by toxicity, but further studies are underway. To date, head-to-head trials comparing various PARP inhibitors have not been conducted, so questions remain in terms of choosing a PARP inhibitor to administer when indications overlap, as well as how to sequence these medications. Here we review both completed and ongoing clinical trials involving PARP inhibitors and mechanisms of resistance to this class of drugs.

Objective: To examine the association between ovarian conservation and oncologic outcome in surgically-treated young women with early-stage, low-grade endometrial cancer., Methods: This multicenter retrospective study examined women aged <50 with stage I grade 1-2 endometrioid endometrial cancer who underwent primary surgery with hysterectomy from 2000 to 2014 (US cohort n = 1196, and Japan cohort n = 495). Recurrence patterns, survival, and the presence of a metachronous secondary malignancy were assessed based on ovarian conservation versus oophorectomy., Results: During the study period, the ovarian conservation rate significantly increased in the US cohort from 5.4% to 16.4% (P = 0.020) whereas the rate was unchanged in the Japan cohort (6.3-8.7%, P = 0.787). In the US cohort, ovarian conservation was not associated with disease-free survival (hazard ratio [HR] 0.829, 95% confidence interval [CI] 0.188-3.663, P = 0.805), overall survival (HR not estimated, P = 0.981), or metachronous secondary malignancy (HR 1.787, 95% CI 0.603-5.295, P = 0.295). In the Japan cohort, ovarian conservation was associated with decreased disease-free survival (HR 5.214, 95% CI 1.557-17.464, P = 0.007) and an increased risk of a metachronous secondary malignancy, particularly ovarian cancer (HR 7.119, 95% CI 1.349-37.554, P = 0.021), but was not associated with overall survival (HR not estimated, P = 0.987). Ovarian recurrence or metachronous secondary ovarian cancer occurred after a median time of 5.9 years, and all cases were salvaged., Conclusion: Our study suggests that adoption of ovarian conservation in young women with early-stage low-grade endometrial cancer varies by population. Ovarian conservation for young women with early-stage, low-grade endometrial cancer may be potentially associated with increased risks of ovarian recurrence or metachronous secondary ovarian cancer in certain populations; nevertheless, ovarian conservation did not negatively impact overall survival., (Copyright © 2019. Published by Elsevier Inc.)

Dicer1 functions as a tumor suppressor in mouse models. In humans, somatic mutations are associated with many cancers in adults, and patients with DICER1 syndrome with DICER1 germline mutations are susceptible to childhood cancers. Dicer is phosphorylated by the ERK-MAP kinase pathway and because this pathway is activated in human cancers, we asked whether phosphorylated Dicer1 contributed to tumor development. In human endometrioid cancers, we discovered that phosphorylated DICER1 is significantly associated with invasive disease. To test a direct involvement of Dicer1 phosphorylation in tumor development, we studied mice with phosphomimetic alterations at the two conserved serines phosphorylated by ERK and discovered that a phosphomimetic Dicer1 drives tumor development and dissemination in two independent murine cancer models ( KRas +/LA1 and p53 +/- ). Our findings demonstrate that phosphomimetic Dicer1 promotes tumor development and invasion. SIGNIFICANCE: This work highlights the relevance of Dicer1 phosphorylation in mammalian tumor development and dissemination., (©2019 American Association for Cancer Research.)

Background: Late-line treatment options for patients with ovarian cancer are few, with the proportion of patients achieving an overall response typically less than 10%, and median overall survival after third-line therapy of 5-9 months. In this study (QUADRA), we investigated the activity of niraparib monotherapy as the fourth or later line of therapy., Methods: QUADRA was a multicentre, open-label, single-arm, phase 2 study that evaluated the safety and activity of niraparib in adult patients (≥18 years) with relapsed, high-grade serous (grade 2 or 3) epithelial ovarian, fallopian tube, or primary peritoneal cancer who had been treated with three or more previous chemotherapy regimens. The study was done in the USA and Canada, and 56 sites screened patients (50 sites treated at least one patient). Patients received oral niraparib 300 mg once daily continuously, beginning on day 1 and every cycle (28 days) thereafter until disease progression. The primary objective was the proportion of patients achieving an investigator-assessed confirmed overall response in patients with homologous recombination deficiency (HRD)-positive tumours (including patients with BRCA and without BRCA mutations) sensitive to their last platinum-based therapy who had received three or four previous anticancer therapy regimens (primary efficacy population). Efficacy analyses were additionally done in all dosed patients with measurable disease at baseline., Findings: Between April 1, 2015 and Nov 1, 2017, we screened 729 patients for eligibility and enrolled 463 patients, who were initiated on niraparib therapy. At the time of database lock (April 11, 2018), enrolment had closed and the study was ongoing, with 21 patients still on treatment. Patients had received a median of four (IQR 3-5) previous lines of therapy, and the median follow-up for overall survival was 12·2 months (IQR 3·7-22·1). 151 (33%) of 463 patients were resistant and 161 (35%) of 463 patients were refractory to the last administered platinum therapy. 13 (28%) of 47 patients in the primary efficacy population achieved an overall response according to RECIST (95% CI 15·6-42·6; one-sided p=0·00053). The most common drug-related grade 3 or worse treatment-emergent adverse events were anaemia (113 [24%] of 463 patients) and thrombocytopenia (95 [21%] of 463 patients). The most common treatment-emergent serious adverse events were small intestinal obstruction (34 [7%] of 463 patients), thrombocytopenia (34 [7%] of 463 patients), and vomiting (27 [6%] of 463 patients). One death due to gastric haemorrhage was considered treatment related., Interpretation: We observed clinically relevant activity of niraparib among women with heavily pretreated ovarian cancer, especially in patients with HRD-positive platinum-sensitive disease, which includes not only patients with a BRCA mutation but also a population with BRCA wild-type disease. We identified no new safety signals. Our data support expansion of the treatment indication for poly(ADP-ribose) polymerase inhibitors to include patients with HRD-positive ovarian cancer beyond those with BRCA mutations., Funding: Tesaro., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Olaparib is a poly(ADP-ribose) polymerase inhibitor and cediranib is an oral anti-angiogenic. In the primary analysis of this phase II study, combination cediranib/olaparib improved progression-free survival (PFS) compared with olaparib alone in relapsed platinum-sensitive ovarian cancer. This updated analysis was conducted to characterize overall survival (OS) and update PFS outcomes., Patients and Methods: Ninety patients were enrolled to this randomized, open-label, phase II study between October 2011 and June 2013 across nine United States-based academic centers. Data cut-off was 21 December 2016, with a median follow-up of 46 months. Participants had relapsed platinum-sensitive ovarian cancer of high-grade serous or endometrioid histology or had a deleterious germline BRCA1/2 mutation (gBRCAm). Participants were randomized to receive olaparib capsules 400 mg twice daily or cediranib 30 mg daily and olaparib capsules 200 mg twice daily until disease progression., Results: In this updated analysis, median PFS remained significantly longer with cediranib/olaparib compared with olaparib alone (16.5 versus 8.2 months, hazard ratio 0.50; P = 0.007). Subset analyses within stratum defined by BRCA status demonstrated statistically significant improvement in PFS (23.7 versus 5.7 months, P = 0.002) and OS (37.8 versus 23.0 months, P = 0.047) in gBRCA wild-type/unknown patients, although OS was not statistically different in the overall study population (44.2 versus 33.3 months, hazard ratio 0.64; P = 0.11). PFS and OS appeared similar between the two arms in gBRCAm patients. The most common CTCAE grade 3/4 adverse events with cediranib/olaparib remained fatigue, diarrhea, and hypertension., Conclusions: Combination cediranib/olaparib significantly extends PFS compared with olaparib alone in relapsed platinum-sensitive ovarian cancer. Subset analyses suggest this margin of benefit is driven by PFS prolongation in patients without gBRCAm. OS was also significantly increased by the cediranib/olaparib combination in this subset of patients. Additional studies of this combination are ongoing and should incorporate analyses based upon BRCA status., Trial Registration: Clinicaltrials.gov Identifier NCT0111648., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

An objective evaluation of patient performance status (PS) is difficult because patients spend the majority of their time outside of the clinic, self-report to providers, and undergo dynamic changes throughout their treatment experience. Real-time, objective activity data may allow for a more accurate assessment of PS and physical function, while reducing the subjectivity and bias associated with current assessments. Consenting patients with advanced cancer wore a wearble activity monitor for three consecutive visits in a prospective, single-cohort clinical trial. Provider-assessed PS (ECOG/Karnofsky) and NIH PROMIS® patient-reported outcomes (PROs) were assessed at each visit. Associations between wearable activity monitor metrics (steps, distance, stairs) and PS, clinical outcomes (adverse events, hospitalizations, survival), and PROs were assessed using correlation statistics and in multivariable logistic regression models. Thirty-seven patients were evaluated (54% male, median 62 years). Patients averaged 3700 steps, 1.7 miles, and 3 flights of stairs per day. Highest correlations were observed between average daily steps and ECOG-PS and KPS ( r   =  0.63 and r   =  0.69, respectively p  < 0.01). Each 1000 steps/day increase was associated with reduced odds for adverse events (OR: 0.34, 95% CI 0.13, 0.94), hospitalizations (OR: 0.21 95% CI 0.56, 0.79), and hazard for death (HR: 0.48 95% CI 0.28-0.83). Significant correlations were also observed between activity metrics and PROs. Our trial demonstrates the feasibility of using wearable activity monitors to assess PS in advanced cancer patients and suggests their potential use to predict clinical and patient-reported outcomes. These findings should be validated in larger, randomized trials., Competing Interests: Competing interestsThe authors declare no competing interests.

This retrospective observational study examined trends, characteristics, and survival of women with synchronous endometrial and ovarian cancer (SEOC) in the Surveillance, Epidemiology, and End Results Program between 1973 and 2013. Among 235,454 women with primary endometrial cancer, synchronous ovarian cancer was seen in 4,082 (1.7%) women with the proportion being decreased from 2.0% to 1.6% between 1983 and 2013 ( P =0.049); and the proportion of concurrent endometrioid tumors in the two cancer sites has increased from 24.2% to 49.9% among SEOC women ( P <0.001). When compared to endometrial cancer without synchronous ovarian cancer, endometrioid histology in the two cancer sites was associated with improved cause-specific survival while non-endometrioid histology in the ovarian cancer was associated with decreased cause-specific survival (adjusted- P <0.01). Among 110,063 women with primary epithelial ovarian cancer, synchronous endometrial cancer was seen in 3,940 (3.6%) women with the proportion being increased from 2.2% to 4.4% between 1973 and 2013 ( P <0.001); and the proportion of concurrent endometrioid tumors in the two cancer sites had increased from 24.3% to 50.2% among SEOC women ( P <0.001). When compared to primary epithelial ovarian cancer without synchronous endometrial cancer, SEOC was associated with better cause-specific survival if ovarian cancer is endometrioid type or if endometrial cancer is endometrioid type (adjusted- P <0.001). Across the two cohorts, the proportion of SEOC reached to the peak in the late-40 years of age and then decreased significantly ( P <0.001). In conclusion, our study suggests that synchronous ovarian cancer has decreased among endometrial cancer whereas synchronous endometrial cancer has increased among epithelial ovarian cancer., Competing Interests: CONFLICTS OF INTEREST Dr. Wright has served as a consultant for Clovis Oncology and Tesaro. Dr. Rimel has served as a consultant for Tesaro, AstraZeneca, and Genentech. The other authors have nothing to disclose.