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Asian American and Pacific Islanders (AAPI) are the fastest growing racial group in the United States. Data on AAPI communities, however, are significantly limited. The oversimplification and underreporting of this ethnically and socioeconomically heterogenous population through the use of aggregated data has deleterious effects and worsens disparities in patient treatment, outcomes, and experiences. Gynecologic oncology disparities do not exist in a vacuum, and are rooted in larger cultural gaps in our understanding and delivery of healthcare. In this paper, we aim to demonstrate how AAPI data inequities have negative downstream effects on research and public health policies and initiatives, and also provide a call to action with specific recommendations on how to improve AAPI data equity within these realms. • Asian American Pacific Islander (AAPI) data inequities stem from over-aggregation and limited granular data collection. • Lack of disaggregated data masks health disparities leading to ineffective policies and resource allocation. • Improved data collection and community-oriented initiatives are crucial for health equity. [ABSTRACT FROM AUTHOR]

Ovarian cancer (OC) is a global health problem, and the mortality-to-incidence ratio is expected to increase, especially in low- and middle-income countries. These regions face disparities in access to OC care, including lack of awareness, limited access to genetic and tumor testing, paucity of surgical expertise, time to approval of novel therapeutics, and treatment costs. By addressing these inequities, the core aim of this paper is to promote action through collaboration in order to overcome these barriers and promote health equity in OC management and treatment. • Rising mortality to incidence ratio in ovarian cancer is expected, related to limited access in low and middle income areas. • Data reflecting population heterogeneity, genetic testing, drug access, and clinical trial diversity need to be prioritized. • Unite international team of health care providers in order to promote global equity in ovarian cancer care. [ABSTRACT FROM AUTHOR]

Over recent years, there has been significant progress in the development of immunotherapeutic molecules designed to block the PD-1/PD-L1 axis. These molecules have demonstrated their ability to enhance the immune response by prompting T cells to identify and suppress neoplastic cells. PD-L1 is a type 1 transmembrane protein ligand expressed on T lymphocytes, B lymphocytes, and antigen-presenting cells and is considered a key inhibitory checkpoint involved in cancer immune regulation. PD-L1 immunohistochemical expression in gynecological malignancies is extremely variable based on tumor stage and molecular subtypes. As a result, a class of monoclonal antibodies targeting the PD-1 receptor and PD-L1, known as immune checkpoint inhibitors, has found successful application in clinical settings. In clinical practice, the standard method for identifying suitable candidates for immune checkpoint inhibitor therapy involves immunohistochemical assessment of PD-L1 expression in neoplastic tissues. The most commonly used PD-L1 assays in clinical trials are SP142, 28–8, 22C3, and SP263, each of which has been rigorously validated on specific platforms. Gynecologic cancers encompass a wide spectrum of malignancies originating from the ovaries, uterus, cervix, and vulva. These neoplasms have shown variable response to immunotherapy which appears to be influenced by genetic and protein expression profiles, including factors such as mismatch repair status, tumor mutational burden, and checkpoint ligand expression. In the present paper, an extensive review of PD-L1 expression in various gynecologic cancer types is discussed, providing a guide for their pathological assessment and reporting. • Immune checkpoint inhibitors targeting PD-1 and PD-L1 found successful applications in clinical settings. • Immunohistochemistry for PD-L1 represents the standard method to select patients for immunotherapy. • PD-L1 expression in gynecologic malignancies is extremely variable, based on tumor stage and molecular subtypes. • Gynecologic cancers have shown variable response to immunotherapy. • PD-L1 expression in different gynecologic malignancies is discussed, with a guide for assessment and reporting. [ABSTRACT FROM AUTHOR]

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/policies/article-withdrawal). This article has been retracted at the request of the Authors. The authors have independently identified an error in the formula that was utilized to calculate the Quality Adjusted Life Years which invalidates the data and the conclusion of the paper. The authors have contacted the journal requesting to retract the article. Apologies are offered to the readers of the journal for any confusion or inconvenience that may have resulted from the publication of this article. [ABSTRACT FROM AUTHOR]

Letters of recommendation (LOR) play a significant role in applicant selection for gynecologic oncology (GO) fellowship. LORs can be agentic, associated with competence, independence and strength, or communal, associated with being accommodating, cooperative and empathetic. Agentic LORs have been shown to reflect favorably on applicants, making them more likely to be selected for interview. The primary goal of this study was to determine linguistic differences in LORs for applicants applying to GO fellowship based on applicant gender and race. All applications to a single academic institution from the years 2018–2020 were analyzed. LORs were extracted from all applicants who self-reported their gender and race/ethnicity. Analysis was performed using Linguistic Inquiry Word Count (LIWC) in terms of agentic and communal language. All analysis was done using SAS version 9.4. From 2018 to 2020, there were 239 GO fellowship applications to a single academic institution. There were 186 (78.1%) applicants who identified as female and 52 (21.8%) who identified as male. Female applicants were more likely to have more research (p = 0.047) and volunteer activities (p = 0.02) than male applicants. There were no differences between female and male applicants in terms of age, geographic location of residency, USMLE scores, AOA status, number of publications or attending a Doximitiy-rated top 20 residency program. There were 139 (60.7%) applicants who identified as White, 46 (20.1%) as Asian, 16 (7.0%) as Black, 19 (8.3%) as Latinx and 9 (3.9%) as other. On multivariable analysis, LORs written for male applicants had higher agentic scores compared to females (p < 0.05), and LORs of female applicants received higher communal scores (p < 0.05). LORs for applicants who identified as Black or Latinx were found to have lower agentic scores compared to individuals who identified as White(p < 0.05 for both). There were demonstrated linguistic differences in LOR for GO fellowship based on applicant gender and race/ethnicity. LORs written for white, male applicants were more likely to have higher agentic scores compared to minority, female applicants. LORs written for female applicants were more likely to have higher communal scores. As LORs have been shown to be instrumental in GO fellowship interview selection and linguistic differences exist based on applicant gender and race/ethnicity, this study highlights the need for a more objective GO fellowship application process. Portion of this paper was presented at the Society for Gynecologic Oncology as part of a focus plenary. • There were linguistic differences between GO fellowship applicants based on applicant demographics • LORs written for male applicants to GO fellowship had higher agentic scores and lower communal scores • LORs for applicants who identified as Black or Latinx were found to have lower agentic scores [ABSTRACT FROM AUTHOR]

The goal of this practice statement is to help members and their multidisciplinary teams recognize infusion reactions and hypersensitivity reactions in the clinical setting. It will provide recommendations to help guide response to reactions and desensitization when appropriate, to promote safe use of chemotherapeutic agents among all providers in the delivery process. A multi-disciplinary team of healthcare professionals from the Society of Gynecologic Oncology Education Committee collaborated to review peer reviewed literature and guidelines to develop a practice statement on the management of chemotherapy hypersensitivity reactions and desensitization regimens. There is always potential for a patient to have a reaction to any medication, with both infusion reactions and hypersensitivity reactions potentially occurring in the treatment of gynecologic cancers. Premedication to prevent reactions should be given at least prior to infusion for regimens that include the most common agents associated with reactions. At the time when reaction is occurring it might be difficult to distinguish between an infusion reaction versus true hypersensitivity given the similarities in signs and symptoms, therefore it is important that orders to manage reactions be included in every chemotherapy order set so the infusion nurse can provide immediate interventions while waiting for the provider to arrive to assess the patient. Desensitization is a potential option to allow the patient to continue to receive the offending agent. While a variety of desensitization regimens have been presented in the literature, the goal is to minimize steps and variability to decrease opportunity for errors during chemotherapy preparation or administration. Incorporating a review of the literature and clinical experience from the SGO Education Committee, this paper provides an overview of current approaches for prevention and management of reactions to commonly used chemotherapy agents for gynecologic cancers. • Hypersensitivity and infusion reactions to antineoplastic therapies challenge the treatment of cancer patients. • Reactions require a multi-disciplinary team to decide on a protocol best suited to their patients within their institution. • Every effort should be made to streamline the process and protocols to reduce error during mixing and administration. • An overview is provided of approaches for prevention and management of reactions to agents used for gynecologic cancers. [ABSTRACT FROM AUTHOR]

Objectives: In a previously published study, we used a paper-based assessment to screen for and address social needs, the downstream actionable modifiers of the social determinants of health that contribute to racial/ethnic and socioeconomic disparities in gynecologic cancer care. Here, we examine completion rates and acceptability of social needs screening after integrating into the electronic medical record (EMR) and routine clinic workflow. Methods: We initiated paper-based social needs screening at our urban, academic gynecologic oncology clinic in 2017. In 2021, we integrated these validated assessments and referral orders into the EMR as part of routine clinic workflow (Figure 1). From July to September 2021, the screening was distributed via an online patient portal prior to the visit, or if not completed, verbally administered and entered into the EMR by clinic staff at the visit. We compared the current screening completion rate to our historical paper-based screening. To assess patient acceptance, we used multivariate Poisson regression to identify factors associated with patients desiring referral to community-based resources and opting out of future screenings. Results: Of 405 eligible patients, 92% (n =373) completed the assessment, significantly increased from the 54% historical completion rate (p<0.001). Of those who completed screening, the median age was 60 years (range: 49-69), 58% were non-Hispanic White (NHW), and 29% were non-Hispanic Black. Half (51%) had private insurance. A total of 20% (n =74) of those screened had at least one social need (range: 0-7). The most common needs were financial (14%), transportation (5%), and needing help reading hospital materials (5%). Among those with needs (n =74), 57% desired a referral for resources. Ninety percent of automatically-generated referral orders were signed. On univariate analysis, having food (n =10), housing (n =12), utility (n =5), transportation (n =19), and household items (n =19) needs was associated with an over 50% higher likelihood of desiring referral compared to patients without those needs (p<0.05). Controlling for marital status and screening modality, only Hispanic/other race compared to NHW (RR: 2.1, 95% CI: 0.8-6.2) and having two or more needs compared to one (RR: 1.5, 95% CI: 1.03-2.2) were associated with desiring referral. Of the 299 individuals without needs, 64% (n =192) opted out of future screenings. Only modality (in-person compared to online) was independently associated with opting out (RR: 1.3, 95% CI: 1.03-1.7). Insurance type was neither associated with desiring referral nor opting out. Conclusions: EMR-integration of social needs assessments and resource referral improves screening completion and reaches nearly all patients. We are conducting ongoing work to identify the optimal approach to integrate social needs screening and implement interventions to address social needs that maximize reach and acceptability in a diverse gynecologic oncology population. [Display omitted] [ABSTRACT FROM AUTHOR]

Immuno-oncology (IO) has rapidly evolved, with many IO therapies either approved or under investigation for multiple malignancies. Biomarkers exist that can predict response to IO therapies including PD-L1 expression, microsatellite instability (MSI), and total mutation burden (TMB). This paper serves to analyze the presence of these biomarkers across gynecologic cancers. A total of 16,300 gynecologic cancer specimens submitted for molecular profiling to Caris Life Sciences were reviewed. Immunohistochemistry was performed using the SP142 anti-PD-L1 clone and assessed for intensity. Next-generation sequencing, immunohistochemistry, and fragment analysis were used to determine MSI status. TMB was measured by counting all non-synonymous missense mutations found per tumor not previously described as germline alterations. Chi-Square, Fisher Exact, and the Kruskal-Wallis test were used to compare cohorts. Of 16,300 specimens, 54.1% were ovarian, 37.2% uterine, 7.2% cervical, 0.3% vulvar, 1.2% vaginal, with 0.1% unspecified. MSI-H was most frequent in uterine cancer (17.7%) and only 1% of ovarian cancers. PD-L1 expression was present in 38.3% of cervical and 62.5% of vulvar cancers, but less than 8% of ovarian and uterine cancers. TMB-H was present in 21.1% cervical, 19.7% uterine, and 5% ovarian cancers. Few specimens exhibited a "triple positive" phenotype - 0.3% ovarian, 1.5% uterine, and 1.5% cervical. Associations were seen between MSI, TMB, and PD-L1 across all cancer types. The frequency of individual biomarkers pertinent to IO therapy varies by cancer type. HPV-driven genital tract cancers have higher frequencies of PD-L1 expression, MSI-H, and TMB H. Endometrial cancers are characterized by MSI-H and TMB, whereas ovarian cancers have a low frequency of MSI-H and modest PD-L1 or TMB H. The incidence of 'triple positive" cases was less than 2%. • This study analyzes PD-L1, MSI, and TMB in 16,300 gynecologic cancer specimens. • Gynecologic cancers have markedly variable response to immunotherapy. • Gynecologic cancers with one immune biomarker are more likely to be positive for others. [ABSTRACT FROM AUTHOR]

Objectives: To compare long-term oncologic outcomes of robotic- assisted (ROBOT) with laparoscopic (LAP) or laparotomic (OPEN) radical hysterectomy based on comparative studies in the published literature. Methods: A systematic literature review and meta-analysis for timedependent oncologic outcomes were conducted in accordance with the PRISMA statement, the Cochrane guidelines and registered with PROSPERO. PubMed, Scopus, and Embase databases were searched. Studies included those comparing robotic to non-robotic hysterectomy with 20 or more cases for each comparator from January 1, 2010, to September 1, 2020. Additionally, studies needed to report on hysterectomy for cancer, distinguish robotic from non-robotic cases, with a minimum follow-up of 12 months or more, and report at least one outcome of interest; disease-free/recurrence-free (DFS) or overall survival (OS). A hierarchical decision tree was developed to calculate and combine hazard ratios (HR) based on information available in each paper, maximizing the number of studies for consideration. Comparisons of long-term oncologic results for ROBOT versus OPEN were reported. Results: There were 6,477 unique references identified from initial search, from which 27 studies were included based on an adjusted analysis of HRs with heterogeneity tests. The weighted HR for DFS for ROBOT (n =670) versus LAP (n =1057) was 1.12 (95% CI:0.87-1.44; p=0.39; I2=0%), and ROBOT (n =3320) versus OPEN (n =11,991) was 1.13 (95% CI:0.89-1.44; p=0.31; I2=47%). The weighted HR for OS for ROBOT (n =746) versus LAP (n =1082) was 1.01 (95% CI: 0.56-1.80; p=098; I2=46%) and ROBOT (n =3945) versus OPEN (n =13,050) was 1.18 (95% CI: 0.99-1.41; p=0.06; I2=32%). Conclusions: Compared to OPEN and LAP radical hysterectomy, the studies show that ROBOT radical hysterectomy does not result in worse oncologic outcomes with respect to DFS and OS. The noted outcomes with ROBOT need further validation and investigation. [ABSTRACT FROM AUTHOR]

Objectives: To calculate the change in the rate of adoption of sentinel lymph node dissection (SLND) in endometrial cancer (EC) related to findings from the FIRES trial. Methods: We queried the SEER dataset for all patients (pts) with EC diagnosed from 2003-2018 who had a complete hysterectomy (hyst). We excluded pts who had a supra-cervical hyst, whose tumors could not be classified as type I or type II by Bokhman criteria, or whose method of lymph node dissection (LND) was unknown. Pts who had SLND alone, and those who had SLND prior to non-sentinel LND, were classified as having had SLND. We performed joinpoint (JP) regression analyses to assess change in rates. JP regression is a statistical method to test for changes in time series data associated with events of interest. An interim analysis of the FIRES trial was presented at the SGO Annual Meeting on Women's Cancer in March 2014; the paper was published online in January 2017. We hypothesized that a JP, indicating a rise in the rate of adoption of SLND, would be identified in proximity to those dates. Results were considered significant at a p-value of < 0.05. Results: The study cohort consisted of 127,198 pts; 70% had type I EC, 30% had type II EC. Figure 1 shows the frequency of SLND by month (mo). Although SLND among EC pts had been increasing for years (at 0.1%/mo), we found a 6-fold acceleration in the rate, to 0.6%/mo, beginning in September 2016. Analyses to assess factors contributing to this change showed that at approximately the same time (late 2016), the rise in the proportion of LND done as SLND increased to a rate of 0.8%/mo and the rise in frequency of any LND among EC pts, which had previously been decreasing at 0.05%/mo, increased to a rate of 0.3%/mo. Findings in patients with type I tumors were similar to those in the entire study population. The rise in frequency of SLND among all type I pts increased to 0.7%/mo, rise in the proportion of LND done as SLND increased to 0.9%/mo, and the rise in frequency of any LND increased to 0.4%/mo. In type II pts, the rise in frequency of SLND increased to 0.5%/mo, and the rise in the proportion of LND done as SLND increased to 0.6%/mo. The frequency of any LND in type II EC did not change. Each reported increased rate was significantly different from the rate during the 4-5 years immediately preceding late 2016. Component analysis, using 2018 frequencies of SLND and LND and above rates of change, showed that 50% of the increase in SLND was attributable to more frequent SLND in pts with type I EC. [Display omitted] Conclusions: The rate of adoption of SLND in EC accelerated in association with awareness of the FIRES trial results. The acceleration was driven, in equal parts, by a shift from non-sentinel to sentinel node dissections in both high and low-risk populations and by more frequent SLND in low-risk patients. It is possible that the SLND technique, since it calls for lymph node evaluation before intra-operative assessment of the uterus can be made, may be a contributing factor, as could per-protocol LND after failed mapping. [ABSTRACT FROM AUTHOR]

Objectives: To examine the perception and beliefs of the human papillomavirus (HPV) vaccine amongst those with and without a history of cervical dysplasia and to examine perceptions of the HPV vaccine for their children. Methods: Patients in a large urban academic hospital visiting two gynecology clinics were recruited to complete a paper survey assessing opinions and knowledge about the HPV vaccine for both themselves and their children. Patients in colposcopy clinic who had a history of abnormal Pap smears and patients in a benign gynecology clinic without a history of abnormal pap smears were offered the survey and consented. Eligible participants were those over the age of 21, English-speaking, non-pregnant and non-incarcerated. Participants' medical records were reviewed to document HPV vaccine status, pap smear, and biopsy results. Demographics and survey answers were described, and Fisher's exact test was used to compare the two populations. This study is IRB-approved. Results: A total of 157 patients participated: 59 patients in colposcopy clinic and 98 patients from benign gynecology clinic. The mean age of participants across both clinics was 36.5 years. The majority of patients self-identified as Black (74.6% colposcopy, 68.4% benign), and a sizeable minority made less than $20,000 a year (47.5% colposcopy, 26.5% benign). Overall, differences in opinions and knowledge about the HPV vaccine for themselves or their children were not statistically significant between the two clinic populations. The majority of respondents in both clinics reported either not having received or being unsure of HPV vaccine receipt (81.4% colposcopy, 71.4% benign, p = 0.126). In benign clinic, more patients agreed the HPV vaccine was a good way to protect oneself from disease (37.3% colposcopy, 46.9% benign, p = 0.083), stating they generally follow their doctor's recommendation regarding vaccination (39.0% colposcopy, 45.9% benign, p = 0.97). However, most respondents in both clinics were not sure about the effectiveness of the HPV vaccine, if it carries more risk compared to other vaccines, or if the information they received about the vaccine is reliable. Nearly three-fourths of colposcopy and benign clinic respondents were parents, and the majority have or planned to vaccinate their children against HPV (60.6% colposcopy, 56.1% benign, p = 0.83). Most parents in both clinics felt the HPV vaccine was important for their child's health (35.7% colposcopy, 49.2% benign, p = 0.42), and follow their doctor's recommendations about vaccination (33.4% colposcopy, 44.9% benign, p = 0.16). A large proportion of subjects in both clinics were likely to vaccinate their children against HPV, and this increases when a doctor recommends the vaccine (45% and 52% in colposcopy, respectively; 52% and 60.9% in benign, respectively). However, the majority were unsure/had no opinion on if the HPV vaccine was effective at preventing disease in their children or if the HPV vaccine is a good way to protect their children. Conclusions: Our survey examined opinions and attitudes on the HPV vaccine in a majority Black, low-income clinic. There was no statistically significant difference in opinions between those who had a history of cervical dysplasia and those who had normal pap smear history, suggesting that those who have experienced the effects of HPV are no more likely to feel strongly in favor of the vaccine for themselves or their children. Our results indicate that patients, regardless of pap smear history, would benefit from more education on the HPV vaccine. [ABSTRACT FROM AUTHOR]

Objectives: To compare long-term oncologic outcomes of robotic- assisted (ROBOT) procedures with laparoscopy (LAP) and laparo- tomic (OPEN) hysterectomy based on comparative studies in the published literature. Methods: A systematic literature review and meta-analysis for timedependent oncologic outcomes were conducted in accordance with the PRISMA statement, the Cochrane guidelines and registered with PROSPERO. PubMed, Scopus, and Embase databases were searched. Studies included those comparing robotic to non-robotic hysterectomy with 20 or more cases for each comparator from January 1, 2010, to September 1, 2020. Additionally, studies needed to report on hysterectomy for cancer, distinguish robotic from non-robotic cases, with a minimum follow-up of 12 months or more, and report at least one outcome of interest; disease-free/recurrence-free (DFS) or overall survival (OS). A hierarchical decision tree was developed to calculate and combine hazard ratios (HR) based on information available in each paper, maximizing the number of studies for consideration. Comparisons of long-term oncologic results for ROBOT versus OPEN and LAP were reported. Results: There were 6,477 unique references identified from initial search from which 19 studies were included based on an adjusted analysis of HRs with heterogeneity tests. The weighted HR for DFS for ROBOT (n =1152) versus LAP (n =1029) was 0.94 (95% CI: 0.71-1.26; p=0.68; I2=0%), and ROBOT (n =887) versus OPEN (n =1035) was 0.84 (95% CI: 0.64-1.11; p=0.22; I2=0%). The weighted HR for OS for ROBOT (n =4675) versus LAP (n =2643) was 0.98 (95% CI: 0.82-1.16; p=0.78; I2=0%) and ROBOT (n =27,647) versus OPEN (n =23,923) was 0.77 (95% CI: 0.71-0.83; p<0.0001; I2=18%). Conclusions: When compared with OPEN and LAP hysterectomy, ROBOT hysterectomy does not result in worse oncologic outcomes with respect to DFS and shows improved OS results compared to OPEN. The noted improved outcomes with ROBOT need further validation and investigation. [ABSTRACT FROM AUTHOR]

Background: Ovarian clear cell carcinoma (OCCC) is a unique subtype of epithelial ovarian cancer. Advanced OCCC display a poor prognosis. Therefore, we aimed to make risk stratification for precise medicine., Methods: We performed a large next generation sequencing (NGS) gene panel on 44 patients with OCCC in FIGO stage II-IV. Then, by machine learning algorithms, including extreme gradient boosting (XGBoost), random survival forest (RSF), and Cox regression, we screened for feature genes associated with prognosis and constructed a 5-gene panel for risk stratification. The prediction efficacy of the 5-gene panel was compared with FIGO stage and residual disease by receiver operating characteristic curve and decision curve analysis., Results: The feature mutated genes related to prognosis, selected by machine learning algorithms, include MUC16, ATM, NOTCH3, KMT2A, and CTNNA1. The 5-gene panel can effectively distinguish the prognosis, as well as platinum response, of advanced OCCC in both internal and external cohorts, with the predictive capability superior to FIGO stage and residual disease., Conclusions: Mutations in genes, including MUC16, ATM, NOTCH3, KMT2A, and CTNNA1, were associated with the poor prognosis of advanced OCCC. The risk stratification according to these genes demonstrated acceptable prediction power of prognosis and platinum response, suggesting the potential to be a novel target for precision medicine., 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., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To assess the associations between active CMV infection and patient-reported symptoms of cancer-related cognitive impairment (CRCI) and peripheral neuropathy in ovarian cancer survivors., Methods: We conducted a cross-sectional study among individuals with a diagnosis of ovarian cancer, primary peritoneal cancer, or fallopian tube cancer from academic and community cancer clinics at any time point after completion of front-line chemotherapy. Participants completed a one-time survey and provided a blood sample. Plasma virus DNA levels were measured using digital PCR, with ≥100 copies/mL of plasma considered active infection (CMV+, EBV+ as a control). We measured symptoms of CRCI and peripheral neuropathy using the Patient-Reported Outcomes Measurement Information System (PROMIS) Cognitive Function short form 8a and Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity (FACT/GOG-NTX) subscale measurements, respectively. Symptoms were compared by active CMV infection status in the full group and among the subgroup receiving active treatment using t-tests and linear regression models., Results: 152 participants were included. A total of 59 (38.8 %) participants were CMV+. After adjustment for potential confounding variables, individuals who were CMV+ self-reported significantly more symptoms of peripheral neuropathy that those who were CMV- (p = 0.04). In the subgroup of participants currently receiving chemotherapy, individuals who were CMV+ had significantly lower perceived cognitive functioning compared to individuals who were CMV- (p = 0.03); this was not observed in the full cohort. No associations were observed between outcomes and EBV infection., Conclusions: Active CMV infection is common in this survivor population and may be associated with more symptoms of CRCI and neuropathy., 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., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To examine the impact of the COVID-19 pandemic on cervical cancer screening rates of Hispanic individuals compared to non-Hispanic White (NHW) individuals in the United States, whether a responsive surge in catch-up screenings occurred as society adapted to pandemic changes, and to investigate the sociodemographic characteristics between the study populations., Methods: Using cross-sectional data from the All of Us Research Program, which incorporates electronic health record data and survey data from a demographically, geographically, and medically diverse participant group, we assessed the annual cervical cancer screening rates during 2019-2021 by race/ethnicity among eligible individuals ages 21-64., Results: Among 116,052 unique individuals (78,829 NHW and 37,223 Hispanic), Hispanic individuals had lower annual cervical cancer screening rates than NHWI across the three years studied. They experienced a more significant decrease in screening from 2019 to 2020 (39.27 %) compared to NHWIs (21.15 %) and less of a rebound increase in the following year, 2021 (10.33 % vs 13.83 %). Hispanic individuals aged 50-64 experienced the sharpest decline in screening rates (-43.01 % from 2019 to 2020). Hispanic individuals also experienced greater adverse social conditions, including lack of insurance or employment, lower educational attainment, and lower household income., Conclusions: Hispanic individuals experienced a more significant decrease in cervical cancer screening rates with the onset of the COVID-19 pandemic compared with NHW individuals and did not experience a robust rebound in cervical cancer screening rates in 2021. As a result, the disparity in cervical cancer screening rates between NHW and Hispanic individuals considerably worsened with the COVID-19 pandemic., 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., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: This study compares baseline clinical characteristics, physical function testing, and patient-reported outcomes for patients undergoing primary cytoreductive surgery versus neoadjuvant chemotherapy, with the goal of better understanding unique patient needs at diagnosis., Methods: Patients with suspected advanced stage (IIIC/IV) epithelial ovarian cancer undergoing either primary cytoreductive surgery or neoadjuvant chemotherapy were enrolled in a single-institution, non-randomized prospective behavioral intervention trial of prehabilitation. Baseline clinical characteristics were abstracted. Physical function was evaluated using the Short Physical Performance Battery, Fried Frailty Index, gait speed, and grip strength. Patient-reported outcomes were evaluated using Patient-Reported Outcomes Measurement Information System metrics and the Perceived Stress Scale., Results: There were no significant differences in demographics or clinical characteristics between cohorts at enrollment, with the exception of performance status, clinical stage, and albumin. While gait speed and grip strength were lower amongst neoadjuvant chemotherapy patients, there were no significant differences in physical function using the Short Physical Performance Battery and Fried Frailty Index. Patients in the neoadjuvant chemotherapy cohort reported decreased perception of physical function and increased fatigue on Patient-Reported Outcomes Measurement Information System metrics. A larger proportion of patients in the neoadjuvant cohort reported severe levels of emotional distress and anxiety, as well as greater perceived stress at diagnosis., Conclusions: Our findings suggest that patients undergoing neoadjuvant chemotherapy for advanced ovarian cancer present with increased psychosocial distress and decreased perception of physical function at diagnosis and may benefit most from early introduction of supportive care., 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., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Ovarian cancer, a leading cause of cancer-related deaths in women, remains a formidable challenge, especially in the context of platinum-resistant disease. This study investigated the potential of the benzimidazole derivative BNZ-111 as a novel treatment strategy for platinum-resistant ovarian cancer., Methods: The human EOC cell lines A2780, HeyA8, SKOV3ip1, A2780-CP20, HeyA8-MDR, and SKOV3-TR were treated with BNZ-111, and cell proliferation, apoptosis, and cell cycle were assessed., Results: It demonstrated strong cytotoxicity in both chemo-sensitive and chemo-resistant epithelial ovarian cancer cell lines, inducing apoptosis and G2/M cell cycle arrest. In vivo experiments using orthotopic and patient-derived xenograft models showed significant tumor growth inhibition without apparent toxicity to vital organs. Unlike paclitaxel, BNZ-111 proved effective in paclitaxel-resistant cells, potentially by bypassing interaction with MDR1 and modulating β-3 tubulin expression to suppress microtubule dynamics., Conclusion: BNZ-111, with favorable drug-like properties, holds promise as a therapeutic option for platinum-resistant ovarian cancer, addressing a critical clinical need in gynecologic oncology., 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 authors declare that they have no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: To examine the efficacy and safety of minimally invasive surgery (MIS) and conventional abdominal surgery for epithelial ovarian cancer (EOC), stratified by treatment type., Methods: A systematic review and meta-analysis were conducted by an Expert Panel of the Japan Society of Gynecologic Oncology Ovarian Cancer Committee. Several academic databases, including PubMed/MEDLINE, Cochrane Database, and Ichushi were searched by the Japan Medical Library Association on November 11, 2023, using the keywords "epithelial ovarian cancer", "minimally invasive surgery", "laparoscopic", and "robot-assisted". Articles describing MIS treatment for EOC compared with conventional abdominal surgery were independently assessed by two authors. The primary outcomes were survival and perioperative adverse events., Results: After screening 1114 studies, 35 articles were identified, including primary staging surgery (PSS) for early-stage EOC EOC (n = 20) and neoadjuvant chemotherapy following interval debulking surgery (NACT-IDS; n = 10) and upfront primary debulking surgery (PDS; n = 5) for advanced-stage EOC. These studies included 29,888 patients (7661 undergoing MIS and 22,227 undergoing abdominal surgery). Patients receiving MIS and abdominal surgery had similar overall survival (PSS: odds ratio [OR] 1.02, 95% confidence interval [CI] 0.75-1.37; NACT-IDS: OR 0.93, 95%CI 0.25-3.44 and PDS: OR 0.66, 95%CI 0.36-1.22, all P > 0.05). MIS showed perioperative complication rates comparable to those of abdominal surgery (intraoperative and postoperative, all treatment types P ≥ 0.05). However, the rate of lymph node dissection in early-stage EOC (PSS: OR 0.49, 95%CI0.26-0.91) and multivisceral resections in advanced-stage EOC (NACT-IDS: OR 0.27 95%CI 0.16-0.44 and PDS: OR 0.27, 95%CI 0.16-0.44) was lower in MIS than in abdominal surgery (all P < 0.05)., Conclusion: MIS did not negatively impact the survival and perioperative complications of patients with EOC compared to abdominal surgery. While MIS is a viable option, varied case selection and surgical procedures suggest potential bias, requiring further validation studies., Competing Interests: Declaration of competing interest Tokai University Research Organization (H.M). All other authors report no conflicts of 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., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To elucidate the clinicopathological characteristics and oncological outcomes of a special group of patients with gestational trophoblastic neoplasia (GTN) initially presenting with isolated lung lesions, elevated human chorionic gonadotropin (hCG) levels, and unobserved pelvic lesions., Methods: Overall, 2358 patients with GTN treated at our hospital between 2000 and 2023 were retrospectively reviewed, and 40 patients were evaluated. The demographic characteristics, clinicopathological features, treatment data, and follow-up information of each patient were collected. The primary outcome was progression free survival. Kaplan-Meier analysis and univariate and multivariate Cox proportional hazard analyses were used to identify the risk factors., Results: Among the 40 patients, 95.0 % had solitary lung lesions, with a median size of 1.9 cm. Moreover, 72.5 % of patients were pathologically confirmed as epithelioid trophoblastic tumors (ETT). During a median follow-up period of 53.5 months (range, 2-143), 11 patients experienced recurrence, including all patients who received chemotherapy alone as the initial treatment, and no death was observed. Relapse treatment involved lung segmentectomy and lobectomy combined with chemotherapy and immunotherapy. Univariate and multivariate Cox analyses identified comparing with surgery±chemotherapy, chemotherapy alone as the initial treatment (hazard ratio [HR] =7.738, 95 % confidence interval [CI] 1.698-35.269, P = 0.008) as independent risk factor for recurrence., Conclusions: In patients with a history of pregnancy exhibiting isolated pulmonary lesions, elevated hCG levels (mostly <1000 mIU/mL), and unobserved pelvic lesions, ETT should be considered first. Surgical resection of lung lesion is crucial for optimal management. When chemotherapy is considered, multidrug regimen is recommended., 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., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Enhanced recovery after surgery (ERAS) pathways utilize multimodal analgesia. In pathways already utilizing incisional injection of liposomal bupivacaine (ILB), we assessed the benefit of adding intrathecal opioid analgesia (ITA)., Methods: In this randomized controlled non-inferiority trial in patients undergoing laparotomy for gynecologic malignancy, we allocated patients 1:1 to ILB alone versus ITA + ILB with 150 μg intrathecal hydromorphone. The primary endpoint was the Overall Benefit of Analgesia Score (OBAS) at 24 h following surgery. Secondary endpoints included pain scores, intravenous opioid use, and cost of care., Results: Demographic and surgical factors were balanced for 105 patients. For the primary endpoint, ILB alone was non-inferior to ITA + ILB (median OBAS at 24 h of 4 vs 4; p = 0.70). We observed a significant reduction in the need for intravenous opioids (26% vs 71%; p < 0.001) and total opioid requirements (median 7.5 vs 39.3 mg morphine equivalents, p < 0.001) in the first 24 h. Clinically relevant improvements in pain scores were identified in the first 16 h after surgery favoring ITA + ILB. Total cost of the index episode, pharmacy costs, and costs at 30 days were not statistically different., Conclusions: Using OBAS as the primary endpoint, ILB alone was non-inferior to ITA + ILB. However, important cost-neutral benefits for ITA + ILB in the first 24 h post-operatively included lower pain scores and reduced need for intravenous opioids. These early, incremental benefits of adding ITA to ERAS bundles already utilizing ILB should be considered to optimize immediate post-operative pain., 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., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Endometrial serous carcinoma (ESC) and tubo-ovarian high-grade serous carcinoma (HGSC) are characterized by late-stage presentation and high mortality. Current guidelines for prevention recommend risk-reducing salpingo-oophorectomy (RRSO) in patients with hereditary mutations in cancer susceptibility genes. However, HGSC displays extensive genetic heterogeneity with alterations in 168 genes identified in TCGA study, but current germline testing panels are often limited to the handful of recurrently mutated genes, leaving families with rare hereditary gene mutations potentially at-risk., Objective: To determine if there are rare germline mutations that may aid in early identification of more patients at-risk for ESC and/or HGSC by evaluating patients with concurrent ESC, HGSC or precursor lesions, and endometrial atypical hyperplasia (CAH) or low-grade endometrial endometrioid adenocarcinoma (LGEEA)., Methods: We performed targeted next-generation sequencing using TSO 500, a 523 gene panel, on formalin-fixed paraffin-embedded tumor and matched benign non-tumor tissue blocks from 5 patients with concurrent ESC, HGSC or precursor lesions, and CAH or LGEEA., Results: We identified germline pathogenic, likely pathogenic or uncertain significance variants in cancer susceptibility genes in 4 of 5 patients - affected genes included GLI1, PIK3R1, FOXP1, FANCD2, INPP4B and H3F3C. Notably, none of these genes were included in the commercially available germline testing panels initially used to evaluate the patients at the time of their diagnoses., Conclusion: Comprehensive germline testing of patients with concurrent LGEEA or CAH and ESC, HGSC or precursor lesions may aid in early identification of relatives at-risk for cancer who may be candidates for RRSO with hysterectomy., 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. One of the authors (RE) is an Editorial Board Member/Editor-in-Chief/Associate Editor/Guest Editor for [Gynecologic oncology] and was not involved in the editorial review or the decision to publish this article. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: KMF has received honoraria as a speaker for Illumina – unrelated to the current manuscript; RE receives/has received research funding from Clovis oncology, GSK, Merck and AstraZeneca – unrelated to the current manuscript; RE has received consulting fees and/or honoraria from AstraZeneca, Clovis, Eisai, GSK, Daiichi Sankyo, PMV Pharmaceuticals, Immunogen, Mersana, Myriad, Novocure, Onconova, Elevar therapeutics and Renegenron – unrelated to the current manuscript. WS has received honoraria from Guardant Health – unrelated to the current manuscript., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to describe the long-term outcome of asymptomatic BRCA1/2 germline pathogenic variant (GPV) carriers with high-grade serous carcinoma (HGSC) in their risk-reducing salpingo-oophorectomy (RRSO) specimen., Methods: In a previously described cohort of asymptomatic BRCA1/2 GPV carriers derived from the Hereditary Breast and Ovarian cancer in the Netherlands (HEBON) study, women with HGSC at RRSO were identified. Main outcome was ten-year disease-free survival (DFS). Secondary outcomes were time to recurrence, ten-year disease-specific survival (DSS), ten-year overall survival (OS). Patient, disease and treatment characteristics associated with recurrence were described., Results: The 28 included women with HGSC at RRSO were diagnosed at a median age of 55.3 years (range: 33.5-74.3). After staging, eighteen women had (FIGO) stage I, three stage II and five had stage III disease. Two women did not undergo surgical staging and were classified as unknown stage. After a median follow-up of 13.5 years (range: 9.1-24.7), six women with stage I (33%), one woman with stage II (33%), two women with stage III (40%) and none of the women with unknown stage developed a recurrence. Median time to recurrence was 6.9 years (range: 0.8-9.2 years). Ten-year DFS was 68%, ten-year DSS was 88% and ten-year OS was 82%., Conclusion: Most asymptomatic BRCA1/2 GPV carriers with HGSC at RRSO were diagnosed at an early stage. Nevertheless, after a median follow-up of 13.5 years, nine of the 28 women with HGSC at RRSO developed a recurrence after a median of 6.9 years., 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., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the role of BRCA1/2 mutations in early ovarian cancer (eOC) (International Federation of Gynecology and Obstetrics FIGO 2014 stage I-II), and its impact on prognosis after relapse., Methods: In this multicenter retrospective study, clinical and survival data from high-grade serous (HGS)-eOC patients at presentation and recurrence were compared according to BRCA status: BRCA-mutated (BRCAmut) vs. BRCA wild-type (BRCAwt)., Results: Among 191 HGS-eOC patients, 89 were BRCAmut and 102 BRCAwt. There was no significant difference according to the BRCA status in terms of Progression-Free Survival (PFS). A longer Overall Survival (OS) was found in BRCAmut patients. Stage I patients had significantly improved PFS vs stage II, regardless of BRCA status. At multivariate analysis, stage at diagnosis was the only variable with a significant effect on PFS. No factors were significantly relevant on OS, albeit younger age and BRCA mutation showed a slight impact. Post-Recurrence Survival (PRS) in the BRCAmut population was significantly improved compared with BRCAwt. At multivariate analysis, Secondary Cytoreductive Surgery was the strongest predictor for longer PRS, followed by PARPi maintenance at recurrence., Conclusions: BRCA-status is not a prognostic factor in early ovarian cancer regarding PFS. However, our data suggest a better prognosis after relapse in BRCAm population., 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., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: The majority of high-grade serous carcinomas (HGSC) of the ovary, fallopian tube, and peritoneum arise from the precursor lesion called serous tubal intraepithelial carcinoma (STIC). It has been postulated that cells from STICs exfoliate into the peritoneal cavity and give rise to peritoneal HGSC several years later. While co-existent STICs and HGSCs have been reported to share similarities in their mutational profiles, clonal relationship between temporally distant STICs and HGSCs have been infrequently studied and the natural history of STICs remains poorly understood., Methods: We performed focused searches in two national databases from the Netherlands and identified a series of BRCA1/2 germline pathogenic variant (GPV) carriers (n = 7) who had STIC, and no detectable invasive carcinoma, at the time of their risk-reducing salpingo-oophorectomy (RRSO), and later developed peritoneal HGSC. The clonal relationship between these STICs and HGSCs was investigated by comparing their genetic mutational profile by performing next-generation targeted sequencing., Results: Identical pathogenic mutations and loss of heterozygosity of TP53 were identified in the STICs and HGSCs of five of the seven patients (71%), confirming the clonal relationship of the lesions. Median interval for developing HGSC after RRSO was 59 months (range: 24-118 months)., Conclusion: Our results indicate that cells from STIC can shed into the peritoneal cavity and give rise to HGSC after long lag periods in BRCA1/2 GPV carriers, and argues in favor of the hypothesis that STIC lesions may metastasize., 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., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

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.)

Objectives: To identify predictors of referral and completion of germline genetic testing among newly diagnosed ovarian cancer patients, with a focus on geographic social deprivation, oncologist-level practices, and time between diagnosis and completion of testing., Methods: Clinical and sociodemographic data were abstracted from medical records of patients newly diagnosed with ovarian cancer between 2014 and 2019 in the University of North Carolina Health System. Factors associated with referral for genetic counseling, completion of germline testing, and time between diagnosis and test results were identified using multivariable regression., Results: 307/459 (67%) patients were referred for genetic counseling and 285/459 (62%) completed testing. The predicted probability of test completion was 0.83 (95% CI: 0.77-0.88) for patients with a referral compared to 0.27 (95% CI: 0.18-0.35) for patients without a referral. The predicted probability of referral was 0.75 (95% CI: 0.69-0.82) for patients at the 25th percentile of ZIP code-level Social Deprivation Index (SDI) and 0.67 (0.60-0.74) for patients at the 75th percentile of SDI. Referral varied by oncologist, with predicted probabilities ranging from 0.47 (95% CI: 0.32-0.62) to 0.93 (95% CI: 0.85-1.00) across oncologists. The median time between diagnosis and test results was 137 days (IQR: 55-248 days). This interval decreased by a predicted 24.46 days per year (95% CI: 37.75-11.16)., Conclusions: We report relatively high germline testing and a promising trend in time from diagnosis to results, with variation by oncologist and patient factors. Automated referral, remote genetic counseling and sample collection, reduced out-of-pocket costs, and educational interventions should be explored., 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., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The Cancer Genome Atlas (TCGA) Research Network described 4 molecular subgroups of endometrial carcinomas with different outcome: 1) POLE ultramutated endometrioid carcinomas which have an indolent behavior; 2) microsatellite instability hypermutated endometrioid carcinomas associated with intermediate prognosis; 3) copy-number low endometrioid carcinomas also with intermediate prognosis; and 4) copy-number high predominantly serous (non-endometrioid) but also serous-like endometrioid carcinomas, almost always carrying TP53 mutations, with poor clinical outcome. After 10 years of comprehensive analysis, it appears that the only real contribution of TCGA to the clinical management of these patients would be limited to the infrequent high-grade, early-stage endometrioid carcinomas with POLE exonuclease domain mutations, as these patients could benefit from a de-escalating treatment; knowledge about the other three subgroups has not changed significantly. The copy-number low (or non-specific genetic profile) which is the most frequent subgroup, is a mixture subgroup where investigators are currently trying to establish prognostic markers; for example, unexpected variations in a relatively small percentage of cases (i.e., CTNNB1 mutated or p53 aberrant low-grade and low-stage endometrioid carcinomas associated with unfavorable prognosis). On the other hand, TCGA has underlined that a small number of grade 3 endometrioid carcinomas, all TP53 mutated, overlap with copy-number high serous carcinomas. Recently, TCGA molecular subgroups have been integrated into the 2023 International Federation of Gynecology and Obstetrics (FIGO) staging classification which incorporates other non-anatomic parameters like histotype, tumor grade, and lymphovascular space invasion. The result is a complicated and non-intuitive classification that makes its clinical application difficult and does not facilitate correspondence with the 2009 FIGO staging., 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., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: Alterations in the tumor suppressor TP53 gene are the most common mutations in high grade serous ovarian carcinoma. The impact of TP53 mutations on clinical outcomes and platinum resistance is controversial. We sought to evaluate the genomic profile of high grade serous ovarian carcinoma and explore the association of TP53 mutations with platinum resistance., Methods: Next generation sequencing data was obtained from our institutional database for patients with high grade serous ovarian carcinoma undergoing primary treatment. Sequencing data, demographic, and clinical information was reviewed. The primary outcome analyzed was time to recurrence or refractory diagnosis. Associations between the primary outcome and different classification schemes for TP53 mutations (structural, functional, hot spot, pathogenicity scores, immunohistochemical staining patterns) were performed., Results: 209 patients met inclusion criteria. TP53 mutations were the most common mutation. There were no differences in platinum response with TP53 hotspot mutations or high pathogenicity scores. Presence of TP53 gain-of-function mutations or measure of TP53 gain-of function activity were not associated with platinum resistance. Immunohistochemical staining patterns correlated with expected TP53 protein function and were not associated with platinum resistance., Conclusions: TP53 hotspot mutations or high pathogenicity scores were not associated with platinum resistance or refractory disease. Contrary to prior studies, TP53 gain-of-function mutations were not associated with platinum resistance. Estimation of TP53 gain-of-function effect using missense mutation phenotype scores was not associated with platinum resistance. The polymorphic nature of TP53 mutations may be too complex to demonstrate effect using simple models, or response to platinum therapy may be independent of initiating TP53 mutation., Competing Interests: Declaration of competing interest The authors declare there are no applicable conflicts of interest associated with this paper. JDL is supported by a grant from the National Institutes for Health's National Cancer Institute (K99/R00 CA234391)., (Published by Elsevier Inc.)

Objectives: To determine the incidence of thromboembolic events (TEEs) in ovarian cancer patients and to identify risk factors that are significantly associated with the development of venous thromboembolism (VTE), arterial thromboembolism (ATE), or overall TEEs in this population., Methods: This is a retrospective cohort study of 4491 patients with epithelial ovarian cancer identified in the British Columbia cancer registry between 1996 and 2017. The presence of TEEs and risk factors were identified in administrative health records from fee-for-service provider visits and hospital data using ICD-9-CM and ICD-10-CM billing codes. Statistical analysis was performed using Chi-squared test and Fischer's exact test., Results: Of 4491 patients with epithelial ovarian cancer included in this study, 1.74% experienced ATE and (9.44%) experienced VTE. There was a significant association found between the occurrence of TEEs and all-cause mortality. Sepsis was significantly associated with both venous and arterial thromboembolism. The top three risk factors for arterial thromboembolism included peripheral vascular disease (PVD), open wound, and aneurysm., Conclusions: Risk factors predictive of thrombosis in ovarian cancer patients are not consistent between ATE and VTE, thus thrombotic events should not be combined for analysis. Differential thrombosis risk assessment is needed to improve prevention strategies and guide thromboprophylaxis for these patients., 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., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Vulvar squamous cell carcinoma (VSCC) can be stratified into three molecular subtypes based on the immunoexpression of p16 and p53: HPV-independent p53-abnormal (p53abn) (most common, biologically aggressive), HPV-associated, with p16-overexpression (second most common, prognostically more favourable) and more recently recognised HPV-independent p53-wildtype (p53wt) (rarest subtype, prognostically intermediate). Our aim was to determine whether molecular subtypes can be reliably identified in pre-operative biopsies and whether these correspond to the subsequent vulvectomy specimen., Methods: Matched-paired pre-surgical biopsies and subsequent resection specimen of 57 patients with VSCC were analysed for the immunohistochemical expression of p16 and p53 by performing a three-tiered molecular subtyping to test the accuracy rate., Results: Most cases 36/57 (63.2%) belonged to the HPV-independent (p53-abn) molecular subtype, followed by HPV-associated 17/57 (29.8%) and HPV-independent (p53wt) 4/57 (7.0%). The overall accuracy rate on biopsy was 91.2% (52/57): 97.3% for p53-abnormal, 94.1% for p16-overexpression and 50% for p16-neg/p53-wt VSCC. Incorrect interpretation of immunohistochemical p53 staining pattern was the reason for discordant results in molecular subtyping in all five cases. In one case there was an underestimation of p53 pattern (wildtype instead of abnormal/aberrant) and in one case an overestimation of the p53 staining pattern (abnormal/aberrant instead of wildtype). In 3/5 there was a "double positive" staining result (p16 overexpression and abnormal/aberrant p53 staining pattern). In that cases additional molecular workup is required for correct molecular subtyping, resulting in an overall need for molecular examination of 3/57 (3.5%)., Conclusions: Compared to the final resections specimen, the three-tiered molecular classification of VSCC can be determined on pre-surgical biopsies with a high accuracy rate. This enables more precise surgical planning, prediction of the response to (chemo) radiation, selection of targeted therapies and planning of the optimal follow-up strategy for patients in the age of personalised medicine., 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., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: To assess risk factors associated with loss to follow up in patients referred for colposcopy after abnormal cervical cytology during pregnancy in a Southern safety net hospital population., Methods: An urban colposcopy center was queried for patients referred for follow up of abnormal cervical cytology during pregnancy and the postpartum period. Patients were identified through a standardized referral code in the electronic medical record. Multivariable logistic regression was used to compare patient characteristics between those who followed up for colposcopy and those lost to follow up. Independent risk factors assessed included age, parity, race, insurance, HIV status, history of mental illness, BMI, gestational age and trimester at screening, cytology at colposcopy referral, interval days until colposcopy, and biopsy histology., Results: 1063 patients were identified, with 40.8% of patients who completed referred colposcopy. Patient characteristics predictive for colposcopy follow up included: maternal age at referral cervical cytology >30 years (1.67; 1.27-2.20; < 0.003), gestational age < 18 weeks at abnormal cervical cytology (1.57; 1.23-2.01; <0.0002), maternal race non-African American (2.20; 1.32-3.65; <0.0024) and with high grade cervical cytology (2.42; 1.81-3.24; <0.0001)., Conclusion: In this population, inadequate follow up for abnormal cervical cytology during pregnancy is prominent, especially among those with younger maternal age, African American (AA) race, cervical cytology completed at later gestational ages of pregnancy, and low-grade initial cytology. Higher no-show rate among AA patients supports well-documented health disparities and need for further investigation and protocols to identify those at risk for loss to follow up., Competing Interests: Declaration of competing interest The authors declare no relevant or financial interests in the research described in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Telemedicine rapidly increased with the COVID-19 pandemic and could reduce cancer care disparities. Our objective was to evaluate sociodemographic (race, insurance), patient, health system, and cancer factors associated with telemedicine use in gynecologic cancers., Methods: We conducted a retrospective cohort study of patients with endometrial cancer and epithelial ovarian cancer with at least one visit from March 2020 to October 2021, using a real-world electronic health record-derived database, representing approximately 800 sites in US academic (14%) and community practices (86%). We used multivariable Poisson regression modeling to analyze the association of ever using telemedicine with patient, sociodemographic, health system, and cancer factors., Results: Of 3950 patients with ovarian cancer, 1119 (28.3%) had at least one telemedicine visit. Of 2510 patients with endometrial cancer, 720 (28.7%) had at least one telemedicine visit. At community cancer practices, patients who identified as Black were less likely to have a telemedicine visit than patients who identified as white in both ovarian and endometrial cancer (Ovarian: RR 0.62, 95% CI 0.42-0.9; Endometrial: RR 0.56, 95% CI 0.38-0.83). Patients in the Southeast, Midwest, West, and Puerto Rico were less likely to have telemedicine visits than patients in the Northeast. Uninsured patients were less likely, and patients with Medicare were more likely, to have one or more telemedicine visit than patients with private insurance., Conclusions: In this national cohort study, <30% of patients ever used telemedicine, and significant racial and regional disparities existed in utilization. Telemedicine expansion efforts should include programs to improve equity in access to telemedicine., 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., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Little is known about cervical cancer screening strategy utilization (cytology alone, cytology plus high-risk human papillomavirus [HPV] testing [cotesting], primary HPV testing) and test results in the United States., Methods: Data from the Centers for Disease Control and Prevention's National Breast and Cervical Cancer Early Detection Program were analyzed for 199,578 persons aged 21-65 years screened from 2019 to 2020. Screening test utilization and results were stratified by demographic characteristics and geographic region. Age-standardized pooled HPV test positivity and genotyping test positivity were estimated within cytology result categories., Results: Primary HPV testing was performed in 592 persons (0.3%). Among the remaining 176,290 persons aged 30-65 years, cotesting was utilized in 72.1% (95% confidence interval [CI] 71.9-72.3%), and cytology alone was utilized in 27.9% (95% CI 27.7-28.1%). Utilization of cytology alone varied by geographic region, ranging from 18.3% (95% CI 17.4-19.1%) to 49.0% (95% CI 48.4-49.6%). HPV genotyping test utilization among those with positive pooled HPV test results was 33.9%. In persons aged ≥30 years, variations in age-adjusted test results by region were observed for pooled HPV-positive test results and for HPV genotyping-positive test results., Conclusions: Cervical cancer screening strategy utilization and test results vary substantially by geographic region within a national screening program. Variation in utilization may be due to regional differences in screening test availability or the preferences of healthcare systems, screened persons and/or clinicians. Test result variations may reflect differing risk factors for HPV infections by geographic region., 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., (Published by Elsevier Inc.)

Objective: Ovarian cancer (OC) is the leading cause of death from gynecologic malignancy in the United States, and biomarkers of patient outcomes are limited. Data using immunohistochemical (IHC) analysis are mixed regarding whether and which tumor infiltrating lymphocytes (TILs) impact survival, and IHC does not adequately quantify rare cell populations, including CD137+ (4-1BB) tumor-reactive TILs. Our study investigates if a higher percentage of CD3+ CD137+ TILs is associated with improved overall survival (OS) in OC., Methods: Flow cytometry was performed on viably banked OC digests. Chart review and statistical analysis were performed. Forty-seven patients were included, 40 of whom were diagnosed with high-grade serous ovarian carcinoma (HGSOC), papillary serous carcinoma, or undifferentiated histology., Results: A high percentage of CD3+ CD137+ TILs correlated with improved OS (n = 40, r = 0.48, P = 0.0016). Subjects were divided into CD3+ CD137+ TIL high and low groups by the median. Subjects with high CD3+CD137+ TIL frequencies (>9.6%) had longer OS (Wilcoxon rank-sum test; P = 0.0032) and improved OS (logrank test; P = 0.007). Differences in CD3+ or CD3+ CD8+ TILs did not impact survival. CD3+ CD137+ TILs were predictive of OS regardless of germline mutation or debulking status. Analysis of subgroups including late stage HGSOC and late stage HGSOC with primary optimal cytoreduction indicated CD3+ CD137+ TILs correlated with improved OS after adjusting for age and PARP inhibitor use (P = 0.034 and P = 0.016, respectively)., Conclusions: Prevalence of CD3+ CD137+ TILs in digested OC specimens is associated with improved OS, while general TIL markers are not. CD137 has the potential to be a novel biomarker for survival in OC., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: DJP holds patents and received royalties on CD137-specific cell enrichment methodologies and treatments. DJP received payments for advisory service from InsTIL Bio related to TIL therapy products. All other 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., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: To investigate whether intensive follow-up (INT) after surgery for endometrial cancer impact health-related quality of life (HRQoL) and healthcare costs compared to minimalist follow-up (MIN), in the absence of evidence supporting any benefit on 5-year overall survival., Methods: In the TOTEM trial, HRQoL was assessed using the SF-12 and the Psychological General Well-Being (PGWB) questionnaires at baseline, after 6 and 12 months and then annually up to 5 years of follow-up. Costs were analyzed after 4 years of follow-up from a National Health Service perspective, stratified by risk level. The probability of missing data was analyzed for both endpoints., Results: 1847 patients were included in the analyses. The probability of missing data was not influenced by the study arms (MIN vs INT OR: 0.97 95%CI: 0.87-1.08). Longitudinal changes in HRQoL scores did not differ between the two follow-up regimens (MIN vs INT SF-12 PCS: -0.573, CI95%: -1.31; 0.16; SF-12 MCS: -0.243, CI95%: -1.08; 0.59; PGWB: -0.057, CI95%: -0,88; 0,77). The mean cost difference between the intensive and minimalist arm was €531 for low-risk patients and €683 for high-risk patients., Conclusion: In the follow-up of endometrial cancer after surgery, a minimalist treatment regimen did not affect quality of life and was cost-saving in both low-risk and high-risk recurrence patients. As previous results showed no survival benefit, a minimalist approach is justified. The relevant proportion of missing data on secondary outcomes of interest could be a critical point that deserves special attention., 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., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To determine the utility of sentinel lymph node (SLN) evaluation during hysterectomy for endometrial intraepithelial neoplasia (EIN) in a community hospital setting and identify descriptive trends among pathology reports from those diagnosed with endometrial cancer (EC)., Methods: We reviewed patients who underwent hysterectomy from January 2015 to July 2022 for a pathologically confirmed diagnosis of EIN obtained by endometrial biopsy (EMB) or dilation and curettage. Data was obtained via detailed chart review. Statistical testing was utilized for between-group comparisons and multivariate logistic regression modeling., Results: Of the 177 patients with EIN who underwent hysterectomy during the study period, 105 (59.3%) had a final diagnosis of EC. At least stage IB disease was found in 29 of these patients who then underwent adjuvant therapy. Pathology report descriptors suspicious for cancer and initial specimen type obtained by EMB were independently and significantly associated with increased odds of EC diagnosis (aOR 8.192, p < 0.001;3.746, p < 0.001, respectively). Operative times were not increased by performance of SLN sampling while frozen specimen evaluation added an average of 28 min to procedure length. Short-term surgical outcomes were also similar between groups., Conclusion: Patients treated for EIN at community-based institutions might be more likely to upstage preoperative EIN diagnoses and have an increased risk of later stage disease than previous research suggests. Given no surgical time or short-term outcome differences, SLN evaluation should be more strongly considered in this practice setting, especially for patients diagnosed by EMB or with pathology reports indicating suspicion for EC., 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., (Copyright © 2024. Published by Elsevier Inc.)

Objective: To investigate pathologic complete response (pCR) and recurrence outcomes using various progestin treatment strategies in patients with atypical hyperplasia/endometrial intraepithelial neoplasia (AH/EIN)., Methods: Medical records of patients diagnosed with AH/EIN and undergoing follow-up endometrial biopsy after progestin treatment between 2011 and 2020 were retrospectively reviewed. Clinical factors and treatment outcomes were analyzed according to initial progestin treatment (oral progestin [OP], levonorgestrel-releasing intrauterine device [LNG-IUD], and combination), OP dose, and maintenance treatment using Pearson's χ 2 , Fisher's exact test, and Kaplan-Meier analysis., Results: Of 124 patients included, 74, 37, and 13 were in the OP, LNG-IUD, and combination groups, respectively. The pCR rate was 79.8% and recurrence rate was 21.2%. The pCR rates within 3 and 6 months were significantly higher in the OP group than in the LNG-IUD group, but were not significantly different within 12 and 24 months. Recurrence rate was significantly higher in the OP group than in the LNG-IUD group. The pCR rate and recurrence rate had no significant differences between the combination group and the other groups. Excluding the LNG-IUD group, 53 and 34 patients received low- and high-dose OP, respectively. The pCR and recurrence rates were comparable between the low- and high-dose OP groups. Maintenance therapy was significantly associated with lower recurrence rate., Conclusions: Although OP alone achieved more short-term pCR than the other groups, more recurrences occurred after pCR than LNG-IUD alone. High-dose OP as well as combination of OP and LNG-IUD did not increase pCR or reduce recurrence. Maintenance therapy may reduce the recurrence rate after pCR., 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., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: We present the rare case of a 21 year old woman with small cell carcinoma of the right ovary of the hypercalcemic type with dramatic response to checkpoint inhibitor., Methods: Case report., Results and Conclusions: Our patient, a 22-year old woman with small cell carcinoma of the hypercalcemic type with hepatic metastases, is currently 43 months under treatment with pembrolizumab. Last MRI revealed no viable liver metastases nor other signs of recurrence. This is the longest survival of a patient with small cell carcinoma of the ovary under therapy with checkpoint inhibitors reported in the literature so far. With this report we emphasize the importance of immunohistological testing for PD-L 1. Treating clinicians should keep off-label use of immune checkpoint blockade in mind when treating this highly aggressive tumor if all other treatment options fail., 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., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the association between industry payments to physicians related to poly (ADP-ribose) polymerase inhibitors (PARPis) and physicians' prescribing behaviors for PARPis., Methods: This panel-data analysis used the publicly accessible Open Payments Database and Medicare Part D database between 2017 and 2021. All physicians who reported >10 claims for either olaparib, rucaparib, or niraparib were included in this study. Non-research payments for the PARPis to the physicians from the PARPi manufacturers were extracted from the Open Payments Database. Associations between the physicians' receipt of payments and likelihood of prescribing PARPis were assessed with logistic generalized estimating equations (GEEs). Dose-response associations between the number of payments and prescription volumes and Medicare expenditures were evaluated with linear GEEs., Results: Of the 1686 eligible physician prescribers, 68.7% received one or more non-research payments related to any of the three PARPis from the manufacturers between 2017 and 2021. Median annual payments per physician were $57 for olaparib, $39 for rucaparib, and $62 for niraparib. Receipt of payments for each PARPi was associated with higher odds of prescribing olaparib (odds ratio [OR]: 1.30 [95% CI: 1.14-1.48], p < 0.001), rucaparib (OR: 2.07 [95% CI: 1.58-2.72], p < 0.001), and niraparib (OR: 1.49 [95% CI: 1.22-1.81], p < 0.001). Dose-response effects were observed between the number of annual payments and the number of prescriptions and/or Medicare expenditures for olaparib and rucaparib., Conclusion: Non-research payments to physician prescribers of PARP inhibitors from the manufacturers were significantly associated with increased prescriptions and Medicare expenditures for olaparib and rucaparib in the United States., 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., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: The International Federation of Gynecology and Obstetrics (FIGO) scoring system uses the sum of eight risk-factors to predict single-agent chemotherapy resistance in Gestational Trophoblastic Neoplasia (GTN). To improve ease of use, this study aimed to generate: (i) streamlined models that match FIGO performance and; (ii) visual-decision aids (nomograms) for guiding management., Methods: Using training (n = 4191) and validation datasets (n = 144) of GTN patients from two UK specialist centres, logistic regression analysis generated two-factor models for cross-validation and exploration. Performance was assessed using true and false positive rate, positive and negative predictive values, Bland-Altman calibration plots, receiver operating characteristic (ROC) curves, decision-curve analysis (DCA) and contingency tables. Nomograms were developed from estimated model parameters and performance cross-checked upon the training and validation dataset., Results: Three streamlined, two-factor models were selected for analysis: (i) M1, pre-treatment hCG + history of failed chemotherapy; (ii) M2, pre-treatment hCG + site of metastases and; (iii) M3, pre-treatment hCG + number of metastases. Using both training and validation datasets, these models showed no evidence of significant discordance from FIGO (McNemar's test p > 0.78) or across a range of performance parameters. This behaviour was maintained when applying algorithms simulating the logic of the nomograms., Conclusions: Our streamlined models could be used to assess GTN patients and replace FIGO, statistically matching performance. Given the importance of imaging parameters in guiding treatment, M2 and M3 are favoured for ongoing validation. In resource-poor countries, where access to specialist centres is problematic, M1 could be pragmatically implemented. Further prospective validation on a larger cohort is recommended., 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., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)