A Qualitative Assessment of Patient Experience following Systematic Implementation of Goals of Care Conversations in the Ambulatory Gynecologic Oncology Setting.

Objective: Although skilled goals of care (GOC) conversations are known to reduce aggressive futile end-of-life care, they have not been widely implemented nor standardized in the care of gynecologic malignancies. Clinicians express concern regarding patient readiness and willingness to participate in these conversations, which may be a barrier to GOC discussions. Methods: This is a qualitative study, conducted at an academic institution in the United States, of patients with gynecologic malignancies at high risk of death within six months and who had recently completed a GOC discussion with their oncology clinician during an ambulatory visit. Within 10 days of this conversation, patients were approached for potential participation in an hour-long semistructured interview. Patients enrolled in hospice or who were non-English speaking were excluded. Participants were enrolled until thematic saturation was reached. Interviews were transcribed and coded using the five-stage thematic approach. Results: Ten women were consented and participated in semistructured interviews, which occurred a median of 4 (range 1-18) days after the index GOC discussion. The median age was 64 (range 37-78), and the most common diagnosis (50%) was recurrent platinum-resistant ovarian cancer. Four themes were identified: (1) delivery of the GOC conversation, (2) importance of prioritizing individual values, (3) involving family in decision making, and (4) openness to discussing discontinuation of anticancer treatment and hospice. Patients generally felt these GOC conversations were useful, providing a space to express their values and did not compromise the patient-clinician relationship. Conclusions: Patients seemed willing to engage in GOC conversations and were appreciative of their clinicians' communication skills. Often, they used this conversation as an opportunity to convey personal values affecting their care.

HER2 in Uterine Serous Carcinoma: Testing platforms and implications for targeted therapy.

OBJECTIVE: HER2 is an important prognostic and therapeutic target in uterine serous carcinoma (USC). Optimal HER2 testing platforms have not been defined and guidelines for testing have changed over time. Our objective is to assess the concordance of HER2 positivity based on chromogenic in situ hybridization (CISH), immunohistochemistry (IHC), and next generation sequencing (NGS) and to determine the rate of downstream mutations that may affect response to HER2 directed therapy. METHODS: Utilizing the Caris tumor registry, 2192 USC tumors were identified and analyzed using NGS (NextSeq, 592 Genes and WES, NovaSEQ), IHC, and CISH. PD-L1 expression was tested by IHC. Microsatellite instability was tested by fragment analysis, IHC, and NGS. Tumor mutational burden (TMB) was measured by totaling somatic mutations per tumor. HER2 positivity through IHC and CISH was determined based on 2007 and 2018 ASCO/CAP HER2 breast cancer guidelines. RESULTS: There was a higher rate of HER2 positivity by IHC when using the 2018 guidelines compared to the 2007 guidelines (16.3% vs 12.3%). Concordance between IHC and CISH was 98.9%. ERBB2 amplification was identified by NGS in 10.5% of tumors. Compared to CISH results, this corresponds to a concordance rate of 91.6% and a positive predictive value (PPV) of 60.3%. Single gene alterations in HER2 amplified tumors that may implicate HER2 therapy resistance included PI3K (33.1%), KRAS (2.5%), and PTEN (1.3%). CONCLUSIONS: There was high concordance between HER2 positivity based on CISH and IHC. Rate of HER2 positivity is the lowest by NGS. Ultimately these testing platforms need to be validated by response to targeted therapy.

Improved Rates of Same-day Discharge in Patients Undergoing Surgery for Endometrial Cancer Following the COVID-19 Pandemic.

STUDY OBJECTIVE: To determine the effect of the coronavirus disease 2019 (COVID-19) pandemic on the rate of same-day discharge (SDD) after minimally invasive surgery for endometrial cancer. DESIGN: Retrospective cohort. SETTING: Teaching hospital. PATIENTS: A total of 166 patients underwent a minimally invasive surgery procedure for the indication of endometrial cancer at a large academic institution from September 1, 2019, to October 1, 2020-80 patients before the implementation of the COVID-19 restrictions and 86 patients after. INTERVENTIONS: COVID-19 pandemic with visitor restrictions and hospital policy changes placed on March 17, 2020. MEASUREMENTS AND MAIN RESULTS: SDD rate was increased by 18% after the start of the COVID-19 pandemic (40% vs 58%, p = .02). There were no differences between the 2 groups with regard to operative time (p = .07), estimated blood loss (p = .21), uterine weight (p = .12), age (p = .06), body mass index (p = .42), or surgery start time (p = .15). In a multivariable logistic regression model, subjects in the COVID-19 group had 3.08 times (95% confidence interval, 1.40-6.74; p = .01) higher odds of SDD than those in the pre-COVID-19 group. There was no difference in 30-day readmission rates (7.5% vs 5.8%, p = .66). CONCLUSION: There was a significant increase in the SDD of patients with endometrial cancer since the start of the COVID-19 pandemic. The pandemic has strained hospital resources and motivated patients and physicians to avoid hospitalization. This shows that with proper motivation, an increase in SDD rates is possible without an increase in complications or rehospitalization.

Enhanced recovery after surgery (ERAS) protocol is associated with lower post-operative opioid use and a reduced office burden after minimally invasive surgery.

OBJECTIVE: Enhanced recovery after surgery (ERAS) has decreased hospital opioid use, but less attention has been directed towards its impact on clinic burden with respect to post-operative care. Our objective was to determine the impact of an ERAS protocol on post-operative opioid prescribing, and the subsequent number of pain medication refill requests and unscheduled patient-provider interactions in the 30-day post-operative period. METHODS: IRB-approved retrospective study comparing post-operative opioid prescription practices 10 months before and 10 months after ERAS protocol implementation after minimally invasive gynecologic surgery. Opioid doses in morphine milligram equivalents (MMEs), number of unscheduled visits, and phone calls were compared before and after ERAS implementation. RESULTS: A total of 791 patients were included; 445 without and 346 with ERAS implementation. ERAS was associated with higher rates of same day discharge (49% vs 39%, p = 0.003) and lower readmission rates (2.0% vs 5.6%, p = 0.011). Post-operatively, patients who received the ERAS protocol were prescribed less opioids (197.8 vs. 223.5 MMEs, p = 0.0087). There was a trend towards less refill requests with ERAS (1.7% vs 3.6%, p = 0.11). ERAS was associated with a decreased number of post-operative phone calls (38% vs 46%, p = 0.023), including calls for pain (10% vs 16%, p = 0.021), and fewer unscheduled visits related to pain (1.5% vs 5.8%, p = 0.001). CONCLUSIONS: Implementation of the ERAS protocol resulted in a decrease in post-operative opioid prescribing. Despite the lower amount of prescribed post-operative opioids, the ERAS protocol translated into a decrease in the need for post-operative interactions with the clinic staff, specifically encounters associated with pain.

Promoting timely goals of care conversations between gynecologic cancer patients at high-risk of death and their providers.

OBJECTIVE: We designed a multi-faceted intervention to increase the rate of outpatient goals of care (GOC) conversations in women with gynecologic cancers who are at high-risk of death. METHODS AND MATERIALS: A multidisciplinary team developed an educational program around GOC conversations at end-of-life and chose criteria to prospectively identify patients at high-risk of death who might benefit from timely GOC conversations: recurrent or metastatic endometrial, cervical or vulvar cancer or platinum-resistant ovarian cancer. Gynecologic oncology provider consensus was built regarding the need to improve the quality and timing of GOC conversations. Eligible outpatients were prospectively identified and providers alerted pre-encounter; timely GOC documentation within 3 visits of high-risk identification was tracked. Our institution concurrently and subsequently tracked GOC documentation during the last 6 months of life among all established oncology patients. RESULTS: Of 220 pilot period high-risk patients (96 pre- and 124 during pilot period 2017-2018), timely GOC discussion documentation increased from 30.2% to 88.7% (p < 0.001) and this increase was sustained over time. In the post-pilot period (2019-2020), among patients seen by oncologists during last 6 months of life, compared to other cancer types, gynecologic cancer patients had a higher rate of GOC documentation (81% versus 9%; p < 0.001), a lower rate of receiving chemotherapy during the last 14 days of life (2% vs 5%; p = 0.051), and no difference in end-of-life admissions (29% vs 31%; p = NS). CONCLUSIONS: Implementation of systematic outpatient identification of high-risk gynecologic oncology patients is feasible, sustainable, and increases the timely conduct of GOC conversations.

Molecular Classification to Prognosticate Response in Medically Managed Endometrial Cancers and Endometrial Intraepithelial Neoplasia.

BACKGROUND: The aim of this study was to evaluate whether molecular classification prognosticates treatment response in women with endometrial cancers and endometrial intraepithelial neoplasia (EIN) treated with levonorgestrel intrauterine system (LNG-IUS). METHODS: Patients treated with LNG-IUS for endometrial cancer or EIN from 2013 to 2018 were evaluated. Using immunohistochemistry and single gene sequencing of POLE, patients were classified into four groups as per the Proactive Molecular Risk Classifier for Endometrial cancer (ProMisE): POLE-mutated, mismatch repair-deficient (MMRd), p53 wild type (p53wt), and p53-abnormal (p53abn). Groups were assessed relative to the primary outcome of progression or receipt of definitive treatment. RESULTS: Fifty-eight subjects with endometrioid endometrial cancer or EIN treated with LNG-IUS were included. Of these, 22 subjects (37.9%) had endometrial cancer and 36 subjects (62.1%) had EIN. Per the ProMisE algorithm, 44 patients (75.9%) were classified as p53wt, 6 (10.3%) as MMRd, 4 (6.9%) as p53abn, and 4 (6.9%) as POLE-mutated. Of the 58 patients, 11 (19.0%) progressed or opted for definitive therapy. Median time to progression or definitive therapy was 7.5 months, with p53abn tumors having the shortest time to progression or definitive therapy. CONCLUSIONS: Molecular classification of endometrial cancer and EIN prior to management with LNG-IUS is feasible and may predict patients at risk of progression.

Chemotherapy discontinuation processes in a gynecologic oncology population.

OBJECTIVE: We sought to categorize the processes by which gynecologic oncology patients stop chemotherapy and to evaluate associations between these processes and end-of-life outcome metrics. METHODS: A cohort of patients with metastatic or recurrent gynecologic cancer in an outpatient setting from January 2016 to May 2018 was identified. All deceased patients in this cohort were included for analysis. Processes of discontinuing chemotherapy were categorized as: 1) definitive decision inpatient; 2) definitive decision outpatient; 3) delayed decision (eg: treatment break and never resumed chemotherapy); 4) no decision. Associations between patient characteristics and clinical outcomes of those who made a definitive outpatient decision versus those who made any other type of decision were assessed. RESULTS: 220 patients were identified; 205 patients were deceased at time of analysis. Of these, 36.6% made a definitive decision to stop chemotherapy as an outpatient, while 41.5% never made a decision to discontinue chemotherapy. Making a definitive decision as an outpatient, when compared to all other decision types, was associated with significantly lower incidence of death in the hospital (5.6% vs 21.1%, p < 0.004) and hospitalization within 30 days of death (20.8% vs 56.6%, p < 0.001), and significantly increased median time from last chemotherapy to death (135.5 vs 62 days, p < 0.001). CONCLUSION: Only one in three women in this cohort of patients deceased from gynecologic cancer made a definitive decision to discontinue chemotherapy in an outpatient setting, and this process was associated with improved end-of-life outcomes. Future efforts should examine the impact of interventions designed to increase the proportion of patients who transition away from chemotherapy via shared decision making in the outpatient setting.

Endometrial Adenocarcinomas With No Specific Molecular Profile: Morphologic Features and Molecular Alterations of "Copy-number Low" Tumors.

The study evaluated morphologic patterns, mutational profiles, and ß-catenin immunohistochemistry (IHC) in copy-number low (CNL) endometrial adenocarcinomas (EAs). CNL EAs (n=19) with next-generation or whole genome sequencing results and available tissue for IHC were identified from our institutional database. Clinical data and histologic slides were reviewed. IHC for ß-catenin was performed and correlated with mutation status. Images of digital slides of CNL EAs from The Cancer Genome Atlas (TCGA) database (n=90) were blindly reviewed by 4 pathologists, and morphology was correlated with mutation status. Categorical variables were analyzed using the Fisher exact test, and agreement was assessed using Fleiss κ. CTNNB1 mutations were present in 63% (12/19) of CNL EAs. ß-catenin nuclear localization was present in 83% of CTNNB1-mutated tumors (10/12) and in 0% (0/7) of CTNNB1-wildtype tumors (sensitivity 0.83, specificity 1.00). Squamous differentiation (SD) was present in 47% (9/19) and was more often observed in CTNNB1-mutated tumors (P=0.02). Mucinous differentiation (MD) was associated with KRAS mutations (P<0.01). Digital image review of TCGA CNL EAs revealed that pathologist agreement on SD was strong (κ=0.82), whereas agreement on MD was weak (κ=0.48). Pathologists identified SD in 22% (20/90), which was significantly associated with the presence of CTNNB1 mutations (P<0.01). CNL EAs demonstrate several morphologies with divergent molecular profiles. SD was significantly associated with CTNNB1 mutations and nuclear localization of ß-catenin in these tumors. Nuclear expression of ß-catenin is a sensitive and specific IHC marker for CTNNB1 mutations in CNL EAs. CNL EAs with KRAS mutations often displayed MD.

Place of death by region and urbanization among gynecologic cancer patients: 2006-2016.

OBJECTIVE: To evaluate associations between US region of residence and urbanization and the place of death among women with gynecologic malignancies in the United States. METHODS: A retrospective cross-sectional study was performed using publicly available death certificate data from the National Center for Health Statistics. All gynecologic cancer deaths were included from 2006 to 2016. Comparisons among categories were performed with a two-tailed chi-square test, with p-values <0.05 considered significant. RESULTS: From 2006 to 2016, 328,026 women died from gynecologic malignancies in the US. Of these deaths, 40.1% (n = 134,333) occurred in the patient's home, 24.9%(n = 81,823) in the hospital, and 11.3% (37,188) in an inpatient hospice facility. Place of death varied by geographic region. The Northeast had the largest percentage of gynecologic cancer patients (31.3%) die as a hospital inpatient. The West had the highest percentage of deaths (49.3%) at home. Deaths in a hospice facility were the highest (14.1%) in the South. Place of death varied by urbanization; patients residing in large central metro or rural counties were the most likely to die during hospital admission (28.7% and 27.1%, respectively). Patients living in medium-sized metro areas were the least likely to die in hospitals (21.8%) and most likely to die in a hospice facility (14.3%). All comparisons were significant by study definition. CONCLUSION: The place of death for patients with gynecologic malignancies varies by US region and urbanization. These disparities are multifactorial in nature, likely influenced by both sociodemographic factors and regional resource availability. In this study, however, rural and central metro areas are identified as regions that may benefit from further hospice development and advocacy.

Gender variation in Medicare utilization and payments in gynecologic oncology.

OBJECTIVES: The Medicare Provider Utilization and Payment Data: Physician and Other Supplier Public Use File (POSPUF) and Medicare Physician and Other Supplier National Provider Identifier (POS NPI) Aggregate Report are publicly available files from the Center for Medicare and Medicaid Services that include payments to providers who care for fee-for-service Medicare recipients. The aim of this study was to analyze variability in gynecologic oncologists' Medicare reimbursements, with attention to differences in provider gender and time in practice. METHODS: The 2015 POSPUF and POS NPI were analyzed with respect to gynecologic oncologists. We searched external publicly available data sources to confirm subspecialty and to determine each provider's number of years in practice. Evaluation and management (E&M) and procedure/surgery codes were analyzed; drug delivery codes were excluded due to variability in billing by facility/hospital. RESULTS: The POS NPI file included 733 gynecologic oncologist providers receiving $55,626,739 in total payments. Female providers comprised 39% of gynecologic oncologists and received 31% of reimbursements (30% of E&M reimbursements and 24% of surgical reimbursements). During the first ten years in practice, female providers comprised 58% of providers and accounted for 52% of reimbursed services, compared to 38% of providers/26% of reimbursed services (11-20 years), and 18% of providers/19% of reimbursed services (>20 years). CONCLUSION: Male gynecologic oncologists perform more Medicare services than their female counterparts. There is a comparable number of services performed between genders among both the most senior and the most junior providers, with a gender gap in services and reimbursements among mid-career providers.

Care and Cancer Screening of the Transgender Population.

As sex and gender are assigned at birth before gender identity development, many individuals experience feelings of discordance between their gender identity and their sex and gender assigned at birth. The transgender community has not been well understood by medical and mental health fields. As such, this marginalized and vulnerable community faces multiple barriers to receiving health maintenance and specialized care, both at the community and patient-specific level. Many transgender individuals undergo some form of transition to the gender that matches their gender identity. Transition efforts look different for each patient because gender and gender identity occur along a continuum. Transition may include social, hormonal, and/or surgical components. As providers are caring for transgender patients, it is imperative to understand where a patient is in their gender transition and how hormonal and/or surgical therapies affect their cancer risk and screening. The aim of this article is to describe appropriate cancer screening practices and important care considerations for the primary care physician and generalist gynecologist taking care of transgender individuals.

The association between progesterone receptor expression and survival in women with adult granulosa cell tumors.

BACKGROUND: Granulosa cell tumors (GCT) variably express estrogen receptors (ER) and progesterone receptors (PR). The goal of this study is to evaluate the relationship between ER and PR expression patterns and clinical outcomes in women with GCT. METHODS: A multicenter, retrospective analysis was performed of all cases of GCT diagnosed between 1989 and 2012. Immunohistochemical staining for ER and PR was performed on formalin-fixed paraffin embedded (FFPE) tumor tissue and interpreted using a semiquantitative scoring system that incorporated tumor cell staining proportion and intensity. Demographics, disease status, and survival information were collected. Associations between ER and PR staining scores and recurrence-free and overall survival were assessed using univariate Cox proportional hazards models. RESULTS: FFPE tumor blocks were available for 149/186 GCT patients. The majority of the women had clinical stage I disease (76%). ER and PR expression was present in 52% and 98% of subjects, respectively. The median composite scores of ER and PR staining were 1 (range 0-8) and 9 (range 0-15), respectively. In univariate analysis, PR composite score >9 was strongly associated with decreased recurrence-free survival (HR = 2.9, 95% CI = 1.5-5.5) and decreased overall survival (HR = 3.7, CI 1.3-10.2). ER composite score was not a significant predictor of recurrence-free survival or overall survival (p = 0.7, HR = 1.1, 95% CI 0.6-2.0 and p = 0.06, HR = 1.1, 95% CI 0.4-2.9, respectively). CONCLUSIONS: Our results reveal that high PR composite score (≥9) was associated with both decreased recurrence-free and overall survival in patients with GCT while ER expression was not associated with survival outcomes.

Gender trends in gynecologic oncology authorship: Implications for the critical evaluation of gender distribution in academic rank and leadership positions.

OBJECTIVE: To investigate trends in the representation of women as first, last, or co-authors in Gynecologic Oncology (GO) publications over the past 15 years. To compare rates of female authorship in GO versus general Obstetrics and Gynecology (Ob/Gyn) and with the gender distribution of membership in the Society of Gynecologic Oncology (SGO). METHODS: Gender was determined for first and last authors of GO publications from three major journals for 2000, 2005, 2010, and 2015. The Z test was used to assess differences in proportions of female authors between 2000 and 2015 and first versus last female authors in each year. GO authorship trends were compared to those of general Ob/Gyn and new and total membership in SGO using the chi squared test. RESULTS: 1815 publications were included. Percentages of female first, last, and co-authors increased over time (p < 0.001), reaching 52%, 39%, and 23%, respectively, by 2015. Fewer women were listed as last than as first authors at each time point (p < 0.01). Proportions of female authors in general Ob/Gyn exceeded those of GO. Women comprised a growing proportion of both new and total SGO members over time (p < 0.01). New female SGO membership outpaced rates of female GO authorship, but GO female first authorship surpassed total female SGO membership (p < 0.001). CONCLUSIONS: Women comprise a growing proportion of GO providers and SGO members and have become increasingly productive in academic GO. Differences in publication authorship alone cannot account for gender disparities in the distribution of academic rank and leadership positions in the field.

Use of a novel sentinel lymph node mapping algorithm reduces the need for pelvic lymphadenectomy in low-grade endometrial cancer.

OBJECTIVES: To evaluate the capability of a novel sentinel lymph node (SLN) mapping algorithm to reduce the need for pelvic lymphadenectomy (PLND) in patients with low-grade (G1-2) endometrial cancer (LGEC). METHODS: Patients with LGEC underwent evaluation according to a novel lymphatic assessment algorithm during hysterectomy with SLN biopsy at two academic gynecologic oncology programs. Side-specific PLND was only performed if ipsilateral SLN mapping failed and high-risk uterine features were identified on frozen section (FS). Side-specific and PLND rates were compared to theoretical PLND rates based on the NCCN EC SLN mapping algorithm. RESULTS: Since 11/2015, 113 LGEC patients have been managed according to the algorithm. SLN mapping was bilateral (81%), unilateral (12%), or neither (6%). Nine patients (8.0%) had LN metastases identified. Of the 21 patients requiring intraoperative FS due to failed SLN mapping, high-risk uterine features were identified in eight (38%). These patients underwent either bilateral (2) or unilateral (6) PLND. Side-specific and overall PLND rates were 5.3% and 7.1%, respectively. If all patients with failed mapping had undergone PLND according to the NCCN algorithm, side-specific and overall PLND rates would have been higher, 12.4% and 18.6%, respectively (P=0.01). All patients who failed to map and did not undergo side-specific PLND had low-risk uterine features on final pathology. CONCLUSIONS: Lymphatic assessment using SLN mapping followed by selective FS to determine need for PLND is feasible. When compared to the NCCN algorithm, this novel "Reflex Frozen Section" strategy eliminates PLND in patients at lowest risk for metastasis without compromising identification of metastatic nodal disease.

Risk factors for post-operative wound infection in the setting of chorioamnionitis and cesarean delivery.

OBJECTIVE: The objective of this study was to identify factors associated with an increased risk of post-operative wound infection in women with chorioamnionitis who undergo cesarean delivery. METHODS: We conducted a retrospective cohort study of women with clinical chorioamnionitis who underwent cesarean delivery at a tertiary-care center between June 2010 and May 2013. Demographic data, labor and delivery details and post-operative outcomes were collected. Women with and without post-operative wound infections were compared. RESULTS: Of 213 women with clinical chorioamnionitis who underwent cesarean delivery, 32 (15%) developed wound infections. Women with wound infection were more likely to have a body mass index (BMI) greater than or equal to 40 (p = 0.04), chronic hypertension (p = 0.03), leukocytosis on presentation (p = 0.046) or use tobacco (p = 0.002). Women who received ertapenem postpartum were less likely to develop wound infection than those who did not receive antibiotics (p = 0.02) or those that received ampicillin, gentamicin and clindamycin (p = 0.005). CONCLUSIONS: Elevated BMI, tobacco use, chronic hypertension and leukocytosis at admission were associated with an increased risk of wound infection. Ertapenem appeared to reduce the risk of post-operative wound infections in women who had chorioamnionitis and underwent cesarean delivery. This could be considered as a treatment option for this high-risk population.