Long-term disease-free survival with chemotherapy and pembrolizumab in a patient with unmeasurable, advanced stage dedifferentiated endometrial carcinoma.

Dedifferentiated endometrial carcinoma is a rare, highly aggressive subtype of endometrial cancer associated with poor survival outcomes. Current guidelines recommend treatment of advanced-stage disease with surgical staging or cytoreduction and platinum/taxane-based chemotherapy. Despite these approaches, the achievement of long-term remission or prolonged survival is challenging. Recent Phase III studies demonstrate that the addition of PD-1 inhibitors to standard chemotherapy significantly improves progression-free survival in patients with measurable, mismatch repair deficient (dMMR) and proficient (pMMR) advanced-stage or recurrent endometrial carcinoma. However, the role of PD-1 blockade in the treatment of undifferentiated and dedifferentiated endometrial carcinoma remains unclear, as very few patients with these cancer subtypes were included in the trials. In this case report, we present a patient with dMMR dedifferentiated endometrial carcinoma, treated with primary surgery to no gross residual disease, followed by carboplatin/paclitaxel chemotherapy and a short course of maintenance pembrolizumab. To date, the patient remains with a prolonged disease-free survival of 61 months, supporting the potential use of PD-1 inhibitors in the upfront treatment of unmeasurable, advanced-stage, dMMR dedifferentiated endometrial carcinoma.

Pembrolizumab with bevacizumab and cyclophosphamide for the treatment of recurrent ovarian clear cell carcinoma: A case series.

Introduction: Treatment for recurrent ovarian clear cell carcinoma (OCCC) is clinically challenging as response rates to traditional chemotherapy are low, and recurrence rates are high. Immunotherapy has shown promise for this ovarian cancer (OC) subtype, and tumor molecular testing allows for the identification of a patient population that might benefit most from this treatment. We describe the clinical course and somatic genomic testing of 4 patients who received pembrolizumab for recurrent OCCC concurrent with a combination of bevacizumab and/or cyclophosphamide. Methods: All patients with OCCC treated with immune checkpoint inhibitors (ICI) within a single health system between 2018 and 2023 (excluding those on clinical trials) were identified via retrospective chart review. Results: Four patients were included. The average age at diagnosis was 56.5 years, and the number of prior treatments ranged from 1 to 6. All patients received pembrolizumab combined with either bevacizumab and/or cyclophosphamide. All patients (n = 3) who received pembrolizumab and bevacizumab experienced a partial response. Responses were durable, ranging from 6 to 15 months. Somatic genomic testing results demonstrated microsatellite stability and low tumor mutational burden in all patient tumors, and 3 had AT-Rich Interaction Domain 1A gene (ARID1A) mutations. Notably, two patients had treatment-limiting toxicities, one with presumed immune-mediated grade 2 myocarditis, and another with grade 5 hepatitis. Conclusions: Pembrolizumab, combined with bevacizumab and cyclophosphamide, is a promising treatment option for patients with recurrent OCCC, though careful risk assessment and counseling regarding toxicities is necessary to maximize the safety and efficacy of this treatment regimen. Prospective studies are needed for validation.

An SGO commentary: U.S. News and World Report gynecologic oncology procedural ratings-Do they reflect high-quality care?

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Overweight and obese women's symptoms, knowledge, and preferences regarding endometrial biopsy for endometrial cancer detection: A threshold technique survey.

Background: The incidence of endometrial cancer (EC) in the United States continues to rise, driven mainly by the obesity epidemic. We sought to determine overweight and obese women's cancer risk knowledge and preferences regarding diagnostic endometrial biopsy (EMB) for EC detection. Methods: An online survey was administered to overweight and obese women without EC recruited through the electronic medical record's online patient portal. Baseline questions queried gynecologic history, cancer risk knowledge, and factors potentially influencing decision-making for EMB. We used the threshold survey technique to identify the minimum acceptable risk (MAR) threshold at which each respondent would be willing to undergo an EMB to detect EC. Results: Of 357 respondents (median age 45 years (interquartile range [IQR]: 38-54); median BMI 39 [IQR: 36.0-44.6]), fewer than half (48.7 %) were aware that obesity is a risk factor for EC, and 10 % considered their risk of EC to be high. Almost half (42 %) of respondents reported MAR thresholds characterized as very low (0-1 %), and these were more common among respondents with higher BMIs. Forty percent identified their weight as a factor influencing their MAR threshold decision, while 76 % identified their perceived personal risk as a factor. Less than half cited immediate risks of the procedure. Conclusion: Many patients reported being willing to undergo an EMB at very low risk thresholds for EC. Perceived personal risk is a stronger factor in decision-making than immediate procedural risks. Providers should focus on communicating patients' risk to motivate EMB to detect EC where appropriate.

Integrating Social Needs Screening and Resource Referral Into Standard Ambulatory Oncology Care: A Quality Improvement Project.

PURPOSE: We previously implemented paper-based screening for health-related social resource needs (HRSN) in our gynecologic oncology clinic and found that 36% of patients who completed the screening reported HRSN. We identified two primary deficiencies with our process. First, only 52% of patients completed the screening. Second, 37% of patients with needs failed to indicate if they desired resource referral or not. Therefore, we conducted a quality improvement project to integrate screening and referral processes into the electronic medical record (EMR) and routine clinic workflow to achieve at least 90% screening compliance and 90% elicited referral preference. METHODS: A multidisciplinary team consisting of physicians, a health outcomes researcher, a computer programmer, project assistants, and the staff of a partner community organization designed and implemented an intervention that screened for HRSN online via the EMR patient platform or in person during visits. The primary outcome was the percentage of eligible patients who completed the HRSN screening (ie, reach). Outcomes were reviewed weekly, and feedback was provided to stakeholders monthly. Iterative changes were incorporated into five successive Plan-Do-Study-Act (PDSA) cycles completed from January 2021 to March 2023. RESULTS: Screening compliance increased from the baseline of 52% (paper-based) to 97% in PDSA 4. Completion via the online patient portal increased from 17% in prelaunch to 49% in PDSA 4. Of patients who reported needs, 100% had a documented referral preference. CONCLUSION: Compared with paper-based screening, an EMR-integrated HRSN screening and referral system significantly improved reach to patients at a gynecologic oncology clinic. Implementation efforts to expand to other ambulatory clinic settings are in process.

Drug Shortages in Oncology: ASCO Clinical Guidance for Alternative Treatments.

PURPOSE: To increase awareness, outline strategies, and offer clinical guidance on navigating the complexities of treatment planning amid antineoplastic drug shortages. METHODS: A multidisciplinary panel of oncologists, ethicists, and patient advocates was assembled to provide rapid clinical guidance to help providers navigate appropriate patient care in cases where rationing or alternative therapies must be considered. The groups of content experts developed general principles for resource allocation during shortages and clinical guidance on alternative therapies for specific disease sites. The recommendations are supported by evidence when available. RESULTS: A total of 44 volunteers with content expertise formed the Advisory Group that developed general guidance on the prioritization of antineoplastic agents in limited supply. Disease site-specific clinical guidance was then produced by subgroups on the basis of members' specialties and expertise. The majority of alternative treatment options were developed in consideration of cisplatin and carboplatin shortages. All guidance is posted on ASCO's website. RECOMMENDATIONS: The prioritization of antineoplastic agents in limited supply should be based on specific goals of the therapy where evidence-based medicine has shown survival outcome and life-extending benefit in both early and advanced stages. Recommendations for specific disease sites are presented. While management options vary according to the disease site, alternatives are presented. For settings in which there are no alternatives with comparable efficacy and safety, it is recommended that patients are referred to an area where the necessary drug is available or can be obtained.Additional information is available at asco.org/drug-shortages.

Case report: prolonged durable clinical benefit and low toxicity from combination endocrine therapy in a patient with recurrent endometrial carcinoma.

Background: Endometrial carcinoma is the most common gynecologic cancer, with increasing incidence and mortality. Combination endocrine therapy comprised of tamoxifen and progestational agents has demonstrated promising results in treating recurrent disease. This case report describes the prolonged clinical benefit of treatment with tamoxifen and megestrol acetate in a woman with recurrent, metastatic endometrial endometrioid carcinoma positive for estrogen (ER) and progesterone receptors (PR). Case: A 71-year-old gravida 1 para 1 woman presented with postmenopausal bleeding and vaginal discharge. Pelvic ultrasound and magnetic resonance imaging confirmed a 4.7 cm endometrial mass. The patient underwent a total laparoscopic hysterectomy, bilateral salpingo-oophorectomy, pelvic and para-aortic lymphadenectomy, and cystoscopy; pathology revealed a FIGO stage IA grade 1 ER/PR-positive endometroid endometrial adenocarcinoma. She continued under active surveillance for approximately 42 months until she experienced bone metastases in her pelvis, for which she received radiation therapy. Five months later, pulmonary metastases were detected, and she received six cycles of carboplatin and paclitaxel. She then started megestrol acetate and tamoxifen and has remained clinically stable with minimal side effects and reasonable quality of life for approximately 57 months. Conclusion: Our case suggests that combination endocrine therapy has the potential to provide substantial long-term clinical benefit in women with recurrent endometrial cancer and bone metastases, despite multiple prior treatments, allowing patients to experience stable disease and quality of life. In patients with recurrent endometrioid, ER/PR-positive disease, endocrine therapy alone or in combination with other targeted therapies are regimens that may be considered due to their low overall toxicity.

The spectrum of MAPK-ERK pathway genomic alterations in gynecologic malignancies: Opportunities for novel therapeutic approaches.

OBJECTIVE: To investigate the incidence of MAPK/ERK pathway genomic alterations among patients with gynecologic malignancies. METHODS: We accessed the American Association of Cancer Research Genomics Evidence of Neoplasia Information Exchange publicly available dataset (v13.0). Patients with malignant tumors of the ovary, uterus, and cervix were identified. Following stratification by tumor site and histology, we examined the prevalence of MAPK/ERK pathway gene alterations (somatic mutation, and/or structural chromosome alterations). We included the following RAS-MAPK pathway genes known to be implicated in the dysregulation of the pathway; KRAS, NRAS, BRAF, HRAS, MAP2K1, RAF1, PTPN11, NF1, and ARAF. Data from the OncoKB database, as provided by cBioPortal, were utilized to determine pathogenic gene alterations. RESULTS: We identified a total of 10,233 patients with gynecologic malignancies; 48.2% (n = 4937) with ovarian, 45.2% (n = 4621) with uterine and 6.6% (n = 675) with cervical cancer respectively. The overall incidence of MAPK pathway gene alterations was 21%; the most commonly altered gene was KRAS (13%), followed by NF1 (7%), NRAS (1.3%), and BRAF (1.2%). The highest incidence was observed among patients with mucinous ovarian (71%), low-grade serous ovarian (48%), endometrioid ovarian (37%), and endometrioid endometrial carcinoma (34%). CONCLUSIONS: Approximately 1 in 5 patients with a gynecologic tumor harbor a MAPK/ERK pathway genomic alteration. Novel treatment strategies capitalizing on these alterations are warranted.

Geographic Disparities in Potential Accessibility to Gynecologic Oncologists in the United States From 2001 to 2020.

OBJECTIVE: To use a spatial modeling approach to capture potential disparities of gynecologic oncologist accessibility in the United States at the county level between 2001 and 2020. METHODS: Physician registries identified the 2001-2020 gynecologic oncology workforce and were aggregated to each county. The at-risk cohort (women aged 18 years or older) was stratified by race and ethnicity and rurality demographics. We computed the distance from at-risk women to physicians. Relative access scores were computed by a spatial model for each contiguous county. Access scores were compared across urban or rural status and racial and ethnic groups. RESULTS: Between 2001 and 2020, the gynecologic oncologist workforce increased. By 2020, there were 1,178 active physicians and 98.3% practiced in urban areas (37.3% of all counties). Geographic disparities were identified, with 1.09 physicians per 100,000 women in urban areas compared with 0.1 physicians per 100,000 women in rural areas. In total, 2,862 counties (57.4 million at-risk women) lacked an active physician. Additionally, there was no increase in rural physicians, with only 1.7% practicing in rural areas in 2016-2020 relative to 2.2% in 2001-2005 ( P =.35). Women in racial and ethnic minority populations, such as American Indian or Alaska Native and Hispanic women, exhibited the lowest level of access to physicians across all time periods. For example, 23.7% of American Indian or Alaska Native women did not have access to a physician within 100 miles between 2016 and 2020, which did not improve over time. Non-Hispanic Black women experienced an increase in relative accessibility, with a 26.2% increase by 2016-2020. However, Asian or Pacific Islander women exhibited significantly better access than non-Hispanic White, non-Hispanic Black, Hispanic, and American Indian or Alaska Native women across all time periods. CONCLUSION: Although the U.S. gynecologic oncologist workforce increased steadily over 20 years, this has not translated into evidence of improved access for many women from rural and underrepresented areas. However, health care utilization and cancer outcomes may not be influenced only by distance and availability. Policies and pipeline programs are needed to address these inequities in gynecologic cancer care.

Low-grade serous ovarian cancer: expert consensus report on the state of the science.

Compared with high-grade serous carcinoma, low-grade serous carcinoma of the ovary or peritoneum is a less frequent epithelial ovarian cancer type that is poorly sensitive to chemotherapy and affects younger women, many of whom endure years of ineffective treatments and poor quality of life. The pathogenesis of this disease and its management remain incompletely understood. However, recent advances in the molecular characterization of the disease and identification of novel targeted therapies with activity in low-grade serous carcinoma offer the promise of improved outcomes. To update clinicians regarding recent scientific and clinical trial advancements and discuss unanswered questions related to low-grade serous carcinoma diagnosis and treatment, a panel of experts convened for a workshop in October 2022 to develop a consensus document addressing pathology, translational research, epidemiology and risk, clinical management, and ongoing research. In addition, the patient perspective was discussed. The recommendations developed by this expert panel-presented in this consensus document-will guide practitioners in all settings regarding the clinical management of women with low-grade serous carcinoma and discuss future opportunities to improve research and patient care.

Effect of pre-operative warm-up on trainee intraoperative performance during robot-assisted hysterectomy: a randomized controlled trial.

INTRODUCTION AND HYPOTHESIS: The objective was to study the effect of immediate pre-operative warm-up using virtual reality simulation on intraoperative robot-assisted laparoscopic hysterectomy (RALH) performance by gynecology trainees (residents and fellows). METHODS: We randomized the first, non-emergent RALH of the day that involved trainees warming up or not warming up. For cases assigned to warm-up, trainees performed a set of exercises on the da Vinci Skills Simulator immediately before the procedure. The supervising attending surgeon, who was not informed whether or not the trainee was assigned to warm-up, assessed the trainee's performance using the Objective Structured Assessment for Technical Skill (OSATS) and the Global Evaluative Assessment of Robotic Skills (GEARS) immediately after each surgery. RESULTS: We randomized 66 cases and analyzed 58 cases (30 warm-up, 28 no warm-up), which involved 21 trainees. Attending surgeons rated trainees similarly irrespective of warm-up randomization with mean (SD) OSATS composite scores of 22.6 (4.3; warm-up) vs 21.8 (3.4; no warm-up) and mean GEARS composite scores of 19.2 (3.8; warm-up) vs 18.8 (3.1; no warm-up). The difference in composite scores between warm-up and no warm-up was 0.34 (95% CI: -1.44, 2.13), and 0.34 (95% CI: -1.22, 1.90) for OSATS and GEARS respectively. Also, we did not observe any significant differences in each of the component/subscale scores within OSATS and GEARS between cases assigned to warm-up and no warm-up. CONCLUSION: Performing a brief virtual reality-based warm-up before RALH did not significantly improve the intraoperative performance of the trainees.

Long-term impact of the Affordable Care Act's dependent coverage mandate on young women with gynecologic cancer.

BACKGROUND: The dependent coverage mandate in the 2010 Affordable Care Act (ACA) allows young adults to stay on a parent's private insurance through age 26. While this mandate is associated with gains in insurance and early-stage cancer diagnosis, its long-term impact on survival is unknown. OBJECTIVE: To compare insurance coverage, stage at diagnosis, and overall survival in patients with gynecologic cancer before and after the ACA's dependent coverage mandate. METHODS: Using difference-in-differences (DiD) analysis, we conducted a retrospective cohort study comparing outcomes before and after the implementation of the ACA's dependent coverage mandate in young patients with gynecologic cancer, ages 18-26 years (exposure group) to patients ages 27-35 (control group). We analyzed insurance coverage, stage at diagnosis, and 1, 2, and 3-year overall survival, adjusted for age and comorbidities, utilizing the 2004-2017 National Cancer Database. IRB exemption was obtained. RESULTS: A total of 3553 cases pre-reform and 4535 cases post-reform were identified for patients 18-26 years compared to 14,420 pre-reform and 19,821 post-reform for patients age 27-35. The ACA's dependent coverage mandate was associated with significant gains in insurance (DiD 2%, 95% CI 0.6-3.5) and early-stage diagnosis (3.1%, 95% CI 0.6-5.7). The ACA's dependent coverage mandate was associated with significant gains in 3-year survival (2.4%, 95% CI 0.4-4.3) and non-significant gains in 1 and 2-year survival. CONCLUSION: The ACA's dependent coverage mandate is associated with improvements in early-stage diagnosis and survival for young patients with gynecologic cancer. Maintaining insurance gains-and expanding to the remaining uninsured-are critical for the health of young patients with gynecologic cancer.

Identifying women 45 years and younger at elevated risk for endometrial hyperplasia or cancer.

OBJECTIVE: To estimate the prevalence of, and identify risk factors associated with, endometrial hyperplasia and/or cancer (EH/EC) in patients ≤45 years old undergoing endometrial sampling for abnormal uterine bleeding (AUB). METHODS: We performed a retrospective cohort study of patients 18-45 years old with AUB who underwent endometrial sampling between 2016 and 2019 within a US-based multi-hospital system using billing code queries. We used multivariable Poisson regression to identify factors associated with EH/EC and calculated prevalence stratified by these factors. We estimated predicted probabilities within combinations of characteristics in order to examine the range of risk in this population. RESULTS: Among 3175 patients, median age was 39 years (interquartile range [IQR]:35-43) and BMI was 29.7 kg/m2 (IQR: 24.2-36.9). Thirty-nine percent were non-Hispanic White, 41% non-Hispanic Black, 9% Hispanic, and 11% Asian/Other/Unknown. BMI and polycystic ovarian syndrome (PCOS) were associated with higher EH/EC risk; non-Hispanic Black race was associated with lower risk. EH/EC prevalence ranged from 2% in BMI <25 to 16% in BMI ≥50 kg/m2 (p-trend <0.001). These prevalence estimates differed by race/ethnicity with the lowest estimates in non-Hispanic Black patients (0.5% BMI <25 vs. 9% BMI ≥50) and highest in Hispanic patients (1.5% BMI <25 vs. 33% BMI ≥50). Accounting for combinations of risk factors, predicted probabilities were highest - 34-36% - among patients with PCOS, diabetes, BMI ≥50, and Hispanic or Asian/Other/Unknown race/ethnicity. CONCLUSIONS: When accounting for combinations of key risk factors, risk of EH/EC in patients ≤45 years old with AUB ranges widely; the more nuanced estimates of risk presented here could help inform clinical decision-making about endometrial sampling in this population.

Pembrolizumab plus Chemotherapy in Advanced Endometrial Cancer.

BACKGROUND: Standard first-line chemotherapy for endometrial cancer is paclitaxel plus carboplatin. The benefit of adding pembrolizumab to chemotherapy remains unclear. METHODS: In this double-blind, placebo-controlled, randomized, phase 3 trial, we assigned 816 patients with measurable disease (stage III or IVA) or stage IVB or recurrent endometrial cancer in a 1:1 ratio to receive pembrolizumab or placebo along with combination therapy with paclitaxel plus carboplatin. The administration of pembrolizumab or placebo was planned in 6 cycles every 3 weeks, followed by up to 14 maintenance cycles every 6 weeks. The patients were stratified into two cohorts according to whether they had mismatch repair-deficient (dMMR) or mismatch repair-proficient (pMMR) disease. Previous adjuvant chemotherapy was permitted if the treatment-free interval was at least 12 months. The primary outcome was progression-free survival in the two cohorts. Interim analyses were scheduled to be triggered after the occurrence of at least 84 events of death or progression in the dMMR cohort and at least 196 events in the pMMR cohort. RESULTS: In the 12-month analysis, Kaplan-Meier estimates of progression-free survival in the dMMR cohort were 74% in the pembrolizumab group and 38% in the placebo group (hazard ratio for progression or death, 0.30; 95% confidence interval [CI], 0.19 to 0.48; P<0.001), a 70% difference in relative risk. In the pMMR cohort, median progression-free survival was 13.1 months with pembrolizumab and 8.7 months with placebo (hazard ratio, 0.54; 95% CI, 0.41 to 0.71; P<0.001). Adverse events were as expected for pembrolizumab and combination chemotherapy. CONCLUSIONS: In patients with advanced or recurrent endometrial cancer, the addition of pembrolizumab to standard chemotherapy resulted in significantly longer progression-free survival than with chemotherapy alone. (Funded by the National Cancer Institute and others; NRG-GY018 ClinicalTrials.gov number, NCT03914612.).

Clinical outcomes in patients with COVID-19 and gynecologic cancer: A society of gynecologic oncology COVID-19 and gynecologic cancer registry study.

OBJECTIVES: Patients with gynecologic malignancies may have varied responses to COVID-19 infection. We aimed to describe clinical courses, treatment changes, and short-term clinical outcomes for gynecologic oncology patients with concurrent COVID-19 in the United States. METHODS: The Society of Gynecologic Oncology COVID-19 and Gynecologic Cancer Registry was created to capture clinical courses of gynecologic oncology patients with COVID-19. Logistic regression models were employed to evaluate factors for an association with hospitalization and death, respectively, within 30 days of COVID-19 diagnosis. RESULTS: Data were available for 348 patients across 7 institutions. At COVID-19 diagnosis, 125 patients (36%) had active malignancy. Delay (n = 88) or discontinuation (n = 10) of treatment due to COVID-19 infection occurred in 28% with those on chemotherapy (53/88) or recently receiving surgery (32/88) most frequently delayed. In addition to age, performance status, diabetes, and specific COVID symptoms, both non-White race (adjusted odds ratio (aOR) = 3.93, 95% CI 2.06-7.50) and active malignancy (aOR = 2.34, 95% CI 1.30-4.20) were associated with an increased odds of hospitalization. Eight percent of hospitalized patients (8/101) died of COVID-19 complications and 5% (17/348) of the entire cohort died within 30 days after diagnosis. CONCLUSIONS: Gynecologic oncology patients diagnosed with COVID-19 are at risk for hospitalization, delay of anti-cancer treatments, and death. One in 20 gynecologic oncology patients with COVID-19 died within 30 days after diagnosis. Racial disparities exist in patient hospitalizations for COVID-19, a surrogate of disease severity. Additional studies are needed to determine long-term outcomes and the impact of race.

Optimizing Perioperative Venous Thromboembolism Chemoprophylaxis on a Gynecologic Oncology Service.

BACKGROUND: Perioperative venous thromboembolism (VTE) is a significant cause of morbidity and mortality after gynecologic cancer surgery. Here we report a quality improvement intervention to increase perioperative VTE chemoprophylaxis compliance. STUDY DESIGN: All operations performed by a gynecologic oncologist at a tertiary urban university medical center admitted to the hospital for at least one midnight were included. Using a pre/post design with a washout period, we sought to increase perioperative VTE chemoprophylaxis compliance from 22% in the historical control (HC) cohort to 90% in the quality improvement (QI) cohort. The perioperative VTE chemoprophylaxis process was standardized by addressing four domains: preoperative VTE chemoprophylaxis, surgical time-out, postoperative VTE chemoprophylaxis, and intervention education and compliance tracking. Pearson's chi-square test was used to compare HC vs QI cohort compliance. RESULTS: There were 130 surgical cases in the HC cohort and 131 in the QI cohort. Forty-two percent underwent laparotomy, and 57% had cancer at the time of operation. VTE chemoprophylaxis compliance improved from 22% in the HC cohort to 82% in the QI cohort (p < 0.001). Preoperative VTE chemoprophylaxis compliance improved from 76% in the HC cohort to 94% in the QI cohort (p < 0.001), and postoperative VTE chemoprophylaxis compliance improved from 27% to 87% (p < 0.001). Thirty-day postoperative VTE occurred in three patients (2%) in the HC cohort and none in the QI cohort (p = 0.08). CONCLUSIONS: A low-cost and low-technology QI initiative intervention improved perioperative compliance with VTE chemoprophylaxis.