Cost-effectiveness of BRCA1 testing at time of obstetrical prenatal carrier screening for cancer prevention.

BACKGROUND: Improved technologies paired with an increase in access to genetic testing have led to the availability of expanded carrier screening evaluating hundreds of disorders. Currently, most autosomal dominant mutations, such as BRCA1, are not included in expanded carrier assays. Screening pregnant or preconception reproductive-aged women for BRCA1 may present a unique opportunity to perform population-based screening for patients at a time when precancer screening, chemoprevention, and/or risk-reducing surgery may be beneficial. OBJECTIVE: This study aimed to inform clinical decision-making as to whether the universal incorporation of BRCA1 testing at the time of obstetrical prenatal carrier screening is cost-effective. STUDY DESIGN: A decision analysis and Markov model was created. The initial decision point in the model was BRCA1 testing at the time of expanded carrier screening. Model probabilities, cost, and utility values were derived from published literature. For BRCA1-positive patients, the model simulated breast cancer screening and risk-reducing surgical interventions. A cycle length of 1 year and a time horizon of 47 years were used to simulate the lifespan of patients. The setting was obstetrical clinics in the United States, and the participants were a theoretical cohort of 1,429,074 pregnant patients who annually underwent expanded carrier screening. RESULTS: Among our cohort, BRCA1 testing resulted in the identification of an additional 3716 BRCA1-positive patients, the prevention of 1394 breast and ovarian cancer cases, and 1084 fewer deaths. BRCA1 testing was a cost-effective strategy compared with no BRCA1 testing with an incremental cost-effectiveness ratio of $86,001 per quality-adjusted life years. In a 1-way sensitivity analysis, we varied the prevalence of BRCA1 in the population from 0.00% to 20.00% and found that BRCA1 testing continued to be the cost-effective strategy until the prevalence rate was reduced to 0.16%. Multiple additional sensitivity analyses did not substantially affect the cost-effectiveness. CONCLUSION: The addition of BRCA1 testing to obstetrical prenatal carrier screening is a cost-effective management strategy to identify at-risk women at a time when cancer screening and preventive strategies can be effective. Despite the burden of additional genetic counseling, prenatal care represents a unique opportunity to implement population-based genetic testing.

Levonorgestrel-releasing intrauterine device therapy vs oral progestin treatment for reproductive-aged patients with endometrial intraepithelial neoplasia: a systematic review and meta-analysis.

BACKGROUND: We conducted a systematic review and meta-analysis to examine outcomes of patients with endometrial intraepithelial neoplasia treated with oral progestins or a levonorgestrel-releasing intrauterine device (IUD). METHODS: We conducted a systematic review across 5 databases to examine outcomes of progestational treatment (oral progestins or levonorgestrel-releasing IUD) for patients with endometrial intraepithelial neoplasia. The primary outcome was the best complete response rate within 12 months of primary progestational treatment. Sensitivity analyses were performed by removing studies with extreme effect sizes. Secondary outcomes included the pooled pregnancy rate. RESULTS: We identified 21 eligible studies, including 824 premenopausal patients with endometrial intraepithelial neoplasia, for our meta-analysis. Among these, 459 patients received oral progestin, and 365 patients received levonorgestrel-releasing IUD as a primary progestational treatment. The pooled best complete response proportion within 12 months was 82% (95% confidence interval [CI] = 69% to 91%) following oral progestin treatment and 95% (95% CI = 81% to 99%) following levonorgestrel-releasing IUD treatment. After removing outlier studies, the pooled proportion was 86% (95% CI = 75% to 92%) for the oral progestin group and 96% (95% CI = 91% to 99%) for the levonorgestrel-releasing IUD group, with reduced heterogeneity. The pooled pregnancy rate was 50% (95% CI = 35% to 65%) after oral progestin and 35% (95% CI = 23% to 49%) after levonorgestrel-releasing IUD treatment. CONCLUSIONS: This meta-analysis provides data on the effectiveness of oral progestins and levonorgestrel-releasing IUD treatment within 12 months of treatment among premenopausal patients with endometrial intraepithelial neoplasia. Although based on small numbers, the rate of pregnancy after treatment is modest. These data may be beneficial for selecting progestational therapies that allow fertility preservation for patients with endometrial intraepithelial neoplasia.

Survival rates in Hispanic/Latinx subpopulations with cervical cancer associated with disparities in guideline-concordant care.

BACKGROUND: Failure to deliver guideline-concordant treatment may contribute to disparities among Hispanic/Latinx cervical cancer patients. This study investigated the association between survival rates in Hispanic/Latinx subpopulations and the provision of guideline-concordant care. METHODS: We analyzed patients with primary cervical cancer from 2004 to 2019 (National Cancer Database). We developed nine quality metrics based on FIGO staging (2009). Clinical and demographic covariates were analyzed using Chi-squared tests. Adjusted associations between receipt of guideline-concordant care and races and ethnicities were analyzed using multivariable marginal Poisson regression models. Adjusted Cox proportional hazard models were utilized to evaluate survival probability. RESULTS: A total of 95,589 patients were included. Hispanic/Latinx and Non-Hispanic Black (NHB) populations were less likely to receive guideline-concordant care in four and five out of nine quality metrics, respectively. Nonetheless, the Hispanic/Latinx group exhibited better survival outcomes in seven of nine quality metrics. Compared to Mexican patients, Cuban patients were 1.17 times as likely to receive timely initiation of treatment in early-stage disease (RR 1.17, 95% CI 1.04-1.37, p < 0.001). Puerto Rican and Dominican patients were, respectively, 1.16 (RR 1.16, 95% CI 1.07-1.27, p < 0.001) and 1.19 (RR 1.19, 95% 1.04-1.37, p > 0.01) times as likely to undergo timely initiation of treatment in early-stage disease. Patients of South or Central American (RR 1.18, 95% CI 1.10-1.27, p < 0.001) origin were more likely to undergo timely initiation of treatment in locally advanced disease. CONCLUSION: Significant differences in survival were identified among our cohort despite the receipt of guideline concordant care, with notably higher survival among Hispanic/Latinx populations.

Cost-effectiveness of lenvatinib plus pembrolizumab versus chemotherapy for recurrent mismatch repair-proficient endometrial cancer after platinum-based therapy.

OBJECTIVE: The recent Study 309-KEYNOTE-775 showed improved survival for lenvatinib plus pembrolizumab compared to chemotherapy in patients with recurrent endometrial cancer. We created a decision model to compare the cost-effectiveness of lenvatinib plus pembrolizumab in patients with recurrent mismatch repair-proficient (pMMR) endometrial cancer who had progressed after first-line chemotherapy. METHODS: A Markov model was created to simulate the clinical trajectory of 10,000 patients with recurrent pMMR endometrial cancer. The initial decision point in the model was treatment with ether lenvatinib plus pembrolizumab or chemotherapy (doxorubicin or dose-dense paclitaxel). Model probabilities, utility values and costs were derived with assumptions drawn from published literature. A cycle length of 3 months and a time horizon of 2 years was used. The effectiveness was calculated in terms of average quality adjusted life years (QALYs) gained. The primary outcome was incremental cost-effectiveness ratios (ICERs), expressed in 2020 US dollars/QALYs. One-way, two-way and probabilistic sensitivity analyses were performed. RESULTS: Chemotherapy was the least costly strategy at $66,693 followed by lenvatinib plus pembrolizumab ($193,590). Lenvatinib plus pembrolizumab resulted in more patients being alive at 2 years (lenvatinib plus pembrolizumab: 367, chemotherapy: 109). Chemotherapy was cost-effective compared with lenvatinib plus pembrolizumab (ICER: $164,493/QALYs). Lenvatinib plus pembrolizumab became cost-effective when its cost was reduced by $1553 per month (7.8% reduction). CONCLUSION: For patients with recurrent pMMR endometrial cancer Lenvatinib plus pembrolizumab is associated with greater survival but is more costly than chemotherapy. The cost of lenvatinib and pembrolizumab would have to be reduced by approximately 7% to be considered cost-effective.

Region of origin and cervical cancer stage in multiethnic Hispanic/Latinx patients living in the United States.

BACKGROUND: Hispanic/Latinx people have the second highest cervical cancer incidence rates in the U.S. However, there is a lack of disaggregated data on clinical outcomes for this diverse and populous group, which is critical to direct resources and funding where they are most needed. This study assessed differences in stage at diagnosis of cervical cancer among Hispanic/Latinx subpopulations and associated factors. METHODS: We analyzed patients with primary cervical cancer from 2004 to 2019 in the National Cancer Database. Hispanic/Latinx patients were further categorized into Mexican, Puerto Rican (PR), Cuban, Dominican, and Central/South American, as per standard NCDB categories, and evaluated based on stage at diagnosis and sociodemographic characteristics. Multinomial logistic regression quantified the odds of advanced stage at presentation. Regression models were adjusted for age, education, neighborhood income, insurance status, and additional factors. RESULTS: Hispanic/Latinx cervical cancer patients were more likely to be uninsured (18.9% vs. 6.0%, p < 0.001) and more likely to live in low-income neighborhoods (28.6% vs. 16.9%, p < 0.001) when compared to non-Hispanic White populations. Uninsured Hispanic/Latinx patients had 37.0% higher odds of presenting with regional versus localized disease (OR 1.37; 95% CI, 1.19-1.58) and 47.0% higher odds of presenting with distant versus. Localized disease than insured patients (OR 1.47; 95% CI, 1.33-1.62). When adjusting for age, education, neighborhood income, and insurance status, PR patients were 48% more likely than Mexican patients to present with stage IV versus stage I disease (OR 1.48; 95% CI, 1.34-1.64). CONCLUSION: Disaggregating health data revealed differences in stage at cervical cancer presentation among Hispanic/Latinx subpopulations, with insurance status as a major predictor. Further work targeting structural factors, such as insurance status, within specific Hispanic/Latinx subpopulations is needed.

Association between neighborhood socioeconomic status, built environment and SARS-CoV-2 infection among cancer patients treated at a Tertiary Cancer Center in New York City.

BACKGROUND: Racial and ethnic minority groups experience a disproportionate burden of SARS-CoV-2 illness and studies suggest that cancer patients are at a particular risk for severe SARS-CoV-2 infection. AIMS: The objective of this study was examine the association between neighborhood characteristics and SARS-CoV-2 infection among patients with cancer. METHODS AND RESULTS: We performed a cross-sectional study of New York City residents receiving treatment for cancer at a tertiary cancer center. Patients were linked by their address to data from the US Census Bureau's American Community Survey and to real estate tax data from New York's Department of City Planning. Models were used to both to estimate odds ratios (ORs) per unit increase and to predict probabilities (and 95% CI) of SARS-CoV2 infection. We identified 2350 New York City residents with cancer receiving treatment. Overall, 214 (9.1%) were infected with SARS-CoV-2. In adjusted models, the percentage of Hispanic/Latino population (aOR = 1.01; 95% CI, 1.005-1.02), unemployment rate (aOR = 1.10; 95% CI, 1.05-1.16), poverty rates (aOR = 1.02; 95% CI, 1.0002-1.03), rate of >1 person per room (aOR = 1.04; 95% CI, 1.01-1.07), average household size (aOR = 1.79; 95% CI, 1.23-2.59) and population density (aOR = 1.86; 95% CI, 1.27-2.72) were associated with SARS-CoV-2 infection. CONCLUSION: Among cancer patients in New York City receiving anti-cancer therapy, SARS-CoV-2 infection was associated with neighborhood- and building-level markers of larger household membership, household crowding, and low socioeconomic status. NOVELTY AND IMPACT: We performed a cross-sectional analysis of residents of New York City receiving treatment for cancer in which we linked subjects to census and real estate date. This linkage is a novel way to examine the neighborhood characteristics that influence SARS-COV-2 infection. We found that among patients receiving anti-cancer therapy, SARS-CoV-2 infection was associated with building and neighborhood-level markers of household crowding, larger household membership, and low socioeconomic status. With ongoing surges of SARS-CoV-2 infections, these data may help in the development of interventions to decrease the morbidity and mortality associated with SARS-CoV-2 among cancer patients.

Dostarlimab for recurrent mismatch repair-deficient endometrial cancer: A cost-effectiveness study.

OBJECTIVE: Patients with recurrent endometrial cancer treated with carboplatin and paclitaxel whose disease progresses have few effective treatment options. Based on promising clinical trial data, the anti-programmed cell death 1 (anti-PD-1) antibody dostarlimab was recently granted accelerated approval for endometrial cancer by the US Food and Drug Administration. We developed a decision model to examine the cost-effectiveness of dostarlimab for patients with progressive/recurrent deficient mismatch repair (dMMR) endometrial cancer whose disease has progressed with first-line chemotherapy. DESIGN: Cost-effectiveness study. POPULATION: Hypothetical cohort of 6000 women with progressive/recurrent dMMR endometrial cancer. METHODS: The initial decision point in the Markov model was treatment with dostarlimab, pembrolizumab or pegylated liposomal doxorubicin (PLD). Model probabilities, and cost and utility values were derived with assumptions drawn from published literature. Effectiveness was estimated as average quality-adjusted life years (QALYs) gained. One-way, two-way and probabilistic sensitivity analyses were performed to vary the assumptions across a range of plausible values. MAIN OUTCOME MEASURES: The primary outcome was the incremental cost-effectiveness ratio (ICER). RESULTS: Pegylated liposomal doxorubicin (PLD) was the least costly strategy, at $55,732, followed by dostarlimab ($151,533) and pembrolizumab ($154,597). Based on a willingness-to-pay threshold of $100,000/QALY, PLD was cost-effective compared with dostarlimab, with an ICER of $331,913 per QALY gained for dostarlimab, whereas pembrolizumab was ruled out by extended dominance (less effective, more costly), compared with dostarlimab. In one-way sensitivity analyses, dostarlimab was cost-effective when its cost was reduced to $4905 (52% reduction). These results were robust in a variety of sensitivity analyses. CONCLUSIONS: Dostarlimab is associated with greater survival compared with other treatments for women with recurrent dMMR endometrial cancer. Although the agent is substantially more costly, dostarlimab became cost-effective when its cost was reduced to $5489 per cycle.

Role of tertiary cytoreductive surgery in recurrent epithelial ovarian cancer: Systematic review and meta-analysis.

OBJECTIVE: To evaluate the clinical utility of tertiary cytoreductive surgery (TCS) in recurrent ovarian cancer. METHODS: MEDLINE via PubMed, Embase (Elsevier), ClinicalTrials.gov, Scopus (Elsevier) and Web of Science for studies from inception to 4/09/2021. Studies reporting disease specific survival (DSS) and overall survival (OS) among women who underwent optimal cytoreductive surgery as compared to those who had a suboptimal cytoreductive surgery at time of TCS were abstracted. Study quality was assessed with the Quality In Prognosis Studies (QUIPS) tool. The data were extracted independently by multiple observers. Random-effects models were used to pool associations and to analyze the association between survival and surgical outcomes. RESULTS: 10 studies met all the criteria for inclusion in the systematic review. Patients with optimal tertiary cytoreductive surgery had better DSS (HR = 0.35; 95% CI, 0.19-0.64, P < 0.001), with low heterogeneity (I2 = 0%, P = 0.41) when compared to those with suboptimal tertiary cytoreductive surgery. Pooled results from these studies also demonstrated a better OS (HR = 0.34; 95% CI, 0.15-0.74, P < 0.007) with moderate heterogeneity (I2 = 59%, P = 0.09) when compared to patients with a suboptimal tertiary cytoreductive surgery. This remained significant in a series of sensitivity analyses. Due to the limited number of studies, we were unable to do further subgroup analyses looking at outcomes comparing tertiary cytoreductive surgery to chemotherapy. CONCLUSION: In this systematic review and meta-analysis of observational studies examining tertiary cytoreductive surgery for recurrent ovarian cancer, optimal tertiary cytoreductive surgery was associated with improved OS and DSS survival compared to suboptimal tertiary cytoreductive surgery.

Uptake and outcomes of sentinel lymph node mapping in women undergoing minimally invasive surgery for endometrial cancer.

OBJECTIVE: To examine the patterns and outcomes of sentinel lymph node (SLN) assessment in women with endometrial cancer. DESIGN: Retrospective cohort study. SETTING: United States inpatient and outpatient hospital services. POPULATION: Women with endometrial cancer who underwent a laparoscopic or robotic-assisted hysterectomy. METHODS: The Perspective Database from 2012 to 2018 was used. Performance of lymph node dissection was classified as SLN mapping, lymph node dissection or no nodal evaluation. Adjusted regression models were developed to examine the association between SLN mapping and morbidity and cost. MAIN OUTCOME MEASURES: Utilisation rates, morbidity and cost of both lymph node dissection and SLN mapping. RESULTS: Among 45 381 patients, SLN mapping was performed for 7768 patients (17.1%), lymph node dissection was performed for 23 214 patients (51.2%) and no lymphatic evaluation was performed for 14 399 patients (31.7%). SLN mapping increased from 1.8% in 2012 to 35.3% in 2018, whereas the rate of lymph node dissection decreased from 63.5% to 39.1% (p < 0.001). Among women who underwent nodal evaluation, residence in the west, White race and use of robotic-assisted hysterectomy were associated with SLN mapping (p < 0.05 for all). The complication rate was 5.9% for SLN mapping, compared with 7.3% in those that underwent lymph node dissection (aRR 0.85, 95% CI 0.77-0.95). The median hospital costs for women who underwent SLN mapping ($10 479) and lymph node dissection ($10 747) were higher than for those who did not undergo nodal assessment ($9149) (p < 0.001). CONCLUSIONS: The performance of SLN mapping is increasing for endometrial cancer. Compared with lymph node dissection, SLN mapping is associated with lower morbidity. SLN mapping significantly increases the costs compared with hysterectomy alone. TWEETABLE ABSTRACT: SLN mapping is increasing rapidly for endometrial cancer and is associated with decreased perioperative morbidity.

Trends in the Use of Minimally Invasive Adnexal Surgery in the United States.

OBJECTIVE: To examine the utilization of minimally invasive adnexal surgery, including ovarian cystectomy and oophorectomy, among women with benign gynecologic diseases and compare the associated morbidity and mortality of minimally invasive and open surgery. METHODS: Women with benign ovarian pathology who underwent an ovarian cystectomy or oophorectomy from 2016 through 2018 in the Nationwide Ambulatory Surgery Sample and Nationwide Inpatient Sample databases were included. Patients with a diagnosis of gynecologic malignancy or concurrent hysterectomy were excluded. Population-level weighted estimates were developed, and perioperative morbidity, mortality, and hospital charges were examined based on surgical approach for each procedure. RESULTS: The cohort included 351,207 women who underwent oophorectomy and 220,893 women who underwent cystectomy, when weighted representing 547,836 and 328,408 patients, respectively, nationwide. A minimally invasive surgical approach was used in 294,190 (89.6%) patients who underwent ovarian cystectomy, and in 478,402 (87.3%) of patients who underwent oophorectomy. Use of minimally invasive surgery for cystectomy increased from 88.7% in 2016 to 91.0% in 2018, and the rate of minimally invasive surgery for oophorectomy increased from 85.8% to 88.7% over the same time period (P<.001 for both). The complication rates for ovarian cystectomy were 2.7% for minimally invasive surgery and 8.8% for laparotomy (P<.001); for oophorectomy the complication rate was 3.1% for minimally invasive surgery and 22.9% for laparotomy (P<.001). CONCLUSION: Minimally invasive surgery is used in the majority of women who are undergoing oophorectomy and ovarian cystectomy for benign indications. Compared with laparotomy, minimally invasive surgery is associated with fewer complications.

Intraoperative Rupture of the Ovarian Capsule in Early-Stage Ovarian Cancer: A Meta-analysis.

OBJECTIVE: To examine the effects of intraoperative ovarian capsule rupture on progression-free survival and overall survival in women who are undergoing surgery for early-stage ovarian cancer. DATA SOURCES: MEDLINE using PubMed, EMBASE (Elsevier), ClinicalTrials.gov, and Scopus (Elsevier) were searched from inception until August 11, 2020. METHODS OF STUDY SELECTION: High-quality studies reporting survival outcomes comparing ovarian capsule rupture to no capsule rupture among patients with early-stage epithelial ovarian cancer who underwent surgical management were abstracted. Study quality was assessed with the Newcastle-Ottawa Scale, and studies with scores of at least 7 points were included. TABULATION, INTEGRATION, AND RESULTS: The data were extracted independently by multiple observers. Random-effects models were used to pool associations and to analyze the association between ovarian capsule rupture and oncologic outcomes. Seventeen studies met all the criteria for inclusion in the meta-analysis. Twelve thousand seven hundred fifty-six (62.6%) patients did not have capsule rupture and had disease confined to the ovary on final pathology; 5,532 (33.7%) patients had intraoperative capsule rupture of an otherwise early-stage ovarian cancer. Patients with intraoperative capsule rupture had worse progression-free survival (hazard ratio [HR] 1.92, 95% CI 1.34-2.76, P<.001), with moderate heterogeneity (I2=41%, P=.07) when compared with those without capsule rupture. Pooled results from these studies showed a worse overall survival (HR 1.48, 95% CI 1.15-1.91, P=.003), with moderate heterogeneity (I2=53%, P=.02) when compared with patients without intraoperative capsule rupture. This remained significant in a series of sensitivity analyses. CONCLUSION: This systematic review and meta-analysis of high-quality observational studies shows that intraoperative ovarian capsule rupture results in decreased progression-free survival and overall survival in women with early-stage ovarian cancer who are undergoing initial surgical management. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42021216561.

Uptake and Outcomes of Sentinel Lymph Node Mapping in Women With Atypical Endometrial Hyperplasia.

OBJECTIVE: To examine the utilization, morbidity, and cost of sentinel lymph node mapping in women undergoing hysterectomy for complex atypical endometrial hyperplasia. METHODS: Women with complex atypical endometrial hyperplasia who underwent hysterectomy from 2012 to 2018 in the Perspective database were examined. Perioperative morbidity, mortality, and cost were examined based on performance of sentinel lymph node mapping, lymph node dissection or no nodal evaluation. RESULTS: Among 10,266 women, sentinel lymph node mapping was performed in 620 (6.0%), lymph node dissection in 538 (5.2%), and no lymphatic evaluation in 9,108 (88.7%). Use of sentinel lymph node mapping increased from 0.8% in 2012 to 14.0% in 2018, and the rate of lymph node dissection rose from 5.7% to 6.4% (P<.001). In an adjusted model, residence in the western United States, treatment by high-volume hospitals and use of robotic-assisted hysterectomy were associated with sentinel lymph node mapping (P<.05 for all). The complication rates were similar between the three groups. The median cost for sentinel lymph node mapping ($9,673) and lymph node dissection ($9,754) were higher than in those who did not undergo nodal assessment ($8,435) (P<.001). CONCLUSION: Performance of sentinel lymph node mapping is increasing rapidly for women with complex atypical endometrial hyperplasia but is not associated with increased perioperative morbidity or mortality.

Necessity of routine cardiac evaluation in patients receiving pegylated liposomal doxorubicin for gynecologic cancer.

OBJECTIVE: Pegylated liposomal doxorubicin (PLD) has similar reported clinical efficacy compared with conventional doxorubicin with less cardiotoxicity. The manufacturer of PLD advises that cardiac function should be evaluated with endomyocardial biopsy, echocardiography or multigated radionucleotide scan (MUGA) pre-treatment and during therapy. This study was designed to assess the necessity of pre-treatment cardiac evaluation in patients receiving PLD. METHODS: After IRB approval, a retrospective study of all women with gynecologic cancer who received PLD from 2006 to 2018 was performed. Demographic information, treatment records, cardiac risk factors, and cardiac surveillance testing were examined. Wilcoxon signed rank sum test and logistic regression were used to evaluate the association of cumulative PLD exposure with cardiotoxicity. RESULTS: A total of 235 patients received PLD for gynecologic cancer. Patients received a median of 3 cycles of PLD with a cumulative dosage of 237 mg over a median follow-up time of 24 months. Sixteen patients in the cohort (7%) had no cardiac surveillance at all. Of the remaining patients who underwent cardiac testing, 183 (84%) received MUGA scans and 36 (16%) had echocardiography. Of the 56 patients who had both pre- and post-treatment cardiac testing, there was no significant difference in median ejection fraction (p = 0.17). Three patients developed PLD-associated cardiac toxicity but only one patient had severe manifestations requiring discontinuation of PLD therapy. CONCLUSIONS: Routine cardiac testing before, during or after treatment with PLD may be unnecessary. Cardiac testing may be more appropriate for individual patients for whom the clinical suspicion of PLD-related cardiac toxicity is high.

Preoperative PET/CT does not accurately detect extrauterine disease in patients with newly diagnosed high-risk endometrial cancer: A prospective study.

BACKGROUND: The identification of extrauterine disease is critical to the management of patients with high-risk endometrial cancer. The purpose of the current study was to determine the accuracy of preoperative positron emission tomography (PET)/computed tomography (CT) in the detection of extrauterine disease. METHODS: Women with high-risk endometrial cancer were enrolled prospectively and underwent preoperative PET/CT followed by surgery, including sentinel lymph node biopsy and lymphadenectomy. Primary tumor factors on PET/CT were correlated with lymph node pathology. The sensitivity, specificity, positive predictive value, and negative predictive value were calculated for the detection of lymphadenopathy and peritoneal disease by PET/CT. RESULTS: A total of 112 patients were enrolled and underwent PET/CT between April 2013 and May 2016, 108 of whom were evaluable. On PET/CT, 21 patients (19.4%) were found to have extrauterine disease, 18 (17%) had positive lymph nodes, and 8 (7%) had peritoneal disease. A total of 108 patients underwent surgery, 103 of whom (95%) underwent lymphadenectomy. The sensitivity of PET/CT to detect positive lymph nodes was 45.8%, with a specificity of 91.1%, positive predictive value of 61.1%, and negative predictive value of 84.7%. The false-negative rate was 54.2%. There was no difference in primary tumor characteristics on imaging noted between patients with positive and negative lymph nodes. The sensitivity of PET/CT to detect peritoneal disease was 37.5%, with a specificity of 97.8%, positive predictive value of 75%, and negative predictive value of 90.0%. The false-negative rate was 62.5%. CONCLUSIONS: Preoperative PET/CT did not reliably predict the presence of extrauterine disease in women with high-risk endometrial cancer. Given the high false-negative rates, PET/CT should not be used in the preoperative treatment planning of these patients.

Utilizing the Patient Reported Outcomes Measurement Information System (PROMIS®) to increase referral to ancillary support services for severely symptomatic patients with gynecologic cancer.

OBJECTIVE: The Patient-Reported Outcomes Measurement Information System (PROMIS®) Network has developed a comprehensive repository of electronic patient reported outcomes measures (ePROs) of major symptom domains that have been validated in cancer patients. Their use for patients with gynecologic cancer has been understudied. Our objective was to establish feasibility and acceptability of PROMIS ePRO integration in a gynecologic oncology outpatient clinic and assess if it can help identify severely symptomatic patients and increase referral to supportive services. METHODS: English-speaking patients with a confirmed history of gynecologic cancer completed PROMIS ePROs on iPads in the waiting area of an outpatient gynecologic oncology clinic. Symptom scores were calculated for each respondent and grouped using documented severity thresholds. Response data was compared with clinicopathologic characteristics across symptom domains. Severely symptomatic patients were offered referral to ancillary services and asked to complete post-exposure surveys assessing acceptability of the ePRO. RESULTS: Of the 336 patients who completed ePROs, 35% had active disease and 19% had experienced at least one disease recurrence. Sixty-nine percent of the cohort demonstrated moderate to severe physical dysfunction (60%), pain (36%), fatigue (28%), anxiety (9%), depression (8%), and sexual dysfunction (32%). Thirty-nine (12%) severely symptomatic patients were referred to services such as psychiatry, palliative care, pain management, social work or integrative oncology care. Most survey respondents identified the ePROs as helpful (78%) and easy to complete (92%). CONCLUSIONS: Outpatient PROMIS ePRO administration is feasible and acceptable to gynecologic oncology patients and can help identify severely symptomatic patients for referral to ancillary support services.

Characterization of Risk Factors and Timing of Venous Thromboembolism in Patients With Uterine Serous Carcinoma.

OBJECTIVE: To characterize risk factors and timing of venous thromboembolism in women with uterine serous carcinoma. METHODS: A retrospective cohort study was performed including all women diagnosed with uterine serous carcinoma from 1999 to 2016 at our institution. Clinicopathologic data and information regarding timing of venous thromboembolism were abstracted from the medical record. Logistic regression and Cox proportional hazards modeling were used to examine the association between covariates and risk and timing of venous thromboembolism. RESULTS: Seventy of the 413 included patients (17%) developed venous thromboembolism, with a median time from presentation to venous thromboembolism of 7.2 months (interquartile range 1.0-24.8) and from surgery to venous thromboembolism of 13.2 months (interquartile range 3.5-33.6). Fifty-nine of the 70 patients (84%) who developed venous thromboembolism were diagnosed either before surgery or greater than 6 weeks postoperatively. Twenty-two of the 70 patients (31%) who developed clots were on chemotherapy at the time of diagnosis. Venous thromboembolism was highly associated with cancer stage and presence of hypertension (P<.01). Cox proportional hazards modeling revealed that only cancer stages III and IV (hazard ratio [HR] 3.20, 95% CI 1.54-6.64 and HR 8.68, 95% CI 4.50-16.73, respectively) and hypertensive or cardiovascular diseases (HR 2.29, 95% CI 1.08-4.85 and HR 1.82, 95% CI 1.05-3.13) were associated with time to venous thromboembolism. CONCLUSION: Patients with uterine serous carcinoma are at high risk of developing venous thromboembolism even many months after their cancer diagnosis. This study generates the hypothesis that venous thromboembolism prophylaxis may be beneficial in patients with uterine serous carcinoma during other time points along the continuum of disease rather than only in the postoperative period, especially for those with advanced cancer.

Unplanned hospitalizations in a racially and ethnically diverse population of women receiving chemotherapy for epithelial ovarian cancer.

OBJECTIVES: Unplanned hospital admission following chemotherapy is a measure of quality cancer care. Large retrospective datasets have shown admission rates of 10-35% for women with ovarian cancer receiving chemotherapy. We sought to evaluate the prevalence and associated risk factors for hospital admission following chemotherapy in our racially diverse urban population. METHODS: After IRB approval, clinicopathologic and treatment data were abstracted from all patients with newly diagnosed epithelial ovarian cancer who received chemotherapy at our institution from 2005 to 2016. Two-sided statistical analyses and Cox regression analysis were performed using Stata. RESULTS: Of 217 evaluable patients, 87 (40%) had unplanned admissions following chemotherapy: adjuvant 64 (74%) and neoadjuvant 23(26%). Thirty (14%) had more than one admission. In total, there were 1314 days of hospitalization. The median readmission duration was 3 days. Body mass index and hypertension were predictive of readmission (p < 0.05). When comparing those readmitted more than once to those admitted once, both race and aspirin use were predictive of readmission (p < 0.05). Of those admitted more than once the self-identified race and ethnicity was 12 (40%) Hispanic, 8 (27%) White, 8 (27%) Black and 2 (7%) other. There was a significant difference in disease free (p = 0.01) and overall survival (p = 0.004) for patients with unplanned admission after chemotherapy as compared to those without admission. CONCLUSIONS: Readmission rates in our racially diverse patient population were higher than previously reported in the literature. Identifying patients at risk of readmission may play a role in chemotherapy decision-making, and resource allocation including patient care navigators.

Setting Benchmarks for the New User: Training on the Robotic Simulator.

BACKGROUND AND OBJECTIVES: Data showing the impact of the robotic simulator on fellowship training are limited. This study was conducted to determine whether simulator scores reflect the experience of the robotic gynecologic surgeon and to develop a simulator curriculum for trainees in gynecologic oncology. METHODS: All faculty and fellows in the Department of Gynecologic Oncology and Reproductive Medicine were asked to participate. For phase 1, all participants were divided into 2 groups based on robotic surgical experience: beginner (0-50 cases) and experienced (>50 cases). Each participant completed 9 modules 3 times each to establish baseline data. Median module scores for the experienced group defined the benchmarks scores. In phase 2, all trainees who did not meet the benchmark score on a module were asked to repeat the module until they reached the score twice. RESULTS: Twenty-four participants were included: 18 beginners and 6 experienced surgeons. For all modules, experienced surgeons received higher median scores than beginners. There was a significant difference between the scores of the 2 groups in the Energy Switching 1 (87.5 vs 92.5; P = .002) and Suture Sponge 2 (75.0 vs 87.3; P = .011) modules. Thirteen trainees participated in phase 2. For 8 of 9 of the modules, >75% of trainees met proficiency, with a median of 3 to 6 attempts (range, 2-24). CONCLUSION: Based on the findings, scores reflected each surgeon's experience. With repetition, most of the trainees were able to reach the benchmark scores. Further study is needed to determine the impact of surgical simulation on true intraoperative performance.

A prospective validation study of sentinel lymph node mapping for high-risk endometrial cancer.

OBJECTIVE: Sentinel lymph node (SLN) mapping continues to evolve in the surgical staging of endometrial cancer (EC). The purpose of this trial was to identify the sensitivity, false negative rate (FNR) and FN predictive value (FNPV) of SLN compared to complete pelvic and para-aortic lymphadenectomy (LAD) in women with high-risk EC. METHODS: Women with high-risk EC (grade 3, serous, clear cell, carcinosarcoma) were enrolled in this prospective surgical trial. All patients underwent preoperative PET/CT and intraoperative SLN biopsy followed by LAD. Patients with peritoneal disease on imaging or at the time of surgery were excluded. Patients were evaluable if SLN was attempted and complete LAD was performed. RESULTS: 123 patients were enrolled between 4/13 and 5/16; 101 were evaluable. At least 1 SLN was identified in 89% (90); bilateral detection 58%, unilateral pelvic 40%, para-aortic only 2%. Indocyanine green was used in 61%, blue dye in 28%, and blue dye and technetium in 11%. Twenty-three pts. (23%) had ≥1 positive node. In 20/23, ≥1 SLN was identified and in 19/20 the SLN was positive. Only 1 patient had bilateral negative SLN and positive non-SLNs on final pathology. Overall, sensitivity of SLN was 95% (19/20), FNR was 5% (1/20) and FNPV was 1.4% (1/71). If side-specific LAD was performed when a SLN was not detected, the FNR decreased to 4.3% (1/23). CONCLUSION: This prospective trial demonstrated that SLN biopsy plus side-specific LAD, when SLN is not detected, is a reasonable alternative to a complete LAD in high-risk endometrial cancer.