Disease progression, survival, and molecular disparities in Black and White patients with endometrioid endometrial carcinoma in real-world registries and GOG/NRG oncology randomized phase III clinical trials.

OBJECTIVE: Investigate racial disparities in outcomes and molecular features in Black and White patients with endometrioid endometrial carcinoma (EEC). METHODS: Black and White patients diagnosed with EEC who underwent hysterectomy ± adjuvant treatment in SEER, National Cancer Database (NCDB), the Genomics Evidence Neoplasia Information Exchange (GENIE) project (v.13.0), and eight NCI-sponsored randomized phase III clinical trials (RCTs) were studied. Hazard ratio (HR) and 95% confidence interval (CI) were estimated for cancer-related death (CRD), non-cancer death (NCD), and all-cause death. RESULTS: Black (n = 4397) vs. White (n = 47,959) patients in SEER had a HR (95% CI) of 2.04 (1.87-2.23) for CRD and 1.22 (1.09-1.36) for NCD. In NCDB, the HR (95% CI) for death in Black (n = 13,468) vs. White (n = 155,706) patients was 1.52 (1.46-1.58) dropping to 1.29 (1.23-1.36) after propensity-score matching for age, comorbidity, income, insurance, grade, stage, LVSI, and treatment. In GENIE, Black (n = 109) vs. White (n = 1780) patients had fewer PTEN, PIK3R1, FBXW7, NF1, mTOR, CCND1, and PI3K-pathway-related gene mutations. In contrast, TP53 and DNA-repair-related gene mutation frequency as well as tumor mutational burden-high status were similar in Black and White patients. In RCTs, Black (n = 187) vs. White (n = 2877) patients were more likely to have advanced or recurrent disease, higher grade, worse performance status and progressive disease. Risk of death in Black vs. White patients in RCTs was 2.19 (1.77-2.71) persisting to 1.32 (1.09-1.61) after matching for grade, stage, and treatment arm while balancing age and performance status. CONCLUSIONS: Differences exist in clinical presentation, outcomes, and molecular features in Black vs. White patients with EEC in real-world registries and RCTs. Targeted-drug development, strategies to modify social determinants, and diverse inclusion in RCTs are approaches to reduce disparities.

Immuno-Molecular Targeted Therapy Use and Survival Benefit in Patients with Stage IVB Cervical Carcinoma in Commission on Cancer®-Accredited Facilities in the United States.

PURPOSE: To investigate IMT use and survival in real-world stage IVB cervical cancer patients outside randomized clinical trials. METHODS: Patients diagnosed with stage IVB cervical cancer during 2013-2019 in the National Cancer Database and treated with chemotherapy (CT) ± external beam radiation (EBRT) ± intracavitary brachytherapy (ICBT) ± IMT were studied. The adjusted hazard ratio (AHR) and 95% confidence interval (CI) for risk of death were estimated in patients treated with vs. without IMT after applying propensity score analysis to balance the clinical covariates. RESULTS: There were 3164 evaluable patients, including 969 (31%) who were treated with IMT. The use of IMT increased from 11% in 2013 to 46% in 2019. Age, insurance, facility type, sites of distant metastasis, and type of first-line treatment were independently associated with using IMT. In propensity-score-balanced patients, the median survival was 18.6 vs. 13.1 months for with vs. without IMT (p < 0.001). The AHR was 0.72 (95% CI = 0.64-0.80) for adding IMT overall, 0.72 for IMT + CT, 0.66 for IMT + CT + EBRT, and 0.69 for IMT + CT + EBRT + ICBT. IMT-associated survival improvements were suggested in all subgroups by age, race/ethnicity, comorbidity score, facility type, tumor grade, tumor size, and site of metastasis. CONCLUSIONS: IMT was associated with a consistent survival benefit in real-world patients with stage IVB cervical cancer.

Survival disparities in non-Hispanic Black and White cervical cancer patients vary by histology and are largely explained by modifiable factors.

PURPOSE: We investigated racial disparities in survival by histology in cervical cancer and examined the factors contributing to these disparities. METHODS: Non-Hispanic Black and non-Hispanic White (hereafter known as Black and White) patients with stage I-IV cervical carcinoma diagnosed between 2004 and 2017 in the National Cancer Database were studied. Survival differences were compared using Cox modeling to estimate hazard ratio (HR) or adjusted HR (AHR) and 95% confidence interval (CI). The contribution of demographic, socioeconomic and clinical factors to the Black vs White differences in survival was estimated after applying propensity score weighting in patients with squamous cell carcinoma (SCC) or adenocarcinoma (AC). RESULTS: This study included 10,111 Black and 43,252 White patients with cervical cancer. Black patients had worse survival than White cervical cancer patients (HR = 1.40, 95% CI = 1.35-1.45). Survival disparities between Black and White patients varied significantly by histology (HR = 1.20, 95% CI = 1.15-1.24 for SCC; HR = 2.32, 95% CI = 2.12-2.54 for AC, interaction p < 0.0001). After balancing the selected demographic, socioeconomic and clinical factors, survival in Black vs. White patients was no longer different in those with SCC (AHR = 1.01, 95% CI 0.97-1.06) or AC (AHR = 1.09, 95% CI = 0.96-1.24). In SCC, the largest contributors to survival disparities were neighborhood income and insurance. In AC, age was the most significant contributor followed by neighborhood income, insurance, and stage. Diagnosis of AC (but not SCC) at ≥65 years old was more common in Black vs. White patients (26% vs. 13%, respectively). CONCLUSIONS: Histology matters in survival disparities and diagnosis at ≥65 years old between Black and White cervical cancer patients. These disparities were largely explained by modifiable factors.

Uterine cancer among Asian Americans - Disparities & clinical characteristics.

OBJECTIVE: To evaluate the patterns and trends of uterine cancer among Asian subgroups living in the U.S. METHODS: Data were obtained from United States Cancer Statistics (2001-2017), National Cancer Database (2004-2015), and World Population Review (2023). SEER*Stat version 8.3.9.2, Joinpoint regression program 4.9.0.0, and SAS v 9.4 were employed for statistical analysis. RESULTS: Based on data from 778,891 women in the United States Cancer Statistics database, Asians had a 3.4-fold higher rate of incident uterine cancer compared to White populations (2.14% vs. 0.63%; p < 0.001). Using the National Cancer Database, 7,641 Asian women from six subgroups were analyzed: Filipino, Korean, Indian/Pakistani, Vietnamese, Chinese, and Japanese. Indian and Pakistani women had the greatest increase in the proportion of cancer diagnoses (5.0% to 14.4%; p = 0.0003). Additionally, Indian and Pakistani patients had higher comorbidity scores while Koreans had the lowest (22.7% vs. 10.7%, p < 0.0001). Regarding stage of disease, 25.3% of Filipinos presented with advanced stage disease compared to 19.2% of Indians and Pakistanis (p = 0.0001). Furthermore, Filipinos had the highest proportion of non-endometrioid cancers at 18.4% compared to other subgroups (p = 0.0003). Using the World Population Review, female obesity was highest in Pakistan (8.6%) and the Philippines (7.5%) and lowest in Vietnam (2.6%). CONCLUSION: Uterine cancer incidence increased at higher rates among Asians compared to White populations. Specifically, Indian and Pakistani uterine cancer patients were more likely to have higher comorbidity rates and Filipino patients had more advanced stage cancer with non-endometrioid histologies than other Asian subgroups. Further research is warranted to better understand these trends.

Racial, ethnic and country of origin disparities in aggressive endometrial cancer histologic subtypes.

OBJECTIVE: This study investigated the risk of an aggressive endometrial cancer (EC) diagnosis by race, ethnicity, and country of origin to further elucidate histologic disparities in non-Hispanic Black (NHB), Hispanic, Asian/Pacific Islander (API), American Indian/Alaskan Native (AIAN) vs. non-Hispanic White (NHW) patients, particularly in Hispanic or API subgroups. METHODS: Patient diagnosed between 2004 and 2020 with low grade (LG)-endometrioid endometrial cancer (ECC) or an aggressive EC including grade 3 EEC, serous carcinoma, clear cell carcinoma, mixed epithelial carcinoma, or carcinosarcoma in the National Cancer Database were studied. The odds ratio (OR) and 95% confidence interval (CI) for diagnosis of an aggressive EC histology was estimated using logistic modeling. RESULTS: There were 343,868 NHW, 48,897 NHB, 30,013 Hispanic, 15,015 API and 1646 AIAN patients. The OR (95% CI) for an aggressive EC diagnosis was 3.07 (3.01-3.13) for NHB, 1.08 (1.06-1.11) for Hispanic, 1.17 (1.13-1.21) for API and 1.07 (0.96-1.19) for AIAN, relative to NHW patients. Subset analyses by country of origin illustrated the diversity in the OR for an aggressive EC diagnosis among Hispanic (1.18 for Mexican to 1.87 for Dominican), Asian (1.14 Asian Indian-Pakistani to 1.48 Korean) and Pacific Islander (1.00 for Hawaiian to 1.33 for Samoan) descendants. Hispanic, API and AIAN patients were diagnosed 5-years younger that NHW patients, and the risk for an aggressive EC histology were all significantly higher than NHW patients after correcting for age. Insurance status was another independent risk factor for aggressive histology. CONCLUSIONS: Risk of an aggressive EC diagnosis varied by race, ethnicity, and country of origin. NHB patients had the highest risk, followed by Dominican, South/Central American, Cuban, Korean, Thai, Vietnamese, and Filipino descendants.

Underrepresentation of racial and ethnic minority groups in gynecologic oncology: An analysis of over 250 trials.

OBJECTIVE: To describe the participation of racial and ethnic minority groups (REMGs) in gynecologic oncology trials. METHODS: Gynecologic oncology studies registered on ClinicalTrials.gov between 2007 and 2020 were identified. Trials with published results were analyzed based on reporting of race/ethnicity in relation to disease site and trial characteristics. Expected enrollment by race/ethnicity was calculated and compared to actual enrollment, adjusted for 2010 US Census population data. RESULTS: 2146 gynecologic oncology trials were identified. Of published trials (n = 252), 99 (39.3%) reported race/ethnicity data. Recent trials were more likely to report these data (36% from 2007 to 2009; 51% 2013-2015; and 53% from 2016 to 2018, p = 0.01). Of all trials, ovarian cancer trials were least likely to report race/ethnicity data (32.1% vs 39.3%, p = 0.011). Population-adjusted under-enrollment for Blacks was 7-fold in ovarian cancer, Latinx 10-fold for ovarian and 6-fold in uterine cancer trials, Asians 2.5-fold in uterine cancer trials, and American Indian and Alaska Native individuals 6-fold in ovarian trials. Trials for most disease sites have enrolled more REMGs in recent years - REMGs made up 19.6% of trial participants in 2007-2009 compared to 38.1% in 2016-2018 (p < 0.0001). CONCLUSION: Less than half of trials that published results reported race/ethnicity data. Available data reveals that enrollment of REMGs is significantly below expected rates based on national census data. These disparities persisted even after additionally adjusting for population size. Despite improvement in recent years, additional recruitment of REMGs is needed to achieve more representative and equitable participation in gynecologic cancer clinical trials.

Preoperative and pre-chemotherapy CA-125 levels in high-risk early-stage ovarian cancer - An NRG/GOG study.

OBJECTIVES: To determine clinical significance of preoperative and pre-chemotherapy CA-125 in high-risk early-stage epithelial ovarian cancer patients. METHODS: All patients with stage IA/IB and grade 3, stage IC, clear cell, or completed resected stage II cancer were enrolled in a phase III trial and treated with chemotherapy. Kaplan-Meier method and Cox proportional hazards model were used for statistical analyses. RESULTS: 427 patients with high-risk early-stage ovarian cancer were enrolled. Of 213 patients with preoperative CA-125 data, 79% had elevated CA-125. Median preoperative CA-125 level was 103 U/mL. Patients with ≤10, 11-15, and > 15 cm tumors had median preoperative CA-125 levels of 62, 131 and 158 U/mL, respectively (p = 0.002). For the 350 patients with data for pre-chemotherapy CA-125 level, 69% had elevated pre-chemotherapy CA-125 above 35 U/mL with median value of 65 U/mL. However, age, race, stage, cell type and grade of disease were not correlated with CA-125 levels before and after surgery. On multivariate analysis, elevated pre-chemotherapy CA-125 independently predicted worse recurrence-free survival (HR = 2.13, 95% CI: 1.23-3.69; p = 0.007) and overall survival (HR = 1.99, 95% CI: 1.10-3.59; p = 0.022) after adjusting for age, stage, cell type and grade of disease. Compared to those with normal CA-125, patients with elevated pre-chemotherapy CA-125 had lower recurrence-free survival (RFS, 87% vs. 75%; p = 0.007) and overall survival (OS, 88% vs. 82%; p = 0.02). However, preoperative CA-125 was not prognostic of RFS (p = 0.699) or OS (p = 0.701). CONCLUSIONS: Preoperative CA-125 was elevated in nearly 80% of high-risk early-stage ovarian cancer patients. Pre-chemotherapy CA-125 was associated with recurrence-free and overall survival; however, preoperative CA-125 was not prognostic.

Sequential Targeted Therapy for Advanced, Metastatic, and Recurrent Cervical Cancer: A Cost-Effectiveness Analysis of the Patient Journey.

OBJECTIVES: To evaluate outcomes and cost-effectiveness of targeted therapy sequencing for metastatic and recurrent cervical cancer. METHOD: Models were simulated based on phase II and III trials on bevacizumab (bev) from GOG-240, cemiplimab (cemi) from GOG 3016, pembrolizumab (pembro) from KEYNOTE-826, and tisotumab vedotin (tiso) from GOG 3023. Costs were based on IBM Micromedex RED BOOK™ and company listed costs. RESULTS: For [chemo + bev → chemo], total cost was $125,918.04, with median overall survival (mOS) of 21.8 months, and cost-effectiveness ratio (CER) of $119,835.79. For [chemo + bev → cemi], total cost was $187,562.99 with mOS of 28.5 months and CER of $162,039.16. For [chemo + bev + pembro → chemo], total cost was $319,963.78 with mOS 32.9 months and CER of $249,930.10. For [chemo + bev + pembro → tiso], total cost was $455,204.45, with mOS 36.5 months and CER of $320,072.99. CONCLUSION: The combination of immunotherapies and biologics have significantly increased overall survival, but with associated higher costs, primarily related to drug costs.

Ciliated Cells in Ovarian Cancer Decrease with Increasing Tumor Grade and Disease Progression.

Ciliated cell markers expressed in epithelial ovarian cancers (EOC) are associated with improved survival. We examined the distribution of cells expressing ciliated cell markers in various EOC histologies and stages. Immunohistochemistry and/or multiplex immunofluorescence were used to determine the expression of FOXJ1 and/or CAPS (ciliated cell markers) in tissue microarrays including 4 normal fallopian tubes, 6 normal endometria, 16 cystadenomas, 25 borderline tumors, 21 low-grade carcinomas, and 118 high-grade carcinomas (HGSOC) (46 serous, 29 endometrioid, 30 clear cell, 13 mucinous). CAPS+ cells were observed in normal fallopian tubes and endometria and in ~85% of serous benign and borderline tumors and low-grade carcinomas but only in <40% of HGSOC. mRNA data from an independent cohort showed higher FOXJ1 and CAPS expression in serous borderline tumors and low-grade carcinomas compared to HGSOC. In HGSOC, ciliated cell-positive markers were observed in 52% primary tumors compared to 26% of patient-matched synchronous metastases, and 24% metachronous metastases (p = 0.009). mRNA data from an independent HGSOC cohort showed lower levels of CAPS in metastases than in primary tumors (p = 0.03). Overall, the study revealed that ciliated cells were less common in mucinous EOC, the percentage of ciliated cell marker-positive cases decreased with increasing grade, and the percentage of ciliated cells decreased in HGSOC metastases compared to patient-matched primary tumors.

The clinical and prognostic significance of pre-chemotherapy serum CA-125 in high-risk early stage ovarian cancer: An NRG/GOG ancillary study.

OBJECTIVES: To determine the clinical and prognostic significance of CA-125 trends prior to, during, and after chemotherapy in high-risk early-stage epithelial ovarian cancer patients. METHODS: All patients were enrolled in a phase III randomized trial (GOG 157) following upfront surgery for grade 3 stage IA/IB, stage IC, or stage II disease, and had been treated with either three or six cycles of carboplatin/paclitaxel. Kaplan-Meier method and Cox proportional hazards model were used to evaluate recurrence-free survival (RFS) and overall survival (OS). RESULTS: Of 350 patients, the median pre-chemotherapy CA-125 was 65 (IQR: 31-129). 71% of Whites had an elevated CA-125 compared to 47% of non-Whites (p = 0.006). Following the first cycle of chemotherapy, 74% of those with elevated CA-125 had normalization. Those who had normalization of CA-125 after 1 cycle had significantly better 5-year RFS (81% vs. 65%, p = 0.003) and OS (87% vs. 75%, p = 0.009) compared to those who did not normalize (defined as ≤35 U/mL). The pattern of CA-125 change following chemotherapy cycle 1, from normal to normal vs. elevated to normal vs. elevated to elevated had corresponding RFS of 87% vs. 80% vs. 68% (p = 0.013), and OS of 92% vs. 88% vs. 77% (p = 0.009). However, the percent decline (p = 0.993) and absolute nadir normal value of CA-125 (0-10 vs. 11-35 U/mL) were not predictive of outcome (p = 0.4). CONCLUSIONS: Normal baseline CA125 and normalization of this biomarker after the first cycle of chemotherapy were associated with better survival in high-risk early-stage epithelial ovarian cancer patients.

The Role of Diet Compared to Physical Activity on Women's Cancer Mortality: Results From the Third National Health and Nutrition Examination Survey.

Background: Among women in the United States, cancer is the second leading cause of death. Prior studies have examined how lifestyle factors, such as diet and physical activity, influence cancer mortality. However, few have evaluated if diet or physical activity has a stronger protective effect for cancer mortality. Therefore, this study aims to evaluate and compare the impacts of diet and physical activity on women's cancer mortality. Methods: Prospective, cross-sectional data were abstracted from the Third US National Health and Nutrition Examination Survey (NHANES III) on female respondents from 1988 to 1994. Physical activity was derived from the CDC's metabolic equivalent (MET) intensity levels. Dietary classifications were derived from the USDA's healthy eating index (HEI). We utilized the National Death Index to obtain mortality follow-up information on our cohort until December 31, 2015. Chi-squared, multivariable Cox regression, and Kaplan-Meier estimates were employed for statistical analyses. Results: Of 3,590 women (median age: 57, range: 40-89), 30% had an obese BMI (BMI≥30 kg/m2). Additionally, 22% of participants self-reported a healthy diet, 69% needed dietary improvement, and 9% had a poor diet. Furthermore, 21% reported physical inactivity, 44% did not meet physical activity guidelines, and 35% met guidelines. On multivariate analysis, healthy diet (HR: 0.70; 95% CI: 0.51-0.98; p = 0.04), but not physical activity (HR: 0.87; 95% CI: 0.55-1.38; p = 0.55), independently predicted for lower cancer mortality. Participants with a healthy diet but low exercise had decreased cancer mortality compared to participants with an unhealthy diet but high exercise (p = 0.01). Conclusions: A healthful diet was associated with lower cancer mortality in women, even after adjusting for obesity, inflammation, and other covariates. In addition, diet may play a stronger role in reducing cancer mortality in women than physical activity.

How many US obstetrical trials reach publication? A cross-sectional analysis of ClinicalTrials.gov and PubMed from 2007 to 2019.

BACKGROUND: Obstetrical clinical trials are the foundation of evidence-based medicine during pregnancy. As more obstetrical trials are conducted, understanding the publication characteristics of these trials is of utmost importance to advance obstetrical health. OBJECTIVE: This study aimed to characterize the frequency of publication and trial characteristics associated with publication among obstetrical clinical trials in the United States. We additionally sought to examine time from trial completion to publication. STUDY DESIGN: This was a cross-sectional analysis of completed obstetrical trials with an intervention design and at least 1 site in the United States registered to ClinicalTrials.gov from 2007 to 2019. Trial characteristics were cross-referenced with PubMed to determine publication status up to 2021 using the National Clinical Trial identification number. Bivariable analyses were conducted to determine trial characteristics associated with publication. Multivariable logistic regression models controlling for prespecified covariates were generated to estimate the relationship between funding, primary purpose, and therapeutic foci with publication. Additional exploratory analyses of other trial characteristics were conducted. Time to publication was analyzed using Kaplan-Meier curves and Cox regression models. RESULTS: Of the 1879 obstetrical trials with registered completion, a total of 575 (30.6%) had at least 1 site in the United States, were completed before October 1, 2019, and were included in this analysis. Between October 2007 and October 2019, fewer than two-thirds (N=348, 60.5%) of trials reached publication. Annual rates of publication ranged from 46.4% in 2018 to 70.0% in 2007. No difference was observed in publication by funding, primary purpose, or therapeutic foci (all P>.05). Trials with characteristics indicating high trial quality-including randomized allocation scheme, ≥50 participants enrolled, ≥2 sites, and presence of a data safety monitoring committee-had increased odds of publication compared with those without such characteristics (all P<.05). For example, studies with randomized allocation of intervention had 2-fold greater odds of publication than nonrandomized studies (adjusted odds ratio, 2.09; 95% confidence interval, 1.30-3.37). Studies with ≥150 participants had nearly 8-fold odds of publication (adjusted odds ratio, 7.90; 95% confidence interval, 3.78-17.49) relative to studies with <50 participants. Temporal analysis demonstrated variability in time to publication among obstetrical trials, with a median time of 20.1 months after trial completion, and with most trials that reached publication having been published by 40 months. No difference was observed in time to publication by funding, primary purpose, or therapeutic foci (all P>.05). CONCLUSION: Publication of obstetrical trials remains suboptimal, with significant differences observed between trials with indicators of high quality and those without. Most trials that reach publication are published within 2 years of registered completion on ClinicalTrials.gov.

The obstetrical research landscape: a cross-sectional analysis of clinical trials from 2007-2020.

Background: Obstetrical complications affect more than a third of women globally, but are underrepresented in clinical research. Little is known about the comprehensive obstetrical clinical trial landscape, how it compares with other fields, or factors associated with the successful completion of obstetrical trials. Objective: This study aimed to characterize obstetrical clinical trials registered on ClinicalTrials.gov with the primary objective of identifying features associated with early discontinuation and results reporting. Study Design: This is a cross-sectional study with descriptive, logistic regression and Cox regression analyses of clinical trials registered on ClinicalTrials.gov. Our primary exposure variables were trial focus (obstetrical or nonobstetrical) and trial funding (industry, United States government, or academic). We conducted additional exploratory analyses of other trial features including design, enrollment, and therapeutic focus. We examined the associations of exposure variables and other trial features with 2 primary outcomes: early discontinuation and results reporting. Results: We downloaded data for all studies (N=332,417) registered on ClinicalTrials.gov from October 1, 2007, to March 9, 2020, from the Aggregate Analysis of ClinicalTrials.gov database. We excluded studies with a noninterventional design (n=63,697) and those registered before October 1, 2007 (n=45,209). A total of 4276 obstetrical trials (1.9%) (ie, interventional studies) and 219,235 nonobstetric trials (98.1%) were compared. Among all trials, 2.8% of academic-funded trials, 1.9% of United States government-funded trials, and 0.4% of industry-funded trials focused on obstetrics. The quantity of obstetrical trials increased over time (10.8% annual growth rate). Compared with nonobstetrical trials, obstetrical trials had a greater risk of early discontinuation (adjusted hazard ratio, 1.40; 95% confidence interval, 1.21-1.62; P<.0001) and similar odds of results reporting (adjusted odds ratio, 0.89; 95% confidence interval, 0.72-1.10; P=.19). Among obstetrical trials funders after controlling for confounding variables, United States government-funded trials were at the lowest risk of early discontinuation (United States government, adjusted hazard ratio, 0.23; 95% confidence interval, 0.07-0.69; P=.009; industry reference; academic, adjusted hazard ratio, 1.04; 95% confidence interval, 0.62-1.74; P=.88). Academic-funded trials had the lowest odds of results reporting after controlling for confounding variables (academic institutions, adjusted odds ratio, 0.39; 95% confidence interval, 0.22-0.68; P=.0009; industry reference; United States government, adjusted odds ratio, 1.06; 95% confidence interval, 0.53-2.09; P=.87). Conclusion: Obstetrical trials represent only 1.9% of all clinical trials in ClinicalTrials.gov and have comparatively poor completion. All stakeholders should commit to increasing the number of obstetrical trials and improving their completion and dissemination to ensure clinical research reflects the obstetrical burden of disease and advances maternal health.

Long term survival outcomes of stage I mucinous ovarian cancer - A clinical calculator predictive of chemotherapy benefit.

OBJECTIVES: To determine the long-term potential benefit of adjuvant chemotherapy in subgroups of high-risk stage I mucinous ovarian cancer patients using a predictive scoring algorithm. METHODS: Data were collected from the National Cancer Database from 2004 to 2014. Based on demographic and surgical characteristics, a novel 10-year survival prognostic scoring system was developed using Cox regression. RESULTS: There were 2041 eligible patients with stage I mucinous ovarian cancer including 1362 (67%) with stage IA/IB disease, 598 (29%) with stage IC disease, and 81 (4%) with stage I disease not otherwise specified. Median age was 52 with a range of 13-90 years old. 737 (36%) patients were treated with adjuvant chemotherapy. Adjuvant chemotherapy was more common in patients with stage IC relative to stage IA/IB disease (69% vs. 21%, P < 0.001) or with poorly-differentiated relative to well-differentiated tumors (69% vs. 23%, P < 0.001). Unadjusted 10-year survival was 81% relative to 79% for patients treated with vs. without chemotherapy, respectively (P = 0.46). Patients were predicted to exhibit a low- or a high-risk of death using a multivariate Cox regression model with age, stage, grade, lymphovascular space invasion and ascites. Risk of death without vs. with adjuvant chemotherapy was similar in low-risk patients (88% vs. 84%; HR = 0.80, 95%CI = 0.56-1.15, P = 0.23) and worse in high-risk patients (51% vs. 74%; HR = 1.58, 95%CI: 1.05-2.38, P = 0.03) with stage I mucinous ovarian cancer. CONCLUSIONS: A predictive scoring algorithm may provide prognostic information on long-term survival and identify high-risk stage I mucinous ovarian cancer patients who might achieve a survival benefit from adjuvant chemotherapy.

Impact of adjuvant treatment and prognostic factors in stage I uterine leiomyosarcoma patients treated in Commission on Cancer®-accredited facilities.

OBJECTIVES: Determine the impact of adjuvant chemotherapy (ACT) and prognostic factors in surgically managed patients with stage I uterine leiomyosarcoma (ULMS). METHODS: Women who underwent hysterectomy and were diagnosed with stage I ULMS between 2010 and 2014 in the National Cancer Database were eligible for this observation study. Inverse probability of treatment weighting based on propensity score was used to balance clinical characteristics between ACT and no ACT patients. Hazard ratio (HR) and 95% confidence interval (CI) were estimated from Cox modeling. RESULTS: There were 1059 eligible patients with stage I ULMS including 514 treated with ACT and 545 with no ACT. Patient characteristics and tumor features varied in patients treated with ACT vs. no ACT (P < .0001). Multivariate survival analysis demonstrated that patient age, comorbidity score, tumor size, lymphovascular space invasion (LVSI) and grade were independent prognostic factors. After propensity score weighting to control for imbalance of prognostic clinical factors, adjusted five-year survival was 61.7% vs. 61.3% and restricted mean survival time was 39.7 vs. 40.6 months for ACT vs. no ACT, respectively. Risk of death in a weighted Cox analysis of overall survival was similar (HR = 1.08, 95% CI = 0.85-1.37, P = .054) for ACT vs. no ACT patients. Subset analysis demonstrated that survival was similar in ACT vs. no ACT patients categorized by age, tumor size and LVSI or with high grade or ungraded tumors. In contrast, patients with low grade tumors had worse 5-year survival (82.3% vs. 91.5%) and an increased risk of death (HR = 3.79, 95% CI = 1.15-12.40, P = .028) following ACT vs. no ACT. CONCLUSIONS: ACT did not improve survival over no ACT in patients with stage I ULMS and was inferior in patients with low grade tumors.

Celebrity Influence Affecting Public Interest in Plastic Surgery Procedures: Google Trends Analysis.

BACKGROUND: Medical decisions made by celebrities have a profound influence on medical decisions made by the general population. Google Trends (GT) is a free, online resource with virtually no barriers to use that allows for tracking of global search volumes as a proxy for determining public interest. In this study, we utilize GT to characterize the significant and measurable effects that the May 2013 announcement of Angelina Jolie's BRCA-influenced prophylactic mastectomy, May 2015 announcement of Kylie Jenner's lip augmentation, April 2017 announcement of Caitlyn Jenner's gender affirming surgery and February 2014 media attention given to Kim Kardashian's rumored buttock augmentation had on corresponding surgical procedure volumes. METHODS: GT databases of search volumes were collected for terms related to prophylactic mastectomy, lip augmentation, gender affirming surgery and buttock augmentation categories from January 2004 to March 2019 using the "related queries" feature. Mean search volumes prior to respective announcements were compared to that of the period starting 6 months after. Additionally, the percent change from the month preceding respective celebrity announcements was compared to the month of the announcement for each search term. RESULTS: For mastectomy, all terms demonstrated peak interest during May 2013. Following Jolie's announcement, interest in "mastectomy" rose 1328%, "prophylactic mastectomy" rose 324%, "BRCA1" rose 316%, "BRCA2" rose 138% and "BRCA gene" rose 354%. Long-term interest was higher after May 2013 than beforehand for all terms except "prophylactic mastectomy" (each, p < 0.001). Following Kylie Jenner's announcement, interest in "lip augmentation" rose 43%, "lip enhancement" rose 37%, "lip fillers" rose 3233%, "lip implants" rose 8% and "lip injections" rose 13%. Long-term interest was higher after May 2015 than beforehand for all terms except "lip augmentation" and "lip enhancement" (each, p < 0.001). Following Caitlyn Jenner's announcement, "gender affirming surgery" rose 119%, "gender reassignment" rose 186%, "gender reassignment surgery" rose 203% and "transgender surgery" rose 35%. Long-term interest was higher after April 2017 than beforehand for all terms except "sex change" (each, p < 0.001). Following Kardashian's rumored injections, interest in "butt enhancement" rose 34% and "butt implants" rose 100%. Long-term interest was higher after February 2014 than beforehand for all terms (each, p < 0.001). CONCLUSIONS: GT data trends correlate with shifts in real-world healthcare utilization and healthcare-related public interest caused by high-profile public events, making it a useful tool for real-time prediction of trends in public health in response to a variety of observable influences. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

The Quality of Systematic Reviews and Meta-Analyses in Erectile Dysfunction Treatment and Management Published in the Sexual Medicine Literature.

INTRODUCTION: Erectile dysfunction (ED) is a common medical condition that requires high-quality evidence to guide clinical practice; however, systematic reviews (SRs) and meta-analyses (MAs) often vary in quality, raising concerns regarding the validity of their results. AIM: To perform an objective analysis of SRs and MAs in ED treatment and management and to report on the quality of published literature. METHODS: A comprehensive search in PubMed/MEDLINE and EMBASE of 12 high-impact urology journals was used to identify relevant publications. 2 authors independently performed searches, screened citations for eligibility, extracted data for analysis, and graded methodologic quality using A Measurement Tool to Assess Systematic Reviews (AMSTAR) criteria. MAIN OUTCOME MEASURES: The main outcome was AMSTAR score, which is a validated tool to evaluate the quality of SRs and MAs. RESULTS: 31 publications met inclusion criteria and were included in the analysis. The mean AMSTAR score (± SD) among all publications was 6.5 (±2.2) of 11, reflecting "fair to good" quality. 74.2% of systematic reviews and meta-analyses focused on pharmaceutical therapy for ED, with 51.6% studying the effect of phosphodiesterase-5 inhibitors. Only 1 SR/MA studied intracavernosal injection therapy and vacuum erection devices. No publications studied intraurethral injection therapy or implantable penile prostheses. Although not statistically significant, there has been a trend of increasing quality of SRs/MAs over time (P = .072). CLINICAL IMPLICATION: The methodologic quality of SRs/MAs should be assessed to ensure high-quality evidence for clinical practice guidelines in ED treatment and management. STRENGTH & LIMITATION: The data showed that methodologic quality of SRs/MAs in the treatment and management of ED is increasing over time. 12 high-impact urology journals were included in our search, which may introduce selection bias in our results. CONCLUSIONS: This review highlights a need for increased effort to study second- and third-line treatments for patients who fail oral therapy. Greenberg DR, Richardson MT, Tijerina JD, et al. The Quality of Systematic Reviews and Meta-Analyses in Erectile Dysfunction Treatment and Management Published in the Sexual Medicine Literature. J Sex Med 2019;16:394-401.

A Three-Step Letter Advance Directive Procedure to Facilitate Patient-Proxy Alignment in Advance Care Planning.

Background: Little is known about the extent of alignment between hematopoietic stem cell transplant (HSCT) patients and their healthcare proxies with respect to advance care planning (ACP). Aim: To determine if a structured three-step process using the letter advance directive (LAD) could (1) allow for the differences in opinion between patient-proxy dyads to surface and (2) help bridge preexisting discordance about specific treatment choices. Design: Blinded to each other, the HSCT patient (LAD-1) and proxy (LAD-2) each completed the LAD (step 1). They unmasked, compared LAD-1 and LAD-2, and discussed their choices (step 2). They completed a final letter directive (LAD-3) by consensus (step 3). Settings/Participants: Convenience sample of eighty dyads (patient and proxy) at a regional HSCT referral center. Results: The mean patient-proxy concordance was 72.9% for the 12 questions in the LAD. Wanting to be pain free at the end of life was the statement with the most amount of agreement (88.75% in LAD-1, 91.25% in LAD-2, and 90% in LAD-3). Patient-proxy dyads had notable discordance related to specific treatments. The highest discordance was related to ventilator support (46.3% of patients refused it, while 58.8% of proxies refused on behalf of the patient). Overall, proxies were more likely than patients to opt in for dialyses and hospice care but more likely to opt out for cardiac resuscitation and sedation to palliate refractory symptoms. On open discussion, patient-proxy discordance mostly resolved in favor of the patient. Conclusions: The ACP process should allow for patient-proxy differences to surface, facilitate a discussion about the granular details with the goal of reaching consensus. Our three-step approach using the LAD is an effective way to identify areas of patient-proxy concordance and discordance about specific treatment preferences. A structured patient-proxy discussion using the LAD helped reconcile discordance and most often in favor of a patient's original wishes.