Representation of women in clinical trials supporting FDA-approval of contemporary cancer therapies.

Contemporary anticancer therapies frequently have different efficacy and side effects in men and women. Yet, whether women are well-represented in pivotal trials supporting contemporary anticancer drugs is unknown. Leveraging the Drugs@FDA database, clinicaltrials.gov, MEDLINE, and publicly available FDA-drug-reviews, we identified all pivotal (phase II and III) non-sex specific trials supporting FDA-approval of anticancer drugs (1998-2018). Observed-enrollment-rates were compared to expected-population-rates derived from concurrent US-National-Cancer-Institute's Surveillance-Epidemiology-and-End-Results (SEER) reported rates and US-Census databases. Primary outcome was the proportional representation of women across trials, evaluated by a participation-to-prevalence ratio (PPR), according to cancer type. Secondary outcome was the report of any sex-specific analysis of efficacy and/or safety, irrespective of treatment-arm. Overall, there were 148 trials, enrolling 60,216 participants (60.5 ± 4.0 years, 40.7% female, 79.1% biologic, targeted, or immune-based therapies) evaluating 99 drugs. Sex was reported in 146 (98.6%) trials, wherein 40.7% (24,538) were women, compared to 59.3% (35,678) men (p < .01). Altogether, women were under-represented in 66.9% trials compared to the proportional incidence of cancers by respective disease type; weight-average PPR of 0.91 (relative difference: -9.1%, p < .01). Women were most under-represented in gastric (PPR = 0.63), liver (PPR = 0.71), and lung (PPR = .81) cancer trials. Sex-based safety data was reported in 4.0% trials. There was no association between adequate female enrollment and drug efficacy (HR: 0.616 vs. 0.613, p = .96). Over time, there was no difference in the percentage of women recruited into clinical trials. Among pivotal clinical trials supporting contemporary FDA-approved cancer drugs, women were frequently under-represented and sex-specific-efficacy and safety-outcomes were commonly not reported.

Validation of the Combined Clinical Cell-Cycle Risk Score to Prognosticate Early Prostate Cancer Metastasis From Biopsy Specimens and Comparison With Other Routinely Used Risk Classifiers.

PURPOSE: We aim to independently validate the prognostic utility of the combined cell-cycle risk (CCR) multimodality threshold to estimate risk of early metastasis after definitive treatment of prostate cancer and compare this prognostic ability with other validated biomarkers. METHODS: Patients diagnosed with localized prostate cancer were enrolled into a single-institutional registry for the prospective observational cohort study. The primary end point was risk of metastasis within 3 years of diagnostic biopsy. Secondary end points included time to definitive treatment, time to subsequent therapy, and metastasis after completion of initial definitive treatment. Multivariable cause-specific Cox proportional hazards regression models were produced accounting for competing risk of death and stratified on the basis of the CCR active surveillance and multimodality (MM) thresholds. Time-dependent areas under the receiver operating characteristic curve were calculated. RESULTS: The cohort consisted of 554 men with prostate cancer and available CCR score from biopsy. The CCR score was prognostic for metastasis (hazard ratio [HR], 2.32 [95% CI, 1.17 to 4.59]; P = .02), with scores above the MM threshold having a higher risk than those below the threshold (HR, 5.44 [95% CI, 2.72 to 10.91]; P < .001). The AUC for 3-year risk of metastasis on the basis of CCR was 0.736. When men with CCR above the MM threshold received MM therapy, their 3-year risk of metastasis was significantly lower than those receiving single-modality therapy (3% v 14%). Similarly, a CCR score above the active surveillance threshold portended a faster time to first definitive treatment. CONCLUSION: CCR outperforms other commonly used biomarkers for prediction of early metastasis. We illustrate the clinical utility of the CCR active surveillance and multimodality thresholds. Molecular genomic tests can inform patient selection and personalization of treatment for localized prostate cancer.

Portrayal of Women as Physicians in Movies, 1990-2020.

This cross-sectional study quantifies the portrayal of women as physicians in US movies over the past 3 decades.

Racial and Gender Differences in Patient Satisfaction Scores Among Oncologists.

BACKGROUND: Patient satisfaction scores (PSS) have been adopted in health care reimbursement and faculty promotion metrics. Oncology patients face a challenging prognosis, where PSS may be perceived differently. We hypothesized that PSS differed based on gender and racial demographics of oncologists. MATERIALS AND METHODS: This was an institutional review board exempt cross-sectional study utilizing PSS data for outpatient oncologists within a large comprehensive cancer center. Patient demographics included age, gender, race/ethnicity, geographical residence, and disease site. Characteristics of oncologists included gender and race/ethnicity. We used PSS ≥95 to make comparisons. The association between patient and physician characteristics were evaluated using the t test and χ2 test. RESULTS: A total of 15,849 oncology patients were identified between 2011 and 2020. Survey respondents were predominantly female (53.2%), white (93.4%), between 50 and 70 years of age (55.3%), and living in an urban setting (63.6%). There were 303 oncologists with the majority being male (64.4%) and white (58.1%). Compared with white oncologists, Asian and Hispanic oncologists received lower PSS (P=0.001 and 0.0085, respectively). On subset analysis, these differences were significant among patients older than 50 years, living in rural counties, and reporting white or non-Hispanic race/ethnicity, or among patients of either gender (all P<0.05). Patients with genitourinary malignancies provided lower PSS for female oncologists (P=0.005). CONCLUSIONS: Asian and Hispanic oncologists were more likely to receive lower PSS. In addition, female oncologists treating genitourinary malignancies received lower PSS. Appropriate statistical adjustments are needed for PSS among oncologists to account for race, gender, and physician subspecialization to allow for equitable professional opportunities across demographics.

Diversity in modern heart failure trials: Where are we, and where are we going.

Over the last three decades, increased attention has been given to the representation of historically underrepresented groups within the landscape of pivotal clinical trials. However, recent events (i.e., coronavirus pandemic) have laid bare the potential continuation of historic inequities in available clinical trials and studies aimed at the care of broad patient populations. Anecdotally, cardiovascular disease (CVD) has not been immune to these disparities. Within this review, we examine and discuss recent landmark CVD trials, with a specific focus on the representation of Blacks within several critically foundational heart failure clinical trials tied to contemporary treatment strategies and drug approvals. We also discuss solutions for inequities within the landscape of cardiovascular trials. Building a more diverse clinical trial workforce coupled with intentional efforts to increase clinical trial diversity will advance equity in cardiovascular care.

Where Are the Women in Radiation Oncology? A Cross-Sectional Multi-Specialty Comparative Analysis.

PURPOSE: We aimed to evaluate the growth of women within the general radiation oncology (RO) workforce in comparison to the growth among other medical specialties. We also sought to create a predictive model for gender diversity to guide future recruitment efforts. METHODS AND MATERIALS: We identified 16 medical specialties, including RO, for analyses. We used data from the Association of American Colleges and assessed female representation at 4 time points (2006, 2011, 2016, and 2020). Additionally, we determined characteristics of medical specialties that were predictive of increased gender diversity. We performed univariate statistical analysis with linear regression to evaluate factors predictive of greater gender diversity among the medical specialties in our cohort. RESULTS: The proportion of women within the represented specialties increased over time. Obstetrics/gynecology (14,750 [2006], 23,921 [2020]; 18.7% absolute growth) and dermatology (3568 [2006], 6329 [2020]; 15.1% absolute growth) experienced the highest absolute growth in female representation between 2006 and 2020. When assessing changes between various time points in RO, the absolute change in female physicians increased by 1.5% between 2006 and 2011, by 2.2% between 2011 and 2016, and by only 0.4% between 2016 and 2020, which was the lowest growth pattern relative to the other 15 specialties. Factors predictive of gender diversity among specialties were lower average step 1 scores (P = .0056), fewer years of training (P = .0078), fewer work hours (P = .046), the availability of a standard third year clerkship for a given specialty (P = .0061), and a high baseline number of female physicians within a specialty (P = .0078). Research activities (P = .099) and interest among matriculating medical students (P = .28) were not statistically significant. CONCLUSIONS: The percentage of women in RO lags behind other medical specialties and has been notably low in the last few years. Interventions that incorporate novel initiatives proposed within this study may accelerate current recruitment milestones.

Chemoradiation Versus Chemotherapy in Uterine Carcinosarcoma: Patterns of Care and Impact on Overall Survival.

OBJECTIVES: Uterine carcinosarcoma (UCS) is a rare and aggressive cancer with poor survival. Our purpose was to evaluate the patterns-of-care and overall survival (OS) benefit of adjuvant chemoradiation (aCRT) compared with adjuvant chemotherapy (aCT) among UCS patients. METHODS: A query was made in the National Cancer Database to identify patients with UCS diagnosed between 2004 and 2012. Factors predictive of OS were determined using univariate and multivariate Cox regression analysis, as well as Kaplan-Meier and log-rank analysis. Propensity-score matching was employed to decrease the potential influence of selection bias. RESULTS: A total of 3538 patients were identified for analysis, consisting of 1787 patients (50.5%) receiving aCT and 1751 (49.5%) receiving aCRT. The median age of patients was 65 years. The majority of patients in our cohort were white (68.6%), on Medicare insurance (47.9%), with >5 cm tumor size (59.9%), and received a lymph node surgery (87.9%). The following factors were predictive of aCRT use: undergoing lymph node surgery (odds ratio, 1.59, P=0.01), and FIGO stage II (odds ratio, 1.71, P=0.01). Median survival for the aCT and aCRT groups was 24 months and 31.3 months, respectively. When compared with aCT alone, aCRT was associated with a benefit in OS on multivariate analysis (hazard ratio, 0.65, P<0.01). CONCLUSIONS: When compared with aCT alone, the use of aCRT in UCS patients was associated with a significant OS benefit. Multiple demographic and clinical factors significantly influence the choice of adjuvant therapy in this setting.

Predictors of Local Recurrence in Patients With Myxofibrosarcoma.

OBJECTIVES: Myxofibrosarcoma (MFS) is reported to have a higher risk of local recurrence (LR) following definitive surgical excision relative to other soft tissue sarcomas. We reviewed our clinical experience treating MFS to investigate predictors of LR. MATERIALS AND METHODS: We retrospectively reviewed treatment outcomes for MFS patients treated at our institution between 1999 and 2015. A total of 52 patients were identified. Median age was 65 years (range, 21 to 86 y). Site of disease was: upper extremity (27%), lower extremity (46%), trunk (15%), pelvic (8%), and head and neck (4%). Patients had low, intermediate, high-grade, and unknown grade in: 23%, 8%, 67%, and 2% of tumors, respectively. Tumors were categorized as ≤5 cm (35%), >5 cm (56%), or unknown size (9%). In total, 71% received radiotherapy: 19% preoperative, 50% postoperative, and 2% both. All patients underwent surgery. Margins were negative in 71%, close/positive in 21%, and unknown in 8%. In total, 27% of patients received chemotherapy. Univariate Cox regression analysis was utilized to determine associations between clinical and treatment factors with LR. RESULTS: Median follow-up time was 2.9 years (range, 0.4 to 14.3 y). The 3-year actuarial LR, distant metastasis, and overall survival were: 31%, 15%, and 87%, respectively. Predictors of LR were patient age greater than or equal to the median of 65 years (hazard ratio, 13.46, 95% confidence interval, 1.71-106.18, P=0.013), and having close/positive tumor margins (hazard ratio, 3.4, 95% confidence interval, 1-11.53, P=0.049). CONCLUSIONS: In this institutional series of MFS older age and positive/close margins were significantly associated with a higher risk of LR.

The Role of Radiation in All Stages of Nodular Lymphocytic Predominant Hodgkin Lymphoma.

BACKGROUND: The goal of this study was to assess the survival differences seen in early-stage and advanced-stage nodular lymphocytic predominant Hodgkin lymphoma (NLPHL) based on treatment modality. PATIENTS AND METHODS: The National Cancer Database was queried to identify patients diagnosed with NLPHL between 2004 and 2012. Overall survival (OS) was determined using univariate and multivariate Cox regression analysis. Kaplan-Meier and log-rank analysis were used to estimate differences in OS between treatment groups. RESULTS: A total of 1968 patients were identified for analysis, consisting of stage I (40.4%), stage II (29.3%), stage III (22.3%), and stage IV (8.0%) disease. The median age of patients was 46 years. The following factors were predictive of radiotherapy (RT) omission in treatment: increasing age, black race, Medicare insurance, chemotherapy use, stage II to IV disease, and the presence of B-symptoms. On survival analysis, RT was associated with prolonged OS in all stages of NLPHL (50.1 vs. 42.4 months; P < .01). The OS benefit of RT persisted on multivariate analysis (hazard ratio, 0.37; P < .01). On subset analysis, RT was associated with prolonged OS in early disease (49.8 vs. 45.5 months; P < .01), whereas a trend towards an OS benefit was observed in advanced-stage (54.1 vs. 39.6 months; P = .06) NLPHL. Radiotherapy was also associated with prolonged OS among patients with B-symptoms (49.0 vs. 42.6 months; P < .01). CONCLUSION: The use of RT in NLPHL is less likely among those with advanced-stage disease and B-symptoms. However, we found RT to be associated with prolonged OS in all stages of NLPHL, including those with B-symptoms.

The Addition of Adjuvant Chemotherapy to Radiation in Early-Stage High-Risk Endometrial Cancer: Survival Outcomes and Patterns of Care.

OBJECTIVE: Early-stage high-risk endometrial cancer (HREC) treated with adjuvant radiotherapy (aRT) alone has been associated with an increased risk of distant relapse. The addition of chemotherapy to radiotherapy (aCRT) may benefit overall survival (OS). We investigated the patterns-of-care and OS benefit of aCRT in HREC by analyzing a large national registry. METHODS: Our query was limited to patients with the International Federation of Gynecology and Obstetrics stage IB and II HREC with either papillary serous, clear cell, or grade 3 adenocarcinoma, diagnosed between 2004 and 2012. Logistic and Cox regression analyses were utilized to identify predictors of aCRT use and OS, respectively. Survival analysis was performed with Kaplan Meier and log-rank methods. Propensity score matching was employed to decrease the potential influence of selection bias. RESULTS: A total of 11,746 patients were identified for analysis with 8206 (69.9%) receiving aCRT, and 3540 (30.1%) received aRT. Predictors of aCRT included International Federation of Gynecology and Obstetrics stage II (odds ratio [OR], 1.39; 95% confidence interval [CI], 1.22-1.57), papillary serous (OR, 9.44; 95% CI, 8.22-10.85) or clear cell (OR, 3.21; 95% CI, 2.59-3.97) histology, lymph nodes removed (OR, 1.48; 95% CI, 1.31-1.69), and receipt of brachytherapy alone (OR, 1.55; 95% CI, 1.36-1.78). Estimated 5-year OS was 75.2% for patients receiving aRT only and 79.2% for those receiving aCRT (P < 0.001). When compared with aRT, aCRT was associated with improved OS on multivariate (hazard ratio, 0.78; 95% CI, 0.61-0.99) analysis. A univariate shared-frailty Cox regression after propensity score matching revealed persistence of the OS benefit with aCRT (hazard ratio, 0.74; 95% CI, 0.65-0.84). CONCLUSIONS: The addition of adjuvant chemotherapy to radiation in HREC is associated with improved OS. Multiple demographic and clinical factors significantly influence the choice of adjuvant therapy in this setting.