Recent Therapeutic Advances in Gynecologic Oncology: A Review.

Gynecologic malignancies have high incidence rates both nationally and internationally, and cervical, endometrial, and ovarian cancers account for high mortality rates worldwide. Significant research is ongoing to develop targeted therapies to address unmet needs in the field and improve patient outcomes. As tumors mutate and progress through traditional lines of treatment, new therapies must be developed to overcome resistance and target cancer-specific receptors and mutations. Recent advances in the development of immunotherapy and antibody-drug conjugates have resulted in compelling and clinically meaningful results in cervical, endometrial, and ovarian cancers. In the last decade, several immunotherapy agents have received FDA approval or NCCN guideline recommendation for the treatment of gynecologic malignancies, including dostarlimab for advanced or recurrent endometrial cancer and pembrolizumab for advanced or recurrent cervical and endometrial cancers. Several other immunotherapeutic agents are under active investigation. Development of antibody-drug conjugates including tisotumab vedotin in cervical cancer, mirvetuximab soravtansine in ovarian cancer, and trastuzumab deruxtecan in multiple gynecologic cancers has translated into exciting efficacy signals, prompting full drug approvals and additional investigation. This article aims to review recent novel advances in targeted treatments for gynecologic malignancies, highlighting the trials and data underlying these novel interventions.

Risk factors for the presence of residual disease in women after partial mastectomy for invasive breast cancer: A single institution experience.

BACKGROUND: We hypothesize that in addition to specimen margin widths other clinical variables may help predict the presence of residual disease in the lumpectomy bed. METHODS: Patients with Stage I-III invasive breast cancer (BC) who underwent partial mastectomy (PM) and re-excision from July 2010-June 2015 were retrospectively reviewed. Bivariate analyses were conducted using two-sample t-tests for continuous variables and Fisher's Exact tests for categorical variables. A multivariate logistic regression was then performed on significant bivariate analyses variables. RESULTS: ne-hundred and eighty-four patients were included in our analysis; 47% had residual disease on re-excision, while 53% had no residual disease. Tumor and nodal stage, operation type, type of disease present at margin, and number of positive margins were significantly associated with residual disease. On multivariate logistic regression, DCIS alone at the margin (p = 0.02), operation type (PM with cavity margins) (p = 0.003), and number of positive margins (3 or more) (p < 0.001) remained predictive of residual disease at re-excision. CONCLUSION: Based on a more comprehensive review of the initial pathology, there are additional factors that can help predict the likelihood of finding residual disease and help guide the surgeon in the decision for re-excision.

Text-message-based behavioral weight loss for endometrial cancer survivors with obesity: A randomized controlled trial.

OBJECTIVE: To evaluate the ability of a personalized text-message-based intervention to increase weight loss among endometrial cancer survivors with obesity. METHODS: In this randomized, controlled trial, endometrial cancer survivors with obesity (BMI ≥30 kg/m2) were randomized to a personalized SMS text-message-based weight loss intervention or enhanced usual care. Primary outcome was weight loss at 6 months; secondary outcomes were weight loss at 12 months and changes in psychosocial measures. We also compared clinical characteristics and weight change between trial participants and non-participants. RESULTS: Between May 18 and December 31, 2017, 80 endometrial cancer survivors with obesity consented to participate in the randomized trial. There were no differences in clinical characteristics between the two arms. Weight changes were similar in the two arms (P = 0.08). At 6 months, no differences in quality of life, physical activity, or body image were noted. Of 358 eligible patients, 80 became trial participants and 278, non-participants. Trial participants were younger (59.3 vs. 63.4 years, P < 0.001), more likely non-white (P = 0.02), on fewer medications (4 vs. 7, P < 0.001), and had a higher median BMI (38.7 vs. 37.6 kg/m2, P = 0.01) than non-participants. Weight change was similar between participants and non-participants (P = 0.85). At 6 months, similar percentages of participants and non-participants (47.7% vs. 44.4%) had gained weight, and similar percentages (9.2% vs. 11.2%) had lost at least 5% of their body weight. CONCLUSIONS: This text-message-based intervention did not increase weight loss among endometrial cancer survivors with obesity, nor did participation in the trial. Other weight management interventions should be promoted to increase weight loss. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT03169023.

Obese endometrial cancer survivors' perceptions of weight loss strategies and characteristics that may influence participation in behavioral interventions.

We aimed to evaluate obese endometrial cancer (EC) survivors' perceptions of weight loss barriers and previously attempted weight loss methods and to identify characteristics that predicted willingness to enroll in a behavioral intervention trial. We administered a 27-question baseline survey at an academic institution to EC survivors with body mass index ≥ 30 kg/m2. Survivors were asked about their lifestyles, previous weight loss attempts, perceived barriers, and were offered enrollment into an intervention trial. Data was analyzed using Fisher's Exact, Kruskal-Wallis, and univariate and multivariate regressions. 155 of 358 (43%) eligible obese EC survivors were surveyed. Nearly all (n = 148, 96%) had considered losing weight, and 77% (n = 120) had tried two or more strategies. Few had undergone bariatric surgery (n = 5, 3%), psychologic counseling (n = 2, 1%), or met with physical therapists (n = 9, 6%). Lower income was associated with difficulty in accessing interventions. Survivors commented that negative self-perceptions and difficulties with follow-through were barriers to weight loss, and fear of complications and self-perceived lack of qualification were deterrents to bariatric surgery. 80 (52%) of those surveyed enrolled in the trial. In a multivariate model, adjusting for race and stage, survivors without recurrence were 4.3 times more likely to enroll than those with recurrence. Most obese EC survivors have tried multiple strategies to lose weight, but remain interested in weight loss interventions, especially women who have never experienced recurrence. Providers should encourage weight loss interventions early, at the time of initial diagnosis, and promote underutilized strategies such as psychological counseling, physical therapy, and bariatric surgery.

Creating Healthful Work Environments to Deliver on the Quadruple Aim: A Call to Action.

Nurses face workplace stressors that contribute to job dissatisfaction, burnout, and turnover, impacting not only patient safety but the nurses' physical and emotional well-being. At the 2018 American Academy of Nursing conference, a policy dialogue "Creating Healthy Work Environments to Address the Quadruple Aim" was convened focusing on creating healthy work environments by addressing stressors such as violence and bullying. That discussion is encapsulated in this article, providing proven and practical strategies for reducing risk.

Increased Risk of Breast and Uterine Cancer Among Women With Ovarian Granulosa Cell Tumors.

BACKGROUND/AIM: We evaluated the incidence of uterine and breast cancer among women diagnosed with granulosa cell tumors (GCTs) of the ovary. PATIENTS AND METHODS: The US Surveillance, Epidemiology, and End Results (SEER) database was accessed and patients diagnosed with a GCT and had a known follow-up between 1973-2014 were identified. Personal tumor history was extracted and patients with a previous or subsequent malignant breast or uterine tumor were identified. The expected incidence of breast and uterine cancer was calculated based on the U.S age-specific rate of breast and uterine cancer per 100,000 women. Standardized incidence ratio (SIR) with 95% confidence intervals (95% CI) were calculated for each tumor. RESULTS: A total of 1908 cases of GCT were identified. Seventy- nine (4.14%) and 53 (2.78%) patients were diagnosed with a malignant breast and uterine malignancy. The cumulative expected number of malignant breast and uterine tumors was 27 (1.41%) and 6 (0.31%), respectively. The calculated SIR for breast and uterine malignancies was 2.96 (95%CI=2.34, 3.68) and 8.83 (95%CI=6.61, 11.56), respectively. CONCLUSION: An increased incidence of breast and uterine malignancies among patients diagnosed with GCTs was observed.

Prognostic significance of elevated pre-treatment serum CA-125 levels in patients with stage I ovarian sex cord-stromal tumors.

OBJECTIVE: To investigate the prognostic significance of elevated pre-operative serum CA-125 values for patients with early stage ovarian sex cord - stromal tumors (SCSTs). METHODS: Patients diagnosed between 2004 and 2015 with a SCST were drawn from the U.S National Cancer Database. Those with stage I disease, and normal or elevated CA-125 values were selected for further analysis. Overall survival (OS) was evaluated for patients diagnosed between 2004 and 2014 with Kaplan-Meier curves, and compared with the log-rank test. A multivariate Cox analysis was performed to control for known confounders. RESULTS: A total of 1156 patients met the inclusion criteria; 486 (42%) had elevated pre-treatment CA-125 values. Patients with elevated pre-treatment CA-125 (n = 417) had worse OS compared to those with normal values (n = 588), p < 0.001 from log-rank test; 5-yr OS rates were 86.8% and 94.8% respectively. After controlling for patient age (<50 vs > = 50 yrs), the presence of medical co-morbidities, tumor histology (granulosa vs non-granulosa), size (<10 vs > = 10 cm vs unknown) and the performance of lymphadenectomy, elevated pre-treatment CA-125 levels were associated with a worse survival (HR: 1.80, 95% CI: 1.15, 2.82, p = 0.01). CONCLUSIONS: In a large cohort of patients with early stage SCSTs elevated preoperative CA-125 levels were associated with worse survival.

Conservative management of endometrial hyperplasia or carcinoma with the levonorgestrel intrauterine system may be less effective in morbidly obese patients.

•Endometrial hyperplasia/carcinoma regression rates with LNG-IUS were examined by BMI.•Morbidly obese patients with EH/EHA/EC are more likely to progress.•Despite addition of oral progesterone to LNG-IUS, morbid obesity increases the odds of progression.

DeuteRater: a tool for quantifying peptide isotope precision and kinetic proteomics.

MOTIVATION: Using mass spectrometry to measure the concentration and turnover of the individual proteins in a proteome, enables the calculation of individual synthesis and degradation rates for each protein. Software to analyze concentration is readily available, but software to analyze turnover is lacking. Data analysis workflows typically don't access the full breadth of information about instrument precision and accuracy that is present in each peptide isotopic envelope measurement. This method utilizes both isotope distribution and changes in neutromer spacing, which benefits the analysis of both concentration and turnover. RESULTS: We have developed a data analysis tool, DeuteRater, to measure protein turnover from metabolic D 2 O labeling. DeuteRater uses theoretical predictions for label-dependent change in isotope abundance and inter-peak (neutromer) spacing within the isotope envelope to calculate protein turnover rate. We have also used these metrics to evaluate the accuracy and precision of peptide measurements and thereby determined the optimal data acquisition parameters of different instruments, as well as the effect of data processing steps. We show that these combined measurements can be used to remove noise and increase confidence in the protein turnover measurement for each protein. AVAILABILITY AND IMPLEMENTATION: Source code and ReadMe for Python 2 and 3 versions of DeuteRater are available at https://github.com/JC-Price/DeuteRater . Data is at https://chorusproject.org/pages/index.html project number 1147. Critical Intermediate calculation files provided as Tables S3 and S4. Software has only been tested on Windows machines. CONTACT: jcprice@chem.byu.edu. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.