Repeating platinum/bevacizumab in recurrent or progressive cervical cancer yields marginal survival benefits

Our objective was to assess overall survival of cervical cancer patients following prior platinum/bevacizumab chemotherapy, comparing retreatment with platinum/bevacizumab with alternative therapies. A retrospective analysis was performed of women who received platinum/bevacizumab (PB) chemotherapy for cervical cancer at Washington University between July 1, 2005 and December 31, 2015. Wilcoxon rank-sum exact test and Fisher's exact test were used to compare the treatment groups, and Kaplan Meier curves were generated. Cox regression analyses were performed, with treatment free interval and prior therapy response included as covariates. Of 84 patients who received PB chemotherapy, 59 (70%) received no second line chemotherapy, as they did not recur, progressed without further chemotherapy, were lost to follow up, or expired. Of the remaining 25 patients, 9 were retreated with the combination of platinum/bevacizumab (PB), 6 were retreated with a platinum regimen without bevacizumab (P), and 10 were retreated with neither (not-P). The only long-term survivor was in the not-P group and was treated with an immunotherapy agent. Median overall survival of all patients was 7.1 months. There was a marginal difference in survival between women in the PB and not-PB groups (11.8 versus 5.7 months; HR 3.02, 95% CI, 0.98–9.28). There was no difference in survival based on platinum interval (HR 0.81; 95% CI, 0.27–2.45). Outcomes are grim for women retreated after platinum/bevacizumab therapy and are only marginally improved by retreatment with a platinum/bevacizumab regimen. Rather than additional PB therapy, women with cervical cancer who recur after platinum/bevacizumab should consider supportive care or clinical trials

Prolonged Use of the Etonogestrel Implant and Levonorgestrel Intrauterine Device - Two Years Beyond FDA-Approved Duration

The subdermal contraceptive implant, and the 52mg levonorgestrel intrauterine device (IUD) are currently FDA-approved for three and five years of use respectively. Limited available data has suggested both of these methods are effective beyond that time. Demonstration of prolonged effectiveness will improve the cost-effectiveness of the device, and potentially patient continuation and satisfaction. Objective To evaluate the effectiveness of the contraceptive implant and the 52-mg hormonal intrauterine device (IUD) in women using the method for two years beyond the current FDA-approved duration. Study Design We initiated this ongoing prospective cohort study in January 2012. We are enrolling women using the contraceptive implant or 52-mg levonorgestrel IUD for a minimum of 3 and 5 years, respectively (started IUD in 2007 or later or implant in 2009 or later). Demographic and reproductive health histories, as well as objective body mass index (BMI) were collected. Implant users were offered periodic venipuncture for analysis of serum etonogestrel levels. The primary outcome, unintended pregnancy rates, was calculated per 100 woman-years. We analyzed baseline demographic characteristics using chi-square test and Fisher Exact test, and compared serum ENG levels stratified by body mass index using the Kruskal-Wallis test. Results Implant users (n=291) have contributed 444.0 women-years of follow-up. There have been no documented pregnancies in implant users during the two years of post-expiration follow-up. Calculated failure rates in the fourth and fifth years for the implant are calculated as 0 (one-sided %97.5 confidence interval (CI) 0–1.48) per 100 woman years at four years and 0 (one-sided %97.5 CI 0–2.65) per 100 women years at five years. Among 496 levonorgestrel IUD users, 696.9 women-years of follow-up have been completed. Two pregnancies have been reported. The failure rate in the sixth year of use of the levonorgestrel IUD is calculated as 0.25(%95 CI 0.04–1.42) per 100 women year; failure rate during the seventh year is 0.43 (%95 CI 0.08–2.39) per 100 women years. Among implant users with serum etonogestrel results, the median etonogestrel level at the time of method expiration was 207.7 pg/mL (range 63.8–802.6 pg/mL), 166.1 pg/mL (range 67.9 25.0 – 470.5 pg/mL) at the end of the fourth year, and 153.0 pg/mL (range 72.1–538.8 pg/mL) at the end of the fifth year. Median ENG levels were compared by BMI at each time point and a statistical difference was noted at the end of four years of use with overweight women having the highest serum ENG (195.9 pg/ml: range 25.0–450.5) when compared to normal (178.9 pg/ml: range 87.0–463.7) and obese (137.9 pg/ml: range 66.0–470.5) women (p=0.04). Conclusion This study indicates that the contraceptive implant and 52-mg hormonal IUD continue to be highly effective for at least two additional years of use. Serum etonogestrel evaluation demonstrates median levels remain above the ovulation threshold of 90pg/ml for women of in all BMI classes

Comparison of an additional early visit to routine postpartum care on initiation of long-acting reversible contraception: A randomized trial

Objective To investigate whether an early 3-week postpartum visit in addition to the standard 6-week visit increases long-acting reversible contraception (LARC) initiation by 8 weeks postpartum compared to the routine 6-week visit alone. Study design We enrolled pregnant and immediate postpartum women into a prospective randomized, non-blinded trial comparing a single 6-week postpartum visit (routine care) to two visits at 3 and 6 weeks postpartum (intervention), with initiation of contraception at the 3-week visit, if desired. All participants received structured contraceptive counseling. Participants completed surveys in-person at baseline and at the time of each postpartum visit. A sample size of 200 total participants was needed to detect a 2-fold difference in LARC initiation (20% vs. 40%). Results Between May 2016 and March 2017, 200 participants enrolled; outcome data are available for 188. The majority of LARC initiation occurred immediately postpartum (25% of the intervention arm and 27% of the routine care arm). By 8 weeks postpartum, 34% of participants in the intervention arm initiated LARC, compared to 41% in the routine care arm (p=.35). Overall contraceptive initiation by 8 weeks was 83% and 84% in the intervention and routine care arms, respectively (p=.79). There was no difference between the arms in the proportion of women who attended at least one postpartum visit (70% vs. 74%, p=.56). Conclusion The addition of a 3-week postpartum visit to routine care does not increase LARC initiation by 8 weeks postpartum. The majority of LARC users desired immediate rather than interval postpartum initiation

Risk of Maternal Morbidity with Increasing Number of Cesareans

Objective To estimate the risk of perioperative morbidity with increasing number of cesareans. Study Design We conducted a retrospective cohort study from 2004 to 2010. Patients delivered by cesarean were included. Outcome measures were a composite organ injury (bowel or bladder), hysterectomy, hemorrhage requiring transfusion, severe morbidity, or surgical site complications. The Cochran–Armitage's test of trend was used to assess increasing incidence of each morbidity with number of prior cesareans. Multivariable logistic regression was used to estimate adjusted risks for each morbidity with increasing number of cesareans compared with primary cesarean. Results Of the 15,872 women in the cohort, 5,144 had cesarean delivery: 3,113 primary, 1,310 one prior, 510 two prior, and 211 three or more prior cesareans. There was a significant increase in organ injury, hysterectomy, and surgical site complications with increasing number of cesareans. In multivariable analysis, the risk of organ injury and hysterectomy was increased compared with primary cesarean after two prior cesareans, and after three or more cesareans for hemorrhage requiring transfusion and surgical site complications. Conclusion The risks of organ injury and hysterectomy are increased after two or more prior cesareans, and risks of hemorrhage and surgical site complications are increased after three or more cesareans

Disparities in human papillomavirus (HPV) vaccine initiation and completion based on sexual orientation among women in the United States

Objectives We compared HPV vaccine initiation and completion of heterosexual with lesbian and bisexual (LB) women. Methods We aggregated National Health and Nutrition Examination Survey data from 2009 to 2016 for 3,017 women aged 18 to 34 y in the United States. HPV vaccine initiation was defined as reported receipt of ≥1 dose of the vaccine and completion as receipt of the three recommended doses. Weighted percentages and multivariable logistic regression models were used to examine differences in HPV vaccine initiation and completion between heterosexual and LB women. Results Approximately 12% of respondents self-identified as LB women. Overall, a higher percentage of respondents (26%) had initiated the HPV vaccine than completed the three vaccine doses (17%). In the bivariate analysis, LB women had higher initiation ([35% of LB women versus 25% heterosexual]; p = .0012) and completion rates ([24% of LB women versus 17% heterosexual]; p = .0052) than heterosexual women. After adjusting for covariates, compared to heterosexual women, LB women were 60% (aOR = 1.60, 95% CI: 1.16–2.19) more likely to initiate and 63% (aOR = 1.63, 95% CI: 1.12–2.37) more likely to complete the HPV vaccine. Conclusions Although LB women had higher likelihood of HPV vaccine initiation and completion compared with heterosexual women, their HPV vaccine uptake was well below the Healthy People 2020 target (80%). Understanding differences in the drivers of vaccine uptake in the LB population may inform strategies that would further increase HPV vaccine uptake toward achieving the 80% completion target

Aspartate beta-hydroxylase domain containing 1 as a prognostic marker associated with immune infiltration in skin cutaneous melanoma

Abstract Background Skin cutaneous melanoma (SKCM) is an extremely malignant tumor and accounts for the majority of skin cancer deaths. Aspartate beta-hydroxylase domain containing 1 (ASPHD1) may participate in cancer progression through controlling α-ketoglutarate-dependent dioxygenases. However, its role in skin cutaneous melanoma (SKCM) has not been well studied. Methods The gene expression data of ASPDH1 and differentially expressed genes (DEGs) from TCGA and GTEx were evaluated, and verified via the GEO database. Then, we performed GO/KEGG, GSEA, PPI network analysis to analyze the functional implications of the DEGs related to ASPHD1. Then, the association between the ASPHD1 expression and clinical parameters was investigated by Cox regression analysis. Subsequently, the survival time of SKCM patients was evaluated by plotting Kaplan-Meier curves. Moreover, we investigated the correlation between the ASPHD1 expression and lymphocytic infiltration by using the data from TISIDB and TIMER 2.0. Next, we explored the association between ASPHD1 expression and drug sensitivity. Finally, we validate the expression differences by analyzing the results of qPCR, Western blot from human normal epidermal melanocytes and melanoma cells, and immunohistochemistry (IHC) from non-tumor skin as well as melanoma tissues. Results The ASPHD1 expression level was significantly upregulated in several cancers, including SKCM especially SKCM-metastasis tissues, and patients with an increased ASPHD1 expression had longer overall survival time than low expression ones. The functional enrichment analysis of ASPHD1-related DEGs showed an association with cell development regulation and tumorigenic pathways. Furthermore, the increased ASPHD1 expression level was associated with the level of immunostimulors, immunoinhibitors, chemokines, and TILs, such as CD4+, CD8+ T cell, mast cell, Th2 cell, and dendritic cell. More interesting, we found that ASPHD1 expression was tightly associated with CTLA4 and CD276 which are immune checkpoint markers. Moreover, the upregulated expression of ASPHD1 exhibited higher IC50 values for 24 chemotherapy drugs, including doxorubicin, and masitinib. Finally, the differential expression of ASPHD1 in SKCM was validated by the results of qPCR, Western blot, and IHC. Conclusion The expression of ASPHD1 in SKCM patients is closely related to patient survival. ASPHD1 may participate in the regulation of tumor immune microenvironment. Additionally, it may serve as a prognostic biomarker for SKCM and future in-depth studies are necessary to explore its value

Obesity counseling in obstetrics and gynecology: provider perceptions and barriers

To determine how obstetricians and gynecologists (OB/GYNs) perceive the gynecologic health effects of obesity and to identify perceived obstacles to counseling. OB/GYNs with 3 St. Louis health systems were emailed a 46-question survey regarding physicians' role in counseling women on the health risks of obesity and barriers faced in achieving this counseling. Differences between respondents' gender, age, practice type, years in practice, and body mass index were assessed using Chi-square or Fisher's exact tests as appropriate. Of 318 OB/GYNs emailed, 134 completed surveys, including 82 generalists and 52 subspecialists. 93% of respondents believed it was necessary to educate patients on health risks of obesity. 90% and 75%, respectively, cited diagnoses of endometrial hyperplasia and cancer as teachable moments for counseling. The most frequently cited barriers to successful counseling were lack of time, referral services, and patient tools/information. Most did not believe they had adequate reimbursement (65%), training (53%) or educational resources (50%) to counsel patients. Survey answers differed by practice setting, gender, and provider age. Although most OB/GYN providers consider obesity counseling important, execution is hindered by perceived barriers that differ by provider gender, age, and practice type. For OB/GYNs, more effective weight management counseling will require better training and practice-specific strategies. Based on survey responses, better reimbursement combined with increased resources for appropriate referrals and cancer prevention counseling are needed in order to improve weight management implementation in OB/GYN. Keywords: Endometrial cancer, Obesity, Weight management counselin

Inpatient management of hypercalcemia portends a poor prognosis among gynecologic oncology patients: A trigger to initiate hospice care?

We aim to describe survival outcomes of gynecologic oncology inpatients treated with intravenous bisphosphonates for hypercalcemia and develop a risk stratification model that predicts decreased survival to aid with goals of care discussion. In a single-center, retrospective cohort study of gynecologic oncology patients admitted for bisphosphonate therapy for hypercalcemia. Survival from hypercalcemia to death was assessed by Kaplan-Meier method and log-rank test. Univariate log-rank test and Cox proportional hazards modeling were used to develop a risk stratification model. Sixty-five patients were evaluable with a median follow-up of 83.5 months. Mean age was 59.2 years, 64.6% had recurrent disease, and 30.8% had ≥2 previous lines of chemotherapy. Median survival was 38 days. Our analysis identified four risk factors (RFs) [brain metastasis, >1 site of metastasis, serum corrected peak calcium >12.4 (mg/dL), and peak ionized calcium >5.97 (mg/dL)] that predicted survival and were used to build a risk stratification score. Sum of RFs included 35 patients with 1 RF, 11 had 2 RFs, and 19 had ≥3 RF. Median survival for 1, 2, or ≥ 3 RFs was 53, 28, and 26 days respectively (p = .009). Survival at 6 months was 28.6%, 18.2%, and 5.3% for each group respectively. Hospice enrollment was 26.2%, and did not vary by group (p = .51). Among gynecologic oncology patients, inpatient management of hypercalcemia with bisphosphonates portends poor prognosis. Individualized risk stratification may help guide end-of-life discussions and identify patients who may benefit most from hospice care