NRG-GY012: Randomized phase 2 study comparing olaparib, cediranib, and the combination of cediranib/olaparib in women with recurrent, persistent, or metastatic endometrial cancer.

PURPOSE: This paper reports the efficacy of the poly (ADP-ribose) polymerase inhibitor olaparib alone and in combination with the antiangiogenesis agent cediranib compared with cediranib alone in patients with advanced endometrial cancer. METHODS: This was open-label, randomized, phase 2 trial (NCT03660826). Eligible patients had recurrent endometrial cancer, received at least one (<3) prior lines of chemotherapy, and were Eastern Cooperative Oncology Group performance status 0 to 2. Patients were randomly assigned (1:1:1), stratified by histology (serous vs. other) to receive cediranib alone (reference arm), olaparib, or olaparib and cediranib for 28-day cycles until progression or unacceptable toxicity. The primary end point was progression-free survival in the intention-to-treat population. Homologous repair deficiency was explored using the BROCA-GO sequencing panel. RESULTS: A total of 120 patients were enrolled and all were included in the intention-to-treat analysis. Median age was 66 (range, 41-86) years and 47 (39.2%) had serous histology. Median progression-free survival for cediranib was 3.8 months compared with 2.0 months for olaparib (hazard ratio, 1.45 [95% CI, 0.91-2.3] p = .935) and 5.5 months for olaparib/cediranib (hazard ratio, 0.7 [95% CI, 0.43-1.14] p = .064). Four patients receiving the combination had a durable response lasting more than 20 months. The most common grade 3/4 toxicities were hypertension in the cediranib (36%) and olaparib/cediranib (33%) arms, fatigue (20.5% olaparib/cediranib), and diarrhea (17.9% cediranib). The BROCA-GO panel results were not associated with response. CONCLUSION: The combination of cediranib and olaparib demonstrated modest clinical efficacy; however, the primary end point of the study was not met. The combination was safe without unexpected toxicity.

Health-related quality of life in patients with newly diagnosed advanced ovarian cancer treated with niraparib vs placebo: Results from the phase 3 randomized PRIMA/ENGOT-OV26/GOG-3012 trial.

OBJECTIVE: To assess patient-reported health-related quality of life (HRQoL) in patients with ovarian cancer (OC) who received niraparib as first-line maintenance therapy. METHODS: PRIMA/ENGOT-OV26/GOG-3012 (NCT02655016) enrolled patients with newly diagnosed advanced OC who responded to first-line platinum-based chemotherapy. Patients were randomized (2:1) to niraparib or placebo once daily in 28-day cycles until disease progression, intolerable toxicity, or death. HRQoL was assessed as a prespecified secondary end point using patient-reported responses to the European Organisation for Research and Treatment of Cancer QOL Questionnaire (EORTC QLQ-C30), the EORTC QLQ Ovarian Cancer Module (EORTC QLQ-OV28), the Functional Assessment of Cancer Therapy-Ovarian Symptom Index (FOSI), and EQ-5D-5L questionnaires. Assessments were collected at baseline and every 8 weeks (±7 days) for 56 weeks, beginning on cycle 1/day 1, then every 12 weeks (±7 days) thereafter while the patient received study treatment. RESULTS: Among trial participants (niraparib, n = 487; placebo, n = 246), PRO adherence exceeded 80% for all instruments across all cycles. Patients reported no decline over time in HRQoL measured via EORTC QLQ-C30 Global Health Status/QoL and FOSI overall scores. Scores for abdominal/gastrointestinal symptoms (EORTC QLQ-OV28) and nausea and vomiting, appetite loss, and constipation (EORTC QLQ-C30) were higher (worse symptoms) in niraparib-treated patients than placebo-treated patients; except for constipation, these differences resolved over time. Patients did not self-report any worsening from baseline of fatigue, headache, insomnia, or abdominal pain on questionnaires. CONCLUSIONS: Despite some early, largely transient increases in gastrointestinal symptoms, patients with OC treated with niraparib first-line maintenance therapy reported no worsening in overall HRQoL.

The effect of older age on treatment outcomes in women with advanced ovarian cancer receiving chemotherapy: An NRG-Oncology/Gynecologic Oncology Group (GOG-0182-ICON5) ancillary study.

OBJECTIVE: To assess the effect of age on overall survival (OS) in women with ovarian cancer receiving chemotherapy. Secondary objectives were to describe the effect of age on treatment compliance, toxicities, progression free survival (PFS), time from surgery to chemotherapy, and rates of optimal cytoreduction. METHODS: Women enrolled in GOG 0182-ICON5 with stage III or IV epithelial ovarian cancer (EOC) who underwent surgery and chemotherapy between 2001 and 2004 were included. Patients were divided into ages <70 and ≥ 70 years. Baseline characteristics, treatment compliance, toxicities, and clinical outcomes were compared. RESULTS: We included a total of 3686 patients, with 620 patients (16.8%) ≥ 70 years. OS was 37.2 months in older compared to 45.0 months in younger patients (HR 1.21, 95% CI, 1.09-1.34, p < 0.001). Older patients had an increased risk of cancer-specific-death (HR 1.16, 95% CI, 1.04-1.29) as well as non-cancer related deaths (HR 2.78, 95% CI, 2.00-3.87). Median PFS was 15.1 months in older compared to 16.0 months in younger patients (HR 1.10, 95% CI, 1.00-1.20, p = 0.056). In the carboplatin/paclitaxel arm, older patients were just as likely to complete therapy and more likely to develop grade ≥ 2 peripheral neuropathy (35.7 vs 19.7%, p < 0.001). Risk of other toxicities remained equal between groups. CONCLUSIONS: In women with advanced EOC receiving chemotherapy, age ≥ 70 was associated with shorter OS and cancer specific survival. Older patients receiving carboplatin and paclitaxel reported higher rates of grade ≥ 2 neuropathy but were not more likely to suffer from other chemotherapy related toxicities. Clintrials.gov: NCT00011986.

Risk of corticosteroid treatment and hospitalization after checkpoint inhibitor and radiation therapy in patients with cancer.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are potent new cancer therapies but can cause serious immune-related adverse events. ICIs have contributed significantly to improved survival and thereby provide more opportunity for the development of local disease symptomatology requiring palliative radiation. Radiation therapy (RT) has also recently shown benefit in the oligometastatic setting. Data on the interaction and safety of concurrent ICIs and RT are limited. METHODS: In this retrospective cohort study using a large medical claims database from 2010 to 2017, the need for corticosteroid therapy and the risk of hospitalization within 180 days of treatment with an ICI were determined for patients with a diagnosis of malignant melanoma or lung cancer. Patients were stratified by the use of RT within the 30 days before and after ICI therapy. RESULTS: In all, 2020 patients (218 with RT and 1802 without RT) met the inclusion criteria for prednisone analysis, whereas 3519 patients (361 with RT and 3158 without RT) met the inclusion criteria for all other analyses. In a univariable analysis, RT was not associated with the need for prednisone (relative risk [RR], 1.2; 95% confidence interval [CI], 0.8-1.9) or methylprednisolone (RR, 1.1; 95% CI, 0.7-2.0). When the end point was hospitalization, RT was significantly associated with hospitalization after ICI therapy for certain cancer/drug combinations (RR for lung cancer/programmed death 1 receptor inhibitors, 1.4; 95% CI, 1.2-1.6; P < .001; RR for melanoma/ipilimumab, 2.0; 95% CI, 1.0-3.5; P = .03). CONCLUSIONS: In patients treated with ICIs, receiving RT was not associated with a higher risk of requiring corticosteroid therapy in comparison with not receiving RT. However, RT was associated with a higher risk of hospitalization, although this finding may be a result of differences in the underlying patient illness severity or oncologic disease burden at the baseline. LAY SUMMARY: Data on the interaction of immunotherapy (immune checkpoint inhibitors) and radiation therapy and the safety of combining them are limited. Using a large database, this study has found that patients treated concurrently with immune checkpoint inhibitors and radiation therapy are not at increased risk for requiring corticosteroid therapy (which is used as a proxy for immune-related adverse events). However, concurrent therapy is associated with a higher risk of hospitalization, although this finding may be due to differences in the underlying patient illness severity (sicker patients may require both immunotherapy and radiation therapy).

Chaotic Diffusion in Delay Systems: Giant Enhancement by Time Lag Modulation.

We consider a typical class of systems with delayed nonlinearity, which we show to exhibit chaotic diffusion. It is demonstrated that a periodic modulation of the time lag can lead to an enhancement of the diffusion constant by several orders of magnitude. This effect is the largest if the circle map defined by the modulation shows mode locking and, more specifically, fulfills the conditions for laminar chaos. Thus, we establish for the first time a connection between Arnold tongue structures in parameter space and diffusive properties of a system. Counterintuitively, the enhancement of diffusion is accompanied by a strong reduction of the effective dimensionality of the system.

Disparity of ovarian cancer survival between urban and rural settings.

OBJECTIVE: To determine if there is a difference in overall survival of patients with epithelial ovarian cancer in rural, urban, and metropolitan settings in the United States. METHODS: We performed a retrospective cohort study using 2004-2016 National Cancer Database (NCDB) data including high and low grade, stage I-IV disease. Bivariate analyses used Student's t-test for continuous variables and χ2 test for dichotomous variables. Kaplan-Meier curves estimated survival of patients based on location of residence, and univariate analyses using Cox proportional HR assessed survival based on baseline characteristics. Multivariate analysis was performed to account for significant covariates. Propensity score matching was used to validate the multivariate survival model. For all tests, p<0.05 was considered statistically significant. RESULTS: A total of 111 627 patients were included with a mean age of 62.5 years for metroolitan (range 18-90), 64.0 years for rural (range 19-90) and 63.2 years for urban areas (range 18-90). Of all patients included, 94 290 were in a metropolitan area (counties >1 million population or 50 000-999 999), 15 386 were in an urban area (population of 10 000-49 999), and 1951 were in a rural area (non-metropolitan/non-core population). Univariate Cox proportional hazards models showed clinically significant differences in survival in patients from metropolitan, urban, and rural areas. Multivariate Cox proportional hazards models showed a clinically significant increase in HRs for patients in rural settings (HR 1.17; 95% CI 1.06 to 1.29). Increasing age and stage, non-insured status, non-white race, and comorbidity were also significant for poorer survival. CONCLUSION: Patients with ovarian cancer who live in rural settings with small populations and greater distance to tertiary care centers have poorer survival. These differences hold after controlling for stage, age, and other significant risk factors related to poorer outcomes. To improve clinical outcomes, we need further studies to identify which of these factors are actionable.

Investigating the effect of optimal cytoreduction in the context of platinum sensitivity in high-grade serous ovarian cancer.

INTRODUCTION: The survival benefits of surgical cytoreduction in ovarian cancer are well-established. However, the surgical outcome has never been assessed while controlling for the efficacy of chemotherapy. This leaves the possibility that cytoreduction may not be beneficial for patients whose cancer does not respond well to adjuvant treatment. We sought to answer whether surgical cytoreduction independently improves overall survival when controlling for chemotherapy outcome. MATERIAL AND METHODS: We performed a retrospective case-control study using our institution's ovarian cancer database to evaluate the effect of optimal cytoreduction on advanced stage, high-grade serous ovarian cancer. Patients' characteristics were compared using both univariate and multivariate regression modeling to assess for independent predictors of overall survival. RESULTS: A total of 470 patients were assessed for inclusion; 234 responders to chemotherapy and 98 nonresponders. Significant survival characteristics were identified and included in the multivariate analysis. Independent predictors of survival in the multivariate analysis were age, responder status, optimal cytoreduction, neoadjuvant chemotherapy, and number of chemotherapy cycles. Kaplan-Meier survival curves showed improved survival for both patients who responded to chemotherapy and for those undergoing optimal cytoreduction (p < 0.001). We also demonstrated improved survival for patients receiving optimal cytoreduction among both nonresponders and responders (p < 0.001). CONCLUSIONS: Our analysis shows that patients who undergo optimal cytoreduction have an overall survival benefit regardless of their response to chemotherapy. Therefore, cytoreduction should be considered in all patients, even in those with advanced disease, if an optimal result can be achieved. This study was underpowered to assess patients who received neoadjuvant chemotherapy as a separate subgroup, but the order of treatment was controlled for in the overall analysis.

Integration of Genomic and Clinical Retrospective Data to Predict Endometrioid Endometrial Cancer Recurrence.

Endometrial cancer (EC) incidence and mortality continues to rise. Molecular profiling of EC promises improvement of risk assessment and treatment selection. However, we still lack robust and accurate models to predict those at risk of failing treatment. The objective of this pilot study is to create models with clinical and genomic data that will discriminate patients with EC at risk of disease recurrence. We performed a pilot, retrospective, case−control study evaluating patients with EC, endometrioid type: 7 with recurrence of disease (cases), and 55 without (controls). RNA was extracted from frozen specimens and sequenced (RNAseq). Genomic features from RNAseq included transcriptome expression, genomic, and structural variation. Feature selection for variable reduction was performed with univariate ANOVA with cross-validation. Selected variables, informative for EC recurrence, were introduced in multivariate lasso regression models. Validation of models was performed in machine-learning platforms (ML) and independent datasets (TCGA). The best performing prediction models (out of >170) contained the same lncRNA features (AUC of 0.9, and 95% CI: 0.75, 1.0). Models were validated with excellent performance in ML platforms and good performance in an independent dataset. Prediction models of EC recurrence containing lncRNA features have better performance than models with clinical data alone.

Using Genomic Variation to Distinguish Ovarian High-Grade Serous Carcinoma from Benign Fallopian Tubes.

The preoperative diagnosis of pelvic masses has been elusive to date. Methods for characterization such as CA-125 have had limited specificity. We hypothesize that genomic variation can be used to create prediction models which accurately distinguish high grade serous ovarian cancer (HGSC) from benign tissue. METHODS: In this retrospective, pilot study, we extracted DNA and RNA from HGSC specimens and from benign fallopian tubes. Then, we performed whole exome sequencing and RNA sequencing, and identified single nucleotide variants (SNV), copy number variants (CNV) and structural variants (SV). We used these variants to create prediction models to distinguish cancer from benign tissue. The models were then validated in independent datasets and with a machine learning platform. RESULTS: The prediction model with SNV had an AUC of 1.00 (95% CI 1.00-1.00). The models with CNV and SV had AUC of 0.87 and 0.73, respectively. Validated models also had excellent performances. CONCLUSIONS: Genomic variation of HGSC can be used to create prediction models which accurately discriminate cancer from benign tissue. Further refining of these models (early-stage samples, other tumor types) has the potential to lead to detection of ovarian cancer in blood with cell free DNA, even in early stage.

Identification of Novel lncRNAs in Ovarian Cancer and Their Impact on Overall Survival.

Long non-coding RNA's (lncRNA) are RNA sequences that do not encode proteins and are greater than 200 nucleotides in length. They regulate complex cellular mechanisms and have been associated with prognosis in various types of cancer. We aimed to identify lncRNA sequences that are associated with high grade serous ovarian cancer (HGSC) and assess their impact on overall survival. RNA was extracted from 112 HGSC patients and 12 normal fallopian tube samples from our Biobank tissue repository. RNA was sequenced and the Ultrafast and Comprehensive lncRNA detection and quantification pipeline (UClncR) was used for the identification of lncRNA sequences. Univariate logistic and multivariate lasso regression analyses identified lncRNA that was associated with HGSC. Univariate and multivariate Cox proportional hazard ratios were used to evaluate independent predictors of survival. 1943 of 16,325 investigated lncRNA's were differentially expressed in HGSC as compared to controls (p < 0.001). Nine of these demonstrated association with cancer after multivariate lasso regression. Our multivariate analysis of survival identified four lncRNA's associated with survival in HGSC. Three out of these four were found to be independently significant after accounting for all clinical covariates. Lastly, seven lncRNAs were independently associated with initial response to chemotherapy; four portended a worse response, while three were associated with improved response. More research is needed, but there is potential for these lncRNAs to be used as biomarkers of HGSC or predictors of treatment outcome in the future.

Interval debulking surgery is not worth the wait: a National Cancer Database study comparing primary cytoreductive surgery versus neoadjuvant chemotherapy.

OBJECTIVE: In previous studies, neoadjuvant chemotherapy followed by interval debulking surgery was not inferior to primary cytoreductive surgery as initial treatment for advanced epithelial ovarian cancer. Our study aimed to compare surgical and survival outcomes between the two treatments in a large national database. METHODS: Data were extracted from the National Cancer Database from January 2004 to December 2015. Patients with FIGO (International Federation of Gynecologists and Obstetricians) stage III-IV epithelial ovarian cancer and known sequence of treatment were included: primary cytoreductive (surgery=26 717 and neoadjuvant chemotherapy=9885). Tubal and primary peritoneal cancer diagnostic codes were not included. Residual disease after treatment was defined based on recorded data: R0 defined as microscopic or no residual disease; R1 defined as macroscopic residual disease. Multivariate Cox proportional HR was used for survival analysis. Multivariate logistic regression analysis was utilized to compare mortality between groups. Outcomes were adjusted for significant covariates. Validation was performed using propensity score matching of significant covariates. RESULTS: A total of 36 602 patients were included in the analysis. Patients who underwent primary cytoreductive surgery had better survival than those treated with neoadjuvant chemotherapy followed by interval surgery, after adjusting for age, co-morbidities, stage, and residual disease (p<0.001). Primary cytoreductive surgery patients with R0 disease had best median survival (62.6 months, 95% CI 60.5-64.5). Neoadjuvant chemotherapy patients with R1 disease had worst median survival (29.5 months, 95% CI 28.4-31.9). There were small survival differences between primary cytoreductive surgery with R1 (38.9 months) and neoadjuvant chemotherapy with R0 (41.8 months) (HR 0.93, 95% CI 0.87 to 1.0), after adjusting for age, co-morbidities, grade, histology, and stage. Neoadjuvant chemotherapy had 3.5 times higher 30-day mortality after surgery than primary cytoreductive surgery (95% CI 2.46 to 5.64). The 90-day mortality was higher for neoadjuvant chemotherapy in multivariate analysis (HR 1.31, 95% CI 1.06 to 1.61) but similar to primary cytoreductive surgery after excluding high-risk patients. CONCLUSIONS: Most patients with advanced epithelial ovarian cancer may benefit from primary cytoreductive surgery. Patients treated with neoadjuvant chemotherapy should be those with co-morbidities unfit for surgery.

Minimally Invasive Robotic Surgery for Gynecologic Cancers: A Review.

Minimally invasive robotic surgery has become an effective surgical technique for the treatment of gynecologic malignancies. This article reviews the current utilization of robotic surgery and its role for future treatment in gynecologic oncology.

Effects of Probiotic (Bacillus subtilis) Supplementation During Offseason Resistance Training in Female Division I Athletes.

Toohey, JC, Townsend, JR, Johnson, SB, Toy, AM, Vantrease, WC, Bender, D, Crimi, CC, Stowers, KL, Ruiz, MD, VanDusseldorp, TA, Feito, Y, and Mangine, GT. Effects of probiotic (Bacillus subtilis) supplementation during offseason resistance training in female Division I athletes. J Strength Cond Res 34(11): 3173-3181, 2020-We examined the effects of probiotic (Bacillus subtilis) supplementation during offseason training in collegiate athletes. Twenty-three Division I female athletes (19.6 ± 1.0 years, 67.5 ± 7.4 kg, and 170.6 ± 6.8 cm) participated in this study and were randomized into either a probiotic (n = 11; DE111) or placebo (n = 12; PL) group while counterbalancing groups for sport. Athletes completed a 10-week resistance training program during the offseason, which consisted of 3-4 workouts per week of upper- and lower-body exercises and sport-specific training. Athletes consumed DE111 (DE111; 5 billion CFU/day) or PL supplement daily for the entire 10-week program. Before and after training, all athletes underwent 1 repetition maximum (1RM) strength testing (squat, deadlift, and bench press), performance testing (vertical jump and pro-agility), and isometric midthigh pull testing. Body composition (body fat [BF]%) was completed using BODPOD and bioelectrical impedance analysis, as well as muscle thickness (MT) measurement of the rectus femoris (RF) and vastus lateralis using ultrasonography. Separate repeated-measures analyses of variance were used to analyze all data. Significant (p ≤ 0.05) main effects for time were observed for improved squat 1RM, deadlift 1RM, bench press 1RM, vertical jump, RF MT, and BF%. Of these, a significant group × time interaction was noted for BF% (p = 0.015), where greater reductions were observed in DE111 (-2.05 ± 1.38%) compared with PL (-0.2 ± 1.6%). No other group differences were observed. These data suggest that probiotic consumption in conjunction with post-workout nutrition had no effect on physical performance but may improve body composition in female Division I soccer and volleyball players after offseason training.

Laminar Chaos in Experiments: Nonlinear Systems with Time-Varying Delays and Noise.

A new type of dynamics called laminar chaos was recently discovered through a theoretical analysis of a scalar delay differential equation with time-varying delay. Laminar chaos is a low-dimensional dynamics characterized by laminar phases of nearly constant intensity with periodic durations and a chaotic variation of the intensity from one laminar phase to the next laminar phase. This is in stark contrast to the typically observed higher-dimensional turbulent chaos, which is characterized by strong fluctuations. In this Letter we provide the first experimental observation of laminar chaos by studying an optoelectronic feedback loop with time-varying delay. The noise inherent in the experiment requires the development of a nonlinear Langevin equation with variable delay. The results show that laminar chaos can be observed in higher-order systems, and that the phenomenon is robust to noise and a digital implementation of the variable time delay.

A randomized phase II study of cabozantinib versus weekly paclitaxel in the treatment of persistent or recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer: An NRG Oncology/Gynecologic Oncology Group study.

INTRODUCTION: Cabozantinib is a receptor tyrosine kinases inhibitor that targets MET (c-MET), VEGF receptor 2 (VEGFR2), RET, AXL, KIT, FLT-3, and TIE-2 and previously showed promising single agent activity in recurrent ovarian cancer. METHODS: This was an open label, 1:1 randomized study of cabozantinib 60 mg orally (PO) daily versus weekly paclitaxel 80 mg/m2 given 3 out of 4 weeks (NCT01716715); 111 patients were enrolled. Eligibility included persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma and at least one but no >3 prior chemotherapy regimens. RESULTS: Median PFS was similar for both treatment groups and was 5.3 months for cabozantinib and 5.5 months for weekly paclitaxel (HR 1.11 (90% CI 0.77-1.61, p = 0.64)). Secondary analyses of overall survival (OS) and event free survival (EFS) showed that cabozantinib did not perform as well as weekly paclitaxel. Median OS for cabozantinib was 19.4 months and was not reached for weekly paclitaxel (HR 2.27 (90% CI 1.17-4.41, p = 0.04). EFS was also worse in the cabozantinib arm, 3.5 months, compared to weekly paclitaxel at 5.0 months (HR 1.81 (90% CI 1.24-2.63, p = 0.01). Overall response rate (ORR) was less for cabozantinib compared to weekly paclitaxel (7% versus 24.1%). Gastrointestinal toxicities, specifically nausea, diarrhea, and abdominal pain were worse in the cabozantinib arm. CONCLUSIONS: Median PFS was similar for cabozantinib and weekly paclitaxel. However, OS, EFS, and ORR were worse for cabozantinib compared to weekly paclitaxel. Cabozantinib given at this dose and schedule cannot be recommended as a treatment for recurrent ovarian cancer.

Infectious complications of laparoscopic and robotic hysterectomy: a systematic literature review and meta-analysis.

OBJECTIVE: We performed a systematic review of the literature and meta-analysis of the infectious complications of hysterectomy, comparing robotic-assisted hysterectomy to conventional laparoscopic-assisted hysterectomy. METHODS: We searched PubMed, CINAHL, CDSR, and EMBASE through July 2018 for studies evaluating robotic-assisted hysterectomy, laparoscopic-assisted hysterectomy, and infectious complications. We employed random-effect models to obtain pooled OR estimates. Heterogeneity was evaluated with I2 estimation and the Cochran Q statistic. Pooled ORs were calculated separately based on the reason for hysterectomy (eg, benign uterine diseases, endometrial cancer, and cervical cancer). RESULTS: Fifty studies were included in the final review for the meta-analysis with 176 016 patients undergoing hysterectomy. There was no statistically significant difference in the number of infectious complication events between robotic-assisted hysterectomy and laparoscopic-assisted hysterectomy (pooled OR 0.97; 95 % CI 0.74 to 1.28). When we performed a stratified analysis, similar results were found with no statistically significant difference in infectious complications comparing robotic-assisted hysterectomy to laparoscopic-assisted hysterectomy among patients with benign uterine disease (pooled OR 1.10; 95 % CI 0.70 to 1.73), endometrial cancer (pooled OR 0.97; 95 % CI 0.55 to 1.73), or cervical cancer (pooled OR 1.09; 95 % CI 0.60 to 1.97). CONCLUSION: In our meta-analysis the rate of infectious complications associated with robotic-assisted hysterectomy was no different than that associated with conventional laparoscopic-assisted hysterectomy.

Molecular Characterization of Non-responders to Chemotherapy in Serous Ovarian Cancer.

Nearly one-third of patients with high-grade serous ovarian cancer (HGSC) do not respond to initial treatment with platinum-based therapy. Genomic and clinical characterization of these patients may lead to potential alternative therapies. Here, the objective is to classify non-responders into subsets using clinical and molecular features. Using patients from The Cancer Genome Atlas (TCGA) dataset with platinum-resistant or platinum-refractory HGSC, we performed a genome-wide unsupervised cluster analysis that integrated clinical data, gene copy number variations, gene somatic mutations, and DNA promoter methylation. Pathway enrichment analysis was performed for each cluster to identify the targetable processes. Following the unsupervised cluster analysis, three distinct clusters of non-responders emerged. Cluster 1 had overrepresentation of the stage IV disease and suboptimal debulking, under-expression of miRNAs and mRNAs, hypomethylated DNA, "loss of function" TP53 mutations, and the overexpression of genes in the PDGFR pathway. Cluster 2 had low miRNA expression, generalized hypermethylation, MUC17 mutations, and significant activation of the HIF-1 signaling pathway. Cluster 3 had more optimally cytoreduced stage III patients, overexpression of miRNAs, mixed methylation patterns, and "gain of function" TP53 mutations. However, the survival for all clusters was similar. Integration of genomic and clinical data from patients that do not respond to chemotherapy has identified different subgroups or clusters. Pathway analysis further identified the potential alternative therapeutic targets for each cluster.

A Prediction Model for Preoperative Risk Assessment in Endometrial Cancer Utilizing Clinical and Molecular Variables.

The utility of comprehensive surgical staging in patients with low risk disease has been questioned. Thus, a reliable means of determining risk would be quite useful. The aim of our study was to create the best performing prediction model to classify endometrioid endometrial cancer (EEC) patients into low or high risk using a combination of molecular and clinical-pathological variables. We then validated these models with publicly available datasets. Analyses between low and high risk EEC were performed using clinical and pathological data, gene and miRNA expression data, gene copy number variation and somatic mutation data. Variables were selected to be included in the prediction model of risk using cross-validation analysis; prediction models were then constructed using these variables. Model performance was assessed by area under the curve (AUC). Prediction models were validated using appropriate datasets in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. A prediction model with only clinical variables performed at 88%. Integrating clinical and molecular data improved prediction performance up to 97%. The best prediction models included clinical, miRNA expression and/or somatic mutation data, and stratified pre-operative risk in EEC patients. Integrating molecular and clinical data improved the performance of prediction models to over 95%, resulting in potentially useful clinical tests.

Isometric Midthigh Pull Performance Is Associated With Athletic Performance and Sprinting Kinetics in Division I Men and Women's Basketball Players.

Townsend, JR, Bender, D, Vantrease, WC, Hudy, J, Huet, K, Williamson, C, Bechke, E, Serafini, PR, and Mangine, GT. Isometric midthigh pull performance is associated with athletic performance and sprinting kinetics in Division I men and women's basketball players. J Strength Cond Res 33(10): 2665-2673, 2019- The relationships between isometric mid-thigh pull (IMTP) force, athletic performance measures, and sprint kinetics in Division I men's and women's basketball players were investigated. Twenty-three (male = 8, female = 15) Division 1 basketball players completed a maximal 20-m sprint trial while tethered to a device that provided kinetic feedback (peak and average sprinting power, velocity and force). Additionally, 1 repetition maximum (1RM) front squat, 1RM hang clean, vertical jump height, and agility (proagility and lane agility) tests were performed. Rate of force development (RFD) at 50, 100, 150, 200 and 250 milliseconds of IMTP and peak force (PF) were also collected. Pearson's product-moment correlation analysis was used to examine the relationships between these measures. Significant (p ≤ 0.05) relationships were observed between IMTP PF and sprint time over all distances (5-20 m; r = -0.62 to 0.69), average sprint velocity (r = 0.50-0.70), peak sprint velocity (r = 0.50-0.54), average sprint force (r = 0.48-0.69), and average sprint power (r = 0.62-0.73). Sprinting kinetic measures (average force and power) over the first 5 m were also significantly (p ≤ 0.05) related to IMTP RFD (50-250 ms; r = 0.42-0.62). Results indicate that IMTP variables are significantly associated with 20-m sprint kinetics. Specifically, IMTP RFD appears to be related to the initial acceleration kinetics of a sprint. Strength and conditioning professionals can possibly implement the IMTP for improved assessment and monitoring of athletic performance and training.

Life stress as a risk factor for sustained anxiety and cortisol dysregulation during the first year of survivorship in ovarian cancer.

BACKGROUND: Patients with ovarian cancer often report elevated anxiety at diagnosis that decreases posttreatment. However, a minority of patients experience sustained anxiety. Few studies have examined risk factors for persistent anxiety or its physiologic sequelae in ovarian cancer. Therefore, the authors investigated associations between prior life events, anxiety, inflammation (plasma levels of interleukin-6), and diurnal cortisol profiles in patients with ovarian cancer during the first year postdiagnosis. METHODS: Participants (n = 337) completed surveys and had blood and salivary sampling prediagnosis, postchemotherapy (6 months), and 12 months after diagnosis. The Life Events and Difficulties Schedule was administered to a patient subset (n = 127) within 1 month of diagnosis. Linear mixed-effects models were used to analyze relations between anxiety and biologic variables over time. Linear regression models assessed whether anxiety trajectories mediated associations between prior stress exposure and biologic variables. Age, chemotherapy at 1 year, and cancer stage were covariates. RESULTS: Decreased anxiety was associated with a more normalized cortisol slope over time (ß = 0.092; P = .047). Early life adversity was related to flatter cortisol slopes over time (ß = -0.763; P = .002); this relation was partially mediated by anxiety trajectory (P = .046). More danger-related events prediagnosis were associated with sustained anxiety (ß = 0.537; P = .019) and flatter cortisol slopes over time (ß = -0.243; P = .047); anxiety partially mediated the relation between danger and cortisol slope (P = .037). Neither anxiety nor prior stress exposure was related to levels of interleukin-6. CONCLUSIONS: Because dysregulated cortisol has been related to fatigue, poorer quality of life, and shorter survival in patients with ovarian cancer, those who have prior life events and chronic anxiety during the first year postdiagnosis may be at risk for more negative outcomes. Cancer 2018. © 2018 American Cancer Society.