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To determine the prevalence of underlying high-intermediate (high-IM) and high-risk endometrial cancer (EC) in patients with preoperative diagnosis of Endometrial intraepithelial neoplasia (EIN) and to assess the impact of the information retrieved from the sentinel lymph node (SLN) on adjuvant therapy.Retrospective cohort study of women undergoing hysterectomy, optional bilateral salpingo-oophorectomy (BSO) and lymph nodes assessment for EIN between December 2007 and August 2021.One hundred and sixty two (162) eligible patients were included, of whom 101 (62.3%) had a final diagnosis of EIN, while 61 (37.7%) were ultimately diagnosed with carcinoma. Out of 15 patients with high-IM to high-risk disease (9.25% of all EIN), 12 had grade 2-3 EC including 8 with50% myometrial invasion, 2 with serous subtype, 1 with cervical invasion and 2 with pelvic lymph nodes involvement. Of the 3 patients with grade 1 EC, one patient had disease involving the adnexa and 2 patients had tumor invading50% of the myometrium and with lymphovascular space invasion (LVSI). Ten patients received vaginal brachytherapy after surgery, 3 patients with extrauterine spread were treated with systemic chemotherapy followed by vaginal brachytherapy and pelvic external-beam radiotherapy and 2 patients with early-stage serous carcinoma received chemotherapy followed by vaginal brachytherapy.Information from SLN, even when negative, can be helpful in the management of patients with EC after preoperative EIN, as some patients are found to have high-IM to high-risk disease on final pathology. These patients would require either re-staging surgery or adjuvant external beam radiotherapy, both could be avoided by proper staging.

There is an emerging focus on the role of robotic surgery in ovarian cancer. To date, the operational and cost implications of the procedure remain unknown. The objective of the current study was to evaluate the impact of integrating minimally invasive robotic surgery on patient flow, resource utilization, and hospital costs associated with the treatment of ovarian cancer during the in-hospital and post-discharge processes. 261 patients operated for the primary treatment of ovarian cancer between January 2006 and November 2014 at a university-affiliated tertiary hospital were included in this study. Outcomes were compared by surgical approach (robotic vs. open surgery) as well as pre- and post-implementation of the robotics platform for use in ovarian cancer. The in-hospital patient flow and number of emergency room visits within 3 months of surgery were evaluated using multi-state Markov models and generalized linear regression models, respectively. Robotic surgery cases were associated with lower rates of postoperative complications, resulted in a more expedited postoperative patient flow (e.g., shorter time in the recovery room, ICU, and inpatient ward), and were between $10,376 and $7,421 less expensive than the average laparotomy, depending on whether or not depreciation and amortization of the robotic platform were included. After discharge, patients who underwent robotic surgery were less likely to return to the ER (IRR 0.42, p = 0.02, and IRR 0.47, p = 0.055, in the univariate and multivariable models, respectively). With appropriate use of the technology, the addition of robotics to the medical armamentarium for the management of ovarian cancer, when clinically feasible, can bring about operational efficiencies and entails cost savings.

To develop machine-learning models to predict recurrence and time-to-recurrence in high-grade endometrial cancer (HGEC) following surgery and tailored adjuvant treatment.Data were retrospectively collected across eight Canadian centers including 1237 patients. Four models were trained to predict recurrence: random forests, boosted trees, and two neural networks. Receiver operating characteristic curves were used to select the best model based on the highest area under the curve (AUC). For time to recurrence, we compared random forests and Least Absolute Shrinkage and Selection Operator (LASSO) model to Cox proportional hazards.The random forest was the best model to predict recurrence in HGEC; the AUCs were 85.2%, 74.1%, and 71.8% in the training, validation, and test sets, respectively. The top five predictors were: stage, uterus height, specimen weight, adjuvant chemotherapy, and preoperative histology. Performance increased to 77% and 80% when stratified by Stage III and IV, respectively. For time to recurrence, there was no difference between the LASSO and Cox proportional hazards models (c-index 71%). The random forest had a c-index of 60.5%.A bootstrap random forest model may be a more accurate technique to predict recurrence in HGEC using multiple clinicopathologic factors. For time to recurrence, machine-learning methods performed similarly to the Cox proportional hazards model.

Gene expression values

Differential expression results

Supplementary Figure 1: Log-transformed Quantile-Quantile plots of the Univariate Survival Analysis p-values. P-values derived from the univariate survival analysis of the effects of each individual gene was plotted for each fold in which the analysis took place. The horizontal line at 2.52 represents -log(0.003), which was the cutoff for variable selection in the final modeling of survival in the test cohort. Supplementary Figure 2: Abridged representation of the FOXM1 regulatory network. See references [2-5]

Legends for Supplementary Figures.

Mutation list

Supplementary figure S1: representative western blot showing Akt (S473) phosphorylation in HUVEC incubated with the conditioned medium (CM) of SKOV-3 and GOC-A2. Supplementary figure S2: expression of VEGF-A in HUVEC and E4+EC and VEGFR expression in HUVEC and E4+EC. Supplementary figure S3: functional assays performed in the presence of VEGF-A and bevacizumab in HUVECs. Microvascular endothelial cells isolated from ovarian tissue (HOMEC) were treated by bevacizumab to assess growth inhibition. Supplementary figure S4: involvements of Akt and FGF-2/FGFR axis in the resistance to bevacizumab in the activated endothelium. Supplementary figure S5: FGF-2 decreases the sensitivity of HUVEC to bevacizumab.

Ovarian cancer is the second leading cause of cancer-related death in women worldwide. Despite optimal cytoreduction and adequate adjuvant therapies, initial tumor response is often followed by relapse suggesting the existence of a tumor niche. Targeted therapies have been evaluated in ovarian cancer to overcome resistant disease. Among them, antiangiogenic therapies inhibit new blood vessel growth, induce endothelial cell apoptosis, and block the incorporation of hematopoietic and endothelial progenitor cells into new blood vessels. Despite in vitro and in vivo successes, antivascular therapy with bevacizumab targeting VEGF-A has limited efficacy in ovarian cancer. The precise molecular mechanisms underlying clinical resistance to anti-VEGF therapies are not yet well understood. Among them, tumor and stromal heterogeneity might determine the treatment outcomes. The present study investigates whether abnormalities in the tumor endothelium may contribute to treatment resistance to bevacizumab and promote a residual microscopic disease. Here, we showed that ovarian cancer cells activate Akt phosphorylation in endothelial cells inducing resistance to bevacizumab leading to an autocrine loop based on FGF2 secretion. Altogether, our results point out the role of an activated endothelium in the resistance to bevacizumab and in the constitution of a niche for a residual disease. Mol Cancer Ther; 13(12); 3123–36. ©2014 AACR.

Patient characteristics

List of primers used for real time-PCR in this study

Mutation list

Objective To assess the recent trends, acceptability, and effectiveness of digital maternal patient education through summarizing the literature. Methods Articles published in 2010–2020 on patient education, digital tools, and maternal health were searched on PubMed. Abstract and full texts were reviewed to identify eligible studies and extract key information. Results Digital patient education studies covered various topics throughout pregnancy, with the greatest number of studies targeting the prenatal period. Among the 55 studies, 38 (69%) reported significant patient outcomes, with the main benefits of increased knowledge (83.3%), emotional benefits (73.7%), and behavioral changes (60.6%). The number of studies per year increased steadily over the past decade, with frequently utilized formats of texts with images (40%), SMS (30.9%), and videos (25.5%). Video produced the highest rate of positive patient outcomes; however, no statistical significance was found. Conclusion Our study presented evidence supporting the high effectiveness and prevalence of digital tools in maternal patient education, and analyzed the content, platforms, and formats utilized by digital tools of the past decade. Practice implications Digital tools are effective and feasible in conducting maternal patient education. No specific patient education format is found to be superior in improving patient’s health outcomes.

The introduction of robotic surgery in hospitals has raised much debate given the various effects on care, costs, education and medical advancement. Purchasing discussions are often approached with more questions than answers and there is a need for reports that provide a case for whether or not such technologies are advantageous from multiple perspectives, and offer insights into ways such devices can be introduced into a hospital setting. This report provides an evidence-based review of a university-affiliated tertiary care hospital's 12-year experience with robotic surgery in gynecologic oncology and delves into the various takeaways and challenges of implementing robotic surgery. Key findings were that robotic surgery significantly reduced complication rates, lengths of hospital stays for patients and overall hospital costs. Key obstacles were large upfront costs and the need for significant leadership and collaboration. Ongoing challenges to evaluating robotics include assessing long-term survival data, making comparisons with concurrently changing hospital conditions and determining how data can be generalized to other departments and institutions.

There is limited knowledge on non-invasive lymphedema risk-reduction strategies for women with gynecological cancer. Understanding factors influencing the feasibility of randomized controlled trials (RCTs) can guide future research. Our objectives are to report on the design and feasibility of a pilot RCT examining a tailored multidimensional intervention in women treated for gynecological cancer at risk of lymphedema and to explore the preliminary effectiveness of the intervention on lymphedema incidence at 12 months. In this pilot single-blinded, parallel-group, multi-centre RCT, women with newly diagnosed gynecological cancer were randomized to receive post-operative compression stockings and individualized exercise education (intervention group: IG) or education on lymphedema risk-reduction alone (control group: CG). Rates of recruitment, retention and assessment completion were recorded. Intervention safety and feasibility were tracked by monitoring adverse events and adherence. Clinical outcomes were evaluated over 12 months: presence of lymphedema, circumferential and volume measures, body composition and quality of life. Fifty-one women were recruited and 36 received the assigned intervention. Rates of recruitment and 12-month retention were 47% and 78%, respectively. Two participants experienced post-operative cellulitis, prior to intervention delivery. At three and six months post-operatively, 67% and 63% of the IG used compression &ge, 42 h/week, while 56% engaged in &ge, 150 weekly minutes of moderate-vigorous exercise. The cumulative incidence of lymphedema at 12 months was 31% in the CG and 31.9% in the IG (p = 0.88). In affected participants, lymphedema developed after a median time of 3.2 months (range, 2.7&ndash, 5.9) in the CG vs. 8.8 months (range, 2.9&ndash, 11.8) in the IG. Conducting research trials exploring lymphedema risk-reduction strategies in gynecological cancer is feasible but challenging. A tailored intervention of compression and exercise is safe and feasible in this population and may delay the onset of lymphedema. Further research is warranted to establish the role of these strategies in reducing the risk of lymphedema for the gynecological cancer population.

Guidelines for the treatment of tubo-ovarian cancer patients beyond third line are lacking. We aimed to evaluate the effect of response in each line on patient's outcome as well as identify variables that predict response for additional line of chemotherapy. A cohort study was performed including all patients with advanced high-grade ovarian cancer. Survival analysis was performed using Kaplan-Meier curves and log-rank tests. Odds ratios and hazard ratios were calculated using multilevel, mixed-effects logistic regression and Cox regression, adjusting for repeated measures within individual patients. Two-hundred thirty-eight patients were included and underwent up to 10 lines of chemotherapy. The median progression-free survival was 15.6 and overall survival (OS) was 55.6 months. Response rates dropped with each additional line and by line 5, most patients (61%) became refractory and only 16% had any type of response (complete 4% or partial 12%). By line 2, whether a patient had partial disease (PR), stable disease (SD) or progressive disease (PD) did not have an effect on the OS. From line 2, whether a patient had PR, SD or PD did not have an effect on chemotherapy-free interval. Number of previous lines and time from previous line were the only variables that significantly correlated with both outcome of patients and response to the next line. In conclusion, time interval from the previous line of chemotherapy is the major clinical factor that predicts beneficial effect of another line of treatment in patients with ovarian cancer.

Atypical teratoid rhabdoid tumor (ATRT) is a fatal pediatric malignancy of the central neural system lacking effective treatment options. It belongs to the rhabdoid tumor family and is usually caused by biallelic inactivation of SMARCB1, encoding a key subunit of SWI/SNF chromatin remodeling complexes. Previous studies proposed that SMARCB1 loss drives rhabdoid tumor by promoting cell cycle through activating transcription of cyclin D1 while suppressing p16. However, low cyclin D1 protein expression is observed in most ATRT patient tumors. The underlying mechanism and therapeutic implication of this molecular trait remain unknown. Here, we show that SMARCB1 loss in ATRT leads to the reduction of cyclin D1 expression by upregulating MIR17HG, a microRNA (miRNA) cluster known to generate multiple miRNAs targeting CCND1. Furthermore, we find that this cyclin D1 deficiency in ATRT results in marked in vitro and in vivo sensitivity to the CDK4/6 inhibitor palbociclib as a single agent. Our study identifies a novel genetic interaction between SMARCB1 and MIR17HG in regulating cyclin D1 in ATRT and suggests a rationale to treat ATRT patients with FDA-approved CDK4/6 inhibitors. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Objective To evaluate long-term oncological outcomes and the added value of sentinel lymph node sampling (SLN) compared to pelvic lymph node dissection (LND) in patients with endometrial cancer (EC). Methods During the evaluation phase of SLN for EC, we performed LND and SLN and retrospectively compared the oncologic outcome with the immediate non-overlapping historical era during which patients underwent LND. Results From 2007 to 2010, 193 patients underwent LND and from December 2010 to 2014, 250 patients had SLN mapping with completion LND. Both groups had similar clinical characteristics. During a median follow-up period of 6.9 years, addition of SLN was associated with more favorable oncological outcomes compared to LND with 6-year overall survival (OS) of 90% compared to 81% (p = 0.009), and progression free survival (PFS) of 85% compared to 75% (p = 0.01) respectively. SLN was associated with improved OS (HR 0.5, 95% CI 0.3–0.8, p = 0.004), and PFS (HR 0.6, 95% CI 0.4–0.9, p = 0.03) in a multivariable analysis, adjusted for age, ASA score, stage, grade, non-endometrioid histology, and LVSI. Patients who were staged with SLN were less likely to have a recurrence in the pelvis or lymph node basins compared to patients who underwent LND only (6-year recurrence-free survival 95% vs 90%, p = 0.04). Conclusion Addition of SLN to LND was ultimately associated with improved clinical outcomes compared to LND alone in patients with endometrial cancer undergoing surgical staging, suggesting that the data provided by the analysis of the SLN added relevant clinical information, and improved the decision on adjuvant therapy.

Objectives Some hospitals have invested in robotic surgery platforms to stimulate the uptake of minimally invasive surgery (MIS) and offer its benefits to more patients. The objectives were to determine the clinical and financial effects, as well as the policy implications, of a robotics program in an academic gynecologic oncology division over time. Methods Patients treated for endometrial, cervical, and ovarian cancer within a gyn-oncology division between 2003 and 2016 were included in the current study. Clinical outcomes were described in function of surgical approach (laparotomy, laparoscopy, and robotic surgery) and tumor site. The net present value and the return on investment of the robotics program were approximated using previously reported treatment costs from our center. Results The use of MIS soared from a high of 15% to 91% before and after the introduction of robotics in December 2007, respectively. Across all tumor sites, MIS procedures were associated with diminished blood loss and a shorter hospital stay (p Conclusions Robotic surgery was instrumental in catalyzing the shift from open surgery to MIS and amplifying the number of patients who benefited from less invasive surgery. Continued investments in robotics and the digitization of surgery could help further drive innovation and expand its applications.

BackgroundPoly ADP-ribose glycohydrolase (PARG) is responsible for the catabolism of PARP-synthesized PAR to free ADP-ribose. Inhibition of PARG leads to DNA repair interruption and consequently induces cell death. This study aims to evaluate the effect of a PARG inhibitor (PARGi) on epithelial ovarian cancer (OC) cell lines, alone and in combination with a PARP inhibitor (PARPi) and/or Cisplatin.MethodsPARG mRNA levels were studied in three different OC datasets: TCGA, Hendrix, and Meyniel. PARG protein levels were assessed in 100 OC specimens from our bio-bank. The therapeutic efficacy of PARGi was assessed using cell migration and clonogenic formation assays. Flow cytometry was used to evaluate the cell apoptosis rate and the changes in the cell cycle.ResultsPARG protein was highly expressed in 34% of the OC tumors and low expression was found in another 9%. Similarly, Hendrix, Meyneil and TCGA databases showed a significant up-regulation in PARG mRNA expression in OC samples as compared to normal tissue (P=0.001, P=0.005, P=0.005, respectively). The use of PARGi leads to decreased cell migration. PARGi in combination with PARPi or Cisplatin induced decreased survival of cells as compared to each drug alone. In the presence of PARPi and Cisplatin, PARG knockdown cell lines showed significant G2/M cell cycle arrest and cell death induction.ConclusionsPARG inhibition appears as a complementary strategy to PARP inhibition in the treatment of ovarian cancer, especially in the presence of homologous recombination defects.

OBJECTIVE To perform a systematic review of the literature to estimate the prevalence and outcomes of occult tubal carcinoma in BRCA mutation carriers and high-risk patients undergoing risk-reducing salpingo-oophorectomy. DATA SOURCE A search was done using OVID MEDLINE, EMBASE, and ClinicalTrials.gov between 1946 and March 2019 with keywords and MeSH terms selected by an expert medical librarian and coauthors. METHODS OF STUDY SELECTION Two independent reviewers performed study selection with an initial screen on abstracts and a second on full articles. Articles were rejected if they were irrelevant to the study question, pertained to a different population or did not report occult tubal neoplasia. Quality was assessed using methodologic index for nonrandomized studies criteria. TABULATION, INTEGRATION, AND RESULTS Data were extracted and recorded in an Excel database. Forest plots for the prevalence of occult carcinoma were done using STATA. Among 2,402 studies assessed, 27 met the inclusion criteria for qualitative and quantitative analysis. A total of 6,283 patients underwent risk-reducing salpingo-oophorectomy between 2002 and 2019: 2,894 cases were BRCA1, 1,579 BRCA2, and 1,810 high-risk based on family history. Among these, 75 patients were diagnosed with occult tubal carcinoma at the time of surgery. The pooled prevalence was 1.2% (I=7.1%, P=.363) occurring at a median age of 53.2 years (range 42.4-67). In a subanalysis of 18 studies reporting follow-up data, 10 recurrences (18.7%, 95% CI 7.5-53%) and 24 cases of post-risk-reducing salpingo-oophorectomy peritoneal cancer (0.54%, 95% CI 0.4-1.9%) were reported after a median follow-up of 52.5 months. BRCA1, older age, and previous breast cancer were more often associated with occult malignancy. CONCLUSION Occult tubal carcinomas found at risk-reducing salpingo-oophorectomy in high-risk patients and BRCA mutation carriers have significant potential for recurrence despite the frequent administration of postoperative chemotherapy.

Introduction The objective was to assess whether an early response to neoadjuvant chemotherapy in women with advanced ovarian cancer may predict short- and long-term clinical outcome. Material and methods This is a retrospective study of all women with stage III-IV tubo-ovarian cancer treated with neoadjuvant chemotherapy at a single center in Montreal between 2003 and 2014. Logistic regression models were used to evaluate the association between cancer antigen 125 (CA-125) levels during neoadjuvant chemotherapy and debulking success. Cox proportional hazard models were used to estimate hazard ratios and their respective 95% CI for death and recurrence. Harrell's concordance indices were calculated to evaluate which variables best predicted the chemotherapy-free interval and overall survival in our population. Results In all, 105 women were included. Following the first, second, and third cycles of neoadjuvant chemotherapy, CA-125 levels had a median reduction of 43.2%, 85.4%, and 92.9%, respectively, compared with CA-125 levels at diagnosis. As early as the second cycle, CA-125 was associated with overall survival (hazard ratio 1.03, 95% CI 1.01-1.05, per 50 U/mL increment). By the third cycle, CA-125 did not only predict overall survival (hazard ratio 1.04, 95% CI 1.01-1.08), but it predicted overall survival better than the success of debulking surgery (Harrell's concordance index 0.646 vs 0.616). Both absolute CA-125 levels and relative reduction in CA-125 levels after 2 and 3 cycles predicted the chance to achieve complete debulking (P Conclusions Reduction of CA-125 levels during neoadjuvant chemotherapy provides an early predictive tool that strongly correlates with successful cytoreductive surgery and long-term clinical outcome in women with advanced high-grade serous and endometrioid ovarian cancer.

DNA methylation analysis may improve risk stratification in cervical screening. We used a pan-epigenomic approach to identify new methylation markers along the continuum of cervical intraepithelial neoplasia (CIN) to cervical cancer. Physician-collected samples (54 normal, 50 CIN1, 40 CIN2 and 42 CIN3) were randomly selected from women at a single-center colposcopy clinic. Extracted DNA was subjected to Illumina Infinium EPIC array analysis, and methylation was assessed blinded to histopathological and clinical data. CpG sites whose state of methylation correlated with lesion grade were assessed (Spearman correlation), and a weighted methylation score was calculated comparing normal to CIN3. Validation of the top selected genes was performed in an independent cohort (100 normal, 50 CIN1, 50 CIN2, 50 CIN3 and 8 cervical cancers) of new patients, referred for colposcopic examination at three hospitals, using targeted DNA methylation Illumina amplicon sequencing. The relationship between a combined weighted marker score and progression from normal through precancerous lesions and cervical cancer was compared using one-way ANOVA. Our analyses revealed 7,715 CpGs whose methylation level correlated with progression (from normal to CIN1, CIN2 and CIN3), with a significant trend of increased methylation with lesion grade. We shortlisted a bigenic (hyaluronan synthase 1, HAS1 and ATPase phospholipid transporting 10A, ATP10A corresponding to cg03419058 and cg13944175 sites) marker set; r = 0.55, p < 0.0001. Validation of the four most discriminating genes (CA10, DPP10, FMN2 and HAS1) showed a significant correlation between methylation levels and disease progression (p-value < 2.2 × 10-16 , adjusted R2 = 0.952). Translational research of the identified genes to future clinical applications is warranted.

Introduction To evaluate the proportion of endometrial cancers surgically managed in rural centers, and to compare the surgical management and perioperative morbidity of hysterectomies for endometrial cancer performed in rural settings with those performed in urban settings. Materials and methods We conducted a retrospective cohort study using the Nationwide Inpatient Sample (NIS) database from 2003 to 2010. We included all patients diagnosed with endometrial cancer who underwent a hysterectomy and compared surgical approaches, lymph node dissection rates, perioperative complication rates, and lengths of stay according to location of care provided (rural versus urban centers), using multivariate logistic regression models. Results Of the 52,299 women who underwent surgery for endometrial cancer, 6% were performed in rural centers—a proportion that trended down over the study period. A disparity in surgical management was noted between rural versus urban settings, with rural centers having lower rates of laparoscopy and robotics (6.9% vs. 18.5%; OR 0.35, CI 0.30–0.40), and lower rates of lymph node dissection both overall (39.4% vs. 67.0%; OR 0.32, CI 0.30–0.35) and for early (37.2% vs. 66.2%; OR 0.30, 95%CI 0.28–0.33) and advanced (57.7% vs. 71.7%; OR 0.56, 95% CI 0.44–0.70) stage disease. Perioperative morbidity was comparable in both settings, with lower rates of transfusion, sepsis, wound infection, ileus, and prolonged hospitalization in rural settings. Conclusions Although women obtaining care for endometrial cancer in rural centers receive differential surgical management than women cared for in urban centers, perioperative morbidity appears to be overall comparable.

IntroductionWith the rapid uptake of robotic surgery in surgical oncology, its use in the treatment of epithelial ovarian cancers is being evaluated. Complete cytoreduction represents the goal of surgery either at primary cytoreduction or after neoadjuvant chemotherapy in the setting of interval cytoreduction. In selected patients, the extent of disease would enable minimally invasive surgery. The objective of this study was to evaluate the impact of introducing robotic surgery for interval cytoreduction of selected patients with stage III–IV ovarian cancer.MethodsAll patients who underwent surgery from November 2008 to 2014 (concurrent time period when robotic and open surgery were used simultaneously) after receiving neoadjuvant chemotherapy for advanced ovarian cancer (stage III–IV) were compared with all consecutive patients who underwent cytoreductive surgery by laparotomy after neoadjuvant chemotherapy between January 2006 and November 2008. Inclusion criteria included an interval cytoreductive surgery by laparotomy or robotic assistance for stage III–IV non-mucinous epithelial ovarian, fallopian tube, or primary peritoneal cancer. Exclusion criteria included patients treated concurrently for a non-gynecologic cancer, as well as secondary cytoreductive surgeries and diagnostic surgeries without an attempt at tumor reduction. Overall survival, progression-free survival, and peri-operative outcomes were compared for the entire patient cohort with those with advanced ovarian cancer who received neoadjuvant chemotherapy immediately before and after the introduction of robotic surgery.ResultsA total of 91 patients were selected to undergo interval cytoreduction either via robotic surgery (n=57) or laparotomy (n=34) after the administration of neoadjuvant chemotherapy. The median age of the cohort was 65 years (range 24–88), 78% had stage III disease, and the median follow-up time was 37 months (5.6–91.4 months). The median survival was 42.8±3.1 months in the period where both robotic surgery and laparotomy were offered compared with 37.9±9.8 months in the time period preceding when only laparotomy was performed (p=0.6). All patients selected to undergo interval robotic cytoreduction following neoadjuvant chemotherapy had a reduction of cancer antigen 125 by at least 80%, resolution of ascites, and CT findings suggesting the potential to achieve optimal interval cytoreduction. All these patients achieved optimal cytoreduction with ConclusionRobotic interval cytoreductive surgery is feasible in well-selected patients. Future studies should aim to define ideal patients for minimally invasive cytoreductive surgery.

Results of epidemiologic studies of physical activity and ovarian cancer risk are inconsistent. Few have attempted to measure physical activity over the lifetime or in specific age windows, which may better capture etiologically relevant exposures. We examined participation in moderate-to-vigorous recreational physical activity (MVPA) in relation to ovarian cancer risk. In a population-based case-control study conducted in Montreal, Canada from 2011 to 2016 (485 cases and 887 controls), information was collected on lifetime participation in various recreational physical activities, which was used to estimate MVPA for each participant. MVPA was represented as average energy expenditure over the lifetime and in specific age-periods in units of metabolic equivalents (METs)-hours per week. Odds ratios (OR) and 95% confidence intervals (CI) for the relation between average MVPA and ovarian cancer risk were estimated using multivariable logistic regression models. Confounding was assessed using directed acyclic graphs combined with a change-in-estimate approach. The adjusted OR (95% CI) for each 28.5 MET-hr/week increment of lifetime recreational MVPA was 1.11 (0.99-1.24) for ovarian cancer overall. ORs for individual age-periods were weaker. When examined by menopausal status, the OR (95% CI) for lifetime MVPA was 1.21 (1.00-1.45) for those diagnosed before menopause and 1.04 (0.89-1.21) for those diagnosed postmenopausally. The suggestive positive associations were stronger for invasive ovarian cancers and more specifically for high-grade serous carcinomas. These results do not support a reduced ovarian cancer risk associated with MVPA.

Background: Self-sampling has become an attractive proposition now that human papillomavirus (HPV) primary testing is being incorporated into cervical cancer screening programs worldwide. We compared predictive values of HPV testing based on self- and physician-collected samples, and cytology, in detecting high-grade cervical intraepithelial neoplasia (CIN). Methods: The Cervical And Self-Sample In Screening (CASSIS) study enrolled 1,217 women ages 16–70 years prior to scheduled colposcopies. Vaginal specimens were self-collected using the validated HerSwab device. Cervical specimens were collected by gynecologists. Specimens were tested for presence of high-risk HPV (hrHPV) by the Cobas 4800 HPV test. We estimated positive predictive values (PPV) and negative predictive values (NPV) and 95% confidence intervals (CI) for a subset of women (n = 700) who underwent cervical biopsy and cytology at the actual CASSIS visit. Results: hrHPV was detected in 329 women (47%) with HerSwab and in 327 (46.7%) with physician sampling. Respective values for HPV16/18 were 119 (17%) and 121 (17.3%). On histology, 134 women had CIN1, 49 had CIN2, 48 had CIN3, 5 had CIN2/CIN3, and 3 had cancers. PPVs for CIN2+ of any hrHPV were 28% (95% CI, 23.2–33.1) and 29.7% (95% CI, 24.8–34.9) for HerSwab and physician samples, respectively. Corresponding values for HPV16/18 were 43.7% (95% CI, 34.6–53.1) and 43.8% (95% CI, 34.8–53.1). PPV of cytology (ASC-US+) was 26.6% (95% CI, 21.6–32.0). Corresponding NPVs (same order as PPVs) were 96.4% (95% CI, 93.9–98.1), 97.8% (95% CI, 95.6–99), 90.9% (95% CI, 88.2–93.1), 91% (95% CI, 88.4–93.2), and 94.7% (95% CI, 91.8–96.8). Conclusions: Our results confirm that HPV self-sampling has comparable performance with a physician-collected sample in detecting cervical lesions. Impact: HPV self-sampling has the potential to increase coverage in cervical cancer screening.