Combining EHMT and PARP Inhibition: A Strategy to Diminish Therapy-Resistant Ovarian Cancer Tumor Growth while Stimulating Immune Activation.

Despite the success of Poly-ADP-ribose polymerase inhibitors (PARPi) in the clinic, high rates of resistance to PARPi presents a challenge in the treatment of ovarian cancer, thus it is imperative to find therapeutic strategies to combat PARPi resistance. Here, we demonstrate that inhibition of epigenetic modifiers Euchromatic histone lysine methyltransferases 1/2 (EHMT1/2) reduces the growth of multiple PARPi-resistant ovarian cancer cell lines and tumor growth in a PARPi-resistant mouse model of ovarian cancer. We found that combinatory EHMT and PARP inhibition increases immunostimulatory dsRNA formation and elicits several immune signaling pathways in vitro. Using epigenomic profiling and transcriptomics, we found that EHMT2 is bound to transposable elements, and that EHMT inhibition leads to genome-wide epigenetic and transcriptional derepression of transposable elements. We validated EHMT-mediated activation of immune signaling and upregulation of transposable element transcripts in patient-derived, therapy-naïve, primary ovarian tumors, suggesting potential efficacy in PARPi-sensitive disease as well. Importantly, using multispectral immunohistochemistry, we discovered that combinatory therapy increased CD8 T cell activity in the tumor microenvironment of the same patient-derived tissues. In a PARPi-resistant syngeneic murine model, EHMT and PARP inhibition combination inhibited tumor progression and increased Granzyme B+ cells in the tumor. Together, our results provide evidence that combinatory EHMT and PARP inhibition stimulates a cell autologous immune response in vitro, is an effective therapy to reduce PARPi resistant ovarian tumor growth in vivo, and promotes anti-tumor immunity activity in the tumor microenvironment of patient-derived ex vivo tissues of ovarian cancer.

Validation of the Safety and Efficacy of Apixaban as Postoperative Thromboembolism Prophylaxis for Patients with Gynecologic Malignancies.

BACKGROUND: Venous thromboembolism is a preventable complication of gynecologic cancer surgery that leads to postoperative morbidity and mortality. This study compared apixaban with enoxaparin to identify whether apixaban had the same safety and efficacy for patients undergoing gynecologic cancer surgery. METHODS: The study identified patients with a gynecologic malignancy who underwent surgery and were prescribed apixaban at discharge between June 2020 and April 2023. International Classification of Diseases 10 codes were used to identify patients who had a thromboembolism within 90 days or a bleeding event within 60 days after surgery. The rates of events for patients prescribed apixaban were compared with those for a historical cohort of patients who received enoxaparin. Fisher's exact tests were used to compare categorical variables, and t tests were used to compare continuous variables. A logistic regression was performed to compare the odds of thromboembolism between the two groups. RESULTS: Baseline patient characteristics differed in terms of body mass index (BMI), race, route of surgery, and type of cancer. Of the 490 patients in the apixaban cohort, 12 (2.4%) had a thromboembolism compared with 3 (2.1%) of the 138 patients in the enoxaparin group (adjusted odds ratio [aOR], 1.02; 95% confidence interval [CI] 0.30-4.70; p > 0.999). The odds ratio was adjusted for BMI, age, and route of surgery. A bleeding event occurred for 1 (0.2%) of the 490 patients in the apixaban group and for 1 (0.7%) of the 138 patients in the enoxaparin group. CONCLUSIONS: This validation study showed that apixaban is a safe and effective method of postoperative venous thromboembolism prophylaxis. The data provide support to previous data and guideline updates recommending the use of apixaban for postoperative prophylaxis.

Ovarian cancer think tank: An overview of the current status of ovarian cancer screening and recommendations for future directions.

Early diagnosis and screening of ovarian cancer remain significant challenges to improving patient outcomes. There is an urgent need to implement both established and modern strategies to address the "early detection" conundrum, especially as new research continues to uncover the complexities of the disease. The discussion provided is the result of a unique research conference focused on reviewing early detection modalities and providing insight into future approaches.

A rare case of cardiac metastasis of squamous cell carcinoma of the cervix with a review of existing case reports and treatment modalities.

•Cardiac metastasis is a rare complication of squamous cell carcinoma of the cervix.•Biologic agents may be a useful treatment modality for cardiac metastasis of squamous cell carcinoma of the cervix.•Multidisciplinary approach is required to treat cardiac metastasis of squamous cell carcinoma of the cervix.

Prospective Clinical Prognostication of Endometrial Carcinomas Based on Next-Generation Sequencing and Immunohistochemistry-Real-World Implementation and Results at a Tertiary Care Center.

Based on findings from The Cancer Genome Atlas and the Proactive Molecular Risk Classifier for Endometrial Cancer algorithm, endometrial carcinoma can now be stratified into 4 prognostically distinct subgroups based on molecular alterations and immunohistochemical (IHC) aberrations. In this study, we describe the de novo adoption and clinical reporting of prognostic subgroup classification based on next-generation sequencing (NGS) and IHC analyses of all endometrial carcinoma resections at a single institution, framed by the Exploration, Preparation, Implementation, and Sustainment model. Results from the first 13 months show 188 tumors underwent analysis by a combination of IHC and a medium-sized (56 analyzed genes) NGS-based assay. All cases were assigned as either POLE (POLE-mutated) (5.3%), mismatch repair deficient (27.7%), no specific molecular profile (45.7%), or p53 abnormal (21.3%) inclusive of multiple-classifier cases. NGS-based analysis revealed additional distinctions among the subgroups, including reduced levels of PI3K pathway activation in the p53 abnormal subgroup, an increased rate of CTNNB1 activating mutation in the no specific molecular profile subgroup, and lower TP53 mutation variant allele frequencies in POLE and mismatch repair deficient subgroups compared with the p53 abnormal subgroup. Overall, we describe the testing protocol, reporting, and results of a combination of NGS and IHC to prospectively prognosticate endometrial carcinomas at a single tertiary care center.

Cancer and the Risk of Perioperative Arterial Ischemic Events.

BACKGROUND AND AIMS: Most cancer patients require surgery for diagnosis and treatment. This study evaluated whether cancer is a risk factor for perioperative arterial ischemic events. METHODS: The primary cohort included patients registered in the National Surgical Quality Improvement Program (NSQIP) between 2006-2016. The secondary cohort included Healthcare Cost and Utilization Project (HCUP) claims data from 11 U.S. states between 2016-2018. Study populations comprised patients who underwent inpatient (NSQIP, HCUP) or outpatient (NSQIP) surgery. Study exposures were disseminated cancer (NSQIP) and all cancers (HCUP). The primary outcome was a perioperative arterial ischemic event, defined as myocardial infarction or stroke diagnosed within 30 days after surgery. RESULTS: Among 5,609,675 NSQIP surgeries, 2.2% involved patients with disseminated cancer. The perioperative arterial ischemic event rate was 0.96% among patients with disseminated cancer versus 0.48% among patients without (HR, 2.01; 95% CI, 1.90-2.13). In Cox analyses adjusting for demographics, functional status, comorbidities, surgical specialty, anesthesia type, and clinical factors, disseminated cancer remained associated with higher risk of perioperative arterial ischemic events (HR, 1.37; 95% CI, 1.28-1.46). Among 1,341,658 surgical patients in the HCUP cohort, 11.8% had a diagnosis of cancer. A perioperative arterial ischemic event was diagnosed in 0.74% of patients with cancer versus 0.54% of patients without cancer (HR, 1.35; 95% CI, 1.27-1.43). In Cox analyses adjusted for demographics, insurance, comorbidities, and surgery type, cancer remained associated with higher risk of perioperative arterial ischemic events (HR, 1.31; 95% CI, 1.21-1.42). CONCLUSIONS: Cancer is an independent risk factor for perioperative arterial ischemic events.

Prevention of venous thromboembolism in patients with cancer.

Venous thromboembolism (VTE) is a major cause of both morbidity and mortality in patients with cancer. Venous thromboembolism, which includes both deep vein thrombosis and pulmonary embolism, affects a sizable portion of patients with malignancy and can have potentially life threatening complications. Accurate assessment of risk as well as diagnosis and treatment of this process is paramount to preventing death in this high risk population. Various risk models predictive of venous thromboembolism in patients with cancer have been developed, and knowledge of these rubrics is essential for the treating oncologist. Subgroups of particular interest are inpatients receiving chemotherapy, postoperative patients after surgical debulking, and patients undergoing radiotherapy. Numerous newer drugs have become available for the prevention of venous thromboembolism in patients with cancer who are at high risk of developing the disease. These include the class of drugs called direct oral anticoagulants, (DOACs) which do not require the same monitoring that other modalities have previously required and are taken by mouth, preventing the discomfort associated with subcutaneous strategies. The appropriate risk stratification and intervention to prevent venous thromboembolism are vital to the treatment of patients with cancer.

Combinatory EHMT and PARP inhibition induces an interferon response and a CD8 T cell-dependent tumor regression in PARP inhibitor-resistant models.

Euchromatic histone lysine methyltransferases 1 and 2 (EHMT1/2), which catalyze demethylation of histone H3 lysine 9 (H3K9me2), contribute to tumorigenesis and therapy resistance through unknown mechanisms of action. In ovarian cancer, EHMT1/2 and H3K9me2 are directly linked to acquired resistance to poly-ADP-ribose polymerase (PARP) inhibitors and are correlated with poor clinical outcomes. Using a combination of experimental and bioinformatic analyses in several PARP inhibitor resistant ovarian cancer models, we demonstrate that combinatory inhibition of EHMT and PARP is effective in treating PARP inhibitor resistant ovarian cancers. Our in vitro studies show that combinatory therapy reactivates transposable elements, increases immunostimulatory dsRNA formation, and elicits several immune signaling pathways. Our in vivo studies show that both single inhibition of EHMT and combinatory inhibition of EHMT and PARP reduces tumor burden, and that this reduction is dependent on CD8 T cells. Together, our results uncover a direct mechanism by which EHMT inhibition helps to overcome PARP inhibitor resistance and shows how an epigenetic therapy can be used to enhance anti-tumor immunity and address therapy resistance.

Utilizing preoperative arterial embolization to minimize blood loss at time of vulvar sarcoma resection: A case report.

Selective arterial embolization has long been utilized in the field of obstetrics and gynecology as both a prophylactic and therapeutic measure. We present a case of a highly vascularized, poorly differentiated, radiation-related vulvar sarcoma that was resected immediately following selective arterial embolization. Arterial embolization in patients with gynecologic malignancies has been shown to compromise blood supply to the tumor and decrease the risk of hemorrhage and related surgical complications. In this case, the use of embolization prior to surgery appeared to result in a less morbid procedure for the patient with decreased blood loss and improved quality of life thereafter. Based on the presented case, we believe that arterial embolization can be considered a safe preoperative intervention to decrease surgical risk, particularly hemorrhage, at time of resection of highly vascularized vulvar tumors.

Loss of Claudin-4 Reduces DNA Damage Repair and Increases Sensitivity to PARP Inhibitors.

High-grade serous ovarian cancer is the deadliest gynecologic malignancy due to progression to resistant disease. Claudin-4 is classically defined as a tight junction protein and is often associated with epithelial cancers. Claudin-4 is aberrantly expressed in nearly 70% of all ovarian cancer tumors and conveys a worse overall prognosis. Elevated claudin-4 expression correlates to increased DNA repair activity and resistance to DNA damaging agents. PARP inhibitors are emerging as an effective therapeutic option for patients with ovarian cancer and function by promoting DNA damage. The study examines the relationship between claudin-4 expression and the response to PARP inhibitors using both genetic and pharmacologic inhibition of claudin-4 in in vitro and ex vivo models of ovarian cancer to examine DNA repair markers and functional activity. Genetic inhibition of claudin-4 results in the downregulation of several DNA damage repair effectors, including 53BP1 and XRCC1. Claudin-4 knockdown did not change homology-directed repair but inhibited nonhomologous end-joining and reduced 53BP1 foci formation. In 15 primary ovarian cancer tumors, higher claudin-4 expression significantly correlated to a dampened PARP inhibitor-mediated antiproliferation response. Further, claudin-4 inhibition in high claudin-4 tumors sensitized tumor sections to PARP inhibition. These data highlight that claudin-4 expression in ovarian cancer tumors could serve as both a marker of PARP inhibitor response and a therapeutic target to improve PARP inhibitor response.

Beyond Sedlis-A novel histology-specific nomogram for predicting cervical cancer recurrence risk: An NRG/GOG ancillary analysis.

PURPOSE: The Sedlis criteria define risk factors for recurrence warranting post-hysterectomy radiation for early-stage cervical cancer; however, these factors were defined for squamous cell carcinoma (SCC) at an estimated recurrence risk of ≥30%. Our study evaluates and compares risk factors for recurrence for cervical SCC compared with adenocarcinoma (AC) and develops histology-specific nomograms to estimate risk of recurrence and guide adjuvant treatment. METHODS: We performed an ancillary analysis of GOG 49, 92, and 141, and included stage I patients who were surgically managed and received no neoadjuvant/adjuvant therapy. Multivariable Cox proportional hazards models were used to evaluate independent risk factors for recurrence by histology and to generate prognostic histology-specific nomograms for 3-year recurrence risk. RESULTS: We identified 715 patients with SCC and 105 with AC; 20% with SCC and 17% with AC recurred. For SCC, lymphvascular space invasion (LVSI: HR 1.58, CI 1.12-2.22), tumor size (TS ≥4 cm: HR 2.67, CI 1.67-4.29), and depth of invasion (DOI; middle 1/3, HR 4.31, CI 1.81-10.26; deep 1/3, HR 7.05, CI 2.99-16.64) were associated with recurrence. For AC, only TS ≥4 cm, was associated with recurrence (HR 4.69, CI 1.25-17.63). For both histologies, there was an interaction effect between TS and LVSI. For those with SCC, DOI was most associated with recurrence (16% risk); for AC, TS conferred a 15% risk with negative LVSI versus a 25% risk with positive LVSI. CONCLUSIONS: Current treatment standards are based on the Sedlis criteria, specifically derived from data on SCC. However, risk factors for recurrence differ for squamous cell and adenocarcinoma of the cervix. Histology-specific nomograms accurately and linearly represent risk of recurrence for both SCC and AC tumors and may provide a more contemporary and tailored tool for clinicians to base adjuvant treatment recommendations to their patients with cervical cancer.

Assessing Inequities in Cervical Cancer Quality of Care and Survival Related to Ethnicity and Socioeconomic Factors.

OBJECTIVE: This study aimed to assess the effect that race and socioeconomic factors have on the provision of care to cervical cancer patients based on National Comprehensive Cancer Network (NCCN) recommended treatment guidelines. MATERIALS AND METHODS: To do this, we completed a retrospective cohort study using the American College of Surgeon's Nation Cancer Database from 2004 to 2016. We identified all reported cases of cervical cancer in that period. Two cohorts were created using self-reported racial demographic data, Hispanic- and White, non-Hispanic-identified patients. Our primary outcome variables were adherence to NCCN-recommended treatment and 5-year overall survival. Adherence to NCCN-recommended treatment was determined by the provision of surgical and/or radiation and/or chemotherapy treatment based on the clinical stage at time of diagnosis and the presence or absence of lymphovascular space invasion. We used bivariate analyses to compare baseline characteristics between the 2 cohorts, multivariable logistic regression to identify independent predictors of 5-year survival, and Cox proportional hazards models to compute survival by group. RESULTS: The difference in NCCN-adherent care between the 2 cohorts was found to be not statistically significant (p = .880). A log rank (Mantel-Cox) χ2 test showed that there was a statistically significant difference between the 2 groups in overall survival with the Hispanic-identified patients living longer (p < .001). Our study is limited by the effect large databases confer on finding statistical significance. CONCLUSIONS: Hispanic-identified women with cervical cancer receive NCCN-compliant care and live longer than their White, non-Hispanic counterparts.

Post hoc analyses of GOG 9923: Does BRCA status affect toxicities?: An NRG oncology study.

OBJECTIVE: To evaluate how women with epithelial ovarian cancer (EOC), dichotomized by BRCA status, tolerate intravenous (IV) or intraperitoneal (IP) chemotherapy given with veliparib and bevacizumab (bev) on a GOG phase I study (GOG 9923, NCT00989651). METHODS: This is an unplanned, post hoc analysis of an IRB approved, multi-institutional, prospective study (GOG 9923). Clinical characteristics and toxicity data based on BRCA status were evaluated and descriptive statistics were used to summarize baseline patient characteristics and toxicities. The Kaplan Meier method was used to generate survival estimates. RESULTS: Four hundred twenty-four patients were evaluable. Patients were treated with IV carboplatin, paclitaxel, and bev every 21 days (regimen 1), weekly IV paclitaxel with carboplatin and bev (regimen 2) or IV paclitaxel and bev with IP cisplatin (regimen 3). Bev was continued as maintenance in all arms. Within each of these regimens, veliparib was given either twice daily for the entirety of each cycle (continuous) or on days -2 to 5 (intermittent). Ten percent of patients treated on regimen 1, 12% on regimen 2, and 19.8% on regimen 3 had BRCA-associated tumors. Patients with BRCA-associated tumors, when compared to wild type, experienced similar rates of anemia, febrile neutropenia (, abdominal pain, colonic perforation, nausea, vomiting, and peripheral sensory neuropathy. Median progression free survival (PFS) was not significantly different between BRCA-associated and wild type cancers (HR 0.96, CI 0.65-1.42), though this study's primary aim was not to evaluate outcomes. CONCLUSIONS: Germline BRCA mutations positively affect chemosensitivity in EOC, but whether differences in toxicities among BRCA-associated and BRCA wild type tumors existed was previously not reported. In this population with newly diagnosed ovarian cancer no differences in reported toxicity between the two groups was observed.

Treatment of epithelial ovarian cancer.

Ovarian cancer is the third most common gynecologic malignancy worldwide but accounts for the highest mortality rate among these cancers. A stepwise approach to assessment, diagnosis, and treatment is vital to appropriate management of this disease process. An integrated approach with gynecologic oncologists as well as medical oncologists, pathologists, and radiologists is of paramount importance to improving outcomes. Surgical cytoreduction to R0 is the mainstay of treatment, followed by adjuvant chemotherapy. Genetic testing for gene mutations that affect treatment is the standard of care for all women with epithelial ovarian cancer. Nearly all women will have a recurrence, and the treatment of recurrent ovarian cancer continues to be nuanced and requires extensive review of up to date modalities that balance efficacy with the patient's quality of life. Maintenance therapy with poly ADP-ribose polymerase inhibitors, bevacizumab, and/or drugs targeting homologous recombination deficiency is becoming more widely used in the treatment of ovarian cancer, and the advancement of immunotherapy is further revolutionizing treatment targets.

Cost-effectiveness of apixaban for prevention of venous thromboembolic events in patients after gynecologic cancer surgery.

OBJECTIVE: The cost-effectiveness of apixaban was compared with enoxaparin for prevention of postoperative venothromboembolic events (VTE) in gynecologic oncology patients. Current guidelines recommend thromboprophylaxis with low molecular weight heparin for 28 days following gynecologic cancer surgery, but recent trials suggest that oral apixaban may be a safe, patient-preferred alternative. Apixaban was superior to enoxaparin in a Canadian cost-effectiveness analysis using orthopedics trial data. METHODS: Medication costs, adherence rates, event rates, event costs, and utility decrements were estimated using prior clinical trial data and literature review for input into a short-term decision model to simulate outcomes in a hypothetical cohort of 1000 patients. Incremental cost-effectiveness ratios (ICERs) were calculated as net cost difference per quality-adjusted life year (QALY) gained. Input values at which net costs and QALYs were equivalent and ICERs at upper and lower bounds were evaluated. RESULTS: Using aggregated costs, apixaban was less expensive and more effective than enoxaparin, and remained so or had high value in all scenarios on sensitivity analysis. Examining disaggregated ICERs, apixaban was cost-effective for deep venous thrombosis (DVT); of high value for clinically-relevant non-major bleeding (CRNMB) ($411); low value for major bleeding ($183,465), VTE-related death ($2,711,229), and all-cause mortality ($297,522); and not cost-effective for pulmonary embolism prevention. CONCLUSIONS: Apixaban is more cost-effective than enoxaparin for the prevention of postoperative VTE in patients with gynecologic cancer. This appears to be driven largely by DVT and CRNMB prevention.

Adherence to postoperative thromboprophylactic medication among gynecologic oncology patients: A subanalysis.

INTRODUCTION: Venous thromboembolism (VTE) is a major cause of morbidity and mortality among gynecologic cancer patients, especially in the immediate postoperative period. We sought to identify patterns related with patient non-adherence to postoperative prophylactic anticoagulation. METHODS: Participant data (N = 400) were reviewed from a previously conducted randomized controlled trial comparing the safety and efficacy of prophylactic postoperative anticoagulation with enoxaparin versus apixaban among gynecologic oncology patients. Variables hypothesized to be related to medication adherence were pre-selected by the study authors, and adherence was defined as missing ≤2 days of medication (4 pills or 2 injections) in 28 days postoperatively. For univariate comparisons and multivariate modeling, the threshold for statistical significance was set at p < .05. RESULTS: Non-adherence (N = 64) was associated with lower quality of life (QOL) score, history of anxiety disorder, decreased medication satisfaction, taking more medications at baseline, higher baseline heart rate, fewer total intraoperative procedures, not undergoing radical hysterectomy and/or lymph node dissection, not meeting 2-week postoperative milestones, and 28-day emergency department (ED) visit or readmission. African American race, lower mental QOL, difficulty remembering to take medication, and 28-day ED visit or readmission were predictive of non-adherence in a multivariate model. Patients taking enoxaparin versus apixaban more frequently attributed non-adherence to pain or bruising (25.0% vs. 3.1%, P = .01). CONCLUSION: Our findings provide new insights into factors associated with medication adherence that are particularly relevant to gynecologic oncology patients after surgery. Preoperative interventions to identify patients with these risk factors for more intensive followup of postoperative anticoagulation regimen may help increase medication adherence.

Safety and Efficacy of Apixaban vs Enoxaparin for Preventing Postoperative Venous Thromboembolism in Women Undergoing Surgery for Gynecologic Malignant Neoplasm: A Randomized Clinical Trial.

Importance: Current guidelines recommend a 28-day course of enoxaparin for thromboprophylaxis after surgery for gynecologic cancer. The high cost of this medication and the low adherence rates observed in prior studies provide an opportunity to benefit patients by demonstrating the safety of a more cost-effective, easier to use thromboprophylactic. Objective: To investigate the safety and efficacy of an oral treatment alternative for thromboprophylaxis in postoperative patients with gynecologic cancer. Design, Setting, and Participants: This was a patient-based, multicenter, open-label, blinded, end point, randomized clinical trial conducted May 2015 to March 2019 in outpatient and inpatient gynecologic oncology settings. Women undergoing surgery for suspected or confirmed gynecologic cancer were approached for recruitment. The trial compared rates of major bleeding and clinically relevant nonmajor bleeding events during a 90-day follow-up period in patients taking apixaban or enoxaparin for postoperative thromboprophylaxis using a modified intent-to-treat analysis. Data analysis was performed from October to December 2019. Interventions: Women were randomized to 28 days of apixaban (2.5 mg orally twice daily) or enoxaparin (40 mg subcutaneously daily). Main Outcomes and Measures: The primary outcome was major bleeding and clinically relevant nonmajor bleeding events. Secondary outcomes included incidence of venous thromboembolic events, adverse events, medication adherence, participant quality of life, and medication satisfaction. Results: Of 500 women recruited for the study, 400 were enrolled and randomized (median age, 58.0 years; range, 18.0-89.0 years); 204 received apixaban and 196 received enoxaparin. Treatment groups did not differ in terms of race/ethnicity, cancer stage, or surgery modality (open vs robotic). There were no statistically significant differences between the apixaban and enoxaparin groups in terms of rates of major bleeding events (1 patient [0.5%] vs 1 patient [0.5%]; odds ratio [OR], 1.04; 95% CI, 0.07-16.76; P > .99), clinically relevant nonmajor bleeding events (12 patients [5.4%] vs 19 patients [9.7%]; OR, 1.88; 95% CI, 0.87-4.1; P = .11), venous thromboembolic events (2 patients [1.0%] vs 3 patients [1.5%]; OR, 1.57; 95% CI, 0.26-9.50; P = .68), adverse events, medication adherence, or quality of life between the groups. Participant satisfaction was significantly greater in the apixaban group with regard to ease of taking the medication (186 patients [98.9%] vs 110 patients [58.8%]; OR, 0.06; 95% CI, 0.01-0.25; P < .001) and pain associated with taking the medication (4 patients [2.1%] vs 92 patients [49.2%]; OR, 9.20; 95% CI, 2.67-31.82; P < .001). Conclusions and Relevance: These findings suggest that oral apixaban is a potentially safe, less painful, and easier-to-take alternative to subcutaneous enoxaparin for thromboprophylaxis after surgery for gynecologic cancer. The efficacy of apixaban to prevent venous thromboembolic events is hypothesized as being equivalent. Trial Registration: ClinicalTrials.gov Identifier: NCT02366871.