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.

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.

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.

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.

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.

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.

A phase I study of intravenous or intraperitoneal platinum based chemotherapy in combination with veliparib and bevacizumab in newly diagnosed ovarian, primary peritoneal and fallopian tube cancer.

BACKGROUND: Improvements in disease free survival for epithelial ovarian, peritoneal or fallopian tube cancer (EOC) will only come with improved primary therapy. Incorporation of poly-ADP-ribose inhibitors (PARPi) in the frontline setting may represent one strategy. This study sought to determine the maximum tolerated and feasible doses of the PARPi veliparib in combination with chemotherapy for EOC. METHODS: A phase I, 3 + 3 dose escalation evaluated dose-limiting toxicities (DLTs) in cycles 1-2. Once <2/6 patients experienced a DLT, that dose level expanded to evaluate feasibility over 4 cycles. This study opened 10/2009 and closed 8/2016. Eligible patients had untreated, stage II-IV EOC. Veliparib was added either continuous (day 1-21) or intermittent (day - 2 to 5) during 6 cycles of chemotherapy. Three chemotherapy backbones were evaluated (2 intravenous (q3week and weekly) and 1 intraperitoneal (IP)) all inclusive of bevacizumab with and as maintenance to 22 cycles. FINDINGS: Dose evaluations for 424 treated patients were available. Regimen 1 (q3 week), continuous (Reg1c) the maximum tolerated dose (MTD) was 250 mg veliparib BID and feasible dose was 150 mg BID. For regimen 1, intermittent (Reg1i) the MTD and feasible dose were 400 and 250 mg BID. For Reg2c (weekly paclitaxel) the MTD and feasible dose were 150 mg BID. For Reg2i the MTD and feasible dose were 250 and 150 mg BID. For Reg3c (IP) the MTD and feasible dose were 150 mg BID and for Reg3i (IP), the MTD and feasible dose were 400 mg and 300 mg BID. INTERPRETATION: The feasible dose for Reg1c, 2c, 2i and 3c was 150 mg po BID. For Reg1i and 3i the dose was pushed to 250 and 300 mg po BID respectively. There is no apparent difference in efficacy between continuous and intermittent dosing indicating that the higher doses achieved in intermittent dosing may not be needed. (NCT00989651). FUNDING: National Cancer Institute.

African American women with advanced-stage ovarian cancer have worse outcomes regardless of treatment type.

OBJECTIVE: There has been an increase in the use of neoadjuvant chemotherapy in recent years. Our objective was to determine if African American women are more likely to receive neoadjuvant chemotherapy than primary debulking surgery, when compared to their Caucasian counterparts, and the impact of such an approach on oncologic outcomes. METHODS: A retrospective cohort study was performed using the National Cancer Database (NCDB). Women aged 18-90 years, diagnosed with stage IIIC or IV epithelial ovarian cancer between January 2010 through December 2014 were included. Women with unknown treatment or treatments outside of neoadjuvant chemotherapy or primary debulking surgery were excluded. Only women of Caucasian, African American, or Hispanic origin who received either neoadjuvant chemotherapy or primary debulking surgery were included; all other races were excluded. Descriptive statistics were computed, and continuous variables were assessed for normality. Groups were compared using ANOVA or non-parametric medians tests for continuous variables, and chi-squared tests were used for dichotomous or categorical variables. Logistic regression was used to identify predictors of treatment. A p value of 0.05 was considered statistically significant. RESULTS: A total of 19 838 women with stage IIIC and IV epithelial ovarian cancer met the inclusion criteria. A total of 14 988 (75.6%) were treated with primary debulking surgery, while 4850 women (24.4%) were treated with neoadjuvant chemotherapy. Of those treated with neoadjuvant chemotherapy, 24.5% were white, 27.0% were African American, and 22.1% were Hispanic (p=0.005), and when adjusted for confounders, being African American was a predictor of receiving neoadjuvant chemotherapy (adjusted odds ratio (aOR) 1.29, 95% CI 1.10 to 1.51). Ninety-day mortality rates were higher in African American women compared with Caucasian and Hispanic women (2.9% vs 2.0% vs 1.6%, p=0.013). There were no differences in 30-day mortality, 90-day mortality, or status at last contact in African American women, when comparing neoadjuvant chemotherapy and primary debulking surgery. In Caucasian women, outcomes were worse in women receiving neoadjuvant chemotherapy. CONCLUSIONS: Compared to other races, African American women with advanced ovarian cancer are more likely to receive neoadjuvant chemotherapy than primary debulking surgery and had a higher 90-day mortality rate. In African American women there was no difference in outcomes based on treatment type.

Patient-reported outcomes at discontinuation of anti-angiogenesis therapy in the randomized trial of chemotherapy with bevacizumab for advanced cervical cancer: an NRG Oncology Group study.

INTRODUCTION: To describe patient-reported outcomes and toxicities at time of treatment discontinuation secondary to progression or toxicities in advanced/recurrent cervical cancer patients receiving chemotherapy with bevacizumab. METHODS: Summarize toxicity, grade, and health-related quality of life within 1 month of treatment discontinuation for women receiving chemotherapy with bevacizumab in GOG240. RESULTS: Of the 227 patients who received chemotherapy with bevacizumab, 148 discontinued study protocol treatment (90 for disease progression and 58 for toxicity). The median survival time from treatment discontinuation to death was 7.9 months (95% CI 5.0 to 9.0) for those who progressed versus 12.1 months (95% CI 8.9 to 23.2) for those who discontinued therapy due to toxicities. The most common grade 3 or higher toxicities included hematologic, gastrointestinal, and pain. Some 57% (84/148) of patients completed quality of life assessment within 1 month of treatment discontinuation. Those patients who discontinued treatment due to progression had a mean decline in the FACT-Cx TOI of 3.2 points versus 2.2 in patients who discontinued therapy due to toxicity. This was a 9.9 point greater decline in the FACT-Cx TOI scores than those who discontinued treatment due to progression (95% CI 2.8 to 17.0, p=0.007). The decline in quality of life was due to worsening physical and functional well-being. Those who discontinued treatment due to toxicities had worse neurotoxicity and pain. DISCUSSION: Patients who discontinued chemotherapy with bevacizumab for toxicity experienced longer post-protocol survival but significantly greater declination in quality of life than those with progression. Future trial design should include supportive care interventions that optimize physiologic function and performance status for salvage therapies.

Molecular markers in recurrent stage I, grade 1 endometrioid endometrial cancers.

OBJECTIVES: Stage I, grade 1 endometrial cancers have low recurrence rates and often do not receive adjuvant therapy. We compared recurrent cases to matched non-recurrent controls to evaluate for molecular markers associated with higher risk of recurrence. METHODS: A case-control study including all cases of recurrent stage I, grade 1 endometrioid endometrial cancer at one institution in a ten-year period. Cases were matched to controls by age, BMI, weight and stage. Molecular testing and immunohistochemistry were performed on archival tumor specimens: microsatellite instability (MSI-H), mismatch repair status, POLE mutational status, and next-generation sequencing. RESULTS: 15 stage I, grade 1 endometrial cancer cases with recurrent disease and available tumor specimens were identified. CTNNB1 and MSI-H were present at significantly higher rates in cases than controls (CTNNB1 60% vs. 28%, OR 3.9, 95%CI 1.1-14.7, p = 0.04 and MSI-H 53% vs. 21%, OR 4.4, 95%CI 1.1-17.0, p = 0.03). POLE mutations were found in 0% of cases vs. 7% of controls (p = 0.54). Among specimens demonstrating microsatellite stability (MSS), 100% of cases vs. 26% of controls had CTNNB1 mutations (p < 0.001). CTNNB1 wild type tumors were MSI-H in 100% of cases vs. 19% of controls (p < 0.001). CONCLUSIONS: Compared to controls, CTNNB1 mutation is present at significantly higher rates in recurrent stage I, grade 1 endometrial cancers and is found most commonly in MSS tumors. MSI-H is also present at significantly higher rates in recurrent cases. These markers may be useful for prognostic risk stratification and adjuvant therapy decision-making in this otherwise low-risk population.

Recurrence, death, and secondary malignancy after ovarian conservation for young women with early-stage low-grade endometrial cancer.

OBJECTIVE: To examine the association between ovarian conservation and oncologic outcome in surgically-treated young women with early-stage, low-grade endometrial cancer. METHODS: This multicenter retrospective study examined women aged <50 with stage I grade 1-2 endometrioid endometrial cancer who underwent primary surgery with hysterectomy from 2000 to 2014 (US cohort n = 1196, and Japan cohort n = 495). Recurrence patterns, survival, and the presence of a metachronous secondary malignancy were assessed based on ovarian conservation versus oophorectomy. RESULTS: During the study period, the ovarian conservation rate significantly increased in the US cohort from 5.4% to 16.4% (P = 0.020) whereas the rate was unchanged in the Japan cohort (6.3-8.7%, P = 0.787). In the US cohort, ovarian conservation was not associated with disease-free survival (hazard ratio [HR] 0.829, 95% confidence interval [CI] 0.188-3.663, P = 0.805), overall survival (HR not estimated, P = 0.981), or metachronous secondary malignancy (HR 1.787, 95% CI 0.603-5.295, P = 0.295). In the Japan cohort, ovarian conservation was associated with decreased disease-free survival (HR 5.214, 95% CI 1.557-17.464, P = 0.007) and an increased risk of a metachronous secondary malignancy, particularly ovarian cancer (HR 7.119, 95% CI 1.349-37.554, P = 0.021), but was not associated with overall survival (HR not estimated, P = 0.987). Ovarian recurrence or metachronous secondary ovarian cancer occurred after a median time of 5.9 years, and all cases were salvaged. CONCLUSION: Our study suggests that adoption of ovarian conservation in young women with early-stage low-grade endometrial cancer varies by population. Ovarian conservation for young women with early-stage, low-grade endometrial cancer may be potentially associated with increased risks of ovarian recurrence or metachronous secondary ovarian cancer in certain populations; nevertheless, ovarian conservation did not negatively impact overall survival.

Minority Race Predicts Treatment by Non-gynecologic Oncologists in Women with Gynecologic Cancer.

BACKGROUND: Outcomes of women with gynecologic cancer are superior when treated by gynecologic oncologists. The National Surgical Quality Improvement Program (NSQIP) began identifying gynecologic surgeon subspecialty in 2014. We sought to identify characteristics and outcomes of women treated by general gynecologists in comparison with women treated by gynecologic oncologists. PATIENTS AND METHODS: Patients undergoing hysterectomy for gynecologic malignancy in 2014 and 2015 were abstracted from the NSQIP database. Patient characteristics, morbidities, surgeon specialty, and operative outcomes were captured. RESULTS: 7271 hysterectomies were performed for malignant disease, and 669 were performed by generalists. In comparison with generalists, gynecologic oncologists operated on patients who were older (P < 0.001), more likely to be White [odds ratio (OR) 2.1, P < 0.001], had disseminated cancer (OR 3.1, P < 0.001), had ascites (OR 2.6, P < 0.001), and were classified as American Society of Anesthesiologists (ASA) class ≥ 3 (OR 1.7, P < 0.001). Gynecologic oncologists were also more likely to have hospital readmissions (OR 1.7, P = 0.004) and perform lymph node dissections for endometrial cancer (OR 2.2, P < 0.001). On multivariable analysis, older age [adjusted OR (aOR) 1.0, P = 0.021], White race (aOR 2.0, P < 0.001), presence of disseminated cancer (aOR 2.5, P < 0.001), presence of ascites (aOR 1.8, P = 0.036), and ASA class ≥ 3 (aOR 1.6, P < 0.001) remained independent predictive factors for having a gynecologic oncology surgeon. CONCLUSIONS: The majority of gynecologic cancer cases are performed by gynecologic oncologists. Generalists are more likely to operate on minority patients and patients with fewer comorbidities. Further efforts to ensure access to specialized cancer care for all patients are needed.

Receipt of adjuvant endometrial cancer treatment according to race: an NRG Oncology/Gynecologic Oncology Group 210 Study.

BACKGROUND: Black women with endometrial cancer are more likely to die of their disease compared with white women with endometrial cancer. These survival disparities persist even when disproportionately worse tumor characteristics among black women are accounted. Receipt of less complete adjuvant treatment among black patients with endometrial cancer could contribute to this disparity. OBJECTIVE: We assessed the hypothesis that black women with endometrial cancer are less likely than their white counterparts to receive adjuvant treatment within subgroups defined by tumor characteristics in the NRG Oncology/Gynecology Oncology Group 210 Study. STUDY DESIGN: Our analysis included 615 black and 4283 white women with endometrial cancer who underwent hysterectomy. Women completed a questionnaire that assessed race and endometrial cancer risk factors. Tumor characteristics were available from pathology reports and central review. We categorized women as low-, intermediate-, or high-risk based on the European Society for Medical Oncology definition. Adjuvant treatment was documented during postoperative visits and was categorized as no adjuvant treatment (54.3%), radiotherapy only (16.5%), chemotherapy only (15.2%), and radiotherapy plus chemotherapy (14.0%). We used polytomous logistic regression to estimate odds ratios and 95% confidence intervals for multivariable-adjusted associations between race and adjuvant treatment in the overall study population and stratified by tumor subtype, stage, or European Society for Medical Oncology risk category. RESULTS: Overall, black women were more likely to have received chemotherapy only (odds ratio, 1.40; 95% confidence interval, 1.04-1.86) or radiotherapy plus chemotherapy (odds ratio, 2.01; 95% confidence interval, 1.54-2.62) compared with white women in multivariable-adjusted models. No racial difference in the receipt of radiotherapy only was observed. In tumor subtype-stratified models, black women had higher odds of receiving radiotherapy plus chemotherapy than white women when diagnosed with low-grade endometrioid (odds ratio, 2.04; 95% confidence interval, 1.06-3.93) or serous tumors (odds ratio, 1.81; 95% confidence interval, 1.07-3.08). Race was not associated with adjuvant treatment among women who had been diagnosed with other tumor subtypes. In stage-stratified models, we observed no racial differences in the receipt of adjuvant treatment. In models that were stratified by European Society for Medical Oncology risk group, black women with high-risk cancer were more likely to receive radiotherapy plus chemotherapy compared with white women (odds ratio, 1.41; 95% confidence interval, 1.03-1.94). CONCLUSION: Contrary to our hypothesis, we observed higher odds of specific adjuvant treatment regimens among black women as compared with white women within specific subgroups of endometrial cancer characteristics.

Radiation therapy is not an independent risk factor for decreased sexual function in women with gynecologic cancers.

AIM: To evaluate the associations of external beam radiation therapy (EBRT) and intracavitary brachytherapy (IB) with decreased sexual function. BACKGROUND: There's inconsistent evidence on whether radiation for gynecologic cancers has an impact on sexual health. IB, an underutilized treatment modality, is thought to have less adverse effects than EBRT. MATERIALS AND METHODS: A cross-sectional study examining decreased sexual function following radiation for gynecologic cancers. A decrease in sexual function was measured as a change in the Female Sexual Function Index (FSFI) from before to after treatment, with a significant decrease determined by Reliable Change Index Statistic (RCIS). Chi-square and t-tests were employed. RESULTS: 171 women completed the survey; 35% (n = 60) received radiation, of whom 29 received EBRT and IB (48%), 15 EBRT alone (25%), 16 IB alone (27%). Women who received radiation had similar rates of decreased sexual function as women who did not (47% vs. 38%, P = 0.262). EBRT and IB had similar rates of decreased sexual function compared to women with no radiation (50% vs. 38% P = 0.166 and 47% vs. 38% P = 0.309). Women experiencing decreased sexual function were more likely to be under 50 years old (OR 5.4, 95%CI 1.6-18.1), have received chemotherapy (OR 5.7, 95%CI 1.4-22.9), and have cervical cancer (OR 7.8, 95%CI 2.1-28.8). CONCLUSIONS: Treatment with EBRT or IB does not appear to impair sexual function in women with gynecologic cancer. Age less than 50, concurrent chemotherapy, and cervical cancer may place women with gynecologic cancer at higher risk for decreased sexual function following radiation.

Surgical-pathological findings in type 1 and 2 endometrial cancer: An NRG Oncology/Gynecologic Oncology Group study on GOG-210 protocol.

OBJECTIVE: To report clinical and pathologic relationships with disease spread in endometrial cancer patients. METHODS: Surgical candidates with uterine cancer (adenocarcinoma or carcinosarcoma) who were eligible to participate in a surgical pathological study to create a clinically annotated tissue biorepository to support translational and clinical research studies. All patients were to undergo a hysterectomy, bilateral salpingo-oophorectomy, and bilateral pelvic and para-aortic lymphadenectomy. From 2003-2007, open eligibility enrollment was conducted, and from 2007-2011, eligibility was restricted to enrich underrepresented patients or those at high risk. RESULTS: This report details clinical pathological relationships associated with extra uterine disease spread of 5866 evaluable patients including those with endometrioid histology as well as papillary serous, clear cell and carcinosarcoma histologies. Review of unrestricted enrollment was constructed in an effort to capture a cross-section population representative of endometrial cancers seen by the GOG participating members. Evaluation of this group of patients suggested the more natural incidence of different surgical pathological findings as well as demographic information. The addition of 2151 patients enrolled during the restricted time interval allowed a total of 1630 poor histotype patients available for further analysis. As expected, endometrioid (E) cancers represented the largest enrollment and particularly E grade 1 and 2 (G1 and 2) were more frequently confined to the uterus. Grade 3 (G3) endometrioid cancers as well as the poor histotype (papillary serous, clear cell and carcinosarcoma) had a much greater propensity for extant disease. CONCLUSIONS: This study confirms the previously reported surgical pathological findings for endometrioid cancers but in addition, using a large database of papillary serous, clear cell and carcinosarcoma, surgical pathological findings substantiate the categorization of poor histotypes for these cancers.

Risk of metachronous ovarian cancer after ovarian conservation in young women with stage I cervical cancer.

BACKGROUND: While there is an increasing trend of ovarian conservation at the time of surgical treatment for young women with stage I cervical cancer, the risk for subsequent ovarian cancer after ovarian conservation has not been well studied. OBJECTIVE: We sought to examine the incidence of and risk factors for metachronous ovarian cancer among young women with stage I cervical cancer who had ovarian conservation at the time of hysterectomy. STUDY DESIGN: The Surveillance, Epidemiology, and End Results Program was used to identify women aged <50 years who underwent hysterectomy with ovarian conservation for stage I cervical cancer from 1983 through 2013 (n = 4365). Time-dependent analysis was performed for ovarian cancer risk after cervical cancer diagnosis. RESULTS: Mean age at cervical cancer diagnosis was 37 years, and the majority of patients had stage IA disease (68.2%) and squamous histology (72.9%). Median follow-up time was 10.8 years, and there were 13 women who developed metachronous ovarian cancer. The 10- and 20-year cumulative incidences of metachronous ovarian cancer were 0.2% (95% confidence interval, 0.1-0.4) and 0.5% (95% confidence interval, 0.2-0.8), respectively. Mean age at the time of diagnosis of metachronous ovarian cancer was 47.5 years, and stage III-IV disease was seen in 55.6%. Age (≥45 vs <45 years, hazard ratio, 4.22; 95% confidence interval, 1.16-15.4; P = .018), ethnicity (non-white vs white, hazard ratio, 4.29; 95% confidence interval, 1.31-14.0; P = .009), cervical cancer histology (adenocarcinoma or adenosquamous vs squamous, hazard ratio, 3.50; 95% confidence interval, 1.17-10.5; P = .028), and adjuvant radiotherapy use (yes vs no, hazard ratio, 3.69; 95% confidence interval, 1.01-13.4; P = .034) were significantly associated with metachronous ovarian cancer risk. The presence of multiple risk factors was associated with a significantly increased risk of metachronous ovarian cancer compared to the no risk factor group: 1 risk factor (hazard ratio range, 2.96-8.43), 2 risk factors (hazard ratio range, 16.6-31.0), and 3-4 risk factors (hazard ratio range, 62.3-109), respectively. CONCLUSION: Metachronous ovarian cancer risk after ovarian conservation for women with stage I cervical cancer is <1%. Older age, non-white ethnicity, adenocarcinoma or adenosquamous histology, and adjuvant radiotherapy may be associated with an increased metachronous ovarian cancer risk.

Histopathology Discrepancy of Preoperative Endometrial Sampling and Final Specimen: How Does This Influence Selective Lymph Node Dissection?

OBJECTIVE: Preoperative histology is a major component in the perioperative selective lymph node (LN) dissection decision process. Discrepancy between preoperative endometrial sampling and final specimen histopathology is generally accepted. The goals of this project are to determine if discrepancy of histopathology is associated with alteration of adjuvant treatment or outcome. MATERIALS AND METHODS: We performed a retrospective cross-sectional analysis of all patients undergoing surgery for endometrial cancer at a single institution from 2010 to 2014. All patients had preoperative endometrial sampling. Histopathology discrepancy was evaluated for potential in variation of perioperative LN dissection. Criteria for not performing LN dissection was defined as preoperative endometrioid histology, grade 1 or 2 lesion, myometrial invasion of 50% or less, and primary tumor diameter 2 cm or less. RESULTS: A total of 352 patients were identified; 44 were excluded because of no preoperative pathology or no residual disease on final pathology. Discrepancy of histopathology was noted in 64/308 (20.8%; 95% confidence interval [CI], 16.2%-25.3%) patients. Preoperative endometrioid histology was noted in 272 patients, and 17/272 (6.3%; 95% CI, 3.4%-9.1%) had preoperative sampling reviewed as a grade 1 or 2 endometrioid lesion and final specimen was upgraded to grade 3. Downstaging occurred in 3/272 (1.1%; 95% CI, 0%-2.3%) patients with preoperative grade 3 lesion and final specimen demonstrated grade 1 or 2 disease. All 3 patients' primary tumor diameter was greater than 2 cm and therefore received LN dissection. Histopathological discrepancy that would alter perioperative LN dissection decision based on the aforementioned criteria occurred in 2/272 (0.7%; 95% CI, 0%-1.8%). CONCLUSIONS: Despite a 20% discrepancy of preoperative and postoperative histopathology, discrepancy that would alter a perioperative decision for LN dissection occurs in only 0.7% of cases in this retrospective single-institutional experience. Myometrial invasion and tumor size may be more influential than histology in LN selection criteria.

Sexual and Marital Dysfunction in Women With Gynecologic Cancer.

OBJECTIVE: Sexual dysfunction can be a long-term issue for women with gynecologic cancer. This study assesses the extent of sexual and marital dysfunction women face following treatment of a gynecologic cancer. METHODS: A cross-sectional study of women with gynecologic cancer was conducted using a 181-item survey. Sexual dysfunction was measured by change in the Female Sexual Function Index score; marital dysfunction was measured by change in Intimate Bond Measure from prediagnosis to posttreatment. Paired t tests and Fisher exact test were used to compare women with dysfunction to those without dysfunction. RESULTS: Three hundred twenty women were enrolled (mean age, 56.0 [SD, 12.0] years). Among all women, sexual function declined from a score of 21.3 (SD, 10.4) prior to 15.3 (SD, 10.2) (P < 0.001), and sexual activity decreased from 6.1 (SD, 6.8) to 2.6 (SD, 4.9) times per month following treatment (P < 0.001). Among the 208 women who were sexually active at the time of study, sexual dysfunction after treatment was associated with younger age (50.9 [SD, 11.7] years to 57.3 [SD, 12.3] years), ovarian (40.7% vs 30.7%) or cervical (21.0% vs 10.2%) cancer diagnosis, chemotherapy treatment (72.8% vs 50.4%), and being in a relationship (97.3% vs 82.7%). Among women in relationships, 27% experienced marital dysfunction. CONCLUSIONS: Women who are younger, have an ovarian or cervical cancer diagnosis, receive chemotherapy, or are in a committed relationship are at particularly high risk of sexual dysfunction. These women should be provided information about the risks associated with their cancer treatment.