A quality improvement initiative to reduce venous thromboembolism on a gynecologic oncology service.

OBJECTIVE: To describe and evaluate the effects of implementation of a venous thromboembolism (VTE) prophylaxis quality improvement (QI) initiative on a gynecologic oncology service at a single institution. METHODS: Prior to 2018, no consensus gynecologic oncology VTE prophylaxis protocol existed at the authors' academic institution. Published, evidence-based guidelines were reviewed to create a standardized VTE risk stratification algorithm. Interventions to improve perioperative heparin administration and sequential compression device (SCD) compliance as well as provider/patient education efforts were introduced in January 2018. Initial efforts included nursing and patient SCD education, internal dissemination of VTE prophylaxis guidelines, and creation of a VTE 'dashboard' to track performance. During a second phase, VTE prophylaxis guidelines were reviewed and further refined, non-compliant operative cases reviewed weekly, and guidelines incorporated into the electronic medical record. Performance was measured using Tableau data software (www.tableau.com) and by separately evaluating adherence to the developed guidelines in three retrospective cancer-enriched surgical cohorts (2016-2017, 2018, 2019). RESULTS: Compared to the baseline period, we observed a reduction in VTE rate during the 2018-2019 VTE QI implementation period from 2.1% (19/905) to 1.0% (20/2015, p = 0.02) among gynecologic oncology inpatients. In the retrospective cancer-enriched cohorts, adherence to evidence based guidelines improved: 31.0% in 2016-2017, 69.1% in 2018, and 82.4% in 2019 (p < 0.001). There were no significant differences in rates of peri-operative blood transfusion, surgical site infections, hematomas, or vaginal cuff dehiscences. CONCLUSIONS: Implementation of a robust VTE prophylaxis QI initiative has resulted in improved VTE prophylaxis guideline adherence and higher rates of pre-operative heparin administration.

Targeted composite value-based endpoints in platinum-sensitive recurrent ovarian cancer.

OBJECTIVES: FDA-approved treatments for platinum-sensitive recurrent ovarian cancer (PSROC) include bevacizumab and PARP inhibitors (PARPi); clinical decisions regarding therapy must be made prior to initiating chemotherapy. Using the American Society of Clinical Oncology (ASCO) and European Society of Medical Oncology (ESMO) value frameworks, we assessed relative values of concurrent/maintenance biologic therapies in PSROC. METHODS: Value scores were calculated for key maintenance therapies based on randomized controlled trials: bevacizumab (OCEANS, GOG 213); olaparib (Study 19, SOLO2); niraparib (NOVA); rucaparib (ARIEL3). Personalized value scorecards were constructed for patients with germline/somatic-BRCA mutations, homologous recombination deficiency (HRD), and wild-type BRCA (wBRCA). ASCO value scores assess clinical benefit, toxicity, long-term survival, symptom palliation, treatment-free interval, and quality of life (QOL). ESMO value scores assess clinical benefit, toxicity, and QOL. RESULTS: ASCO scores were highest for maintenance PARPi in germline/somatic-BRCA mutation cohorts: olaparib (SOLO2) = 47, (Study 19) = 62; niraparib = 50; rucaparib = 54. HRD cohorts had slightly lower scores: niraparib = 46; rucaparib = 37. wBRCA cohorts had the lowest scores: niraparib = 26; rucaparib = 26; and olaparib (Study 19) = 32, as did patients receiving bevacizumab (OCEANS) = 35, (GOG 213) = 26. ESMO scores demonstrated high-value for maintenance PARPi in germline/somatic-BRCA mutation cohorts and low-value for bevacizumab and PARPi in wBRCA cohorts. CONCLUSIONS: The value of maintenance PARPi therapy depends heavily on BRCA status, with the highest value scores in germline/somatic-BRCA mutation cohorts. Personalized value scorecards provide a visual aid to assess the harm-benefit balance of maintenance PARPi for PSROC.

Gender variation in Medicare utilization and payments in gynecologic oncology.

OBJECTIVES: The Medicare Provider Utilization and Payment Data: Physician and Other Supplier Public Use File (POSPUF) and Medicare Physician and Other Supplier National Provider Identifier (POS NPI) Aggregate Report are publicly available files from the Center for Medicare and Medicaid Services that include payments to providers who care for fee-for-service Medicare recipients. The aim of this study was to analyze variability in gynecologic oncologists' Medicare reimbursements, with attention to differences in provider gender and time in practice. METHODS: The 2015 POSPUF and POS NPI were analyzed with respect to gynecologic oncologists. We searched external publicly available data sources to confirm subspecialty and to determine each provider's number of years in practice. Evaluation and management (E&M) and procedure/surgery codes were analyzed; drug delivery codes were excluded due to variability in billing by facility/hospital. RESULTS: The POS NPI file included 733 gynecologic oncologist providers receiving $55,626,739 in total payments. Female providers comprised 39% of gynecologic oncologists and received 31% of reimbursements (30% of E&M reimbursements and 24% of surgical reimbursements). During the first ten years in practice, female providers comprised 58% of providers and accounted for 52% of reimbursed services, compared to 38% of providers/26% of reimbursed services (11-20 years), and 18% of providers/19% of reimbursed services (>20 years). CONCLUSION: Male gynecologic oncologists perform more Medicare services than their female counterparts. There is a comparable number of services performed between genders among both the most senior and the most junior providers, with a gender gap in services and reimbursements among mid-career providers.

Associations between lymphovascular space invasion, nodal recurrence, and survival in patients with surgical stage I endometrioid endometrial adenocarcinoma.

OBJECTIVE: To investigate the predictive value of lymphovascular space invasion (LVSI) for nodal recurrence and overall survival (OS) in patients with stage I endometrioid endometrial cancer (EC) following surgical staging that included adequate lymph node sampling. METHODS: Retrospective analyses of patients undergoing surgical staging for FIGO stage I endometrioid EC between 1998 and 2015 were performed using an institutional database and the National Cancer Database (NCDB). Using the institutional database, logistic regression modeling identified predictors of nodal recurrence; Cox proportional hazards modeling was used to predict progression-free survival (PFS). Utilizing NCDB, Cox proportional hazards modeling was used to predict OS. The Kaplan-Meier method was used to estimate hazard ratios (HR). Survival curves were compared using the log-rank test. RESULTS: Among 275 institutional cases, LVSI was present in 48 (17.5%). There were 11 nodal recurrences: 18.8% (9/48) of cases with LVSI had a nodal recurrence compared to 0.88% (2/227) of those without LVSI. In multivariate analysis of institutional data, LVSI was the only significant predictor of nodal recurrence (p = 0.002). Among 28,076 NCDB cases, LVSI was present in 3766 (13.5%). In multivariate analysis of NCDB, grade 3, LVSI, and depth of invasion (all p <  0.001) were prognostic for OS after adjusting for adjuvant radiation. CONCLUSION: LVSI is an independent prognostic factor for nodal recurrence in stage I endometrial cancer with lymph node assessment. LVSI is associated with lower OS in NCDB. Given these findings, adjuvant therapy could be considered in these patients.

Predicting 6- and 12-Month Risk of Mortality in Patients With Platinum-Resistant Advanced-Stage Ovarian Cancer: Prognostic Model to Guide Palliative Care Referrals.

OBJECTIVE: Predictive models are increasingly being used in clinical practice. The aim of the study was to develop a predictive model to identify patients with platinum-resistant ovarian cancer with a prognosis of less than 6 to 12 months who may benefit from immediate referral to hospice care. METHODS: A retrospective chart review identified patients with platinum-resistant epithelial ovarian cancer who were treated at our institution between 2000 and 2011. A predictive model for survival was constructed based on the time from development of platinum resistance to death. Multivariate logistic regression modeling was used to identify significant survival predictors and to develop a predictive model. The following variables were included: time from diagnosis to platinum resistance, initial stage, debulking status, number of relapses, comorbidity score, albumin, hemoglobin, CA-125 levels, liver/lung metastasis, and the presence of a significant clinical event (SCE). An SCE was defined as a malignant bowel obstruction, pleural effusion, or ascites occurring on or before the diagnosis of platinum resistance. RESULTS: One hundred sixty-four patients met inclusion criteria. In the regression analysis, only an SCE and the presence of liver or lung metastasis were associated with poorer short-term survival (P < 0.001). Nine percent of patients with an SCE or liver or lung metastasis survived 6 months or greater and 0% survived 12 months or greater, compared with 85% and 67% of patients without an SCE or liver or lung metastasis, respectively. CONCLUSIONS: Patients with platinum-resistant ovarian cancer who have experienced an SCE or liver or lung metastasis have a high risk of death within 6 months and should be considered for immediate referral to hospice care.

Primary Versus Preoperative Radiation for Locally Advanced Vulvar Cancer.

OBJECTIVES: The objective of this study was to evaluate patterns of care and the survival impact of primary radiation and preoperative radiation therapy with surgery in women with locally advanced vulvar cancer using a large national cohort. METHODS AND MATERIALS: Women with vulvar cancer, diagnosed from 2004 to 2012, who received primary or preoperative radiation therapy were identified in the National Cancer Database. Patient characteristics, such as age, race, American Joint Committee on Cancer stage, and comorbidity score, were compared between those that received primary radiation only and those that received preoperative radiation with surgery using the χ, Fisher exact, and Mann-Whitney tests as appropriate. Overall survival (OS) by treatment approaches was estimated via the Kaplan-Meier method and compared using the log-rank test. Factors associated with OS were determined using univariate and multivariate Cox proportional hazards regression models. RESULTS: A total of 2046 women were identified; 1407 of these women (69%) received primary radiation therapy (RT; n = 421) or chemoradiation therapy (CRT; n = 986) (RT/CRT), and 639 women (31%) received preoperative RT (n = 92) or CRT (n = 547) followed by surgery (RT/CRT + S). The American Joint Committee on Cancer staging distributions were as follows: T1 (n = 152), T2 (n = 1436), T3 (n = 405), N0 (n = 899), N1 (n = 480), N2 (n = 445), and N3 (n = 40). Median follow-up was 21.9 months. Primary RT/CRT was associated with compromised OS, compared with preoperative RT/CRT + S (41.7% vs 57.1% at 3 years, respectively; P < 0.001). On multivariate analysis, OS associated with primary RT/CRT with doses more than 55 Gy was not significantly different from RT/CRT + S (hazards ratio, 1.139; 95% confidence interval, 0.969-1.338; P = 0.116). Use of concurrent chemotherapy improved OS of primary RT with doses more than 55 Gy compared with CRT + S (hazards ratio, 1.107; 95% confidence interval, 0.919-1.334; P = 0.234). CONCLUSIONS: In a large nationwide analysis, primary nonsurgical management of vulvar cancer with RT was associated with compromised survival compared with preoperative RT with surgery. However, with doses more than 55 Gy and concurrent chemotherapy, nonoperative approaches had comparable survival compared with preoperative CRT + S.

Impact of Chemotherapy and Radiotherapy on Management of Early Stage Clear Cell and Papillary Serous Carcinoma of the Uterus.

OBJECTIVE: The aim of the study was to assess interaction of lymph node dissection (LND), adjuvant chemotherapy (CT), and radiotherapy (RT) in stage I uterine papillary serous carcinoma (UPSC) and uterine clear cell carcinoma (UCC). METHODS/MATERIALS: The National Cancer Data Base was queried for women diagnosed with International Federation of Gynecology and Obstetrics stage I UPSC and UCC from 1998 to 2012. Overall survival (OS) was estimated for combinations of RT and CT by the Kaplan-Meier method stratified by histology and LND. Multivariate Cox proportional hazard models were generated. RESULTS: Uterine papillary serous carcinoma: 5432 women with UPSC were identified. Uterine papillary serous carcinoma had the highest 5-year OS with CT + RT with (83%) or without LND (76%). On multivariate analyses, CT [hazard ratio (HR), 0.77; P = 0.01] and vaginal cuff brachytherapy (HR, 0.68; P = 0.003) with LND were independently associated with OS. Without LND, vaginal cuff brachytherapy (HR, 0.53; P = 0.03), but not CT (HR, 1.21; P = 0.92), was associated with OS. Uterine clear cell carcinoma: 2516 women with UCC were identified. Uterine clear cell carcinoma with and without LND had comparable 5-year OS for all combinations of CT and RT on univariate and multivariate analyses. CONCLUSIONS: In stage I papillary serous uterine cancer, brachytherapy and CT were associated with increased survival; however, the benefit of chemotherapy was limited to those with surgical staging. In contrast, no adjuvant therapy was associated with survival in stage I uterine clear cell carcinoma, and further investigation to identify more effective therapies is warranted.

Robotic surgical training: Where are we?

BACKGROUND AND OBJECTIVE: Over the past 10years, robotic surgery has revolutionized the advancement of MIS in gynecologic oncology. As the use of robotic surgery has increased, so has the interest in the surgical training of gynecologic oncology fellows. The purpose of this review is to summarize the state of robotic surgical education in Gynecologic Oncology. METHODS: Several electronic databases were searched to identify studies that discussed robotic surgical education in gynecologic oncology. Particular attention was given to articles that discussed educational curriculum. The various curriculums were compared and summarized. RESULTS: The first reports of robotic surgery curriculums in gynecologic oncology emerged in 2008. Prior to that the early adapters had to rely on less structured curriculums that essentially used live animal models and cadaveric dissections on the robot to simulate live surgery. More recent surgical curriculums are more structured and include the same basic components: didactics and a graduated hands-on experience. There is also an accredited robotic educational curriculum, the Fundamentals of Robotic Surgery (FRS), which combine an on-line curriculum with dry lab and operating room components that can be scored using a validated assessment tool. CONCLUSIONS: Robotic surgical education has come a long way in the decade that the robotic platform has been available in the U.S. Although there is still no standardized curriculum, most fellowship training programs in gynecologic oncology have fairly consistent training. Simulation training is another tool that can help a surgeon achieve proficiency quicker.

ASCO Value Framework Highlights the Relative Value of Treatment Options in Ovarian Cancer.

PURPOSE: The ASCO value framework allows physicians and patients to compare the relative value of novel treatments. Our aim was to assess the value of three frontline ovarian cancer therapies by using this framework. METHODS: From phase III, randomized controlled clinical trial (RCT) data, the net health benefits (NHBs) for three frontline ovarian cancer treatment options-dose-dense paclitaxel (Japanese Gynecologic Oncology Group study JGOG 3016), intraperitoneal (IP)/intravenous (IV) chemotherapy (Gynecologic Oncology Group [GOG] study GOG 172), and concurrent plus maintenance bevacizumab (GOG 218 and the Seventh International Collaborative Ovarian Neoplasm study [ICON7])-were calculated. The ASCO value framework calculates the NHB by using six criteria: clinical benefit, toxicity, tail of the curve, symptom palliation, treatment-free interval, and quality of life. Clinical benefit calculation uses ASCO-assigned importance weights for overall survival and progression-free survival. The maximum possible NHB points is 180. NHBs were presented alongside the drug-acquisition cost (DAC) of each therapy. A benefit-cost ratio of NHB points per additional cost was calculated. RESULTS: The NHB of dose-dense paclitaxel was 38, at an additional cost of $16 per cycle. IP cisplatin/IV + IP paclitaxel received 29 NHB points, at an additional cost of $1,629 per cycle. Concurrent plus maintenance bevacizumab received 24 NHB points, at an additional cost of $7,581 per cycle (GOG 218) or six NHB points ($3,790 per cycle; ICON7). The ratios of NHB points-to-dollar were as follows: dose-dense paclitaxel, 2.4 (highest); IP chemotherapy, 0.018; and bevacizumab, 0.003 (lowest). CONCLUSION: Using the ASCO value framework, we constructed value snapshots of three major frontline therapeutic options in ovarian cancer. Dose-dense paclitaxel provided the highest additional value when analysis accounted for NHB and cost. However, additional research is needed to include individual patient preferences and provide personalized value assessments.

Data-Derived Treatment Duration Goal for Cervical Cancer: Should 8 Weeks Remain the Target in the Era of Concurrent Chemoradiation?

PURPOSE: Prior studies have demonstrated the importance of treatment duration (TD) in radiation therapy (RT) for cervical cancer, with an 8-week goal based primarily on RT alone. This study uses a contemporary cohort to estimate the time point by which completion of chemoradiation therapy is most critical. PATIENTS AND METHODS: The National Cancer Database was queried for women with nonmetastatic cervical cancer diagnosed from 2004 to 2012 who underwent chemotherapy, external beam RT, and brachytherapy. Data-derived TD cut points for overall survival (OS) were computed by using recursive partitioning analysis with bootstrapped aggregation (bagging) and 10-fold cross-validation. Models were independently trained with 70% of the population and validated on 30% of the population by log-rank test with and without propensity matching. Multivariable Cox proportional hazards regression was performed for the entire cohort. RESULTS: In all, 7,355 women were identified with a median TD of 57 days. Bagged recursive partitioning analysis converged to a mean cut point of 66.6 days (median, 64.5 days; interquartile range, 63.5 to 68.5 days). Cross-validation yielded a cut point of 63.3 days. Both cut points differentiated OS in validation. Younger age, recent diagnosis, geographic region, nongovernment insurance, shorter distance to treatment facility, metropolitan location, lower comorbidity, squamous cell carcinoma, lower stage, negative lymph nodes, and shorter TD were independently associated with longer OS. With adjustment, TD within the mean cut point (64.9 days; hazard ratio, 0.79; 95% CI, 0.73 to 0.87) and 56 days (hazard ratio, 0.87; 95% CI, 0.80 to 0.95) were associated with longer OS. Exploratory stratification suggested increasing OS detriment beyond 64 days. CONCLUSION: Shorter chemoradiation TD in cervical cancer is associated with longer survival, and TD should be minimized as much as possible. The data-derived cut point was distributed around 64 days, with a continuous relationship between shorter TD and longer OS.

Disparities in the surgical staging of high-grade endometrial cancer in the United States.

BACKGROUND: The National Comprehensive Cancer Network (NCCN) and the Society of Gynecologic Oncology (SGO) recommend lymph node sampling (LNS) as a key component in the surgical staging of high-grade endometrial cancer. Our goal was to examine surgical staging patterns for high-grade endometrial cancer in the United States. METHODS: The National Cancer Data Base (NCDB) was searched for patients who underwent surgery for serous, clear cell, or grade 3 endometrioid endometrial cancer. Outcomes were receipt of LNS and overall survival (OS). Multivariate logistic regression was used to examine receipt of LNS in Stage I-III disease based on race (White vs. Black), income, surgical volume, and distance traveled to care. Multivariate Cox proportional hazards regression modeling was used to assess OS based on stage, race, income, LNS, surgical volume, and distance traveled. RESULTS: Forty-two thousand nine hundred seventy-three patients were identified: 76% White, 53% insured by Medicare/Medicaid, 24% traveled >30 miles, and 33% stage III disease. LNS was similar among White and Black women (81% vs 82%). LNS was more common among >30 miles traveled (84% vs 81%, p < 0.001), higher surgical volume (83% vs 80%, p < 0.001), and academic centers (84% vs 80%, p < 0.001). In multivariate analysis, higher income, higher surgical volume, Charlson-Deyo score, and distance traveled were predictors of LNS. Stage III disease (HR 3.39, 95% CI 3.28-3.50), age (10-year increase; HR 1.63, 95% CI 1.61-1.66), lack of LNS (HR 1.64, 95% CI 1.56-1.69), and low income (HR 1.20, 95% CI 1.14-1.27) were predictors of lower survival. CONCLUSIONS: Surgical care for high-grade endometrial cancer in the United States is not uniform. Improved access to high quality care at high volume centers is needed to improve rates of recommended LNS.

Cost Comparison of Genetic Testing Strategies in Women With Epithelial Ovarian Cancer.

PURPOSE: The advent of multigene panels has increased genetic testing options for women with epithelial ovarian cancer (EOC). We designed a decision model to compare costs and probabilities of identifying a deleterious mutation or variant of uncertain significance (VUS) using different genetic testing strategies. METHODS: A decision model was developed to compare costs and outcomes of two testing strategies for women with EOC: multigene testing (MGT) versus single-gene testing for BRCA1/2. Outcomes were mean cost and number of deleterious mutations and VUSs identified. Model inputs were obtained from published genetic testing data in EOC. One-way sensitivity analyses and Monte Carlo probabilistic sensitivity analyses were performed. RESULTS: No family history model: MGT cost $1,160 more on average than BRCA1/2 testing and identified an additional 3.8 deleterious mutations for every 100 women tested. For each additional deleterious mutation identified, MGT cost $30,812 and identified 5.4 additional VUSs. Family history model: MGT cost $654 more on average and identified an additional 7.0 deleterious mutations for every 100 women tested. For each additional deleterious mutation identified, MGT cost $9,909 and identified 2.6 additional VUSs. CONCLUSION: MGT was associated with a higher additional cost per deleterious mutation identified and a higher ratio of VUS burden to actionable information in women with no family history as compared with women with a family history. Family history should be considered when determining an initial genetic testing platform in women with EOC.

Analysis of in vitro chemoresponse assays in endometrioid endometrial adenocarcinoma: an observational ancillary analysis.

BACKGROUND: Chemotherapy plays a role in the treatment of endometrioid endometrial cancer (EEC); however, tumor grade may affect response. Our objective was to evaluate associations between tumor grade and in vitro chemoresponse. METHODS: We conducted an analysis of primary tumor samples from women with EEC undergoing in vitro chemoresponse testing. Results were classified as sensitive (S), intermediate (I), or resistant (R) to each drug tested. Correlations between tumor grade and response were examined. RESULTS: Data was collected from 159 patients: 28 with grade 1 (18%), 52 with grade 2 (32%), and 79 (50%) with grade 3 tumors. Median age of patients was 62 (range 31-92). Most patients were Caucasian (83%) with advanced disease (Stage III: 50.9%; Stage IV: 13.2%). Overall chemoresponse was similar across all grades. Fifty percent, 56 and 51% for grade 1, 2, and 3 tumors, respectively, demonstrated S results to at least 1 agent. There was no association between grade and in vitro response to chemotherapy agents (p > 0.05) except a marginal association between grade and doxorubicin response (p = 0.08). Grade 1 and 2 cancers were more likely to demonstrate R results for doxorubicin compared to grade 3 cancers (G1: 19% vs G2: 25% vs G3: 8%; p = 0.08). In a subset tested for all 7 agents, only one patient tumor was pan-R and 4 were pan-S. CONCLUSIONS: Based on our data, grades 1-3 EEC have similar in vitro chemoresponse. These findings suggest that chemotherapy may be useful in advanced low grade EECs, but further clinical correlation is needed.

Tumor grade and chemotherapy response in endometrioid endometrial cancer.

The objective of this study is to evaluate the association between tumor grade and response to chemotherapy in patients with endometrioid endometrial adenocarcinoma. Patients with advanced or recurrent endometrioid endometrial adenocarcinoma of known tumor grade who received at least 3 cycles of chemotherapy were retrospectively identified at three institutions. RECIST 1.1 criteria were used to assess response to neoadjuvant, postoperative or salvage chemotherapy. Chi-square testing was used to evaluate the association between tumor grade and chemotherapy response. Ninety-one patients met inclusion criteria: 13 with grade 1, 29 with grade 2 and 49 with grade 3 tumors. Eighty-four percent of patients received chemotherapy for recurrence, 12% for postoperative residual disease, and 4% in the neoadjuvant setting. The majority (85%) received carboplatin and paclitaxel. Forty-six percent (6/13) of grade 1, 72% (21/29) of grade 2 and 43% (21/49) of grade 3 tumors achieved an objective response. Grade 2 tumors were more likely to respond to chemotherapy compared to grade 3 tumors (72% vs. 43%, p = 0.02; Table 2), and specifically more likely to respond to carboplatin/paclitaxel (72% vs. 41%, p = 0.016). Median progression-free survival for patients receiving chemotherapy for recurrence or progression was 9 months for grade 1, 8 months for grade 2, and 5 months for grade 3 tumors. Similar results between grade and treatment response were apparent in the subset of 37 patients with a recently re-assigned tumor grade (G2 88% vs. G3 44%, p = 0.032). In this series of endometrioid endometrial cancers, grade 2 tumors had the best measurable response to chemotherapy.