Despite decades of improvement in the quality and outcomes of cardiovascular care, significant gaps remain. Existing quality improvement strategies are often limited in scope to specific clinical conditions and episodic care. Health services and outcomes research is essential to inform gaps in care but rarely results in the development and implementation of care delivery solutions. Although individual health systems are engaged in projects to improve the quality of care delivery, these efforts often lack a robust study design or implementation evaluation that can inform generalizability and further dissemination. Aligning the work of health care systems and health services and outcomes researchers could serve as a strategy to overcome persisting gaps in cardiovascular quality and outcomes. We describe the inception of the Cardiovascular Quality Improvement and Care Innovation Consortium that seeks to rapidly improve cardiovascular care by (1) developing, implementing, and evaluating multicenter quality improvement projects using innovative care designs; (2) serving as a resource for quality improvement and care innovation partners; and (3) establishing a presence within existing quality improvement and care innovation structures. Success of the collaborative will be defined by projects that result in changes to care delivery with demonstrable impacts on the quality and outcomes of care across multiple health systems. Furthermore, insights gained from implementation of these projects across sites in Cardiovascular Quality Improvement and Care Innovation Consortium will inform and promote broad dissemination for greater impact.

Low-grade, low-stage endometrioid carcinomas (LGLS EC) demonstrate 5-yr survival rates up to 95%. However, a small subset of these tumors recur, and little is known about prognostic markers or established mutation profiles associated with recurrence. The goal of the current study was to identify the molecular profiles of the primary carcinomas and the genomic differences between primary tumors and subsequent recurrences. Four cases of LGLS EC with recurrence and 8 cases without recurrence were evaluated via whole-exome sequencing. Three of the 4 recurrent tumors were evaluated via Oncomine Comprehensive Assay. The resulting molecular profiles of the primary and recurrent tumors were compared. Two of the 3 recurrent cases showed additional mutations in the recurrence. One recurrent tumor included an additional TP53 mutation and the other recurrent tumor showed POLE and DDR2 kinase gene mutation. The POLE mutation occurred outside the exonuclease domain. PIK3CA mutations were detected in 4 of 4 primary LGLS EC with recurrence and in 3 of 8 disease-free cases. LGLS EC with recurrence showed higher MSIsensor scores compared with LGLS without recurrence. The level of copy number gains in LGLS EC with recurrence was larger than LGLS EC without recurrence. This pilot study showed 1 of 3 recurrent cases gained a mutation associated with genetic instability (TP53) and 1 of them also acquired a mutation in the DDR2 kinase, a potential therapeutic target. We also noted a higher level of copy number gains, MSIsensor scores and PIK3CA mutations in the primary tumors that later recurred.

TPS5606 Background: Niraparib (Zejula) a selective poly(ADP-ribose) polymerase (PARP) 1/2 inhibitor, significantly improved progression-free survival (PFS) as a single agent for patients with recurrent ovarian cancer (OC) relative to placebo in the ENGOT-OV16/NOVA trial, regardless of BRCA or HRD status. The ongoing AVANOVA trial (NCT02354131) has shown that niraparib can be safely combined with bevacizumab (bev). This combination is being explored in AVANOVA, as a strategy to increase tumor sensitivity to PARP inhibition. As an anti-angiogenic agent, bev can induce tumor hypoxia, leading to downregulation of BRCA and RAD51, which could sensitize tumors to PARP inhibition, and lead to apoptosis via contextual synthetic lethality. While BRCA and HRD status was insufficient to predict responders to niraparib in NOVA, a longer median PFS was observed for the cohorts with these biomarkers. In the phase 2 OVARIO study (NCT03326193), niraparib plus bev will be evaluated as a maintenance treatment in patients with advanced OC who have recovered from primary debulking surgery and have responded to frontline platinum-based chemotherapy with bev. Methods: Target enrollment is 90 patients, regardless of BRCA or HRD status, with stage 3b and 4 epithelial ovarian, fallopian tube, or peritoneal cancer. Patients must achieve complete response, partial response or no evidence of disease after the frontline platinum-based chemotherapy. The primary objective for OVARIO will be PFS at 18 months landmark. Secondary objectives include evaluation of PFS, overall survival, time to first subsequent therapy, and safety and tolerability. Exploratory objectives will be PFS at 6 and 12 months and patient-reported outcomes. The starting dose of niraparib will be based on the patient’s baseline body weight and/or platelet count. Patients weighing ≥77 kg with a platelet count of ≥150,000/μL will receive 300 mg qd. Patients weighing < 77 kg or with a platelet count of < 150,000/μL will receive 200 mg qd. The bev dose will be 15 mg/kg q3w up to 15 months. Patients will be treated continuously until disease progression or unacceptable toxicity. Clinical trial information: NCT03326193.

Ovarian cancers diagnosed between 2000 and 2013 were examined and cases with and without endometriosis compared. Among 139 epithelial ovarian, there were 49 (35%) with endometriosis and 90 (65%) without endometriosis. Endometriosis associated ovarian cancers were more likely to be confined to the pelvis (54% vs. 9%, p < 0.0001) and lower grade (51% vs. 29%, p = 0.014). Younger age and earlier stage independently predicted the presence of endometriosis (p = 0.0011 and p < 0.0001, respectively). Ovarian cancer patients with endometriosis had improved PFS and OS [(HR = 0.20; 95% CI, 0.09-0.43), (HR = 0.18; 95% CI, 0.04-0.81)], compared to patients without endometriosis; however, endometriosis had no independent prognostic significance.

Clear cell endometrial carcinoma (CCEC) is a rare and lethal uterine malignancy with a propensity for early lymphatic and intraperitoneal spread. Surgery is the mainstay of treatment. Due to the rarity of this histology, prospective outcome data regarding optimal adjuvant therapies are lacking. We undertook this population-based study to test the hypothesis that multimodality regimens incorporating both surgery and adjuvant radiation (SaRT) positively impact survival, and to identify demographic characteristics related to survival. We queried data in 18 registries of the Surveillance, Epidemiology, and End Results (SEER) program, and selected women diagnosed with CCEC between 2002 and 2011, treated with surgery alone (SA) or SaRT. The SEER database does not provide information about chemotherapy use. Outcomes related to therapy and demographic characteristics were compared using Kaplan-Meier analysis. A Cox proportional hazards regression model was then constructed for survival time, and included the type of treatment, age, race, and AJCC stage. Nine-hundred sixteen patients met the inclusion criteria, 58.7% underwent SA, and 41.3% had SaRT. Forty percent of the patients were under 65 years of age, 60.0% were older than 65; 74.3% were white (W), 16.7% were African American (AA), and 9.0% identified with other racial groups; 45.1% presented with AJCC stage I disease, 11.6% - stage II, 24.9% - stage III, and 18.5% - stage IV. AA women were more likely to present with stages III and IV than white women (34.6% vs. 23.8% and 20.3% vs. 18.5%, respectively, P=.006). The uptake of therapy was similar between AA and W women: 57.5% vs. 58.2% received SA, and 42.5% vs. 42.0% received SaRT, p=NS. Patients who received SaRT had superior outcomes compared to SA: 5-year overall survival probability (OS) was 61.6% vs. 53.8% (P=.002), 5-year cause-specific survival probability (CSS) was 68.4% vs. 61.0% (P<.015). Survival was worse for AA compared to W counterparts: 5-year OS 46.7% vs. 58.7%, 5-year CSS was 57.6% vs. 64.4%. In the multivariable analysis SaRT remained favorably associated with OS: HR=1.2 for SA and CSS: HR=1.3 for SA. After controlling for therapy and stage, there remained a trend towards worse survival for AA compared to W women: OS HR=1.3 and CSS HR=1.2. Treatment paradigms that incorporate SaRT result in significant improvement in OS and CSS in patients with CCEC. AA women present at more advanced stages of the disease and have worse survival outcomes than Women; however, treatment with both SA and SaRT is similar among the different races, suggesting the delay in diagnosis as the major contributor to the inferior survival outcomes.

Background: Prior studies have shown that metformin and statin medications may have anti-cancer properties in solid tumors. The study’s objective is to analyze if their use is associated with progression-free survival (PFS) or overall survival (OS) in epithelial ovarian cancer.

Uterine carcinosarcoma (UCS) is rare malignancy with a dismal prognosis. Surgery is the mainstay of treatment. In this study, we examined the impact of adjuvant RT (aRT) on survival in a population-based cohort of patients. Eighteen registries of the Surveillance, Epidemiology and End Results (SEER) database were queried for female patients diagnosed with UCS between 1999 and 2010, and treated with total hysterectomy with or without aRT. The Kaplan-Meier method was used to estimate survival and the log-rank test was used to compare survival between groups. A subgroup analysis was performed by race, stage, and year of diagnosis. A total of 2342 patients meeting the study inclusion criteria were identified. The median age at diagnosis was 67 years (range, 23-85). 74.3% were white, 19.6% were African American (AFAM), 6.1% - other. 69.6% were diagnosed at FIGO stage I, 4.6% at FIGO II, 14.2% at FIGO III, and 11.5% at FIGO IV. There was a significant association between race and FIGO stage at diagnosis (p<0.0005); AFAM were more likely to present with FIGO stages II-IV than other races (35.4% vs. 29.1%; p<0.01). There was no significant difference between AFAM and other races, or between women diagnosed in the period of 1999-2004 vs. 2005-2010, with respect to receiving aRT : 36.5% vs. 39.9% (p = NS), and 39.5% vs. 38.9% (p = NS), respectively. Patients who received aRT had better survival than those who did not: in the entire cohort, OS was 42 mo (95% CI: 37 to 52) vs. 22 mo (95% CI: 19 to 25); p<0.0001. OS for FIGO stages I, II, III and IV was: 48 mo vs. 27 mo (p<0.0001), 39 mo vs. 18 mo (p<0.0086), 37 mo vs. 22 mo (p<0.0003), and 14 mo vs. 9 mo (p<0.1239), respectively. Similarly, patients who received aRT had a better CSS: for the entire cohort, 57 mo (95% CI: 42 to 87) vs. 28 mo (95% CI: 24 to 32; p<0.0001). CSS by FIGO stage was: 71 mo vs. 43 mo (p<0.007), 52 mo vs. 18 mo (p<0.0086), 39 mo vs. 29 mo (p<0.0020), and 14 mo vs. 9 mo (p<0.1033) for stages I, II, III and IV, respectively. AFAM were at a higher risk of UCS death (HR = 1.217, 95% CI: 1.053 to 1.407; P<0.0079). Women diagnosed between 1999 and 2004 had a higher risk of dying than those diagnosed between 2005 and 2010 (HR = 1.793, 95% CI: 1.531 to 2.101; p<0.0001). Treatment paradigms incorporating aRT improve survival in patients with UCS. AFAM women present with later stage disease, either due to variations in the natural history of the disease among the races, or due to the differences in the access to timely diagnosis. Access to radiation therapy after diagnosis is not affected by race. The cohort of patients treated more recently has better survival outcomes.

1573 Background: To determine if Obstetricians and Gynecologists in New York state would offer risk-reducing salpingectomy (RRS) at the time of benign hysterectomy with ovarian preservation or permanent sterilization. Methods: An anonymous survey was administered to Ob/Gyn physicians at the 2013 Annual American College of Obstetricians and Gynecologists district II meeting. Physicians-in-training were excluded. The survey instrument assessed provider practice to offer RRS before and after reading a brief summary of the clinical position by the Society of Gynecologic Oncology of Canada, entitled “Salpingectomy and Ovarian Cancer Prevention.” Results: Ninety physicians completed the survey. Median age was 52 years (range 30-87), and 91% practiced general Ob/Gyn. Median annual surgical volume was 10 hysterectomies (range 0-150) and 11 surgical sterilizations (range 0-100). More physicians were willing to offer RRS at the time of hysterectomy than at the time of permanent sterilization (54% vs. 14%, p < 0.05). After reading the position statement, there was a 27% increase in the number of physicians who would offer RRS at the time of benign hysterectomy (p<0.01) and 42% at the time of surgical sterilization (p=NS). On univariate analysis, physician practice to offer RRS at the time of hysterectomy was associated with previous knowledge of evidence for RRS (96% of physicians aware vs. 82% not aware, p = 0.04), surgeon age (p<0.05), and practice setting (academic > community, p<0.5). Willingness to perform RRS at time of permanent sterilization was associated with the method of sterilization (laparoscopic, 82%, hysteroscopic, 18%, postpartum tubal, 0% p < 0.07) and volume of sterilization cases per year (p<0.05). On multivariate analysis, the only factor associated with offering RRS was the number of years in practice, 1.6 (95% CI 1.01-1.53, p<0.05). Conclusions: Our data suggest that obstetricians and gynecologists would offer RRS at the time of benign hysterectomy in those women who elect ovarian conservation. The link between fallopian tube as the origin of ovarian serous cancer needs to be elaborated to potentially offer high-risk patients a method of prevention with few long-term consequences.

Evaluate tolerability and toxicity of concurrent chemotherapy and vaginal brachytherapy (VB) compared to the sequential approach for patients with early stage high grade endometrial cancer. A retrospective analysis of 102 surgically staged patients with endometrial cancer AJCC 2009 Stages IA-IB treated with adjuvant postoperative vaginal brachytherapy (VB) at our institution from 2001-2012 was conducted. All patients received VB + 6 cycles of adjuvant carboplatin and paclitaxel based chemotherapy. VB mean dose was 20.78 Gy (range, 20 - 21 Gy) with 3-4 weekly applications. Hematologic, gastrointestinal (GI), and genitourinary (GU) toxicities were assessed by Common Toxicity Criteria (CTC) and compared between sequential and concurrent chemotherapy and VB schedules. Among patients that received VB and adjuvant chemotherapy, 62/102 patients (61%) received VB sandwiched between cycles 3 and 4 of chemotherapy. A separate group of 40 patients (39%) were treated with VB during the first 3 cycles of chemotherapy with a weekly application on non-chemotherapy days. Patients treated with VB during chemotherapy had a decreased overall treatment time by 4 weeks (p<0.001; [95% CI: 3.99 - 4.02]) and sustained no difference in CTC graded acute hematologic, GI, or GU toxicities as compared to the patients treated with VB and chemotherapy in a sequential manner (p > 0.05). CTC grade 3 or 4 hematologic, GI, and GU toxicities were zero. Vaginal brachytherapy during chemotherapy is well tolerated, decreases overall treatment time, and does not render more toxicity than the sequential regimen.

Objectives: To characterize ovarian cancers associated with endometriosis and to evaluate the prognostic impact of the presence of endometriosis.

Objective: Uterine clear cell carcinoma (UCC) and uterine malignant mesodermal mixed tumor (UMMMT), also known as uterine carcinosarcoma, are rare but clinically aggressive histologic variants of endometrial carcinoma. The molecular alterations in the oncogenic P13K-alpha pathway have not been studied in detail in these subtypes. In prior studies, 80% of PIK3CA mutations were found in exons 9 and 20 and the remaining 20% were found in exons 1-7. Our objective was to analyze UCC and UMMMT cases for mutations in PIK3CA in exons 1-9 and 20.

Objective: Recent data from risk-reducing salpingectomy and oophorectomy (RRSO) in patients with BRCA mutations suggest that ovarian cancer may arise in the fallopian tube (FT). This offers a new avenue for preventive strategies in the general population, including salpingectomy at the time of benign hysterectomy or permanent sterilization. The objective was to study the willingness to offer risk-reducing salpingectomy (RRS) among general obstetricians/gynecologists.

Purpose: To evaluate the tolerability and toxicity of administering vaginal brachytherapy (VB) concurrently during chemotherapy compared with the sequential approach for patients with endometrial cancer.Methods and Materials: A retrospective analysis of 372 surgically staged patients with endometrial cancer American Joint Committee on Cancer 2009 stages I to IV treated with adjuvant postoperative radiation therapy (RT) at our institution from 2001 to 2012 was conducted. All patients received VB + external beam RT (EBRT) + 6 cycles of adjuvant carboplatin-and paclitaxel-based chemotherapy. The VB mean dose was 15.08 Gy (range, 15-20 Gy), with 3 to 4 weekly applications, and the EBRT mean dose was 45 Gy delivered with 3-dimensional or intensity modulated RT techniques. Hematologic, gastrointestinal (GI), and genitourinary (GU) toxicities were assessed by Common Toxicity Criteria (CTC) and compared between sequential and concurrent chemotherapy and VB schedules.Results: Among patients who received RT and adjuvant chemotherapy, 180 of 372 patients (48%) received RT sandwiched between cycles 3 and 4 of chemotherapy. A separate group of 192 patients (52%) were treated with VB during the first 3 cycles of chemotherapy, with a weekly application on nonchemotherapy days, and received the EBRT portion in a sandwiched fashion. Patients treated with VB during chemotherapy had a decreased overall treatment time by 4 weeks (P<.001; 95% confidence interval: 3.99-4.02) and sustained no difference in CTC-graded acute hematologic, GI, or GU toxicities in comparison with the patients treated with VB and chemotherapy in a sequential manner (P>.05). CTC grade 3 or 4 hematologic, GI, and GU toxicities were zero.Conclusions: VB during chemotherapy is well tolerated, decreases overall treatment time, and does not render more toxicity than the sequential regimen. (C) 2013 Elsevier Inc.

PURPOSE OF INVESTIGATIONThis study evaluates the association of clinical and pathologic characteristics of patients with uterine serous carcinoma (USC) with disease recurrence.MATERIALS AND METHODSSurgically-staged patients with USC at a single institution were identified and clinical and pathologic variables were compared.RESULTSOf the 51 patients included in this analysis, 75% percent received adjuvant chemotherapy, 51% received radiation therapy, and 47% received both. After a median follow-up of 33 months, 42% of patients had disease recurrence. On multivariable analysis, positive pelvic lymph nodes were associated with a shorter interval between surgery and recurrence: 13.6 months progression-free survival (PFS) with positive vs 17.2 months with negative lymph nodes (p = 0.05). Patients with early-stage disease who did not receive any adjuvant treatments had a significantly greater risk of disease recurrence (44.4% vs 7.70%, p = 0.043).CONCLUSIONIn this population of surgically-staged patients with USC, pelvic lymph node metastases were predictive of a shorter PFS.