Faculty Bibliography

Background: The majority of endometrial cancers present as early stage tumors, yet those that are advanced at diagnosis are associated with poor outcomes. The role of radical debulking surgery for endometrial cancer is not clear. However, the use of neoadjuvant chemotherapy is also unproven. We sought to evaluate if utilizing neoadjuvant chemotherapy for advanced endometrial cancer affected outcomes. Methods: A retrospective review from two hospitals served by one academic center from 2002 to 2011 was performed. All patients with stage 3 or 4 disease were identified. Patients with non-epithelial cell types, including carcinosarcoma, were excluded. Patients who received neoadjuvant treatment prior to surgery were identified. A case-control design was utilized matching patients 1:3 or 1:4 stratified by age, stage, grade, histology and performance status. Descriptive statistics and nonparametric analyses were utilized. Results: A total of 115 patients with advanced endometrial cancer were identified. 19 were excluded due to wrong cell type and 1 due to stage 3 disease based on positive cytology. 6 patients had a neoadjuvant treatment approach (NAs). 20 patients were identified as matched controls (CTRLs). The average age was 61 for the NAs, and 63 for the CTRLs. The average BMI was 26.9 for the NAs, and 27.4 for the CTRLs. NAs were more likely to have stage 4 disease-5/6 NAs versus 5/20 CTRLs. Both groups had a high proportion of grade 3 tumors-4/6 NAs versus 15/20 CTRLs. The performance status was similar in both groups. The median number of chemotherapy cycles was 11 in the NAs, and 4 in the CTRLs. 18/20 CTRLs received adjuvant treatment, and 17 included systemic chemotherapy. In the NAs, with a median follow-up of 17 months, 4 were alive with disease (AWD) and 2 were dead of disease (DOD). In the CTRLs, with a median follow-up of 14 months, 7 patients were NED, 8 were AWD, and 5 were DOD. Conclusions: Despite a small sample size, our results indicate that primary surgery remains the preferred s!

OBJECTIVE: : To identify patient characteristics associated with bilateral oophorectomy or removal of remaining ovary at the time of benign hysterectomy, and to estimate trends in the performance of oophorectomy from 2001 to 2006. METHODS: : This was a cross-sectional analysis using the New York State Department of Health Statewide Planning and Research Cooperative System. Women aged 18 years or older undergoing hysterectomies for benign gynecologic conditions were included. We evaluated factors associated with oophorectomy on both univariable and multivariable analyses and assessed for changes in performance of oophorectomy over the course of the study. RESULTS: : Forty-seven percent of 144,877 hysterectomies included oophorectomy. Women who underwent oophorectomy were older and were more likely to have a family history of breast or ovarian cancer, a personal history of breast cancer, ovarian cysts, or endometriosis. Women who underwent vaginal or laparoscopic hysterectomy or had uterine prolapse were less likely to undergo oophorectomy. Both race and insurance status were associated with performance of oophorectomy. From 2001 to 2006, there was an 8% absolute decrease in the performance of oophorectomy at the time of benign hysterectomy for women of all ages, with a 10.4% decrease in women aged younger than 55 (P for trend <.001). CONCLUSION: : Age, route of hysterectomy, and concomitant gynecologic diagnoses influence oophorectomy rate. From 2001 to 2006, a significant decrease in the performance of oophorectomy at the time of benign hysterectomy was noted in women aged younger than 55 years. Recent studies of complications of hormone therapy and prophylactic oophorectomy may have influenced patients' and physicians' decision-making, leading to lower oophorectomy rates. LEVEL OF EVIDENCE: : II

Epithelial ovarian cancer (EOC) patients with BRCA mutations (BRCA+) benefit from platinum-based treatment more than non-carriers. Impaired ability to repair DNA by homologous recombination increases their chemosensitivity. We investigated whether BRCA+ predicts for improved outcome following pegylated liposomal doxorubicin (PLD) for recurrence. Recurrent EOC patients receiving second- or third-line PLD from 1998 to 2009 in 4 institutions (Israel, Italy, NY) were subjected to retrospective comparisons between 40(25.8%) patients who were BRCA+, and 115(74.2%) deemed non-hereditary (NH). Median age was 59 years (range 31-83); 111(72%) had a platinum-free interval >6 months (PLD alone [n=65] and PLD plus platinum[n=90]); 104 received PLD in second-line and 51 in third-line. BRCA+ versus NH comparisons: median time to treatment failure (TTF) 15.8 months (95% CI 11.4-21.6) versus 8.1 months (95% CI 6.1-10.3;p=0.009); overall survival (OS) 56.8 months (95% CI 32.5-indeterminate) versus 22.6 months (95% CI 17.0-34.1;p=0.002). In multivariate Cox models BRCA status was significantly associated with TTF (HR=1.66; 95% CI 1.08-2.55;p=0.02) and OS (adjusted HR 2.07; 95% CI 1.18-3.60;p=0.01). Adjusted HR relating platinum sensitivity to OS was 1.58 (95% CI 0.93-2.68; p=0.09); no significant association found with age at diagnosis, line of PLD or combinations, or institution. In this retrospective analysis, recurrent EOC BRCA mutation carriers treated with PLD had an improved outcome, and this result appeared to be independent of platinum sensitivity. Tumors arising in a background of defective BRCA function are more sensitive than other epithelial ovarian cancers to DNA damaging agents such as PLD, even after acquiring platinum resistance

BACKGROUND: The New York City (NYC) public hospital system includes subspecialty care for gynecologic cancers, providing care to patients regardless of insurance status. The authors sought to determine the surgical patterns of care for ovarian cancer patients in the NYC public hospital system. METHODS: Ovarian cancer cases were identified in the New York State Department of Health Statewide Planning and Research Cooperative System database for years 2001 to 2006. Cases from NYC hospitals were separated into 2 cohorts: public and other NYC hospitals. Surgeons associated with each case were identified using the database and were stratified by volume of cases and presence of subspecialty training. RESULTS: A total of 12,202 admissions for ovarian cancer were identified. Of these, 3639 involved major surgery, and 187 were performed at public hospitals. There were more African American and Asian patients in the public cohort (P < .001). The primary insurer was more likely to be Medicaid or a self-payer in the public cohort (P < 0.001). Urgent or emergent admissions comprised 55% of all admissions in public hospitals, compared with 29% of admissions in other NYC hospitals (P < .001). Patients in public hospitals were less likely to have their surgery performed by a gynecologic oncologist (57% vs 74%, P < .001) and less likely to have their surgery performed by a high-volume surgeon (21% vs 47%; P < .001) compared with patients in other NYC hospitals. CONCLUSIONS: Ovarian cancer patients treated in public hospitals are less likely to have gynecologic oncologists and high-volume surgeons involved in their care. This is a preliminary finding that warrants further investigation

OBJECTIVE:: To estimate whether a surgeon's case volume is related to route of hysterectomy and short-term morbidity. METHODS:: This is a cross-sectional study collecting data on inpatient hysterectomies using the New York State Department of Health database from 2001 through 2006. An acute morbidity and mortality index was created. Surgeons' license numbers were used to generate an annual average number of hysterectomies performed. A multivariable logistic regression model assessing surgical volume on acute morbidity after controlling for known confounders was created. RESULTS:: A total of 146,494 hysterectomies were performed in the state of New York. Of these, 103,181 (70.4%) were abdominal, 26,660 (18.2%) were vaginal, and 16,653 (11.4%) were laparoscopic-assisted. Twenty- six percent of hysterectomies are performed by physicians who perform, on average, fewer than 10 hysterectomies per year. The percentage of abdominal hysterectomies is 81% for surgeons performing fewer than 10 hysterectomies per year compared with 67% for surgeons performing at least 10 hysterectomies per year (P<.001). Postoperative morbidity and mortality were reported as 16.5% and 0.21%, respectively, for surgeons performing fewer than 10 hysterectomies per year as compared with 11.7% and 0.06%, respectively, for those performing at least 10 hysterectomies (P<.001). CONCLUSION:: Surgeons who perform an average of 10 hysterectomies per year are more likely to perform minimally invasive hysterectomies. These surgeons also have a decrease in morbidity and mortality rates when compared with surgeons who perform fewer than 10 hysterectomies per year. LEVEL OF EVIDENCE:: II

OBJECTIVE: Imatinib mesylate (IM, Gleevec), a potent PDGF/PDGFR tyrosine kinase inhibitor, affects stroma and vascular endothelial cells. Our study sought to determine the safety and activity of paclitaxel with an intermittent schedule of IM. MATERIALS AND METHODS: rEOC patients previously treated with platinum/paclitaxel and </=2 regimens for recurrence were enrolled. Paclitaxel 80 mg/m(2) was given on days 3, 10, 17 every 28 days and oral IM 300 mg bid on days 1-4, 8-11, and 13-18. RESULTS: Between 2007-2009, 14 patients enrolled, 12 were evaluable. Nine patients were on study at 12 weeks. Objective responses (by RECIST and/or CA125) occurred in 4 patients. There were no grade 4, and only four grade 3 toxic events: diarrhea, edema and 2 cases of neutropenia. Early study closure was due to sufficient safety information with preliminary encouraging efficacy results. CONCLUSION: This weekly paclitaxel regimen with intermittent IM is tolerable with anti-tumor activity, making it suitable as part of future studies