Faculty Bibliography

INTRODUCTION/BACKGROUND:The purpose of this study is to analyze and compare the demographics, treatment, and survival rates in patients with uterine clear cell carcinoma (UCCC) and ovarian clear cell carcinoma (OCCC). METHODS:The Surveillance, Epidemiology and End Results (SEER) program data for all 18 registries from 1988 to 2010 was reviewed to identify women with OCCC and UCCC. Demographic and clinical data were compared, and the impact of tumor site on survival was analyzed using the Kaplan-Meier method. Factors predictive of outcome were compared using the Cox proportional hazards model. RESULTS:The final study group consisted of 5421 women with clear cell histopathology. 3631 (67%) had OCCC and 1790 (33%) had UCCC. The mean age at diagnosis was 56 (± 12) years for women with OCCC and 67.7 (± 12.0) years for UCCC (P<0.001). Patients with OCCC had a higher rate of late stage disease (38.9% vs. 21.2%; P<0.001). Over the entire study period, after adjusting for known variables, there was no significant difference in cancer specific mortality between UCCC and OCCC, HR 1.05 (0.92-1.19). In the subset analysis by staging, in women with localized disease there was an improved survival in UCCC compared to OCCC. In contrast, in women with distant disease there was an increased mortality in women with UCCC. CONCLUSION/CONCLUSIONS:In the entire population, there was no significant difference in cancer related mortality between the groups. However, in women with localized disease, UCCC had improved survival, but increased mortality in distant disease compared to OCCC.

OBJECTIVE:The aims of this study are to determine if outcomes of patients with ovarian carcinosarcoma (OCS) differ from women with high grade papillary serous ovarian carcinoma when compared by stage as well as to identify any associated clinico-pathologic factors. METHODS:The Surveillance, Epidemiology, and End Results (SEER) Program data for all 18 registries from 1998 to 2009 was reviewed to identify women with OCS and high grade papillary serous carcinoma of the ovary. Demographic and clinical data were compared, and the impact of tumor histology on survival was analyzed using the Kaplan-Meier method. Factors predictive of outcome were compared using the Cox proportional hazard model. RESULTS:The final study group consisted of 14,753 women. 1334 (9.04%) had OCS and 13,419 (90.96%) had high grade papillary serous carcinoma of the ovary. Overall, women with OCS had a worse five-year, disease specific survival rate, 28.2% vs. 38.4% (P<0.001). This difference persisted for each FIGO disease stages I-IV, with five year survival consistently worse for women with OCS compared with papillary serous carcinoma. Over the entire study period, after adjusting for histology, age, period of diagnosis, SEER registry, marital status, stage, surgery, radiotherapy, lymph node dissection, and history of secondary malignancy after the diagnosis of ovarian cancer, carcinosarcoma histology was associated with decreased cancer-specific survival. CONCLUSIONS:OCS is associated with a poor prognosis compared to high grade papillary serous carcinoma of the ovary. This difference was noted across all FIGO stages.

OBJECTIVE:Hospital readmissions are common, costly and increasingly viewed as adverse events. In gynecologic oncology, data on readmissions are limited. The goal of this study was to examine the patient, treatment and discharge factors associated with unplanned readmission after cytoreductive surgery. METHODS:We identified all patients with stages II-IV ovarian cancer who underwent surgical cytoreduction at our institution between 2003 and 2011. A retrospective chart review was performed, and clinical variables were extracted. Utilizing linear and logistic regression, these clinical variables were correlated with risk of readmission. RESULTS:A total of 460 patients were included in the analysis, with the majority having a stage IIIC high grade serous cancer. Optimal cytoreduction (<1.0 cm residual disease) was obtained in 368 patients (81%), and 233 patients (50%) underwent at least one radical procedure. Perioperative complications were observed in 148 patients (32%). A large proportion of our cohort was discharged to rehabilitation facilities (12%) or with a visiting nurse (38%). Fifty five patients (12%) were readmitted within 30 days. On multivariate logistic regression, reoperation and perioperative cardiopulmonary event were the only factors associated with readmission (OR=3.2, 95% CI=1.7-6.0). Discharge home with ancillary services was not protective against readmission, even when controlling for perioperative complications (OR=1.18, 95% CI=0.53-2.64). CONCLUSIONS:Readmission after surgical cytoreduction affected 12% of our population. Multivariate analyses suggested perioperative complications, particularly reoperation and cardiopulmonary event, placed the patient at the greatest risk. Age, comorbidities, surgical radicality and discharge with visiting nurse services/rehabilitation facility did not affect the likelihood of readmission.

OBJECTIVE:The purpose of this study was to examine changes over time in survival for African-American (AA) and white women diagnosed with squamous cell carcinoma of the vulva. STUDY DESIGN/METHODS:The Surveillance, Epidemiology, and End Results (SEER) Program for 1973-2009 was used for this analysis. We evaluated racial differences in survival between AA and white women. Kaplan-Meier and Cox proportional hazards survival methods were used to assess differences in survival by race by decade of diagnosis. RESULTS:The study sample included 5867 women, including 5379 whites (91.6%) and 488 AA (8.3%). AA women were younger (57 vs 67 years; P < .001) and had a higher rate of distant metastasis (6.1% vs 3.7%; P < .001). AA women had surgery less frequently (84.2% vs 87.6%; P = .03) and more frequently radiotherapy (24.2% vs 20.6%; P < .001). AA women had a hazard ratio (HR) of 0.84 (95% confidence interval [CI], 0.74-0.95) of all-cause mortality and 0.66 (95% CI, 0.53-0.82) of vulvar cancer mortality compared with whites. Adjusting for SEER Registry, marital status, stage, age, surgery, radiotherapy, grade, lymph node status, and decade, AA women had an HR of 0.67 (95% CI, 0.53-0.84) of vulvar cancer-related mortality compared with whites. After adjusting for the same variables, there was a significant difference in survival between AA and whites in the periods of 1990-1999 (HR, 0.62; 95% CI, 0.41-0.95) and 2000-2009 (HR, 0.46; 95% CI, 0.30-0.72) but not earlier. CONCLUSION/CONCLUSIONS:AA presented at a significantly younger age compared with white women and had better survival compared with whites.

PURPOSE/OBJECTIVE:Primary debulking surgery (PDS) has historically been the standard treatment for advanced ovarian cancer. Recent data appear to support a paradigm shift toward neoadjuvant chemotherapy with interval debulking surgery (NACT-IDS). We hypothesized that stage IV ovarian cancer patients would likely benefit from NACT-IDS by achieving similar outcomes with less morbidity. METHODS:Patients with stage IV epithelial ovarian cancer who underwent primary treatment between January 1, 1995 and December 31, 2007, were identified. Data were retrospectively extracted. Each patient record was evaluated to subclassify stage IV disease according to the sites of tumor dissemination at the time of diagnosis. The Kaplan-Meier method was used to compare overall survival (OS) data. RESULTS:A total of 242 newly diagnosed stage IV epithelial ovarian cancer patients were included in the final analysis; 176 women (73%) underwent PDS, 45 (18%) NACT-IDS, and 21 (9%) chemotherapy only. The frequency of achieving complete resection to no residual disease was significantly higher in patients with NACT-IDS versus PDS (27% vs. 7.5%; P < 0.001). When compared to women treated with NACT-IDS, women with PDS had longer admissions (12 vs. 8 days; P = 0.01), more frequent intensive care unit admissions (12% vs. 0%; P = 0.01), and a trend toward a higher rate of postoperative complications (27% vs. 15%; P = 0.08). The patients who received only chemotherapy had a median OS of 23 months, compared to 33 months in the NACT-IDS group and 29 months in the PDS group (P = 0.1). CONCLUSIONS:NACT-IDS for stage IV ovarian cancer resulted in higher rates of complete resection to no residual disease, less morbidity, and equivalent OS compared to PDS.

STUDY OBJECTIVE/OBJECTIVE:To identify risk factors for hospital length of stay (LOS) longer than 1 postoperative day in patients undergoing laparoscopic hysterectomy because of endometrial cancer. DESIGN/METHODS:Retrospective observational study (Canadian Task Force classification II-2). SETTING/METHODS:Tertiary-care university hospital. PATIENTS/METHODS:One hundred thirty-three patients undergoing laparoscopic hysterectomy because of endometrial cancer between August 2006 and August 2010. INTERVENTIONS/METHODS:One hundred thirty-three women underwent traditional laparoscopy. In 101 of these patients, lymph node sampling was performed. MEASUREMENTS AND MAIN OUTCOMES/RESULTS:Seventy-four women (55%) were discharged on postoperative day 1. The percentage of women discharged on postoperative day 1 (POD1) vs after POD 1 did not differ by extent of staging. Risk of perioperative complications was associated with hospital LOS longer than POD1 (odds ratio [OR], 11.45; 95% confidence interval [CI], 1.40-94.39). Procedure start time after 3:00 pm (OR, 3.20; 95% CI, 1.14-9.04) and procedure end time after 5:00 pm (OR, 2.47; 95% CI, 1.17-5.20) were independent factors associated with hospital LOS beyond POD1. There was a nonsignificant tendency toward later hospital discharge with administration of intravenous narcotic agents. CONCLUSIONS:Laparoscopic surgery to treat endometrial cancer should be preferentially scheduled early in the day to facilitate discharge on POD1. The extent of staging lymphadenectomy performed does not increase hospital stay beyond POD1.

OBJECTIVE:The aim of this retrospective, multi-institutional study was to evaluate the importance of surgical staging for stage I uterine papillary serous carcinomas (UPSCs) to determine optimal management of this rare tumor. METHODS:With institutional review board approval from both participating institutions, all patients with 2009 International Federation of Gynecology and Obstetrics stage I mixed serous and UPSC diagnosed between January 1, 1992, and December 31, 2007, were identified at the 2 institutions. Clinical factors were correlated using Spearman correlation coefficients, Kaplan-Meier survival estimates and a Cox proportional hazards model. RESULTS:Of the 204 UPSC patients treated during this period, 84 were classified as stage I, with substages as follows: stage IA, n = 71; stage IB, n = 13. Thirty-seven patients (44%) had a history of a second cancer (22 breast tumors, 9 synchronous müllerian cancers). Surgical staging with at least hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and bilateral pelvic lymph node dissection was performed in 60 (71%) of 84 patients. The median survival for all patients was 10 years. Univariate analysis revealed surgical staging (P < 0.001), normal preoperative CA-125 (P < 0.001), and absence of additional cancers (P < 0.01) to be associated with improved survival. Age-adjusted multivariate analysis incorporating these factors revealed that advancing substage (hazard ratio, 4.59; P < 0.05), a second malignancy (hazard ratio, 2.75; P < 0.04), and surgical staging (hazard ratio, 0.18; P < 0.001) were independent factors associated with overall survival. In a subset analysis excluding patients with a second malignancy, substage (hazard ratio, 3.52; P < 0.05), and surgical staging (hazard ratio, 0.16; P < 0.001) were independent factors affecting overall survival. CONCLUSIONS:Independent of adjuvant chemotherapy or radiation, stage of disease, comprehensive surgical staging, and the presence of a second malignancy were predictors of overall survival.

Ovarian cancer is the fifth leading cause of cancer death in women. Ovarian cancers display a high degree of complex genetic alterations involving many oncogenes and tumor suppressor genes. Analysis of the association between genetic alterations and clinical endpoints such as survival will lead to improved patient management via genetic stratification of patients into clinically relevant subgroups. In this study, we aim to define subgroups of high-grade serous ovarian carcinomas that differ with respect to prognosis and overall survival. Genome-wide DNA copy number alterations (CNAs) were measured in 72 clinically annotated, high-grade serous tumors using high-resolution oligonucleotide arrays. Two clinically annotated, independent cohorts were used for validation. Unsupervised hierarchical clustering of copy number data derived from the 72 patient cohort resulted in two clusters with significant difference in progression free survival (PFS) and a marginal difference in overall survival (OS). GISTIC analysis of the two clusters identified altered regions unique to each cluster. Supervised clustering of two independent large cohorts of high-grade serous tumors using the classification scheme derived from the two initial clusters validated our results and identified 8 genomic regions that are distinctly different among the subgroups. These 8 regions map to 8p21.3, 8p23.2, 12p12.1, 17p11.2, 17p12, 19q12, 20q11.21 and 20q13.12; and harbor potential oncogenes and tumor suppressor genes that are likely to be involved in the pathogenesis of ovarian carcinoma. We have identified a set of genetic alterations that could be used for stratification of high-grade serous tumors into clinically relevant treatment subgroups.

OBJECTIVE:The purpose of this study is to analyze and compare the demographics, treatment, recurrence, and survival rates in patients with uterine clear cell carcinoma (UCCC) and ovarian clear cell carcinoma (OCCC). METHODS:A retrospective review of the Cancer Registry database was performed. All patients with UCCC and OCCC who underwent surgical staging at the two participating institutions, between January, 1995 and December, 2007, were identified. Categorical variables were evaluated by Chi square test. Survival estimates were plotted utilizing the Kaplan-Meier method. RESULTS:Analysis of 41 women with UCCC and 121 with OCCC was performed. In patients with OCCC, 48.4% had localized disease, 18.9% had regional spread, 31.1% had distant metastasis, and in 1.6% spread is unknown; compared to UCCC, 41.5% had localized disease, 12.2% regional spread, and 46.3% distant metastasis (p=0.2). The median progression free survival was 31.4 months in women with UCCC, compared to 145 months in patients with OCCC (p=0.04). UCCC women had a median overall survival of 39.5 months, compared to 155.8 months in patients with OCCC (p=0.002). In the multivariate Cox regression model, age>55 years old, tumor extension, optimal cytoreduction, and platinum-based chemotherapy were identified as independent predictors of overall survival. UCCC vs. OCCC was not associated with decreased overall survival in multivariate analysis. CONCLUSION/CONCLUSIONS:OCCC and UCCC have the same rate of localized disease, regional spread and distant metastasis. After controlling for age, tumor extension, optimal cytoreduction, and platinum based chemotherapy, UCCC was not associated with decreased overall survival compared to OCCC.

OBJECTIVES/OBJECTIVE:To examine the distribution and outcomes of recurrent disease in patients with ovarian, fallopian tube and peritoneal cancers after optimal cytoreduction and adjuvant intraperitoneal (IP) chemotherapy. METHODS:All patients diagnosed with ovarian, fallopian tube, or peritoneal cancer between 2004 and 2009 who underwent optimal cytoreductive surgery and received adjuvant intravenous (IV) and IP chemotherapy with paclitaxel and a platinum-based agent were eligible. Age, performance status, tumor origin, stage, and grade were recorded. First recurrences were identified using CA125 values, radiographic studies, operative notes, and pathology reports. Sites of recurrence were classified as intraperitoneal (IP), extraperitoneal (EP) or distant. Kaplan-Meier estimates and Cox multivariate regression models were used to assess the associations between recurrent disease distribution and progression-free survival (PFS) and overall survival (OS). RESULTS:One hundred forty-three patients met the criteria for inclusion. The majority were Stage III (86%) and serous histology (77%). Eighty-four (58.7%) received IV/IP paclitaxel/cisplatin per GOG-172 and 59 (41.3%) received IV/IP paclitaxel/carboplatin. Seventy-two percent completed 6 cycles. Ninety (62.9%) patients manifested a recurrence. One-hundred twelve sites of recurrence were identified with 70 (62.5%) IP and 42 (37.5%) EP and distant sites. Nineteen (21%) recurred in more than one site, i.e. both IP and EP locations. Site of recurrence did not impact OS, however, patients who recurred in multiples sites had significantly worse OS (p<0.001). CONCLUSION/CONCLUSIONS:Approximately 40% of patients treated with IP chemotherapy have a first recurrence outside the peritoneal cavity. Though site of recurrence did not affect OS those with multi-focal recurrence demonstrate worse survival.