Faculty Bibliography

Objectives. To characterize clinical outcomes in patients with intermediate or high-risk endometrial carcinoma who underwent surgical staging with or without para-aortic lymphadenectomy. Methods. This is a retrospective cohort study of patients with intermediate or high-risk endometrial adenocarcinoma who underwent surgical staging with (PPALN group) or without (PLN) para-aortic lymphadenectomy. Data were collected, Kaplan-Meier curves were generated, and univariate and multivariate analyses performed to compare differences in adjuvant therapy, disease recurrence, disease-free survival (DFS), and overall survival (OS). Results. 118 patients were included in the PPALN group and 139 in the PLN group. Patients in the PPALN group were more likely to receive adjuvant vaginal brachytherapy (25.4% versus 11.5%, OR = 2.5, P = 0.03) and less likely to receive adjuvant multimodal combination therapy (17.81% versus 28.8%, OR = 0.28, P = 0.002). DFS was improved in the PLN group as compared to PPALN (80% versus 62%, P = 0.02). OS was equivalent (P = 0.93). Patients in the PPALN group who had less than 10 para-aortic nodes removed were twice as likely to recur than patients who had 10 or more para-aortic nodes or patients in the PLN group (HR 2.08, CI 1.20-3.60, P = 0.009). Conclusions. Patients in the PLN group were more likely to receive multimodal adjuvant therapy and had better DFS than the PPALN group. Pelvic lymphadenectomy followed by adjuvant radiation and chemotherapy may represent an effective treatment option for patients with intermediate or high-risk disease. If systematic para-aortic lymphadenectomy is performed and less than 10 para-aortic lymph nodes are obtained, multimodality adjuvant therapy should be considered to improve DFS.

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.

OBJECTIVE:To assess the influence of hydatidiform mole (HM) management setting (reference center versus other institutions) on gestational trophoblastic neoplasia (GTN) outcomes. METHODS:This cohort study included 270 HM patients attending Botucatu Trophoblastic Diseases Center (BTDC, São Paulo State University, Brazil) between January 1990 and December 2009 (204 undergoing evacuation and entire postmolar follow-up at BTDC and 66 from other institutions [OIs]). GTN characteristics and outcomes were analyzed and compared according to HM management setting. The confounding variables assessed included age, gravidity, parity, number of abortions and HM type (complete or partial). Postmolar GTN outcomes were compared using Mann-Whitney's test, chi2 test or Fisher's exact test. RESULTS:Postmolar GTN occurred in 34 (34/204 = 16.7%) BTDC patients and in 27 (27/66 = 40.9%) of those initially treated in other institutions. BTDC patients showed lower metastasis rate (5.8% vs. 48%, p = 0.003) and lower median FIGO (2002) score (2.00 [1.00, 3.00] vs. 4.00 [2.00, 7.00], p = 0.003]. Multiagent chemotherapy to treat postmolar GTN was required in 2 BTDC cases (5.9%) and in 8 OI cases (29.6%) (p = 0.017). Median time interval between molar evacuation and chemotherapy onset was shorter among BTDC patients (7.0 [6.0, 10.0] vs. 10.0 [7.0, 16.0], p = 0.040). CONCLUSION/CONCLUSIONS:BTDC patients showed GTN characteristics indicative of better prognosis. This underscores the importance of GTD specialist centers.

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.

OBJECTIVE:To describe the clinical presentation of hydatidiform molar pregnancy in women under the age of 20 years. In addition, we sought to understand if this adolescent population manifests differences in clinical factors compared to an adult population that may affect outcome. STUDY DESIGN/METHODS:We used a database from the New England Trophoblastic Disease Center to analyze clinical data from all women followed for molar pregnancy between 1970 and 2009 with complete follow-up information. This population was stratified by age and clinical parameters including presenting signs, molar histology and development of gestational trophoblastic neoplasia (GTN). Univariable and multivariable logistic regression was employed to discern clinical factors that associated with adolescent age. The Partners Human Research Committee approved this study. RESULTS:We identified 1,494 women diagnosed with hydatidiform mole (HM), of which 220 (14.7%) were adolescents defined as age <20 years. The most common presenting clinical signs were vaginal bleeding and an enlarged uterus compared to dates. Median gestational age at diagnosis was 13.4 weeks, not different from that in the adult population. Similarly, no difference in presenting human chorionic gonadotropin was observed between the adult and adolescent populations. Adolescents presented with a significant overrepresentation of complete mole (86% vs. 75%, p < 0.001) compared to adults. Complete mole was associated with a heightened risk of developing GTN (OR 2.6, 95% CI 1.9-3.5), and despite the association of complete mole with young maternal age, univariable analysis showed no difference in the rate of GTN observed between adolescents and adults (24% vs. 30%, p = 0.08). Multivariable analysis controlling for molar histology demonstrated that adolescent age was associated with a decreased risk of GTN (hazard ratio 0.67, 95% CI 0.48-0.93). CONCLUSION/CONCLUSIONS:Adolescents account for a substantial proportion of the population with HM. They commonly present with vaginal bleeding. Though this population develops a complete mole with a higher frequency than adults, adolescents appear to have a significantly decreased risk of developing GTN.

OBJECTIVE:To evaluate the clinical outcomes in adolescents with gestational trophoblastic neoplasia (GTN) compared to adult women. STUDY DESIGN/METHODS:Patients with International Federation of Gynecology and Obstetrics criteria for GTN who underwent treatment between January 1, 1973, and December 31, 2010, were identified from the Donald P. Goldstein, M.D., Trophoblastic Tumor Registry of the New England Trophoblastic Disease Center. Adolescents included patients <20 years old at the time of diagnosis. Standard univariate analyses were performed, as were multivariate analyses with logistic regression to control for potential confounding variables. RESULTS:We identified 423 women with GTN; 50 (12%) patients were adolescents (<20 years old), and 373 (88%) were > or = 20 years old. Both groups had the same rate of low-risk GTN score (98% vs. 98%, p = 0.9). In the adolescent group 47 (94%) women had stage I GTN, and 3 (6%) had stage III. In the adult group 304 (81.5%) women had stage I GTN, 4 (1%) had stage II, 64 (17%) had stage III and only 1 (0.5%) had stage IV disease (p = 0.7). Adolescents at molar presentation had higher rates of anemia (30% vs. 14%, p = 0.001), vaginal bleeding (86% vs. 67%, p = 0.001), and a uterus with size greater than dates (42% vs. 24%, p = 0.007). Factors determined to significantly influence resistance to initial chemotherapeutic treatment on multivariate analysis were beta-hCG level at molar presentation > 100,000 mIU/mL, beta-hCG level at persistence >20,000 mIU/mL, the presence of metastasis, and duration of disease > 4 months. Age <20 years old was not a prognostic factor of resistance to initial chemotherapeutic treatment. CONCLUSION/CONCLUSIONS:There was no difference between adolescents and adult women in the rates of low-risk GTN, stage of GTN, and the frequency of resistance to initial chemotherapeutic treatment.

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.

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.

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.

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.