Survival after Minimally Invasive Radical Hysterectomy for Early-Stage Cervical Cancer.

BACKGROUND: Minimally invasive surgery was adopted as an alternative to laparotomy (open surgery) for radical hysterectomy in patients with early-stage cervical cancer before high-quality evidence regarding its effect on survival was available. We sought to determine the effect of minimally invasive surgery on all-cause mortality among women undergoing radical hysterectomy for cervical cancer. METHODS: We performed a cohort study involving women who underwent radical hysterectomy for stage IA2 or IB1 cervical cancer during the 2010-2013 period at Commission on Cancer-accredited hospitals in the United States. The study used inverse probability of treatment propensity-score weighting. We also conducted an interrupted time-series analysis involving women who underwent radical hysterectomy for cervical cancer during the 2000-2010 period, using the Surveillance, Epidemiology, and End Results program database. RESULTS: In the primary analysis, 1225 of 2461 women (49.8%) underwent minimally invasive surgery. Women treated with minimally invasive surgery were more often white, privately insured, and from ZIP Codes with higher socioeconomic status, had smaller, lower-grade tumors, and were more likely to have received a diagnosis later in the study period than women who underwent open surgery. Over a median follow-up of 45 months, the 4-year mortality was 9.1% among women who underwent minimally invasive surgery and 5.3% among those who underwent open surgery (hazard ratio, 1.65; 95% confidence interval [CI], 1.22 to 2.22; P=0.002 by the log-rank test). Before the adoption of minimally invasive radical hysterectomy (i.e., in the 2000-2006 period), the 4-year relative survival rate among women who underwent radical hysterectomy for cervical cancer remained stable (annual percentage change, 0.3%; 95% CI, -0.1 to 0.6). The adoption of minimally invasive surgery coincided with a decline in the 4-year relative survival rate of 0.8% (95% CI, 0.3 to 1.4) per year after 2006 (P=0.01 for change of trend). CONCLUSIONS: In an epidemiologic study, minimally invasive radical hysterectomy was associated with shorter overall survival than open surgery among women with stage IA2 or IB1 cervical carcinoma. (Funded by the National Cancer Institute and others.).

Association between Cervical Dysplasia and Adverse Pregnancy Outcomes.

OBJECTIVE: The aim of this study was to determine if cervical dysplasia during pregnancy is associated with pregnancy complications, including preterm delivery and pre-eclampsia. STUDY DESIGN: A retrospective cohort analyses was performed with propensity-score matching to compare complication rates between pregnant women without history of abnormal cervical cancer screening and pregnant women referred for cervical dysplasia assessment to colposcopy clinic. A composite outcome of pregnancy complications included intra-amniotic infection, preterm premature rupture of membranes, pre-eclampsia, preterm delivery, low birth weight, oligohydramnios, and intrauterine fetal demise. Complication rates were compared between women with and without cervical dysplasia using logistic regression models. RESULTS: Overall cohort included 2,814 women, 279 of whom attended colposcopy clinic for cervical dysplasia assessment. Propensity score-matched cohort included 1,459 women, 274 of whom attended colposcopy clinic. Composite complications of pregnancy rates were not significantly different between control and colposcopy groups in both cohorts (25.3% and 29.0%, P = 0.20; 26.5% and 29.3%, P = 0.45). Dysplasia was not associated with composite pregnancy complications in overall and matched cohorts (odds ratio [OR] = 1.09, 95% confidence interval [CI]: 0.77-1.56) and (OR = 1.03, 95% CI: 0.72-1.49). When cervical dysplasia was determined on biopsy or colposcopy, dysplasia was not associated with complications in the overall and matched cohorts. CONCLUSION: Biopsy and/or colposcopy determined cervical dysplasia during pregnancy was not associated with pregnancy complications.

Association of chemotherapy and radiotherapy sequence with overall survival in locoregionally advanced endometrial cancer.

OBJECTIVE: The optimal adjuvant management of women with FIGO Stage III-IVA endometrial cancer (EC) is unclear. While recent prospective data suggest that treatment with pelvic radiotherapy (RT) prior to chemotherapy (CT) is not associated with a survival benefit compared to CT alone, no prospective randomized trial has included a treatment arm in which CT is given before RT. METHODS: An observational cohort study was performed on women with FIGO Stage III-IVA Type 1 (grade 1-2, endometrioid) EC who underwent hysterectomy and received multi-agent CT and/or RT from 2004 to 2014 at Commission on Cancer-accredited hospitals. Multivariable parametric accelerated failure time models were performed to estimate the association of sequence of adjuvant CT and RT with overall survival (OS) using propensity score-adjusted matched cohorts. RESULTS: Of 5795 women identified, 1260 (21.7%) received RT only, 2465 (42.5%) received CT only, 593 (9.7%) received RT before CT, and 1506 (26.0%) received RT after CT. Women who received RT after CT experienced significantly longer 5-year OS than women who received RT before CT (5-year OS: 80.1% vs 73.3%; time-ratio (TR) = 1.37, 95% CI = 1.18-1.58, P < 0.001), CT only (68.9%; TR = 1.33, 95% CI = 1.19-1.48, P < 0.001), or RT only (64.5%, TR = 1.50, 95% CI = 1.32-1.70, P < 0.001). CONCLUSIONS: For women with advanced EC, treatment with multi-agent CT followed by RT is associated with longer OS compared with treatment with RT followed by CT or either treatment alone. These hypothesis-generating data support inclusion in future prospective trials of regimens in which multi-agent CT starts prior to RT.

Prognosis and treatment of positive peritoneal cytology in early endometrial cancer: matched cohort analyses from the National Cancer Database.

BACKGROUND: While positive peritoneal cytology is no longer included among the endometrial cancer staging criteria, Federation International de Gynecologie et Obstetrique recommends continued collection of pelvic washings for cytology to produce additional data that may be used to determine the significance of positive cytology for prognosis and treatment of endometrial cancer. OBJECTIVES: The objectives of the study was to validate that positive cytology is a predictor of decreased survival in early endometrial cancer and to test whether adjuvant chemotherapy for positive cytology is associated with increased survival. STUDY DESIGN: We performed an observational retrospective cohort analysis of the 2010-2013 National Cancer Database including women with cytology status and Federation International de Gynecologie et Obstetrique stage IA-II endometrial cancer. Overall cohort and matched cohort survival analyses were performed with and without imputation of missing data. We also performed survival analyses of women with positive cytology grouped by chemotherapy exposure. Multivariable Cox proportional-hazards regressions were performed to adjust for possible confounders. A variety of sensitivity analyses, including robustness of results to possible unmeasured confounding, were reported. RESULTS: A total of 16,851 women including 953 with positive cytology were included. Four-year overall survival was 79.5% (range, 76.2-83.0%) for women with stage I/II with positive cytology vs 92.2% (range, 91.5-92.9%), 83.3% (range, 81.6-84.9%), and 86.8% (range, 85.1-88.5%) for stage IA, IB, and II with negative cytology, respectively (P ≤ .001). Positive cytology was associated with decreased survival (hazard ratio [95% confidence interval], 1.85 [range, 1.54-2.21], P < .001). For women with Federation International de Gynecologie et Obstetrique grade 1/2 endometrioid adenocarcinoma, the hazard of death associated with positive cytology was similar (hazard ratio [95% confidence interval], 1.85 [1.28-2.67], P < .001). Use of adjuvant chemotherapy by women with positive cytology was associated with increased survival (hazard ratio [95% confidence interval], 0.62 [0.40-0.95], P = .03). CONCLUSION: Positive peritoneal cytology was associated with decreased overall survival of women with Federation International de Gynecologie et Obstetrique stage I/II endometrial cancer, including low-grade endometrioid endometrial cancer. Treatment of women with stage I/II endometrial cancer and positive cytology with adjuvant chemotherapy was associated with increased survival.

Discussing sarcoma risks during informed consent for nonhysterectomy management of fibroids: an unmet need.

There is no reliable way to distinguish symptomatic uterine fibroids from sarcoma without a surgical specimen. Many women with a uterine sarcoma are initially managed without hysterectomy under a presumed fibroid diagnosis, without understanding sarcoma risks. Currently many alternatives to hysterectomy, including medical and procedural interventions, for treatment of fibroids are promoted. The sarcoma incidence among women with presumed fibroids is 0.29% (1/340) to 0.05% (1/2000). Nonmetastatic leiomyosarcoma has a 63% 5-year survival rate whereas metastatic leiomyosarcoma has a 14% 5-year survival rate. In uterine sarcoma, we often cannot identify who has sarcoma before making a potentially cure-denying decision by delaying surgery. Therefore, women electing an alternative to hysterectomy for fibroids should undergo an informed consent process that specifically includes discussion of uterine sarcoma incidence and mortality. Alternatives to hysterectomy for presumed fibroids remain preferable treatment options for many women with symptomatic fibroids, so long as underlying sarcoma risks are adequately discussed. The challenge for obstetrician- gynecologists then is how to provide better informed consent and maintain the primacy of patient autonomy over our concern to "First, do no harm." Major threats to patient's autonomy are faced in the sarcoma risk discussion. How we should present sarcoma risk information to avoid being dismissive of sarcoma or frightening women toward hysterectomy is unstudied. Research is needed to determine how to provide sarcoma risk information with less bias during informed consent.

Cost-effectiveness analysis of dose-dense versus standard intravenous chemotherapy for ovarian cancer: An economic analysis of results from the Gynecologic Oncology Group protocol 262 randomized controlled trial.

OBJECTIVES: To determine the cost-effectiveness of dose-dense versus standard intravenous adjuvant chemotherapy for ovarian cancer using results from the no-bevacizumab cohort of the Gynecologic Oncology Group protocol 262 (GOG-262) randomized controlled trial, which reported a smaller absolute progression-free survival (PFS) benefit than the prior Japanese trial. METHODS: A three-state Markov decision model from a healthcare system perspective with a 21day cycle length and 28month time-horizon was used to calculate incremental cost-effectiveness ratio (ICER) values per progression-free life-year saved (PFLYS) using results from GOG-262. Costs of chemotherapy, complications, and surveillance were from Medicare or institutional data. PFS, discontinuation, and complication rates were from GOG-262. Time-dependent transition probabilities and within-cycle corrections were used. One-way and probabilistic sensitivity analyses were performed. RESULTS: The model produces standard and dose-dense cohorts with 84.3% and 68.3% progression event proportions at 28months, matching GOG-262 rates at the trial's median follow-up. With a median PFS of 10.3months after standard chemotherapy and a hazard ratio for progression of 0.62 after dose-dense therapy, the ICER for dose-dense chemotherapy is $8074.25 (95% confidence interval: $7615.97-$10,207.16) per PFLYS. ICER estimates are sensitive only to the hazard ratio estimate but do not exceed $100,000 per PFLYS. 99.8% of ICER estimates met a more stringent willingness-to-pay of $50,000 per PFLYS. The willingness-to-pay value at which there is a 90% probability of dose-dense treatment being cost-effective is $12,000 per PFLYS. CONCLUSIONS: Dose-dense adjuvant chemotherapy is robustly cost-effective for advanced ovarian cancer from a healthcare system perspective based on results from GOG-262.

Ovarian granulosa cell tumor: A National Cancer Database study.

OBJECTIVE: To provide prognostic information from a large cohort of women with granulosa cell tumor we analyzed the National Cancer Database. METHODS: We performed an observational retrospective cohort analysis of 2680 women with ovarian granulosa cell tumor from the 1998-2013 National Cancer Database. Kaplan-Meier and multivariable Cox proportional-hazards survival analyses were performed for the overall cohort and propensity score matched cohorts to examine the association of surgical staging and adjuvant chemotherapy with survival. A random forest was used to determine important prognostic factors in stages II-IV granulosa cell tumor. RESULTS: Adjuvant chemotherapy, hormonal therapy, and radiotherapy were not associated with survival. Older age, more comorbidities, prior malignancy, higher stage, poor differentiation, larger tumor size, incomplete surgical staging, and residual disease at a surgical margin were independently associated with increased hazard of death. Among women with stage I disease, each one centimeter increase in tumor size was associated with 4% (2-6%) increased hazard of death (P<0.001). By matched cohort analyses, the hazard ratio (HR) (95% CI) for death associated with incomplete surgical staging was 1.77 (1.30-2.41), P<0.001 among women with stage I disease. Receiving adjuvant chemotherapy was not associated with increased survival among women with stages II-IV disease compared to no adjuvant treatment. CONCLUSION: Incomplete surgical staging was associated with increased hazard of death. There was no evidence of increased survival with use of adjuvant chemotherapy. Early and complete surgical resection remains the best evidenced treatment for ovarian granulosa cell tumor.

The Hispanic Paradox in endometrial cancer: A National Cancer Database study.

OBJECTIVE: To compare the overall survival of non-Hispanic white and Hispanic women with endometrial cancer. METHODS: We performed an observational retrospective cohort study of Hispanic and non-Hispanic women with endometrial cancer from the 2004-2014 National Cancer Database. Baseline characteristics were compared with the Chi-squared test for categorical variables or the Mann-Whitney U test for ordinal or continuous variables. The Kaplan-Meier method was used to estimate unadjusted survival times, which were compared with the log-rank test. Missing data was imputed using multiple imputation with chained equations. A multivariable parametric accelerated failure time model for survival was used. Sensitivity analyses were performed using matched cohort analyses of the overall cohort, and of subgroups based on stage or type. RESULTS: 112,574 non-Hispanic and 6313 Hispanic women met inclusion criteria. Five-year survival was slightly higher for Hispanic women (83.1% (82.1-84.3%) versus 81.4% (81.2-81.7%), P=0.002). Hispanic women were younger, treated at lower volume hospitals, and more often diagnosed with a type II histology and stage II-IV disease compared to non-Hispanic women (all P<0.001). With multivariable adjustment for measured confounders, Hispanic women lived 8% longer than non-Hispanic women (time-ratio (95% CI) 1.08 (1.02-1.14), P=0.01). When bias-reducing matched cohort analyses were used for sensitivity analyses, Hispanic women did not have significantly different survival than non-Hispanic women. CONCLUSION: Hispanic ethnicity was not associated with a clinically meaningful difference in survival among women with endometrial cancer.

Low-grade and high-grade endometrial stromal sarcoma: A National Cancer Database study.

OBJECTIVE: To provide refined prognostic information from large cohorts of women with low-grade or high-grade endometrial stromal sarcoma (ESS). METHODS: We performed an observational retrospective cohort analysis of women diagnosed with low-grade or high-grade ESS from the 1998-2013 National Cancer Database. Kaplan-Meier and multivariable accelerated failure time survival analyses were performed to identify prognostic factors after multiple imputation of missing data. Recursive partitioning methods were used to rank prognostic factors in high-grade ESS. Matched cohort analyses were performed to hypothesis-test effects of adjuvant treatments. RESULTS: We identified 2414 and 1383 women with low-grade or high-grade ESS, respectively. Women with high-grade ESS had markedly decreased survival compared to women with low-grade ESS (five-year survival (95% CI): 32.6 (30.1-35.3%) versus 90.5% (89.3-91.8%), P<0.001). Among women with high-grade ESS, median survival (95% CI) was only 19.9 (17.1-22.1) months. Increased age and tumor size were associated with decreased survival in low-grade ESS. In high-grade ESS, additional negative prognostic factors were distant or nodal metastasis, omission of lymphadenectomy, and pathologically-positive surgical margins (all P<0.001). Use of adjuvant chemotherapy (time ratio (TR) (95% CI): 1.36 (1.17-1.58), P<0.001) and radiotherapy (TR (95% CI): 1.57 (1.32-1.87), P<0.001) were associated with increased survival for high-grade ESS. CONCLUSION: The contrasting excellent versus poor prognosis of low-grade versus high-grade ESS, respectively, was confirmed. The best treatment of high-grade ESS is early and complete surgical resection including lymphadenectomy. Adjuvant chemotherapy and radiotherapy may increase survival of women with high-grade ESS.

Stage I uterine carcinosarcoma: Matched cohort analyses for lymphadenectomy, chemotherapy, and brachytherapy.

OBJECTIVE: To determine if lymphadenectomy, chemotherapy and radiotherapy are associated with survival benefit among women with stage I uterine carcinosarcoma. METHODS: Women with stage I uterine carcinosarcoma (n=5614) were identified from the 1998-2013 National Cancer Data Base. Kaplan-Meier survival estimates and Cox proportional-hazards regression models were used to evaluate predictors of overall survival. Effects of these predictors were also estimated using propensity score matched analyses for lymphadenectomy, adjuvant chemotherapy, and radiotherapy. RESULTS: 42.0% (2360/5614) of women in the cohort received no adjuvant radiation or chemotherapy. Black race and positive surgical margin status were associated with decreased survival by multivariable Cox regression. Among women with pathologically node-negative disease, the hazard of death increased 5% (4-7%) per each one centimeter increase in tumor size (P=1.9×10-10). From matched cohort analyses, omitting lymphadenectomy was associated with decreased median (interquartile range) survival: 45.2 (36.4-57.6) versus 73.9 (63.8-91.6) months, hazard ratio (HR) (95% CI) 1.38 (1.20-1.59), P=9.4×10-6. Hazard of death decreased by 3% (1-5%) for each five lymph nodes removed (P=0.01). Multiagent chemotherapy and vaginal brachytherapy were associated with decreased hazard of death (HR (95% CI) 0.62 (0.54-0.73), P=1.1×10-9 and HR (95% CI) 0.83 (0.70-0.97), P=0.02, respectively). Highest five-year survival was observed after brachytherapy and multiagent chemotherapy (74.1% (68.3-80.3%), P<2.0×10-16). CONCLUSION: Lymphadenectomy to at least 15-20 removed nodes is associated with increased survival of women with node-negative uterine carcinosarcoma. Adjuvant "cuff and chemo" with vaginal brachytherapy and multiagent chemotherapy is associated with increased survival.

Chemotherapy delay after primary debulking surgery for ovarian cancer.

OBJECTIVE: To determine the association of chemotherapy delay with overall survival (OS) and investigate predictors of delay among a population-representative American ovarian cancer cohort. METHODS: An observational retrospective cohort analysis of women with ovarian cancer who received National Comprehensive Cancer Network guideline-consistent care was performed with the 1998-2011 National Cancer Data Base. Chemotherapy delay was defined as initiation of multiagent chemotherapy >28days from primary debulking surgery. Associations of patient and disease characteristics with chemotherapy delay were tested with multivariate logistic regression. Survival analyses for women diagnosed from 2003 to 2006 approximated a 21-daycycle intravenous platinum-taxane chemotherapy cohort. Overall survival was estimated by Kaplan-Meier analyses and Cox proportional-hazards regressions, with sensitivity analyses using matched cohorts. RESULTS: 58.1% (26,149/45,001) of women experienced chemotherapy delay. Race, insurance status, cancer center type, and community median income were significantly associated with chemotherapy delay (P<0.001). Odds for chemotherapy delay were higher for older or sicker women, women with endometrioid or mucinous histology, lower stage or grade disease, and uninsured or low-income women (P<0.05). Chemotherapy delay >35days from surgery was associated with a 7% (95% confidence interval, 2-13%) increased hazard of death (P=0.01). Relative hazard of death was lowest between 25 and 29days after surgery but was not significantly different within the longer two-week interval from 21 to 35days. CONCLUSION: A survival benefit may be achieved by consistently starting chemotherapy between 21 and 35days from primary debulking surgery. Women at higher risk for chemotherapy delay may be targeted for close follow-up.

Prognosis and treatment of uterine leiomyosarcoma: A National Cancer Database study.

OBJECTIVE: To determine overall survival and factors associated with survival of women with uterine leiomyosarcoma. METHODS: We performed an observational cohort study of women with uterine leiomyosarcoma (n=7455) from the 1998-2013 National Cancer Database. Kaplan-Meier and multivariable accelerated failure time survival analyses were performed to investigate predictors of survival. Sensitivity and matched cohort analyses were performed to evaluate the roles of oophorectomy, lymphadenectomy, and chemotherapy in early leiomyosarcoma and chemotherapy in metastatic leiomyosarcoma. RESULTS: Median (interquartile range) age at diagnosis was 54 (48-63) years. Older age, higher comorbidity, black race, higher stage or grade, larger tumor size, lymph node involvement, metastasis at diagnosis, positive surgical margin, adjuvant chemotherapy, and brachytherapy were independently associated with decreased survival by unmatched cohort analyses. Private insurance was associated with increased survival. By matched cohort analyses, omitting oophorectomy was not associated with survival among women≤51years old at diagnosis (event time ratio (ETR) (95% CI) 1.06 (0.90-1.25), P=0.48). Omitting lymphadenectomy was not associated with survival (ETR (95% CI) 1.02 (0.94-1.10), P=0.60). Among women with stage I leiomyosarcoma, adjuvant chemotherapy was not associated with increased survival (ETR (95% CI) 0.91 (0.78-1.05), P=0.18). Chemotherapy was associated with increased survival of women with metastatic leiomyosarcoma (median survival (95% CI) 19.4 (16.4-23.0) versus 10.9 (7.7-14.3) months, ETR (95% CI) 1.66 (1.46-1.90), P<0.001). CONCLUSION: Early and complete resection is the best-evidenced treatment for uterine leiomyosarcoma. Oophorectomy and lymphadenectomy may be safely omitted for clinically uterus-confined leiomyosarcoma. Chemotherapy increases survival of women with metastatic leiomyosarcoma.

Survival After Primary Debulking Surgery Compared With Neoadjuvant Chemotherapy in Advanced Ovarian Cancer: A National Cancer Database Study.

OBJECTIVE: The aim of this study was to compare overall survival (OS) of women with advanced ovarian cancer treated with primary debulking surgery (PDS) or neoadjuvant chemotherapy (NAC) using a large national cohort. METHODS: The 1998-2011 National Cancer Database was queried to identify women with stage III or IV ovarian cancer treated with multiagent chemotherapy and stage-appropriate surgery. Overall survival was estimated and compared using Kaplan-Meier analysis between women who received PDS followed by multiagent chemotherapy or NAC followed by interval surgery. Multivariable Cox proportional hazards regression model tested for associations of potential explanatory variables with OS. Analyzed confounders included age, composite comorbidity scores, stage, grade, histology, insurance status, income quartile, and race. RESULTS: Overall, 44,907 women (85.9%) underwent PDS, and 7348 women (14.1%) received NAC. Women who received NAC were older (64 vs 61 years, P < 0.001), had higher comorbidity scores (P < 0.001), and more often had stage IV disease (44.1% vs 26.1%, P < 0.001). Median OS was 41.1 (40.5-41.7) months among women who underwent PDS compared with 30.3 (29.3-31.1) months among women who received NAC (log-rank, P < 0.001). Among women with stage III disease, PDS was associated with increased OS compared with NAC (median OS, 44.9 [44.2-45.7] vs 31.4 [30.2-33.0] months; hazard ratio [95% confidence interval], 0.70 [0.66-0.76]; P < 0.001). Among women with stage IV disease, there was no OS difference between PDS and NAC cohorts (median OS, 31.2 [30.4-32.3] vs 28.4 [27.2-30.2] months; hazard ratio [95% confidence interval], 0.93 [0.85-1.02]; P = 0.12). CONCLUSIONS: Primary debulking surgery was associated with increased OS among women with stage III but not stage IV ovarian cancer in a nationally representative cohort with low NAC use. If this finding reflects treatment assignment bias, it suggests that providers often well select candidates for PDS rather than NAC, although median OS times remain low.

Survival After Pelvic Exenteration for Cervical Cancer: A National Cancer Database Study.

OBJECTIVE: To determine overall survival (OS) and factors associated with OS after pelvic exenteration for cervical cancer. METHODS: Women with cervical cancer who underwent exenteration (n = 517) were identified from the 1998 to 2011 National Cancer Database. Kaplan-Meier and multivariate Cox proportional-hazards survival analyses were performed to test for associations of potential explanatory variables with OS. Analyzed confounders included age, insurance status, income, distance from home to treatment center, stage, exenteration type, surgical margin status, and treatment with adjuvant radiation and/or chemotherapy. RESULTS: Among the entire cohort with clinical follow-up (n = 313), median OS was 24 months. Stage (P = 2.5 × 10), lymph node status (P = 1.3 × 10), insurance status (P = 1.5 × 10), and histologic type (P = 0.04) were significantly associated with OS by the log-rank test. Unadjusted median OS was 24.2 and 61.8 months for women with squamous and adenocarcinoma histologies, respectively. By multivariate Cox regression, age, insurance status, stage, margin status, and adjuvant radiation were associated with OS. Histology was not independently associated with OS on multivariate regression. Among women with node-negative disease, median OS was 73.2 months. CONCLUSIONS: Exenteration may be curative for more than half of women with node-negative cervical cancer. Stage, insurance status, lymph node status, and surgical margin are independently associated with differential OS after exenteration.

Survival of women with Mullerian adenosarcoma: A National Cancer Data Base study.

OBJECTIVE: To determine overall survival (OS) and factors associated with OS of women with Mullerian adenosarcoma. METHODS: Women with adenosarcoma of the uterus, cervix or ovary (n=2205) were identified from the 1998-2011 National Cancer Data Base. Kaplan-Meier and multivariate Cox proportional-hazards survival analyses were performed to test for associations of potential explanatory variables with OS. A subset analysis of women with uterine adenosarcoma was also performed. Analyzed confounders included age, insurance status, income, race, surgical margin status, nodal and distant metastasis, surgical procedure type, and treatment with radiation and/or chemotherapy. RESULTS: Primary sites were uterus (n=1884), cervix (n=229) and ovary (n=92), representing 0.43% of uterine, 0.16% of cervical, and 0.04% of ovarian cancers in the NCDB. Only 36/1176 (3.1%) and 2.5% (33/1,342) had nodal and/or distant metastasis, respectively, at diagnosis. Distant metastasis, positive surgical margin, increased age, higher composite comorbidity score and adjuvant radiotherapy were independently associated with decreased OS. Primary site, lymph node status, surgical procedure, chemotherapy use, race, insurance status and income quartiles were not significantly associated with OS. Each 1cm increase in tumor size was associated with increased hazard for death (HR (95% CI) 1.06 (1.01-1.12), p=0.018) among women with uterine adenosarcoma. CONCLUSION: Complete surgical resection remains the only treatment with well-evidenced OS benefit among women with Mullerian adenosarcoma. Early surgical resection may increase survival of Mullerian adenosarcoma.

Survival after pelvic exenteration for uterine malignancy: A National Cancer Data Base study.

OBJECTIVE: To determine overall survival (OS) and factors associated with OS after pelvic exenteration for uterine cancer. METHODS: Women with uterine cancer who underwent exenteration (n=1160) were identified from the 1998-2011 National Cancer Data Base. Kaplan-Meier and multivariate Cox proportional-hazards survival analyses were performed to test for associations of potential explanatory variables with OS. Analyzed confounders included age, comorbidity score, insurance status, income, distance from home to treatment center, stage, distant and nodal metastasis, tumor size, surgical margin status, exenteration type, and treatment with radiation and/or chemotherapy. RESULTS: Among women with follow-up data (n=652), median (IQR) OS was 63.1 (42.2-107.2) and 17.6 (14.7-23.9) months for women with node-negative versus node-positive disease, respectively. Histology (p=1.5×10-4), grade (p=7.9×10-14), race (p=0.0002), lymph node status (p=1.0×10-14), surgical node evaluation (p=2.8×10-8), surgery for distant metastasis (p=0.004), distant metastasis at diagnosis (p=1.3×10-10), positive surgical margins (p=1.6×10-9), radiotherapy (p=0.004), and insurance status (p=6.5×10-6) were significantly associated with differential, unadjusted Kaplan-Meier OS estimates. Exenteration type was not associated with OS (p=0.357). By multivariate regression, increased age, positive surgical margins, nodal metastasis or unknown nodal status, higher histologic grade, and black race were associated with increased hazards for death. CONCLUSION: Exenteration may be curative for well-selected women with uterine cancer, particularly among women with pathologically negative lymph nodes.

Wnt Signaling and Survival of Women With High-Grade Serous Ovarian Cancer: A Brief Report.

OBJECTIVE: Ovarian cancer is the gynecologic malignancy with the highest case-fatality rate due to the development of chemotherapy resistance. Predictors of chemotherapy response are needed to guide chemotherapy selection and improve survival for patients with ovarian cancer. Wnt signaling may impact chemoresistance in ovarian cancer. METHODS: We studied The Cancer Genome Atlas patients with ovarian cancer treated with intraperitoneal or intravenous-only adjuvant chemotherapy. Cox regression tested associations of expression of 26 Wnt pathway genes with progression-free survival and overall survival. Permutation tests compared survival between chemotherapy groups stratified by expression. P values are two-tailed. RESULTS: Increased FZD3 was associated with increased survival (intraperitoneal group, overall survival: hazard ratio [HR], 0.25; 95% confidence interval [CI], 0.11-0.72, P = 0.009; progression-free survival: HR, 0.58; 95% CI, 0.37-0.92, P = 0.020) (intravenous-only group, overall survival: HR, 0.85; 95% CI, 0.72-0.99, P = 0.039; progression-free survival: HR, 0.83; 95% CI, 0.73-0.95, P = 0.006). Low FZD3 predicted decreased overall survival after intraperitoneal versus intravenous-only chemotherapy (21.7 vs 33.3 months, P < 0.0001). Increased APC2 was associated with decreased overall survival (HR, 1.22; 95% CI, 1.05-1.42; P = 0.009) and progression-free survival (HR, 1.28; 95% CI, 1.12-1.45; P = 0.0002). CONCLUSIONS: Up-regulated tumor Wnt signaling predicts increased ovarian cancer survival. FZD3 may predict benefit from intraperitoneal chemotherapy.

Methicillin-Resistant Staphyloccocus aureus intracranial Epidural Abscess with Osteomyelitis During Pregnancy: A Case Report.

BACKGROUND: The incidence of community-acquired methicillin-resistant Staphylococcus aureus (MRSA) infection is increasing, and 0.5-4% of pregnant women are colonized. CASE: A 30-year-old pregnant woman at term presented with intractable headache 1 week after incision and drainage of a MRSA-positive axillary abscess. Imaging demonstrated a right-sided epidural abscess with midline shift and myositis of the overlying temporalis muscle. She underwent cesarean delivery followed by craniectomy of osteomyelitic bone and evacuation of the epidural abscess. CONCLUSION: Central nervous system abscess is rare but should be considered in patients with a history of MRSA infection and new neurologic signs or symptoms. Surgical evacuation and antibiotic therapy in combination with obstetrical care considering delivery timing based upon maternal stability and gestational age may produce excellent outcomes.

TP53 hot spot mutations in ovarian cancer: selective resistance to microtubule stabilizers in vitro and differential survival outcomes from The Cancer Genome Atlas.

OBJECTIVE: To test if TP53 hot spot mutations (HSMs) confer differential chemotherapy resistance or survival outcomes, the effects of microtubule stabilizers on human ovarian carcinoma cells (OCCs) expressing TP53 HSMs were studied in vitro. Survival outcomes of patients with high grade serous epithelial ovarian carcinoma (HGS EOC) expressing matched HSMs were compared using The Cancer Genome Atlas (TCGA) data. METHODS: Growth inhibition of OCCs transfected with a HSM (m175, m248 or m273) was measured during treatment with paclitaxel, epothilone B (epoB), or ixabepilone. Effects of epoB on p53 expression, phosphorylation, and acetylation, as well as p53-regulated expression of p21 and mdm2 proteins, were determined by Western blot analysis. Expression of p53 target genes P21, GADD45, BAX, PIDD, NF-kB2, PAI-1, and MDR1 was measured by RT-PCR. cBioPortal.org identified patients with codon R175, R248 or R273 HSMs from TCGA data. Survival outcomes were characterized. RESULTS: p53-m248 confers chemoresistance and is not acetylated during epoB treatment. m273 demonstrated high MDR1 expression and resistance to paclitaxel. P21, GADD45 and PAI-1 expression were down-regulated in mutant OCCs. Optimally cytoreduced patients with codon R273 (n=17), R248 (n=13), R175 (n=7) HSMs, or any other TP53 mutation demonstrated median 14.9, 17.6, 17.8 and 16.9months (p=0.806) progression free survival and 84.1, 33.6, 62.1 and 44.5months (p=0.040) overall survival, respectively. CONCLUSIONS: Human OCCs harboring different TP53 HSMs were selectively resistant to microtubule stabilizers. Patients with different HSMs had significantly different overall survival. Both in vitro data and clinical experience support further studying the outcomes of particular TP53 HSMs.

Inguinal Node Metastasis of Low-Grade Endometrial Endometrioid Adenocarcinoma in a Morbidly Obese Patient.

BACKGROUND: The accurate preoperative evaluation of endometrial cancer is needed to inform disease staging, but the evaluation may be more prone to error if the physical signs of advanced stage disease are difficult to appreciate in morbidly obese patients. CASE: A morbidly obese (BMI = 56.9 kg/m2) 67-year-old woman with postmenopausal uterine bleeding was diagnosed with low-grade stage IB endometrial endometrioid adenocarcinoma after surgical staging. She received adjuvant vaginal brachytherapy. Fourteen months after surgery she presented with an ulcerating left inguinal mass. Fine-needle biopsy demonstrated adenocarcinoma consistent with her primary endometrioid adenocarcinoma. At the time of initial diagnosis, a preoperative physical examination was negative for inguinal lymphadenopathy and a computed tomography(CT) demonstrated inguinal lymphadenopathy that was not appreciated. CONCLUSION: In morbidly obese patients, the sensitivity of a physical examination is limited by body habitus. Obese patients with limited physical examinations may benefit from imaging studies to aid early diagnosis of extraperitoneal disease.