Hospice utilization in advanced cervical malignancies: An analysis of the National Inpatient Sample.

OBJECTIVE: Hospice services improve quality of life and outcomes for patients and caretakers, compared to inpatient mortality. This study identifies factors that exert the strongest influence on end-of-life care modalities in patients with cervical cancer. METHODS: Admissions with a diagnosis of cervical cancer that were discharged to hospice or died in-hospital were identified in the National Inpatient Sample years 2007-2011, excluding admissions coded for hysterectomy. Logistic regression models were used to examine differences in age, race, length of stay, primary payer, hospital region, admission type, hospital bedsize, hospital teaching status, income quartile, and Elixhauser comorbidity index score between the groups. RESULTS: 2073 admissions with a diagnosis of cervical cancer resulting in hospice discharge (n = 1290) or inpatient death (n = 783) were identified. Age (P = 0.01), hospital region (P = 0.01), length of hospitalization (P < 0.01), Elixhauser comorbidity index score (P = 0.03), and urban vs. rural location (P = 0.01) had a significant impact on disposition in univariate analysis. Admissions of patients categorized as Asian/Pacific Islander (OR = 2.24, 95% CI 1.11-4.49), hospitalizations lasting 0-3 days (OR = 1.57, 95% CI 1.21-2.03), and admissions in rural areas (OR = 1.62, 95% CI 1.12-2.36) had higher rates of in-hospital death compared to the reference groups. Patients aged 18-45 years (OR = 0.69, 95% CI 0.52-0.90) and those treated in the South (OR 0.59, 95% CI 0.45-0.77) and West (OR = 0.50, 95% CI 0.30-0.81) had lower odds ratios of inpatient mortality. CONCLUSION: Modalities of care in terminal cervical cancer vary among sociodemographic and clinical factors. This data underscores the continued push for improved end-of-life care among cervical cancer patients and can guide clinicians in appropriate targeted counseling to increase utilization of hospice resources.

Synergy between Paclitaxel and Anti-Cancer Peptide PNC-27 in the Treatment of Ovarian Cancer.

OBJECTIVES: Paclitaxel is widely used in the treatment of gynecologic malignancies. It targets tumor cells in the M phase of the cell cycle. Cells in other phases survive the insult and repopulate the tumor. PNC-27 is a peptide synthesized of amino acids of the p53-MDM-2 binding domain. It kills various cancer cell lines in a dose-dependent manner. The goal of this study is to assess ovarian cancer cells' sensitivity to PNC-27 after surviving exposure to paclitaxel and to investigate the potential for synergy between PNC-27 and paclitaxel in the treatment of ovarian cancer. METHODS: The impact of exposure to paclitaxel on the surface expression of MDM-2 was assessed with the use of flow cytometry. For measurement of cytotoxicity in vitro, ID8 cells were exposed to paclitaxel for 12 hours in various concentrations. At 12 hours, the drug containing media was removed and the cells were cultured in media containing various concentrations of PNC-27 for 24 hours. Viability was assessed with the use of an MTT assay. Survival fractions were plotted against drug concentrations and the data were fit to logistic dose-response curves. Isoeffective combinations were used to create isobolograms. The combined treatment with weekly paclitaxel and PNC-27 was tested in an intraperitoneal mouse model of ovarian cancer (ID8). RESULTS: Exposure to paclitaxel rendered incomplete time-dependent killing, while PNC-27 mediated comprehensive, dose-dependent killing of ID8 cells. The cytotoxic effect of PNC-27 was dependent on its binding to MDM-2. Blocking MDM-2 inhibited the killing by PNC-27. ID8 cells surviving paclitaxel demonstrated increased expression of MDM-2 and increased susceptibility to PNC-27. Isobologram for dose combinations that were isoeffective indicates synergistic effect between the 2 agents (Combination index <1). In an in vivo model of ovarian cancer (ID8), the addition of PNC-27 to weekly paclitaxel administration significantly reduces tumor growth. CONCLUSIONS: These data demonstrate synergism between PNC-27 and paclitaxel. PNC-27 could target cells surviving paclitaxel and improve its antitumor effect.

Hyperemesis Gravidarum: A Review of Recent Literature.

BACKGROUND: In the United States, hyperemesis gravidarum is the most common cause of hospitalization during the first half of pregnancy and is second only to preterm labor for hospitalizations in pregnancy overall. In approximately 0.3-3% of pregnancies, hyperemesis gravidarum is prevalent and this percentage varies on account of different diagnostic criteria and ethnic variation in study populations. Despite extensive research in this field, the mechanism of the disease is largely unknown. Although cases of mortality are rare, hyperemesis gravidarum has been associated with both maternal and fetal morbidity. The current mainstay of treatment relies heavily on supportive measures until improvement of symptoms as part of the natural course of hyperemesis gravidarum, which occurs with progression of gestational age. However, studies have reported that severe, refractory disease manifestations have led to serious adverse outcomes and to termination of pregnancies. SUMMARY: Despite extensive research in the field, the pathogenesis of hyperemesis gravidarum remains unknown. Recent literature points to a genetic predisposition in addition to previously studied factors such as infectious, psychiatric, and hormonal contributions. Maternal morbidity is common and includes psychological effects, financial burden, clinical complications from nutritional deficiencies, gastrointestinal trauma, and in rare cases, neurological damage. The effect of hyperemesis gravidarum on neonatal health is still debated in literature with conflicting results regarding outcomes of birth weight and prematurity. Available therapy options remain largely unchanged in the past several decades and focus on parenteral antiemetic medications, electrolyte repletion, and nutritional support. Most studies of therapeutic options do not consist of randomized control studies and cross-study analysis is difficult due to considerable variation of diagnostic criteria. Key Messages: Hyperemesis gravidarum carries a significant burden on maternal health and US health care. Most published research on pathogenesis is observational and suggests multifactorial associations with hyperemesis gravidarum. Precise, strictly defined criteria for clinical diagnosis are likely to benefit meta-analyses of further research studies regarding pathogenesis as well as therapeutic options.

Association of birth outcomes with fetal exposure to parabens, triclosan and triclocarban in an immigrant population in Brooklyn, New York.

BACKGROUND: Prior studies suggest associations between fetal exposure to antimicrobial and paraben compounds with adverse reproductive outcomes, mainly in animal models. We have previously reported elevated levels of these compounds for a cohort of mothers and neonates. OBJECTIVE: We examined the relationship between human exposure to parabens and antimicrobial compounds and birth outcomes including birth weight, body length and head size, and gestational age at birth. METHODS: Maternal third trimester urinary and umbilical cord blood plasma concentrations of methylparaben (MePB), ethylparaben (EtPB), propylparaben (PrPB), butylparaben (BuPB), benzylparaben (BePB), triclosan (2,4,4'-trichloro-2'-hydroxydiphenyl ether or TCS) and triclocarban (1-(4-chlorophenyl)-3-(3,4-dichlorophenyl) urea or TCC), were measured in 185 mothers and 34 paired singleton neonates in New York, 2007-2009. RESULTS: In regression models adjusting for confounders, adverse exposure-outcome associations observed included increased odds of PTB (BuPB), decreased gestational age at birth (BuPB and TCC) and birth weight (BuPB), decreased body length (PrPB) and protective effects on PTB (BePB) and LBW (3'-Cl-TCC) (p<0.05). No associations were observed for MePB, EtPB, or TCS. CONCLUSIONS: This study provides the first evidence of associations between antimicrobials and potential adverse birth outcomes in neonates. Findings are consistent with animal data suggesting endocrine-disrupting potential resulting in developmental and reproductive toxicity.

Ex vivo Efficacy of Anti-Cancer Drug PNC-27 in the Treatment of Patient-Derived Epithelial Ovarian Cancer.

OBJECTIVE: Despite an 80% response rate to chemotherapy, epithelial ovarian cancer has the highest case fatality rate of all gynecologic malignancies. Several studies have shown the efficiency of anticancer peptides PNC-27 and PNC-28 in killing a variety of cancer cells selectively in vitro and in vivo. The purpose of this study was to evaluate the efficacy of PNC-27 against human primary epithelial ovarian cancer. METHODS: We established primary cultures of freshly isolated epithelial ovarian cancer cells from patients with newly diagnosed ovarian cystadenocarcinomas. Two cell lines were obtained, one from mucinous cystadenocarcinoma, and the other from high-grade papillary serous carcinoma. The cancerous properties of these cells were characterized in vitro morphologically, by their growth requirements and serum independence. Treatment effects with PNC-27 were followed qualitatively by light microscopy, and quantitatively by measuring inhibition of cell growth using the MTT cell proliferation assay and direct cytotoxicity by measuring lactate dehydrogenase (LDH). RESULTS: PNC-27 inhibits in a dose-dependent manner the growth of and is cytotoxic to human primary cancer cells that had been freshly isolated from two ovarian epithelial cancers. The results further show that the control peptide PNC-29 has no effect on the primary cancer cells. Our results also show that PNC-27 is cytotoxic to cells from long-established and chemotherapy-resistant human ovarian cancer cell lines. CONCLUSION: These findings show, for the first time, the efficacy of PNC-27 on freshly isolated, primary human cancer cells. Our results indicate the potential of PNC-27 peptide as an efficient alternative treatment of previously untreated ovarian cancer as well as for ovarian cancers that have become resistant to present chemotherapies.

Peripartum Primary Prophylaxis Inferior Vena Cava Filter Placement in a Patient with Stage IV B-Cell Lymphoma Presenting with a Pathologic Femur Fracture.

Background Pulmonary embolus (PE) remains a leading etiology of maternal mortality in the developed world. Increasing utilization of retrievable inferior vena cava (IVC) filter placement currently includes pregnant patients. Case A 22-year-old woman at 27 weeks' gestation was diagnosed with Stage IV high-grade malignant B cell lymphoma following pathologic femur fracture. Significant risk factors for PE led to placement of primary prophylaxis IVC filter before cesarean delivery, open reduction and internal fixation of the fractured femur, and chemotherapy. Conclusion This case supports that primary prophylaxis placement of IVC filters in highly selected pregnant patients may assist in decreasing PE-associated maternal mortality.

Extent of lymph node dissection and overall survival in patients with uterine carcinosarcoma, papillary serous and endometrioid adenocarcinoma: A retrospective cohort study.

OBJECTIVE: To evaluate the interaction between extent of lymph node dissection (LND) and overall survival (OS) in patients with various histologic types of uterine cancer. METHODS: We retrospectively identified 834 patients who had primary surgery in our institution for uterine carcinosarcoma (CS), papillary serous (UPSC) and endometrioid adenocarcinoma between 1984 and 2009. Stage, grade, total lymph node count (LNC), positive LNC, adjuvant therapy, age, race and OS were collected. OS was calculated using the Kaplan-Meier method. Predictive factors were compared with the log rank test and Cox regression analysis. RESULTS: Our cohort included 158 patients with CS, 115 patients with UPSC and 561 patients with endometrioid adenocarcinoma. Of the cohort, 38% of the patients had Stage III or IV disease. LND was performed in 73% of patients with CS, 68% of patients with UPSC and 79% of patients with endometrioid adenocarcinoma. LND was performed in 82% of Stage I-II and in 68% of Stage III-IV cases. The median total LNC was 13 (range 1-75) and there was no significant difference in the total LNC between the different histologies. Median OS was 21 months for CS, 18 months for UPSC and 200 months for patients with endometrioid adenocarcinoma. A positive association between the total and positive LNC was present in all three histologic types (Spearman coefficient, p < 0.001). The cohort was divided in quartiles based on the total LNC and a Kaplan-Meier survival analysis was performed. A continuum of improved OS was noted in correlation with increased LNC. OS was 27 months for the group with 0 nodes, 112 months for the group with 1-8 nodes, 117 months for the group with 9-16 nodes and 196 months for the group with >17 nodes. Doubling the total LNC was associated with 28% risk of death reduction (HR 0.724, CI 0.66-0.794, p < 0.001) for the first year and 14% risk reduction (HR 0.858, CI 0.761-0.967, p = 0.012) for the second year. CONCLUSIONS: In our cohort, the performance of LND is associated with improved OS. This effect appears to be uniform across pathology types. The extent of the LND is inversely correlated with the risk of death for the first 2 years.

Maternal and fetal exposure to parabens in a multiethnic urban U.S. population.

Fetal exposure to five parabens was investigated due to their endocrine-disrupting potential and possible impact on fetal development. Body burdens occurring from real-world exposures were determined typically as total concentrations after conjugate hydrolysis in 181 maternal urine and 38 umbilical cord blood plasma samples from a multiethnic cohort of 185 predominantly-black, pregnant women recruited in Brooklyn, New York between 2007/9. For 33 participants, both sample types (maternal urine and cord blood) were available. Methyl- (MePB), ethyl- (EtPB), propyl- (PrPB), butyl- (BuPB), and benzylparaben (BePB) were detected in 100, 73.5, 100, 66.3 and 0.0% of the urine samples at median concentrations of 279, 1.44, 75.3, 0.39, and <0.02µg/L, respectively. Median concentrations of MePB and PrPB were, respectively 4.4- and 8.7-fold higher compared to those reported previously for the general U.S. population (NHANES, 2005/6). Listed in the order above, the five parabens were detected in 97.4, 94.7, 47.4, 47.4, and 44.7% of cord blood plasma samples at median total concentrations of 25.0, 0.36, <0.27, <0.09, and <0.10µg/L, respectively. Free MePB, EtPB, and PrPB were detected in a subset of cord blood plasma samples at, respectively, 3.9, 71.7, and 6.4% of their total concentrations, whereas free BuPB and BePB were not detected. Literature data and those reported here show the urban community studied here to rank highest in the world for MePB and PrPB exposure in pregnant women, whereas it ranks among the lowest for EtPB and BuPB. This study is the first to report the occurrence of parabens in human umbilical cord blood. Maternal exposure to parabens is widespread, and substantial differences were found to exist between communities and countries both in the spectrum and degree of paraben exposures.

Metronomic cyclophosphamide with bevacizumab provides disease stabilization in patients with advanced uterine cancer.

•We present two cases of advanced uterine cancer that were treated with the combination of metronomic cyclophosphamide and bevacizumab.•Targeting angiogenesis can provide disease control in patients with advanced uterine cancer.•Randomized controlled trials comparing metronomic and conventional regimens in advanced uterine cancer are required.

Survival impact of cytoreduction to microscopic disease for advanced stage cancer of the uterine corpus: a retrospective cohort study.

OBJECTIVE: To assess the impact of cytoreduction to no gross residual disease (R0) on overall survival (OS) in patients with stage III-IV uterine carcinosarcoma (CS), papillary serous/clear cell (UPSC/CC) and endometrioid carcinoma (EC). METHODS: We retrospectively identified 168 patients who underwent primary surgery for advanced uterine cancer between 1984 and 2009 in two teaching hospitals in Brooklyn, New York. Histology, stage, grade, residual disease (RD), adjuvant therapy, age, race and OS were collected. OS was calculated using the Kaplan-Meier method. Predictive factors were compared using the log-rank test and Cox regression analysis. RESULTS: Our cohort included 54 patients with CS (stage III, n = 32; stage IV, n = 22), 54 patients with UPSC/CC (stage III, n = 20; stage IV, n = 34) and 60 patients with EC (stage III, n = 45; stage IV, n = 15). R0 was achieved in 64% of patients with CS, in 53% of patients with UPSC/CC and in 68% of patients with EC. There was no interaction between histologic subtype and feasibility of complete cytoreduction (p = 0.39). R0 was associated with a median OS of 25 months (95% CI [18, 33]) versus 13 months (95% CI [8, 18]) in patients with gross RD (p = 0.03). This effect was uniform among histologic subtypes. On multivariate analysis, predictors of increased mortality were gross residual disease (HR = 2.0, 95% CI [1.1, 3.7], p = 0.01), stage IV (HR = 1.8, 95% CI [1.1, 3.1], p = 0.02) and age (HR = 1.04 per year of age, 95% CI [1.02, 1.07], p = 0.002). CONCLUSION: Cytoreductive surgery to R0 is associated with improved OS in advanced uterine cancer. This effect is uniform among histologies. There is no interaction between histologic subtype and feasibility of complete cytoreduction.

Use of amniotic fluid for determining pregnancies at risk of preterm birth and for studying diseases of potential environmental etiology.

Amniotic fluid (AF) is a biological medium uniquely suited for the study of early exposure of the human fetus to environmental contaminants acquired by the mother before and during pregnancy. Traditional diagnostic applications of AF have focused almost exclusively on the diagnosis of genetic aberrations such as Trisomy-21 and on heritable diseases in high-risk pregnancies. Since more than 50 anthropogenic compounds have been detected in AF, there is considerable potential in utilizing fetal protein biomarkers as indicators of health effects related to prenatal toxic exposure. Here, we focus on preterm birth (PTB) to illustrate opportunities and limitations of using AF as a diagnostic matrix. Representing a pervasive public health challenge worldwide, PTB cannot be managed simply by improving hygiene and broadening access to healthcare. This is illustrated by 15-year increases of PTB in the U.S. from 1989 to 2004. AF is uniquely suited as a matrix for early detection of the association between fetal exposures and PTB due to its fetal origin and the fact that it is sampled from women who are at higher risk of PTB. This critical review shows the occurrence in AF of a number of xenobiotics, including endocrine-disrupting compounds (EDCs), which are known or may reasonably be expected to shorten fetal gestation. It is not yet known whether EDCs, including bisphenol A, phytoestrogens, and polychlorinated biphenyls (PCBs), can affect the expression of proteins considered viable or potential biomarkers for the onset of PTB. As such, the diagnostic value of AF is broad and has not yet been fully explored for prenatal diagnosis of pregnancies at risk from toxic, environmental exposures and for the elucidation of mechanisms underlying important public health challenges including PTB.

Maternal mercury exposure, season of conception and adverse birth outcomes in an urban immigrant community in Brooklyn, New York, U.S.A.

Adverse birth outcomes including preterm birth (PTB: <37 weeks gestation) and low birth weight (LBW: <2500 g) can result in severe infant morbidity and mortality. In the United States, there are racial and ethnic differences in the prevalence of PTB and LBW. We investigated the association between PTB and LBW with prenatal mercury (Hg) exposure and season of conception in an urban immigrant community in Brooklyn, New York. We recruited 191 pregnant women aged 18-45 in a Brooklyn Prenatal Clinic and followed them until delivery. Urine specimens were collected from the participants during the 6th to 9th month of pregnancy. Cord blood specimens and neonate anthropometric data were collected at birth. We used multivariate logistic regression models to investigate the odds of LBW or PTB with either maternal urinary mercury or neonate cord blood mercury. We used linear regression models to investigate the association between continuous anthropometric outcomes and maternal urinary mercury or neonate cord blood mercury. We also examined the association between LBW and PTB and the season that pregnancy began. Results showed higher rates of PTB and LBW in this cohort of women compared to other studies. Pregnancies beginning in winter (December, January, February) were at increased odds of LBW births compared with births from pregnancies that began in all other months (OR7.52 [95% CI 1.65, 34.29]). We observed no association between maternal exposure to Hg, and either LBW or PTB. The apparent lack of association is consistent with other studies. Further examination of seasonal association with LBW is warranted.

Human fetal exposure to triclosan and triclocarban in an urban population from Brooklyn, New York.

Triclosan (TCS) and triclocarban (TCC) are antimicrobial agents formulated in a wide variety of consumer products (including soaps, toothpaste, medical devices, plastics, and fabrics) that are regulated by the U.S. Food and Drug Administration (FDA) and U.S. Environmental Protection Agency. In late 2014, the FDA will consider regulating the use of both chemicals, which are under scrutiny regarding lack of effectiveness, potential for endocrine disruption, and potential contribution to bacterial resistance to antibiotics. Here, we report on body burdens of TCS and TCC resulting from real-world exposures during pregnancy. Using liquid chromatography tandem mass spectrometry, we determined the concentrations of TCS, TCC, and its human metabolites (2'-hydroxy-TCC and 3'-hydroxy-TCC) as well as the manufacturing byproduct (3'-chloro-TCC) as total concentrations (Σ-) after conjugate hydrolysis in maternal urine and cord blood plasma from a cohort of 181 expecting mother/infant pairs in an urban multiethnic population from Brooklyn, NY recruited in 2007-09. TCS was detected in 100% of urine and 51% of cord blood samples after conjugate hydrolysis. The interquartile range (IQR) of detected TCS concentrations in urine was highly similar to the IQR reported previously for the age-matched population of the National Health and Nutrition Examination Survey (NHANES) from 2003 to 2004, but typically higher than the IQR reported previously for the general population (detection frequency = 74.6%). Urinary levels of TCC are reported here for the first time from real-world exposures during pregnancy, showing a median concentration of 0.21 µg/L. Urinary concentrations of TCC correlated well with its phase-I metabolite ∑-2'-hydroxy-TCC (r = 0.49) and the manufacturing byproduct ∑-3'-chloro-TCC C (r = 0.79), and ∑-2'-hydroxy-TCC correlated strongly with ∑-3'-hydroxy-TCC (r = 0.99). This human biomonitoring study presents the first body burden data for TCC from exposures occurring during pregnancy and provides additional data on composite exposure to TCS (i.e., from both consumer-product use and environmental sources) in the maternal-fetal unit for an urban population in the United States.

External validation of a nomogram for predicting survival of women with uterine cancer in a cohort of African American patients.

OBJECTIVE: This study aimed to externally validate a nomogram for predicting overall survival of women with uterine cancer in an African American population. METHODS: After the institutional review board approval, data from the uterine cancer database from 2 major teaching hospitals in Brooklyn, NY, were analyzed. The predicted survival for each patient was calculated with the use of the nonogram; the data were clustered in deciles and compared with the observed survival data. RESULTS: High incidence of aggressive histologic types (22% carcinosarcoma, 16% serous/clear cell), poorly differentiated (53% grade 3), and advanced stage (38% stage III or IV) tumors was found in our study population. The median follow-up for survivors was 52 months (range, 1-274 months). The observed and predicted 3-year overall survival probabilities were significantly different (62.5% vs 72.6%, P < 0.001). Similarly, the observed 5-year overall survival probability was significantly lower than the predicted by the nomogram (55.5% vs 63.4%, P < 0.001). The discrepancy between predicted and observed survival was more pronounced in the midrisk groups. CONCLUSIONS: The nomogram is not an adequate tool to predict survival in the African American population with cancer of the uterine corpus. Race seems to be a significant, independent factor that affects survival and should be included in predictive models.

Port-site recurrence in a patient undergoing robotic hysterectomy and lymph node dissection for endometrioid adenocarcinoma of the uterus.

•We present a case of port-site recurrence of endometrioid adenocarcinoma after robotic hysterectomy and staging.•Port-site recurrence is commonly an indicator of multifocal disease with poor prognosis.•Surgical techniques that decrease the risk of this complication should be implemented.

Lapatinib and potential prognostic value of EGFR mutations in a Gynecologic Oncology Group phase II trial of persistent or recurrent endometrial cancer.

OBJECTIVE: A phase II trial was performed to evaluate the efficacy and safety of the tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR) and HER2, lapatinib, and to explore EGFR, HER2 (EGFR2), phosphorylated ERK MAP kinase (pERK), and Ki67 expression, as well as EGFR mutations in persistent/recurrent endometrial cancer (EC). METHODS: Women with histologically-confirmed, measurable, persistent/recurrent EC following one or two prior regimens were eligible and treated with 1500 mg oral lapatinib daily until progression or severe toxicity. A 2-stage group sequential design was used to evaluate the regimen with 6 month PFS as the primary endpoint. The trial had a 10% type I error rate with 90% power. EGFR, HER2, pERK, and Ki67 were evaluated by immunohistochemistry (IHC) from hysterectomy specimens, pre-treatment biopsies, and post-treatment biopsies (when available). Exons 18-21 of EGFR were sequenced. RESULTS: Three patients of 30 evaluable had PFS ≥6 months, one had a partial response, seven had stable disease, 21 had progressive disease and one was indeterminate. Three mutations in EGFR were identified. Two of these, L688F and K754E, were not associated with response or PFS. However, a newly identified mutation in exon 18, E690K, occurred in the patient with a partial response and progression-free survival extending past six months. CONCLUSION: While lapatinib has limited activity in unselected cases, the identification of a previously unreported mutation in EGFR (E690K) with a response suggests that lapatinib may be beneficial in some cases of EC.

A phase II trial of thalidomide in patients with refractory uterine carcinosarcoma and correlation with biomarkers of angiogenesis: a Gynecologic Oncology Group study.

OBJECTIVES: To evaluate the efficacy and adverse events of thalidomide in previously-treated, measurable, persistent or recurrent carcinosarcoma of the uterus, and to explore associations between angiogenic markers with patient demographics and clinical outcome. METHODS: Eligible, consenting patients were treated until disease progression or toxicity intervened with daily starting dose of 200 mg thalidomide/day that was increased by 200 mg every 2 weeks to a target dose of 1000 mg/day. Endpoints included progression-free survival (PFS)≥6 months (primary), toxicity, response, overall PFS and survival. Pre- and post-treatment plasma were evaluated for a panel of angiogenic biomarkers and assessed against clinical outcomes. RESULTS: Of 55 enrolled patients, 45 were evaluable for toxicity and survival. Two patients (4%; 90% CI 1-13%) experienced a partial response, and 8 (18%; 90% CI 9-30%) had PFS≥6 months. Median PFS was 1.9 months and median survival was 5.9 months. Grade 2-3 sensory neuropathy was noted in 6 patients, and 4, 3, and 3 patients experienced grade 3 sedation, fatigue, and constipation, respectively. Three patients had grade 4 adverse events (2 thromboembolic, 1 anemia). High pre-treatment VEGFA levels were associated with poorer PFS and survival. CONCLUSIONS: Treatment with thalidomide met the protocol specified goal of prolonging PFS at 6 months. However, based on results with newer agents, the activity was insufficient to support further investigation. Association between pre-treatment VEGFA and prognosis in this population supports further evaluation of anti-angiogenic therapies in uterine carcinosarcoma.

Hemoglobin A1c and the relationship to stage and grade of endometrial cancer.

OBJECTIVES: To determine if elevated markers of poor glycemic control (HgA1c and fasting glucose levels) in patients surgically staged for type I endometrial cancer is related to a higher stage or higher grade at the time of diagnosis. Also, to assess if these markers impact overall survival. METHODS: A retrospective chart review was performed from January 2000 to June 2010 at three academic medical centers. Patients were included if they underwent surgical staging and had HgA1c drawn within 3 months before surgery. Demographic data, fasting blood glucose levels and overall survival data were also obtained. RESULTS: Eighty-two patients fitting the inclusion criteria were identified during the study period. There was a strong positive correlation between HgA1c and fasting glucose. There was no statistical difference with regard to stage alone, grade alone, or when stratified together with regard to HgA1c or fasting glucose levels. There was a trend toward increased mean HgA1c across increasing stages, but this was not statistically significant. Diabetes, HgA1c and tumor grade did not affect overall survival, but advanced stage was a poor prognostic measure for overall survival. CONCLUSIONS: Elevated preoperative HgA1c has a trend toward a higher stage at the time of diagnosis. Advanced stage is a poor prognostic measure for overall survival.