COVID-19 outcomes of patients with gynecologic cancer in New York City: An updated analysis from the initial surge of the pandemic.

BACKGROUND: Despite significant increase in COVID-19 publications, characterization of COVID-19 infection in patients with gynecologic cancer remains limited. Here we present an update of COVID-19 outcomes among people with gynecologic cancer in New York City (NYC) during the initial surge of severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019 [COVID-19]). METHODS: Data were abstracted from gynecologic oncology patients with COVID-19 infection among 8 NYC area hospital systems between March and June 2020. Multivariable logistic regression was utilized to estimate associations between factors and COVID-19 related hospitalization and mortality. RESULTS: Of 193 patients with gynecologic cancer and COVID-19, the median age at diagnosis was 65.0 years (interquartile range (IQR), 53.0-73.0 years). One hundred six of the 193 patients (54.9%) required hospitalization; among the hospitalized patients, 13 (12.3%) required invasive mechanical ventilation, 39 (36.8%) required ICU admission. Half of the cohort (49.2%) had not received anti-cancer treatment prior to COVID-19 diagnosis. No patients requiring mechanical ventilation survived. Thirty-four of 193 (17.6%) patients died of COVID-19 complications. In multivariable analysis, hospitalization was associated with an age ≥ 65 years (odds ratio [OR] 2.12, 95% confidence interval [CI] 1.11, 4.07), Black race (OR 2.53, CI 1.24, 5.32), performance status ≥2 (OR 3.67, CI 1.25, 13.55) and ≥ 3 comorbidities (OR 2.00, CI 1.05, 3.84). Only former or current history of smoking (OR 2.75, CI 1.21, 6.22) was associated with death due to COVID-19 in multivariable analysis. Administration of cytotoxic chemotherapy within 90 days of COVID-19 diagnosis was not predictive of COVID-19 hospitalization (OR 0.83, CI 0.41, 1.68) or mortality (OR 1.56, CI 0.67, 3.53). CONCLUSIONS: The case fatality rate among patients with gynecologic malignancy with COVID-19 infection was 17.6%. Cancer-directed therapy was not associated with an increased risk of mortality related to COVID-19 infection.

Improved survival with combination chemotherapy and external beam radiation therapy in uterine carcinosarcoma.

OBJECTIVES: To evaluate differences in survival and recurrence patterns in stage I-IV uterine carcinosarcoma patients treated with surgery followed by adjuvant chemotherapy alone, radiation alone, or a combination of both chemotherapy and radiation therapy. METHODS: A multicenter retrospective analysis of patients with surgically staged carcinosarcoma receiving adjuvant therapy from January 2000 to December 2019 was conducted. Inclusion criteria were patients with carcinosarcoma who had received primary surgical treatment, followed by adjuvant therapy with chemotherapy alone, radiation therapy alone, or a combination of chemoradiation. Patients were excluded for incomplete surgical staging data, adjuvant brachytherapy alone, adjuvant chemotherapy and brachytherapy without external beam radiation therapy, receipt of neoadjuvant chemotherapy and/or pre-operative pelvic radiation, and death due to non-cancer causes. Sites of recurrence were analyzed by adjuvant treatment modality using Pearson's χ2 test. Progression-free and overall survival were calculated using Kaplan-Meier estimates. Multivariate analysis was performed using Cox proportional hazards model. RESULTS: Of 176 evaluable patients, 27% (n=47) had stage I, 14% (n=24) stage II, 37% (n=66) stage III, and 22% (n=39) stage IV disease. Among them, 33% (n=59) received chemotherapy alone, 17% (n=29) received radiation therapy alone, and 50% (n=88) received chemoradiation. Patients with stage I disease recurred less frequently (64%) versus stage II (83%), stage III (85%), and stage IV (90%) (p<0.001). Stage I disease demonstrated improved progression-free and overall survival relative to all other stages (p<0.01). Across all stages, patients receiving chemoradiation experienced superior progression-free (p=0.01) and overall survival (p=0.05) versus single modality therapy. However, when analyzed in a stage-specific manor, stage III disease derived the greatest survival benefit from chemoradiation versus all other stages (p<0.01). On multivariant analysis, only stage and receipt of chemoradiation were independent predictors of survival. CONCLUSION: Stage I disease demonstrated improved survival compared with other stages regardless of adjuvant treatment modality. Chemoradiation was associated with improved survival and better distant and local disease control for all stages of disease. Patients with stage III disease derived the most benefit from chemoradiation.

Racial disparities in patients with coronavirus disease 2019 infection and gynecologic malignancy.

BACKGROUND: Mounting evidence suggests disproportionate coronavirus disease 2019 (COVID-19) hospitalizations and deaths because of racial disparities. The association of race in a cohort of gynecologic oncology patients with severe acute respiratory syndrome-coronavirus 2 infection is unknown. METHODS: Data were abstracted from gynecologic oncology patients with COVID-19 infection among 8 New York City area hospital systems. A multivariable mixed-effects logistic regression model accounting for county clustering was used to analyze COVID-19-related hospitalization and mortality. RESULTS: Of 193 patients who had gynecologic cancer and COVID-19, 67 (34.7%) were Black, and 126 (65.3%) were non-Black. Black patients were more likely to require hospitalization compared with non-Black patients (71.6% [48 of 67] vs 46.0% [58 of 126]; P = .001). Of 34 (17.6%) patients who died from COVID-19, 14 (41.2%) were Black. Among those who were hospitalized, compared with non-Black patients, Black patients were more likely to: have ≥3 comorbidities (81.1% [30 of 37] vs 59.2% [29 of 49]; P = .05), to reside in Brooklyn (81.0% [17 of 21] vs 44.4% [12 of 27]; P = .02), to live with family (69.4% [25 of 36] vs 41.6% [37 of 89]; P = .009), and to have public insurance (79.6% [39 of 49] vs 53.4% [39 of 73]; P = .006). In multivariable analysis, among patients aged <65 years, Black patients were more likely to require hospitalization compared with non-Black patients (odds ratio, 4.87; 95% CI, 1.82-12.99; P = .002). CONCLUSIONS: Although Black patients represented only one-third of patients with gynecologic cancer, they accounted for disproportionate rates of hospitalization (>45%) and death (>40%) because of COVID-19 infection; younger Black patients had a nearly 5-fold greater risk of hospitalization. Efforts to understand and improve these disparities in COVID-19 outcomes among Black patients are critical.

Beyond Sedlis-A novel histology-specific nomogram for predicting cervical cancer recurrence risk: An NRG/GOG ancillary analysis.

PURPOSE: The Sedlis criteria define risk factors for recurrence warranting post-hysterectomy radiation for early-stage cervical cancer; however, these factors were defined for squamous cell carcinoma (SCC) at an estimated recurrence risk of ≥30%. Our study evaluates and compares risk factors for recurrence for cervical SCC compared with adenocarcinoma (AC) and develops histology-specific nomograms to estimate risk of recurrence and guide adjuvant treatment. METHODS: We performed an ancillary analysis of GOG 49, 92, and 141, and included stage I patients who were surgically managed and received no neoadjuvant/adjuvant therapy. Multivariable Cox proportional hazards models were used to evaluate independent risk factors for recurrence by histology and to generate prognostic histology-specific nomograms for 3-year recurrence risk. RESULTS: We identified 715 patients with SCC and 105 with AC; 20% with SCC and 17% with AC recurred. For SCC, lymphvascular space invasion (LVSI: HR 1.58, CI 1.12-2.22), tumor size (TS ≥4 cm: HR 2.67, CI 1.67-4.29), and depth of invasion (DOI; middle 1/3, HR 4.31, CI 1.81-10.26; deep 1/3, HR 7.05, CI 2.99-16.64) were associated with recurrence. For AC, only TS ≥4 cm, was associated with recurrence (HR 4.69, CI 1.25-17.63). For both histologies, there was an interaction effect between TS and LVSI. For those with SCC, DOI was most associated with recurrence (16% risk); for AC, TS conferred a 15% risk with negative LVSI versus a 25% risk with positive LVSI. CONCLUSIONS: Current treatment standards are based on the Sedlis criteria, specifically derived from data on SCC. However, risk factors for recurrence differ for squamous cell and adenocarcinoma of the cervix. Histology-specific nomograms accurately and linearly represent risk of recurrence for both SCC and AC tumors and may provide a more contemporary and tailored tool for clinicians to base adjuvant treatment recommendations to their patients with cervical cancer.

Prevalence of Positive Cervical Cancer Screening Tests Past the Age of 65 Years With Prior Adequate Negative Screening.

OBJECTIVES: Cervical cancer screening recommendations suggest that cessation can be offered above the age of 65 years if specific prior negative screening criteria are met. We investigated the prevalence of abnormal results in individuals who continue screening despite satisfying the American Society for Colposcopy and Cervical Pathology guidelines for cessation. MATERIALS AND METHODS: In this retrospective study, medical records 2008-2019 from a single urban hospital-based clinic were queried. Charts were manually reviewed to determine which patients met the American Society for Colposcopy and Cervical Pathology exit criteria but continued screening. Findings detected during the extended surveillance period beyond the age of 65 years were analyzed. RESULTS: Two hundred ninety-six patients met the criteria of additional screening despite meeting guidelines for cessation. Length of the continued additional surveillance period ranged from 1 to 15 years with a mean of 3.98 years and median of 3 years. Thirty-nine individuals had abnormalities during additional surveillance: 25 high-risk human papillomavirus (HR-HPV) positive only with negative cytology, 8 atypical squamous cells of undetermined significance, 3 low-grade squamous intraepithelial lesions, 2 atypical glandular cells of undetermined significance, and 1 high-grade squamous intraepithelial lesion. No cases of cervical cancer were detected. Total rate of abnormalities including HR-HPV positive only was 332.20 per 10,000 person-years, and cytologic abnormalities alone at 119.25 per 10,000 person-years. CONCLUSIONS: Most findings were HR-HPV positive with negative cytology, which studies suggest may confer low risk of progression in older individuals. In addition, no patient was found to develop cervical malignancy. Despite controversy regarding this recommendation, our data suggest screening cessation may be appropriate with adequate negative screening history.

COVID-19 outcomes of patients with gynecologic cancer in New York City.

BACKGROUND: New York City (NYC) is the epicenter of severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019 [COVID-19]) in the United States. Clinical characteristics and outcomes of vulnerable populations, such as those with gynecologic cancer who develop COVID-19 infections, is limited. METHODS: Patients from 6 NYC-area hospital systems with known gynecologic cancer and a COVID-19 diagnosis were identified. Demographic and clinical outcome data were abstracted through a review of electronic medical records. RESULTS: Records for 121 patients with gynecologic cancer and COVID-19 were abstracted; the median age at the COVID-19 diagnosis was 64.0 years (interquartile range, 51.0-73.0 years). Sixty-six of the 121 patients (54.5%) required hospitalization; among the hospitalized patients, 45 (68.2%) required respiratory intervention, 20 (30.3%) were admitted to the intensive care unit, and 9 (13.6%) underwent invasive mechanical ventilation. Seventeen patients (14.0%) died of COVID-19 complications. No patient requiring mechanical ventilation survived. On multivariable analysis, hospitalization was associated with an age ≥64 years (risk ratio [RR], 1.73; 95% confidence interval [CI], 1.18-2.51), African American race (RR, 1.56; 95% CI, 1.13-2.15), and 3 or more comorbidities (RR, 1.43; 95% CI, 1.03-1.98). Only recent immunotherapy use (RR, 3.49; 95% CI, 1.08-11.27) was associated with death due to COVID-19 on multivariable analysis; chemotherapy treatment and recent major surgery were not predictive of COVID-19 severity or mortality. CONCLUSIONS: The case fatality rate among gynecologic oncology patients with a COVID-19 infection is 14.0%. Recent immunotherapy use is associated with an increased risk of mortality related to COVID-19 infection. LAY SUMMARY: The case fatality rate among gynecologic oncology patients with a coronavirus disease 2019 (COVID-19) infection is 14.0%; there is no association between cytotoxic chemotherapy and cancer-directed surgery and COVID-19 severity or death. As such, patients can be counseled regarding the safety of continued anticancer treatments during the pandemic. This is important because the ability to continue cancer therapies for cancer control and cure is critical.

Inflammatory markers in gynecologic oncology patients hospitalized with COVID-19 infection.

OBJECTIVE: Elevated inflammatory markers are predictive of COVID-19 infection severity and mortality. It is unclear if these markers are associated with severe infection in patients with cancer due to underlying tumor related inflammation. We sought to further understand the inflammatory response related to COVID-19 infection in patients with gynecologic cancer. METHODS: Patients with a history of gynecologic cancer hospitalized for COVID-19 infection with available laboratory data were identified. Admission laboratory values and clinical outcomes were abstracted from electronic medical records. Severe infection was defined as infection requiring ICU admission, mechanical ventilation, or resulting in death. RESULTS: 86 patients with gynecologic cancer were hospitalized with COVID-19 infection with a median age of 68.5 years (interquartile range (IQR), 59.0-74.8). Of the 86 patients, 29 (33.7%) patients required ICU admission and 25 (29.1%) patients died of COVID-19 complications. Fifty (58.1%) patients had active cancer and 36 (41.9%) were in remission. Patients with severe infection had significantly higher ferritin (median 1163.0 vs 624.0 ng/mL, p < 0.01), procalcitonin (median 0.8 vs 0.2 ng/mL, p < 0.01), and C-reactive protein (median 142.0 vs 62.3 mg/L, p = 0.02) levels compared to those with moderate infection. White blood cell count, lactate, and creatinine were also associated with severe infection. D-dimer levels were not significantly associated with severe infection (p = 0.20). CONCLUSIONS: The inflammatory markers ferritin, procalcitonin, and CRP were associated with COVID-19 severity in gynecologic cancer patients and may be used as prognostic markers at the time of admission.

Multimodality adjuvant therapy and survival outcomes in stage I-IV uterine carcinosarcoma.

OBJECTIVES: Uterine carcinosarcoma is a rare, aggressive form of uterine cancer with a high recurrence rate and poor survival at all stages. We sought to evaluate the outcomes of patients treated with chemotherapy versus a combination of chemotherapy and radiation (chemoradiation) to determine survival. METHODS: A multicenter retrospective analysis of patients with stage I-IV carcinosarcoma was conducted from January 2000 to December 2017. Inclusion criteria were primary surgical management, defined as hysterectomy ± salpingo-oophorectomy, comprehensive surgical staging and/or tumor debulking, followed by adjuvant chemotherapy or chemoradiation. Differences in the frequencies of stage, cytoreduction status, treatment delays and sites of disease recurrence were identified using Pearson's χ2 test. Progression-free and overall survival rates were calculated using Kaplan-Meier estimates. RESULTS: Final analysis included 148 patients; 40.5% (n=60) chemotherapy and 59.5% (n=88) chemoradiation. The mean age was 67 years (range 39-89). Stage distribution included 24.3% stage I, 12.2% stage II, 37.2% stage III, and 26.3% stage IV. There was no difference in the frequency of stage (p=0.81), cytoreduction status (p=0.61), treatment delays (p=0.57), or location of recurrence (p=0.97) between cohorts. The most frequent location of recurrence was the abdomen (50.0%). The median progression-free survival favored chemoradiation over chemotherapy (15 vs 11 months, respectively), as did the median overall survival (26 vs 20 months, respectively). Chemoradiation was associated with a statistically significant improvement in 2 year progression-free survival (22.5% vs 13.6%; p=0.006) and 2 year overall survival (50.0% vs 35.6%; p=0.018) compared with chemotherapy alone. On subanalysis of patients receiving chemoradiation, 'sandwich sequencing' (chemotherapy-radiation-chemotherapy) was associated with superior overall survival compared with alternate therapy sequences (chemotherapy-radiation and radiation-chemotherapy) (34 months vs 14 months and 14 months, respectively) (p=0.038). CONCLUSIONS: Chemoradiation was associated with improvement in both progression-free and overall survival for all stages of carcinosarcoma compared with chemotherapy alone.

Arginine Vasopressin Modulates Ion and Acid/Base Balance by Regulating Cell Numbers of Sodium Chloride Cotransporter and H+-ATPase Rich Ionocytes.

Arginine vasopressin (Avp) is a conserved pleiotropic hormone that is known to regulate both water reabsorption and ion balance; however, many of the mechanisms underlying its effects remain unclear. Here, we used zebrafish embryos to investigate how Avp modulates ion and acid-base homeostasis. After incubating embryos in double-deionized water for 24 h, avp mRNA expression levels were significantly upregulated. Knockdown of Avp protein expression by an antisense morpholino oligonucleotide (MO) reduced the expression of ionocyte-related genes and downregulated whole-body Cl- content and H+ secretion, while Na+ and Ca2+ levels were not affected. Incubation of Avp antagonist SR49059 also downregulated the mRNA expression of sodium chloride cotransporter 2b (ncc2b), which is a transporter responsible for Cl- uptake. Correspondingly, avp morphants showed lower NCC and H+-ATPase rich (HR) cell numbers, but Na+/K+-ATPase rich (NaR) cell numbers remained unchanged. avp MO also downregulated the numbers of foxi3a- and p63-expressing cells. Finally, the mRNA expression levels of calcitonin gene-related peptide (cgrp) and its receptor, calcitonin receptor-like 1 (crlr1), were downregulated in avp morphants, suggesting that Avp might affect Cgrp and Crlr1 for modulating Cl- balance. Together, our results reveal a molecular/cellular pathway through which Avp regulates ion and acid-base balance, providing new insights into its function.

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.

Clinicopathologic features, incidence, and survival trends of gynecologic neuroendocrine tumors: a SEER database analysis.

BACKGROUND: Primary gynecologic neuroendocrine tumors are uncommon malignant neoplasms associated with poor prognosis. Clinically, these tumors present a significant challenge because of the lack of standardized management guidelines. OBJECTIVE: The objective of this study is to evaluate the clinicopathologic features, incidence, and survival trends in gynecologic neuroendocrine tumors. MATERIALS AND METHODS: The Surveillance, Epidemiology and End Results (SEER) cancer registry was queried for women diagnosed with primary gynecologic neuroendocrine tumors from 1987 to 2012. Data regarding stage, grade, presence of extrauterine disease, receipt of adjuvant radiation, surgical intervention, incidence, and overall survival were extracted. Patients were classified as having early-stage disease (International Federation of Gynecology and Obstetrics Stage I/II) or advanced-stage disease (Stage III/IV). Extrauterine disease was defined as either regional or distant metastasis. χ2 Tests, Pearson correlation, and Kaplan-Meier curves were used for statistical analysis. RESULTS: In all, 559 cases of gynecologic neuroendocrine tumors were identified during the study period: 242 cervical, 160 ovarian, 118 uterine, and 39 vulvar/vaginal. The majority of patients in all subsets of gynecologic neuroendocrine tumors presented with poorly differentiated tumors, extrauterine disease spread, and advanced-stage disease. Poorly differentiated tumors represented 65.0% of cervical tumors, 45.3% of ovarian tumors, and 57.4% of uterine tumors. Extrauterine disease at the time of diagnosis was present in the case of 66.9% of cervical tumors, 83.5% of ovarian tumors, and 83.6% of uterine tumors. The overall incidence of gynecologic neuroendocrine tumors increased 4-fold during the study period, from 0.3 in 1987 to 1.30 per million in 2012. The study period was divided into two 13-year periods (1987-1999 and 2000-2012) for time trend mean survival analysis. We observed no significant change in overall survival across all gynecologic neuroendocrine tumor subtypes. The mean survival time of cervical neuroendocrine tumors was 74.3 vs 45.4 months (P = .31), ovarian neuroendocrine tumors 47.8 vs 41.2 months (P = .56), and uterine neuroendocrine tumors 42.9 vs 47.7 months (P = .44) for each time period, respectively. CONCLUSION: Neuroendocrine tumors of the gynecologic tract are uncommon aggressive malignancies. These poorly differentiated tumors present at advanced stage, with a high incidence of extrauterine disease. Despite 25 years of advances in cancer therapy, we observed no improvement in overall survival.

Patterns of care of IMRT usage in postoperative management of uterine cancer.

OBJECTIVE: To analyze the patterns of care regarding intensity modulated radiation therapy (IMRT) usage in the postoperative management of uterine cancer. METHODS: The National Cancer Database was queried to identify women with endometrial adenocarcinoma who underwent hysterectomy followed by external beam radiation between 2004-2012. Descriptive statistics were used to analyze IMRT usage with comparison via the Chi Square test. Overall survival was also compared between IMRT and three dimensional conformal radiation therapy. Multivariable logistic regression and multivariable Cox Regression were used to identify covariables that impact IMRT usage and improved survival respectively. RESULTS: 7839 women were included in this study. IMRT utilization increased from 1.9% in 2004 to 32.4% in 2012 (p<0.001). The adjusted odds ratio (OR) for IMRT in 2012 compared with 2004 was 24.90, 95% CI 15.24-40.67 (p<0.001). Aside from year, other predictors of IMRT usage on multivariate analysis were positive nodes, higher dose, private insurance and higher income. Black race was associated with lower IMRT usage compared to Whites with an OR of 0.60, 95% CI 0.44-0.81 (p=0.001). IMRT was not associated with significantly increased survival (HR 0.86, 95% CI 0.73-1.01, p=0.06). Black race and positive nodes were associated with decreased survival within the group studied whereas private insurance and higher income were associated with improved survival. CONCLUSIONS: In this hospital-based registry, IMRT has significantly increased in utilization for postoperative radiation in uterine cancer between 2004-2012 although not resulting in significantly improved survival. Socioeconomic and racial disparities exist in the allocation of IMRT usage.

Use of Adjuvant Chemotherapy, Radiation Therapy, or Combined Modality Therapy and the Impact on Survival for Uterine Carcinosarcoma Limited to the Pelvis.

OBJECTIVE: Clinical outcomes for patients with uterine carcinosarcoma are poor after surgical management alone. Adjuvant therapies including chemotherapy (CT) and/or radiation therapy (RT) have been previously investigated, but the optimal management of this disease remains controversial. The purposes of this study were to analyze the patterns of use of adjuvant CT and RT and to assess the impact on survival of each of these treatment regimens using the National Cancer Data Base. METHODS/MATERIALS: The National Cancer Data Base was queried for patients given a diagnosis of uterine carcinosarcoma confined to the pelvis who underwent total hysterectomy/bilateral salpingo-oophorectomy between 2004 and 2011. Patients were excluded if they survived less than 4 months after diagnosis. Data regarding CT and RT use were collected. Overall survival (OS) was analyzed using the Kaplan-Meier method. Multivariable Cox regression analysis was performed to evaluate the effect of covariates on OS. RESULTS: A total of 4906 patients were included in this study. Median age was 67 years (interquartile range, 60-75 years). Median follow-up was 28.9 months (interquartile range, 15.4-52.9 months). There were 1777 patients (36.2%) who received no adjuvant treatment, 971 (19.8%) who received CT alone, 1060 (21.6%) who received RT alone, and 1098 (22.4%) who received both RT and CT. The 5-year OS for patients receiving no adjuvant therapy, adjuvant RT alone, adjuvant CT alone, and combined CT and RT were 44.9%, 47.1%, 47.5%, and 62.9%, respectively. On pairwise analysis, combined CT and RT was associated with improved survival compared with all other subgroups (P < 0.001). On multivariable Cox regression analysis, combined CT and RT (hazard ratio, 0.50; 95% confidence interval, 0.44-0.57; P < 0.001) and CT alone (hazard ratio, 0.78; 95% confidence interval, 0.69-0.88; P < 0.001) were significantly associated with improved OS, whereas RT alone was not. CONCLUSIONS: Combination therapy with CT and RT was associated with significantly improved 5-year OS compared with no further therapy, RT alone, or CT alone.

A Comparison of Outcomes Between Open Hysterectomy and Robotic-Assisted Hysterectomy for Endometrial Cancer Using the National Cancer Database.

PURPOSE: The purpose of this study is to evaluate usage patterns and outcomes of women who underwent open hysterectomy (OH) versus robotic assisted-hysterectomy (RAH) for the treatment of endometrial cancer. METHODS: Women with nonmetastatic endometrial adenocarcinoma diagnosed between 2010 and 2012, who either underwent an OH or RAH, were selected from the National Cancer Database. The χ, Fisher exact, or Mann-Whitney U tests were used where appropriate to compare outcomes between groups. Multivariable logistic regression was used to analyze for predictors for RAH and other outcome variables. RESULTS: A total of 43,985 women were included in this study with a median age of 61 years. Of these, 23,872 (54.3%) underwent RAH and 20,113 (45.7%) underwent OH. The usage of RAH increased from 43.0% in 2010 to 63.8% in 2012 (P < 0.001). Women receiving RAH were more commonly found to have a Charlson comorbidity score of 0 to 1, lower pathologic stage, nonblack race, treatment at a comprehensive center, and had insurance other than Medicaid. Robotic-assisted hysterectomy was associated with a shorter inpatient stay, lower readmission rates, and lower 30- and 90-day mortality rates (P < 0.001 for all comparisons). There was a significant improvement in overall survival favoring RAH, 96.1% versus 94.0%, which persisted on multivariable logistic regression (P < 0.001). CONCLUSIONS: In this large, hospital-based analysis, RAH was associated with decreased length of stay, lower readmission rates, and less perioperative mortality. However, socioeconomic status continues to remain a barrier to equal treatment allocation. Overall survival was improved with RAH, but the follow-up is limited, and this finding must be interpreted with caution.

A novel function of calcitonin gene-related peptide in body fluid Cl- homeostasis.

Vertebrates need to maintain extracellular chloride (Cl(-)) concentrations to ensure the normal operation of physiological processes; the transition from aquatic to terrestrial environments necessitated the development of sophisticated mechanisms to ensure Cl(-) homeostasis in the face of fluctuating Cl(-) levels. Zebrafish calcitonin gene-related peptide (CGRP), unlike its splice variant calcitonin, does not respond to environmental Ca(2+) levels. This study aimed to test the hypothesis that CGRP is involved in the control of body fluid Cl(-) homeostasis. Acclimation to high-Cl(-) artificial water stimulated the mRNA expression of cgrp and the receptor (crlr1) when compared with low-Cl(-) CGRP knockdown induced upregulation of the Na(+)-Cl(-) co-transporter (ncc2b), while overexpression of CGRP resulted in the downregulation of ncc2b mRNA synthesis and a simultaneous decrease in Cl(-) uptake in embryos. Consistent with these findings, knockdown of either cgrp or crlr1 was found to increase the density of NCC2b-expressing cells in embryos. This is the first demonstration that CGRP acts as a hypochloremic hormone through suppressing NCC2b expression and the differentiation of NCC-expressing ionocytes. Elucidation of this novel function of CGRP in fish body fluid Cl(-) homeostasis promises to enhance our understanding of the related physiology in vertebrates.

Utilization of adjuvant therapies and their impact on survival for women with stage IIIC endometrial adenocarcinoma.

PURPOSE/OBJECTIVES: Adjuvant treatment options following surgical staging for women with stage IIIC endometrial carcinoma include chemotherapy (CT) with or without radiation therapy (RT). We utilized the National Cancer Database (NCDB) to investigate utilization of adjuvant CT and RT for this group of patients and assess their impact on overall survival (OS). MATERIALS/METHODS: The NCDB was queried for patients diagnosed with non-metastatic surgically staged uterine adenocarcinoma between 2004 and 2011 with at least one pathologically positive lymph node. Overall survival (OS) was analyzed using the Kaplan-Meier method. Comparison was made between patients receiving no additional therapy, RT alone, CT alone, or a combination of CT and RT (CMT). Multivariable cox regression analysis (MVA) was performed to evaluate the effect of covariates on OS. RESULTS: A total of 6720 patients were included in this study. Of whom, 1409 received no adjuvant treatment, 1533 received CT only, 1265 received RT only, and 2522 received CMT. The 5-year OS for patients receiving no adjuvant therapy, RT alone, CT alone, and CMT were 54.9%, 63.9%, 64.4%, and 72.6%, respectively. On pairwise analysis, CMT was associated with improved survival compared to all other subgroups (p<0.001). On MVA, CMT (HR 0.58, 95% CI 0.52-0.66, p<0.001) was the strongest predictor for improved OS compared to RT alone (HR 0.79, 95% CI 0.69-0.89, p<0.001) or CT alone (HR 0.75, 95% CI 0.66-0.85, p<0.001). CONCLUSIONS: Both adjuvant CT and adjuvant RT were associated with improved OS for women with stage IIIC endometrial adenocarcinoma, but CMT was associated with the largest improvement in OS.

Is age a prognostic biomarker for survival among women with locally advanced cervical cancer treated with chemoradiation? An NRG Oncology/Gynecologic Oncology Group ancillary data analysis.

OBJECTIVE: To determine the effect of age on completion of and toxicities following treatment of local regionally advanced cervical cancer (LACC) on Gynecologic Oncology Group (GOG) Phase I-III trials. METHODS: An ancillary data analysis of GOG protocols 113, 120, 165, 219 data was performed. Wilcoxon, Pearson, and Kruskal-Wallis tests were used for univariate and multivariate analysis. Log rank tests were used to compare survival lengths. RESULTS: One-thousand-three-hundred-nineteen women were included; 60.7% were Caucasian, 15% were age 60-70years and an additional 5% were >70; 87% had squamous histology, 55% had stage IIB disease and 34% had IIIB disease. Performance status declined with age (p=0.006). Histology and tumor stage did not significantly differ. Number of cycles of chemotherapy received, radiation treatment time, nor dose modifications varied with age. Notably, radiation protocol deviations and failure to complete brachytherapy (BT) did increase with age (p=0.022 and p<0.001 respectively). Only all grade lymphatic (p=0.006) and grade≥3 cardiovascular toxicities (p=0.019) were found to vary with age. A 2% increase in the risk of death for every year increase >50 for all-cause mortality (HR 1.02; 95% CI, 1.01-1.04) was found, but no association between age and disease specific mortality was found. CONCLUSION: This represents a large analysis of patients treated for LACC with chemo/radiation, approximately 20% of whom were >60years of age. Older patients, had higher rates of incomplete brachytherapy which is not explained by collected toxicity data. Age did not adversely impact completion of chemotherapy and radiation or toxicities.

Glassy cell carcinoma of the cervix: a systematic review and meta-analysis.

OBJECTIVE: The purpose of this study is to summarize the data on the incidence, clinical behavior and overall survival of patients with glassy cell cervical carcinoma (GCCC). METHODS: Twenty-four case series and fifteen case reports identified by searching PubMed database qualified for inclusion in this study. The published cases were combined with data from a retrospective chart review of patients with GCCC in two major teaching hospitals in Brooklyn, NY. RESULTS: A total of 292 cases were collected through our literature and chart review. Median age at diagnosis was 45 years old (range 12-87 years of age). GCCC incidence ranges from 0.2 to 9.3% of all cervical cancers and 2 to 30.2% of cervical adenocarcinomas. The stage distribution is similar to squamous cell carcinoma with 79% of the patients being diagnosed with Stage I or II disease. Most common sites of recurrence for Stage I patients are the vagina and pelvis. In Stage II patients locoregional and distant metastases are equally common. Recurrence rate was higher among patients treated only with surgery (32.7%), as compared to patients treated with surgery followed by radiation (11%) or patients treated with radiation only (10%). Median overall survival (OS) was 25 months (95% CI 8.4-41.6). Overall 5-year survival for all stages is lower when compared to all cervical cancers (54.8% vs 75%). There was no interaction between race and OS (p=0.66). CONCLUSION: GCCC is a rare histologic type of cervical cancer that presents at a younger age, is associated with high risk for distant failure and carries worse prognosis as compared to the squamous cell type. Radiation therapy is associated with decreased risk of recurrence.