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ObjectivesTo 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.MethodsA 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 χ2test. Progression-free and overall survival were calculated using Kaplan-Meier estimates. Multivariate analysis was performed using Cox proportional hazards model.ResultsOf 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%) (pConclusionStage 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.

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.

Timely adjustment of osmoregulation upon acute salinity stress is essential for the survival of euryhaline fish. This rapid response is thought to be tightly controlled by hormones; however, there are still questions unanswered. In this work, we tested the hypothesis that the endocrine hormone, insulin-like growth factor 1 (Igf1), a slow-acting hormone, is involved in the activation of salt secretion mechanisms in euryhaline medaka (Oryzias melastigma) during acclimation to acute salinity stress. In response to a 30-ppt seawater (SW) challenge, Na+/Cl− secretion was enhanced within 0.5 h, with concomitant organization of ionocyte multicellular complexes and without changes in expression of major transporters. Igf1 receptor inhibitors significantly impair the Na+/Cl− secretion and ionocyte multicellular complex responses without affecting transporter expression. Thus, Igf1 may activate salt secretion as part of the teleost response to acute salinity stress by exerting effects on transporter function and enhancing the formation of ionocyte multicellular complexes. These findings provide new insights into hormonal control of body fluid ionic/osmotic homeostasis during vertebrate evolution.

Highlights • Approximately one-fifth of uterine serous carcinomas (USC) will express WT-1. • WT-1 expression is associated with a significant improvement in platinum sensitivity. • Improved platinum sensitivity among WT-1 positive tumors contributes to a superior PFS vs. WT-1 negative tumors., Background Wilms tumor gene 1 (WT1) expression is a hallmark of ovarian serous carcinoma and considered to be diagnostic marker of these tumors, differentiating them from uterine serous carcinoma (USC), historically thought to rarely express WT1. However, more recent data indicates a significant percentage of USC may express WT1. The clinical implications of WT1 positivity in USC remain unclear. Methods A multicenter retrospective analysis of patients with USC was conducted from 2000 to 2019. Inclusion criteria were patients who had undergone comprehensive surgical staging/tumor debulking with archival tissue available for WT1 assessment via immunohistochemistry (IHC). Chemosensitive patients were defined as those recurring >6 months from last platinum-based chemotherapy. Progression free survival (PFS) and overall survival (OS) analysis was performed using Kaplan-Meier estimates. Multivariate analysis (MVA) was performed using Cox proportional hazards model. Results WT1 status was evaluated in 61 patients with USC. 13 (21.3%) were positive for WT1 by IHC. Stage distribution included 32% stage I, 5% stage II, 25% stage III and 38% stage IV. There was no difference in the stage (p = 0.158), race (p = 0.227) or distribution of recurrence sites (p = 0.581) between WT1 positive and WT1 negative tumors. The majority of patients were chemosensitive (63%). Chemosensitivity was significantly improved in WT1 positive (92.3%) vs. WT1 negative tumors (55.8%) (p = 0.016). We observed a trend towards improved PFS among WT1 positive tumors (21 vs. 16-months, respectively) (p = 0.544). On MVA, stage (p

HIGHLIGHTS Evidence suggests that patients with microsatellite instability (MSI)-high endometrial carcinoma derive greater benefit from radiation therapy than their microsatellite-stable counterparts. We sought to evaluate the outcomes of patients with MSI-high advanced endometrial cancer

Let G = (V, E) be a connected graph with |V|= n and |E|= m. A bijection f : E → {1, 2, … , m} is called a local antimagic lableing if for any two adjacent vertices u and v, w(u) ≠ w(v), where w(u)=...

Objectives: The cornerstone of the management of cervical cancer (CC) traditionally relies on clinical examination (CE) of tumor size (TS) and local extension of disease. The goal of this study is to determine the accuracy of CE in comparison to final pathology (FP) in early operable CC. Methods: This is a multi-center retrospective review of patients with early CC (FIGO 2009 Stage IB1, IIA1). CE of TS, parametrial invasion (PI), and vaginal involvement (VI) were compared to FP. Results: The final analysis included 135 patients. Overall, there was a significant difference between CE of TS compared to FP; mean error of 1.22 cm (p

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.

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.

Pericardial disease is a common manifestation of malignancy. Gynecologic malignancies such as ovarian cancer rarely present with cardiac involvement. Cardiac tamponade may be the initial presentation of malignancy in as many as half of pericardial disease cases. We report the case of a 60-year-old female with known ovarian adenocarcinoma, who achieved initial success with tumor debulking and adjuvant chemotherapy but was lost to follow-up. She presented again three years later with new-onset dyspnea and described a syncopal episode. A chest radiograph showed an enlarged cardiac silhouette and bilateral pleural effusions. Transthoracic echocardiography revealed a large pericardial effusion with diastolic collapse of the right atrium and ventricle, consistent with tamponade physiology. Subxiphoid pericardiocentesis and pigtail drain were placed under fluoroscopy with resolution of symptoms and no recurrence. Neoplastic etiology was confirmed by immunocytochemistry on cell block positive for PAX-8. As an adjunct or alternative to cytologic evaluation, diffusion-weighted magnetic resonance imaging and calculation of the apparent diffusion coefficient can be used to differentiate between malignant and benign effusions. Malignant pericardial effusion in ovarian cancer is a treatable oncologic emergency where timely diagnosis and management may facilitate palliation and prolong life.

Background: We seek to evaluate the difference in recurrence patterns and survival among stage IIIC high-grade endometrial cancer treated with surgery followed by adjuvant chemotherapy alone, radiation therapy alone, or both (chemoradiation). Methods: A multicenter retrospective analysis of surgically staged IIIC HGEC receiving adjuvant therapy was conducted. HGEC was defined as grade 3 endometrioid adenocarcinoma, serous, clear cell and carcinosarcoma. Differences in the frequency of recurrence sites and treatment delays were identified using Pearson’s χ2 test. Progression-free survival (PFS) and overall survival (OS) were calculated using Kaplan–Meier estimates. Results: A total of 155 patients were evaluable: 41.9% carcinosarcoma, 36.8% serous, 17.4% grade 3 and 3.9% clear cell. Of these, 67.1% received chemoradiation, 25.8% received chemotherapy and 7.1% received radiation therapy. There was no difference in the frequency of treatment delays between regimens (p = 0.571). There was a trend towards greater retroperitoneal recurrence with chemotherapy (25.9%) versus chemoradiation (8.4%) and radiation therapy (7.7%) (p = 0.252). Grade 3 tumors had improved progression-free and overall survival (26 and 42 months, respectively) versus serous (17 and 30 months, respectively), carcinosarcoma (14 and 24 months, respectively) and clear cell (24 and 30 months respectively) (p = 0.002, p &lt, 0.001). Overall, chemoradiation was superior to chemotherapy and radiation therapy in PFS (p &lt, 0.001) and OS (p &lt, 0.001). Upon multivariate analysis, only histology and receipt of chemoradiation were independent predictors of survival. Conclusion: The majority of stage IIIC high-grade endometrial carcinomas recurred. Chemoradiation was associated with improved survival and less retroperitoneal recurrence. Grade 3 tumors demonstrated improved survival versus other histologies regardless of adjuvant treatment modality.

We studied the incidence of HPV genotypes in mostly Black women with cervical carcinoma and correlated histopathologic tumor characteristics, immune markers and clinical data with survival. Disease-free survival (DFS) and overall survival (OS) were recorded for 60 months post-diagnosis. Fifty four of the 60 (90%) patients were Black and 36 (60%) were 2 types) were found in 11/40 (27.5%) patients. Patients infected with non-16/18 genotypes, including the most common genotype, HPV 35, had significantly shorter DFS and OS. PD-L1 (p=0.003), MMR expression (p=0.01), clinical stage (p=0.048), histologic grade (p=0.015) and mixed HPV infection (p=0.026) were independent predictors of DFS. A remarkably high proportion of cervical cancer cells in our patients expressed PD-L1 which opens the possibility of the use of immune checkpoint inhibitors to treat these cancers. Exclusion of the common HPV genotypes from the vaccine exacerbates mortality from cervical cancer in underserved Black patients.

We studied the incidence of HPV genotypes in mostly Black women with cervical carcinoma and correlated histopathologic tumor characteristics, immune markers and clinical data with survival. Disease-free survival (DFS) and overall survival (OS) were recorded for 60 months post-diagnosis. Fifty four of the 60 (90%) patients were Black and 36 (60%) were

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.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.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 aged65 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).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.

Objectives: Uterine serous (USC) and clear cell carcinoma (CC) are aggressive variants of endometrial cancer (EC), comprising only 20% of all cases, but accounting for a disproportionately high number of EC related deaths. The molecular profile of USC and CC is distinct from that of other EC, displaying alternations in TP53 and HER2/neu. Human epidermal growth factor receptor 2/neu (HER2) is a key player in singling for cancer cell growth, survival and proliferation. Recent data demonstrates a survival benefit with the use of trastuzumab, a monoclonal antibody against HER2, in combination with chemotherapy for HER2 expressing USC. However, the clinical implications of HER2 status on prognosis remain unclear. Methods: A multicenter retrospective analysis of patients with USC and CC was conducted from 2000 - 2019. Inclusion criteria were patients who had undergone comprehensive surgical staging/tumor debulking with archival tissue available for HER2 assessment via immunohistochemistry (IHC). HER2 positive was defined as IHC score of 3+. Platinum sensitivity was defined as recurrence >6 months from last platinum-based therapy. Differences in the frequencies of stage, race, chemosensitivity and sites of disease recurrence were identified using Pearson's chi-square test. Progression free survival (PFS) and overall survival (OS) analysis was performed using Kaplan-Meier estimates. Multivariate analysis (MVA) was performed using Cox proportional hazards model. Results: HER2 status was evaluated in 56 patients. Histology included 44 (79%) USC, 9 (16%) CC and 3 (6%) mixed serous-clear cell. 11 (19.6%) were positive for HER2; 18.2% USC, 22.2% CC and 33.3% mixed histology. Of these 56 patients, 50 had follow-up information available for review and were included in final analysis. The mean age was 67-years and the majority of patients were African American (88%). Stage distribution included 38% stage I, 8% stage II, 18% stage III and 36% stage IV. 29 (58%) patients recurred during the study period, 7 (70%) of the HER2 positive and 22 (55%) of the HER2 negative cohort (p=0.390). The most common location of recurrence was the abdomen followed by the pelvis and extra-abdominopelvic sites. There was no difference in the stage (p=0.471), race (p=0.323) or distribution of recurrence sites (p=0.813) between HER2 positive and negative tumors. Platinum sensitivity was significantly improved in HER negative (65%) vs. HER2 positive tumors (30%) (p=0.044). For the entire cohort, the median PFS was 21 months and the median OS was 29 months. The median PFS and OS did not differ significantly based on HER2 status (p=0.229 and p=0.255, respectively). However, there was a clinically relevant trend towards improved PFS (26 vs. 7 months) and OS (35 vs. 14 months) in HER2 negative vs. positive tumors. On MVA, platinum sensitivity (p Download : Download high-res image (140KB) Download : Download full-size image Conclusions: In addition to being a tool to guide targeted therapy, HER2 is a valuable prognostic marker in USC and CC. Expression is associated with significantly lower platinum sensitivity and inferior survival compared to tumors not expressing HER2.

Objectives: Wilms tumor gene 1 (WT1) expression is a hallmark of ovarian serous carcinoma (OSC) and considered to be diagnostic marker of these tumors, differentiating them from uterine serous carcinoma (USC), traditionally thought to rarely express WT1. However, recent data indicates a significant percentage of USC may express WT1, limiting its use as a differentiating marker between these two tumors. Additionally, the clinical implications of WT1 positivity in USC remain unclear. Methods: A multicenter retrospective analysis of patients with USC was conducted from 2000 - 2019. Inclusion criteria were patients who had undergone comprehensive surgical staging/tumor debulking with archival tissue available for WT1 assessment via immunohistochemistry (IHC). Platinum-sensitive patients were defined as those recurring >6 months from last platinum-based chemotherapy. Differences in the frequencies of stage, race, chemosensitivity and sites of disease recurrence were identified using Pearson's chi-square test. Progression free survival (PFS) and overall survival (OS) analysis was performed using Kaplan-Meier estimates. Multivariate analysis (MVA) was performed using Cox proportional hazards model. Results: WT1 status was evaluated in 61 patients with USC. 13 (21.3%) were positive for WT1 by IHC. Of these 61 patients, 56 had follow-up information available for review and were included in final analysis. The mean age was 67-years and the majority of patients were African American (97%). Stage distribution included 32% stage I, 5% stage II, 25% stage III and 38% stage IV. The majority of patients were designated as platinum-sensitive (63%). 36 (64%) patients recurred during the study period, 8 (62%) of the WT1 positive and 28 (65%) of the WT1 negative cohort. The most common location of recurrence was the abdomen followed by the pelvis and extra-abdominopelvic sites. There was no difference in the stage (p=0.158), race (p=0.227) or distribution of recurrence sites (p=0.581) between WT1 positive and WT1 negative tumors. Platinum-sensitivity was significantly improved in WT1 positive (92.3%) vs. WT1 negative tumors (55.8%) (p=0.016). For the entire cohort, the median PFS was 20 months and the median OS was 29 months. The median PFS and OS did not differ significantly based on WT1 status (p=0.544 and p=0.759, respectively). However, we did observe a trend towards improved PFS among WT1 positive tumors (21 vs. 16 months, respectively). On MVA, stage (p Download : Download high-res image (147KB) Download : Download full-size image Conclusions: WT1 positivity is observed in over 20% of USC, limiting its utility to differentiating OSC and USC. Additionally, WT1 status holds prognostic significance as expression was associated with improved platinum-sensitivity and a clinically significant 5-month improvement in PFS.

Objectives: Despite a growing body of literature, characterization of COVID-19 infection in patients with gynecologic cancer remains limited. Here we present an update of COVID-19 outcomes in New York City (NYC) from the initial surge of severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019 [COVID-19]). We sought to determine the hospitalization and mortality rates and their associated factors, specifically recent chemotherapy and immunotherapy use. Methods: Data were abstracted from gynecologic oncology patients with COVID-19 infection among 8 New York City (NYC) area hospital systems. Multivariable logistic regression was utilized to analyze 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, 53.0-73.0 years). A total of 106 of the 193 patients (54.9%) required hospitalization; among the hospitalized patients 13 (12.3%) required invasive mechanical ventilation and 39 (36.8%) required ICU admission. No patients requiring mechanical ventilation survived. A total of 34 of 193 (17.6%) patients died of COVID-19 complications. On multivariable analysis, hospitalization was associated with an age greater than or equal to 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 greater than or equal to 2 (OR 3.67, CI 1.25, 13.55) and greater than or equal to 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 on multivariable analysis. A total of 13 of 34 (38.23%) patients who died of COVID-19 complications received cytotoxic chemotherapy, while 4 of 34 (11.76%) patients received immunotherapy. However, recent cytotoxic chemotherapy use was not predictive of COVID-19 hospitalization or mortality on multivariable analysis. Download : Download high-res image (107KB) Download : Download full-size image Conclusions: The case fatality rate among gynecologic oncology patients with COVID-19 infection is 17.6%. Cancer-directed therapy, including immunotherapy use, is not associated with an increased risk of mortality related to COVID-19 infection in this larger cohort.

Objectives To evaluate the difference in recurrence patterns and survival among stage IIIC high-grade endometrial cancer (HGEC) treated with surgery followed by adjuvant chemotherapy, radiation (RT) or both (chemoradiation). Methods A multicenter retrospective analysis of surgically-staged IIIC HGEC was conducted from 2000 to 2018, including grade-3 endometrioid (G3), serous, clear cell (CC) and carcinosarcoma. Differences in the frequency of recurrence sites and treatment delays were identified using Pearson’s χ2-test. PFS and OS were calculated using Kaplan-Meier estimates. Results A total of 155 patients were evaluable; 41.9% carcinosarcoma, 36.8% serous, 17.4% G3 and 3.9% CC; 67.1% received chemoradiation, 25.8% received chemotherapy-alone and 7.1% received RT-alone. Adjuvant therapy regimens were well-balanced between different histologies (p=0.351). There was no difference in the frequency of treatment delays between regimens (p=0.571). G3 tumors recurred less frequently (66.7%) versus serous (80.7%), CC (83.3%) and carcinosarcoma (84.6%)(p=0.269). Abdominal recurrence occurred most often in CC and serous. Carcinosarcoma was most likely to recur in the lung. There was a trend towards greater retroperitoneal recurrence with chemotherapy-alone (25.9%) versus chemoradiation (8.4%) and RT-alone (7.7%)(p=0.252). G3 tumors demonstrated improved PFS and OS (26 and 42-months, respectively) versus serous (17 and 30-months, respectively), carcinosarcoma (14 and 24-months, respectively) and CC (24 and 30-months respectively)(p=0.002, p Conclusion The majority of stage IIIC HGEC recurs. Chemoradiation was associated with improved survival and less retroperitoneal recurrence versus chemotherapy-alone. G3 tumors demonstrated improved survival compared other histologies regardless of adjuvant treatment modality.

Introduction Elevated inflammatory markers in COVID-19 infection are predictive of disease severity and mortality. It is unclear if these markers are associated with severe disease in patients with cancer due to underlying tumor related inflammation. We sought to further understand the inflammatory response related to COVID-19 in gynecologic cancer patients. Methods Patients with history of gynecologic cancer hospitalized for COVID-19 infection with available laboratory data were identified. Laboratory values at the time of hospital admission and clinical outcomes were abstracted from electronic medical records. Severe infection was defined as infection requiring ICU admission or resulting in death. Results 86 patients with gynecologic cancer were hospitalized with COVID-19 infection with median age of 68.5 years (interquartile range (IQR), 59.0 to 74.8 years). Of the 86 patients, 29 (33.7%) patients required ICU admission and 25 (29.1%) patients died of COVID-19 complications. There were 36 (41.9%) patients in remission and 50 (58.1%) had active disease. Patients with severe infection had significantly higher ferritin (median 1163.0, IQR 640.0–1967.0) and C-reactive protein (CRP) (median 142.0, IQR 62.5–217.1) levels than those with non-severe disease (median 624.0, IQR 269.7–954.0, P=0.01; median 62.3, IQR 13.0–159.1, P=0.02 respectively) (table 1). White blood cell count, absolute neutrophil count, and lactate were also associated with severe disease. Procalcitonin and D-Dimer levels were not significantly associated with severe disease (P=0.2; P=0.7 respectively). Conclusion/Implications Inflammatory markers (ferritin and CRP) in gynecologic cancer patients are associated with COVID-19 severity and can be used as prognostic markers at the time of admission.

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, Highlights • Ferritin, procalcitonin, and CRP may have prognostic value for severe COVID-19 infection in gynecologic cancer patients. • Elevated admission white blood cell count, lactate, and creatinine may also be prognostic of severe COVID-19 disease. • D-dimer levels do not appear to be predictive of severe COVID-19 infection in patients with gynecologic cancer.

Highlights • Patients with ovarian cancer were treated with intraperitoneal submicron particle paclitaxel after debulking surgery. • Following surgery, patients received IV chemotherapy without evidence of enhanced systemic toxicity. • By RECIST 1.1 criteria, 66% of patients had progression free survival at 6 months and 1-year following surgery., Submicron particles (~800 nm) of paclitaxel (SPP) contain 1–2 billion molecules of pure drug that release tumoricidal levels of paclitaxel over many weeks. This study compared two dose-levels of SPP instilled into the peritoneal cavity (IP) in 200 ml of saline post-cytoreductive surgery. Eligible patients with primary (n = 6) or recurrent (n = 4) epithelial ovarian cancer who underwent complete cytoreductive surgery were enrolled to receive a single instillation of IP SPP followed by standard IV carboplatin and paclitaxel. Endpoints were PFS and evaluation of treatment emergent adverse events. Clinical response was determined by symptoms, physical exams, CT scans, and serum CA-125 measurements. Of the 24 subjects screened, 10 were enrolled and received treatment: seven patients received 100 mg/m2 and three received 200 mg/m2. Seven subjects completed the 12-month follow-up period. Six patients were evaluable due to one subject who had unevaluable scans throughout the follow-up period and was thus excluded from PFS determination. Upon completion of planned chemotherapy post-SPP instillation, the PFS at 6 months was 66% (4/6) and at 12-months 66% (4/6) using RECIST 1.1. One subject had a complete response at the end of IV treatment but died (unrelated to study treatment) before PFS evaluation. There was one case of incision dehiscence and one case of vaginal cuff leakage after surgery. This pilot study supports further evaluation of IP SPP to treat peritoneal carcinomas.

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.

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&ndash, 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&ndash, base balance, providing new insights into its function.

Objective The optimal sequence of adjuvant chemoradiation in the treatment of advanced endometrial carcinoma (EC) remains unclear. We sought to evaluate the outcomes of patients treated with chemoradiation in sandwich fashion (chemotherapy-radiotherapy-chemotherapy; CRC), versus those treated sequentially (chemotherapy-radiotherapy; CR) (radiotherapy-chemotherapy; RC), to determine if there is a survival advantaged associated with a particular treatment sequence. Methods A multicenter retrospective analysis of patients with stage III and IV EC from 2000-2018 was conducted. Inclusion criteria were patients who had undergone comprehensive surgical staging/tumor debulking; followed by adjuvant chemoradiation. Differences in the frequencies of adverse events were evaluated using Pearson's χ² test. Progression free survival (PFS) and overall survival (OS) rates were calculated using Kaplan-Meier estimates. Results Final analysis included 152 patients; 36.8% (n=56) CRC, 28.9% (n=44) CR, and 34.2% (n=52) RC. Histology included 44.0% endometrioid, 47.5% serous and 8.5% clear cell tumors. There was no difference in the frequency of histology (p=0.973), stage (p=0.143), cytoreduction status (p=0.932), or treatment delays (p=0.571) between adjuvant therapy sequences. The most frequent location of disease recurrence was abdomen. The median PFS favored CRC versus CR or RC (36-months vs. 22-months and 24-months, respectively) (p=0.038), as did the median OS (48-months vs. 28-months and 34-months, respectively) (p=0.003). CRC demonstrated superiority over CR and RC sequencing in terms 3-year PFS (55% vs. 34% and 37%, respectively) and 3-year OS (71% vs. 50% and 52%, respectively). Conclusions Adjuvant chemoradiation delivered in CRC sequence was associated with improvements in both PFS and OS compared to alternant therapy sequencing.

ObjectivesUterine 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.MethodsA 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.ResultsFinal 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).ConclusionsChemoradiation was associated with improvement in both progression-free and overall survival for all stages of carcinosarcoma compared with chemotherapy alone.

Highlights: • Metastasis to the breast is a rare, accounting for, Metastasis of non-mammary tumors to the breast are uncommon, representing

Highlights • Cervical rhabdomyosarcoma does not always present as a cervical mass with vesicles. • Treatment regimens studied in the pediatric population can be used in adults with rhabdomyosarcoma. • More data is needed on outcomes of adult patients treated for rhabdomyosarcoma.

PurposeThe 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.MethodsWomen with nonmetastatic endometrial adenocarcinoma diagnosed between 2010 and 2012, who either underwent an OH or RAH, were selected from the National Cancer Database. The χ2, 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.ResultsA 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).ConclusionsIn 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.

Objectives: Despite recent advances in adjuvant therapy for various gynecologic malignancies, the prognosis of patients presenting with stage IVB uterine serous carcinoma (USC) remains extremely poor, with a reported 5-year survival of Methods: A multicenter retrospective analysis of patients with stage IVB USC was conducted from 2000 - 2018. Inclusion criteria were patients who had undergone comprehensive surgical staging/tumor debulking; followed by adjuvant chemotherapy±external beam radiation therapy (EBRT). Optimal cytoreduction (R1) was defined as residual disease =1cm. Patients receiving neoadjuvant chemotherapy were excluded from analysis. Progression free survival (PFS) and overall survival (OS) analysis was performed using Kaplan-Meier estimates. Multivariate analysis (MVA) was performed using Cox proportional hazards model. Results: Final analysis included 68 patients. 50 (74%) patients were cytoreduced to R1 and 18 (26%) to R2. Additionally, 11 (16%) R1 patients were cytoreduced to no gross residual disease (R0). The mean age was 66 years (range 44-89) and 96% of patients were African American. The majority of patients, 56 (82%), received systemic chemotherapy alone and 12 (18%) received a combination of chemotherapy and EBRT±vaginal brachytherapy (chemoradiation). Adjuvant therapy regimens were well-balanced between R1 and R2 patients (p=0.992). There was no difference in the frequency of treatment delays between regimens (p=0.832). 96% of patients received platinum-based chemotherapy. There was no difference in the age (p=0.227), race (p=0.936), type of radiotherapy (p=0.852) or chemotherapy regimen received (p=0.996) between R1 and R2 cohorts. The median PFS for all patients was 8 months and the median OS was 13 months. Cytoreduction to R1 was associated with a median PFS of 9 months, compared to R2 with a median PFS of 4 months (p Conclusions: In stage IVB USC, the amount of residual disease follow cytoreductive surgery is an important determinant of survival. Optimal cytoreduction should be the goal at the time of primary surgery. The combination of chemoradiation was associated with superior survival compared to chemotherapy alone and should be further investigated in this patient population.

Objectives: Uterine serous carcinoma (USC) presents a clinical challenge due its propensity to present at advanced stages, high recurrence rate and development of chemoresistance. The majority of patients with advanced disease will progress or recur following first-line platinum-based chemotherapy. As a result, new treatment strategies are urgently needed. Poly (lactic-co-glycolic acid)-based (PLGA) microparticles (MP) are a promising tool for delivery of chemotherapy due to prolonged drug elution over a period of several weeks, offering the benefit of sustained anti-cancer activity in the target tissue while limiting systemic toxicity. This is an attractive treatment strategy for USC, which can be accessed vaginally, allowing for the delivery of drug-loaded MP directly to the tumor. Previous work demonstrates paclitaxel and gemcitabine can be successfully loaded to PLGA-MP for drug delivery. Methods: The human endometrial cancer (EC) cell line KLE, representing a poorly differentiated serous-like EC was obtained from ATCC. Cells were treated with paclitaxel-loaded MP only (PMP), gemcitabine-loaded MP only (GMP), PMP-GMP sequence (PG), GMP-PMP sequence (GP) and PMP-GMP delivered concurrently (C). Blank MP (BMP) were used as control for each treatment. Cells were then collected at 6-days post-treatment for isolation of protein and assessment of cytotoxicity by cell viability assay. Protein lysates were analyzed for expression of multiagent chemoresistance protein AXL and paclitaxel resistance protein beta III tubulin (TUBB3) and apoptotic protein cleaved-PARP by Western Blot. Results: We observed morphologic changes and a decrease in cell density in all treatment regimens versus controls. These changes were most marked in the two-drug combination regimens. A significant increase in cleaved-PARP was observed in all treatments compared to controls. Chemoresistance proteins AXL and TUBB3 were not expressed in controls. AXL expression was increased in all treatment regimens. TUBB3 expression was significantly greater in PMP and GP regimens compared to PG (p=0.05). All treatment regimens were associated with a significantly decrease in cell viability versus controls (p Download : Download high-res image (106KB) Download : Download full-size image Conclusions: PMP and GMP demonstrated significant cytotoxicity in a serous-like EC cell line. Concurrent PMP-GMP administration elicited the greatest decrease in cell viability. TUBB3 expression was markedly less when cells received PG, indicating the sequence of paclitaxel followed by gemcitabine may counteract paclitaxel resistance observed with single agent paclitaxel and alternate sequencing. Chemotherapy delivered via MP is an attractive treatment strategy for advanced and recurrent USC. Future in vivo studies are needed to validate this new treatment approach.