bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiomics-based energy metabolism heterogeneity and its regulation by antiparasite drug ivermectin.
Authors: Li Na , Zhan Xianquan 
Published: May 2020

e18080 Background: Energy metabolism heterogeneity is a hallmark in ovarian cancer, namely the Warburg effect and the reverse Warburg effects coexist in ovarian cancer. Exploration of energy metabolism heterogeneity benefits for discovery of the effective biomarkers for ovarian cancers. Methods: Comprehensive analysis of mitochondrial proteomics data (1198 mitochondrial differentially expressed proteins), mitochondrial phosphorpoteomics data (67 mitochondrial phosphorproteins), proteomics data (205 differentially expressed proteins), and transcriptomics data (20115 genes in 419 ovarian cancer samples) was useful. Results: It revealed (i) the upregulations of rate-limiting enzymes PKM2 in glycolysis, IDH2 in Kreb’s cycle, and UQCRH in oxidative phosphorylation (OXPHOS) pathways, (ii) the upregulation of PDHB that converts pyruvate from glycolysis into acetyl-CoA in Kreb’s cycle. Anti-parasite drug ivermectin demonstrated its strong abilities to inhibit proliferation and cell cycle progression and promote apoptosis in EOC cells, through molecular networks to target PFKP in glycolysis, IDH2 and IDH3B in Kreb’s cycle, ND2, ND5, CYTB, and UQCRH in OXPHOS, and MCT1 and MCT4 in lactate shuttle to inhibit EOC growth. Those results were further confirmed in the ovarian cancer cell models and tissues. Conclusions: It clearly concluded that ivermectin might have new potential for ovarian cancer treatment through regulating energy metabolism pathways. These findings provide more accurate understanding of molecular mechanisms of ovarian cancers and discovery of effective energy-metabolism-heterogeneity-based therapeutic drugs for ovarian cancers.
Pressurized intra peritoneal aerosol chemotherapy (PIPAC) vs. intravenous chemotherapy to assess quality of life & response rates in unresectable peritoneal metastases secondary to platinum resistant ovarian cancer: A comparative study.
Authors: Somashekhar S.P. , C. Rohit Kumar , Rajgopal Ashwin K. , Rauthan Amit , Patil Poonam , Kapoor Priya 
Published: May 2020

e18091 Background: The primary objective of this study is to assess Qol & response rates in platinum resistant ovarian cancer patients with peritoneal metastasis treated with PIPAC procedure in comparison with conventional systemic intravenous chemotherapy. Methods: Between October 2017 and December 2019, 31 PIPAC applications were done in 15 patients with cisplatin 10.5mg/m2 and doxorubicin 2.1mg/m2. During same period 20 patients received systemic chemotherapy with clinician’s choice of drug ((mono-therapy consisting of pegylated liposomal doxorubicin or topotecan or gemcitabine or paclitaxel weekly with or without bevacizumab).The response rate (With MRI & Ca-125) & quality of life assessment (QLQ C-30) of both the group was done periodically and recorded. Results: Overall 35 patients were analysed in this study. The results have been presented in Table. Conclusions: PIPAC in comparison to intravenous chemotherapy for platinum resistant ovarian cancer with peritoneal metastasis showed better response rates (66.6 vs. 22.4%) and improved quality of life score. PIPAC has shown promising results and should be in the arsenal of the clinicians managing patients with platinum resistant ovarian cancer. [Table: see text]
Efficacy and toxicity of immunotherapy with immune checkpoint inhibitors in gynecologic cancers.
Authors: Kuznicki Michelle , Joehlin-Price Amy , Rose Peter Graham , Mahdi Haider 
Published: May 2020

e18092 Background: There is limited data on outcomes for gynecologic cancer patients treated with immune checkpoint inhibitors (ICI) outside the scope of clinical trials. Here we present our Institutional experience with a cohort of endometrial (EC) and ovarian cancer (OC) treated with ICI. Methods: 59 patients who received ICI were included (23 OC and 36 EC). Progression-free (PFS) and Overall survivals (OS) were determined by Kaplan-Meier (KM) curve and log rank test. Comparison of duration of response (DOR) and stable disease (DOSD) was done with unpaired t-test or one-way ANOVA. Rates of objective response (ORR) including partial response (PR) and complete response (CR), and stable disease (SD) were compared by Fischer’s exact test. Results: Median age was 66 years. 23 patients were microsatellite stable (MSS), 23 microsatellite instability high (MSI-H). Median number of prior lines was 2 (0-11). PFS and OS for EC and OC were overlapping; therefore outcomes for both were combined [(PFS 6.4m OC vs 7.3 m EC, p = 0.61), (OS 15.9 m OC vs 14.2 m EC, p = 0.78)]. Response rates consisted of 20.3% PR, 8.5% CR, 37.3% SD. Differences in responses were noted for clear cell carcinoma (CC) (33.3% PR, 11.1% CR, 33.3% SD) and MSI-H (36.4% PR, 18.2% CR, 22.7% SD) compared to MSS (11.8% PR, 0% CR, 47% SD). MSI-H had higher ORR vs. MSS (54.1% vs 11.8%, p = 0.0078). CC trended toward improved ORR vs. MSS (44.4% vs 11.8%, p = 0.14). PFS was improved for MSI-H vs. MSS (10m v 5.0m, p = 0.03). OS for CC compared to any other histology was improved (NR vs 12.8m respectively, p = 0.009). 5 recurrent MSI-H EC patients received ICI as first line monotherapy. Responses included 4 PR and 1 SD (80% ORR, 100% clinical benefit). PFS was 9.2m (3.3-13.3). 80% remained progression-free at last follow up. Overall, 38.9% experienced toxicity: hypothyroidism (15%), dermatitis (5%), pneumonitis (10%), LFT elevation (2%), amylase/lipase elevation (3%), colitis or diarrhea (5%), uveitis (2%) or nephritis (5%). 10% of patients required discontinuation of ICI secondary to toxicity. Trends for PFS and OS favored improved outcomes in patients with toxicity vs. no toxicity [(PFS 12.9m vs 5.6m, p = 0.07), (OS 22.9m vs 13.1m, p = NS)] respectively. Conclusions: In this study, immunotherapy with ICI outcomes favor MSI-H and CC compared to MSS disease. CC had promising OS compared to other histology types. ICI showed promising efficacy in MSI-H EC with 100% clinical benefit rate in chemonaive patients. First line ICI should be investigated in these patients. Positive correlation between toxicity and outcome is noted and will be further investigated.
Impact of neoadjuvant chemotherapy on survival in women with endometrial cancer: A National Cancer Database analysis.
Authors: Chambers Laura , Jia Xuefei , Alhilli Mariam 
Published: May 2020

e18094 Background: To evaluate overall survival (OS), prognostic factors for survival, and treatment outcomes in patients with Stage III/IV endometrial cancer (EC) undergoing neoadjuvant chemotherapy +/- surgery compared to surgery followed by adjuvant chemotherapy. Methods: The National Cancer Database (NCDB) was queried to identify patients with Stage III/IV EC who were treated with chemotherapy. Univariable and multivariable Cox proportional hazards analyses were used to determine independent prognostic factors for OS. Survival was measured from date of diagnosis to the date of last contact or death. Results: From 2004-2012, 31,726 women with stage III/IV EC were identified. . Treatment groups consisted of: 3424 (10.8%) chemotherapy alone (C), 26926 (84.9%) surgery followed by chemotherapy (S+C), and 1412 (4.4%) neoadjuvant chemotherapy followed by surgery (NACT+S). The median age at diagnosis was 64 years (19-90), and 65.8% (n = 35402) of patients had Stage III disease. Reasons for no surgery were: not part of primary treatment plan (77.7%; n = 5859), contraindicated due to patient factors (11.3%, n = 850) or patient refusal (3.6%; n = 268). The majority of patients (86.8%) received multiple chemotherapy agents and 1988 (6.3%) received single agent chemotherapy. Charlson-Deyo score was 0 for 75.3% (n = 2578) of C, 76.7% (n = 20652) of S+C and 77.8% (n = 1098) of NACT+S patients (p < 0.001). Compared to patients who received C alone, S+C and NACT+S were associated with improved median OS (10.9 months vs. 63.3 (HR 0.27 CI 0.26-0.28, p < 0.001) and 24.6 months (HR 0.50, 95% CI 0.47-0.54, p < 0.001), respectively). On multivariate analysis advanced age (HR 1.03, p < 0.001), stage IV disease (HR 2.70, p < 0.001), Charlson Deyo Score (1 – HR 1.13, p < 0.001; 2 – HR 1.32, p < 0.001), and African American race (HR 1.53, p < 0.001) were associated with worse OS.Private insurance (HR 0.87, p < 0.001), income > $63,000 (HR 0.86, p < 0.001) and treatment with S+C (HR = 0.32, p < 0.001) or NACT+S (HR 0.44, p < 0.001) versus C alone were predictive of improved OS. Conclusions: In this analysis of the NCDB, receipt of chemotherapy alone is associated with markedly worse OS than S+C or NACT +S in stage III/IV patients. . Socioeconomic factors including African American race, insurance status and income are independent predictors for survival in this cohort. Where feasible, surgery should be should be incorporated into treatment planning for women with Stage III/IV EC.
Chemotherapy response score as a prognostic tool in advanced-stage endometrial cancer patients treated with neoadjuvant chemotherapy.
Authors: Jani Ina , Lastra Ricardo R. , Brito Katherine , Liao Chuanhong , Lazo Isabel , Lee Nita Karnik , Yamada Seiko Diane 
Published: May 2020

e18095 Background: Chemotherapy response score (CRS) applied to omental metastases obtained at the time of interval debulking surgery (IDS) has been used to quantify response to neoadjuvant chemotherapy (NACT) in advanced stage ovarian cancer patients. The score has been correlated with both progression free survival (PFS) and overall survival (OS). This CRS score has not been studied in advanced stage endometrial cancer. The aim of the current study is 1) to apply the CRS to omental and adnexal metastases obtained at IDS of advanced stage endometrial cancer patients and 2) to investigate the association between the CRS score and surgical outcome, PFS and OS. Methods: Patients with clinical stage III-IV endometrial cancer (endometrioid, serous, clear cell, carcinosarcoma) were identified through the endometrial cancer database, billing data and tumor board notes (2003-2019) from the University of Chicago. Patients were included if they received NACT followed by IDS (R0 no gross residual, optimal < 1 cm residual or suboptimal ≥ 1 cm residual disease). Patients who received pre-operative radiotherapy were excluded. Pathology specimens from primary and metastatic sites were reviewed by the study pathologist blinded to clinical outcome. Histologic specimens from the omental and adnexal metastases were assigned a single quantitative score of 1 (no/minimal tumor response), 2 (appreciable tumor response with viable tumor) or 3 (complete/near complete response) using the CRS system as previously described by Bohm et al (JCO 2015; 33:2457-63). Results: A total of 40 patients were available for analysis. Median age 63.5, median BMI 32 kg/m2. There is a significant association between omental CRS and optimal IDS (p = 0.029) but no significant association between the adnexal CRS and optimal IDS (p = 0.145). Cox regression analysis identified CRS omentum [2: HR = 0.095, p = 0.001; 3 HR = 0.088, p = 0.004] and CRS adnexa [2: HR = 0.24, p = 0.007] predictive of PFS. There was not enough evidence to comment on any association between CRS with OS. Conclusions: Omental CRS2, CRS3 are associated with optimal IDS. Omental CRS2, CRS3 and adnexal CRS2 are prognostic for improved PFS in stage III – IV endometrial cancer patients after neoadjuvant chemotherapy. [Table: see text]
Seven-year survival analysis in women with unsuspected uterine malignancy after laparotomic versus laparoscopic hysterectomy: A national claim data retrospective cohort study.
Authors: Lee Jung Hun , Yuk Jin-Sung 
Published: May 2020

e18096 Background: The primary aim of this study was to compare the overall survival of women with unsuspected uterine malignancy (UUM) diagnosed after laparotomic versus laparoscopic hysterectomy for benign gynecological diseases. Methods: A national health insurance database was analyzed from January 2006 to December 2010 to estimate the incidence and mortality of UUM diagnosed after hysterectomy for benign gynecologic diseases using diagnostic and procedure codes. Results: From the database (24 million women annually), 157,232 women were extracted. These women were divided into a laparotomic group (n = 103,631) and a laparoscopic group (n = 53,601). The overall incidences of UUM, unsuspected endometrial cancer, and UUM other than endometrial cancer were 0.65%, 0.46%, and 0.19%, respectively. Women with UUM diagnosed after hysterectomy showed no difference in mean age, incidence of UUM, or socioeconomic status in either group. Kaplan-Meier survival analysis and Cox regression analysis showed that the laparoscopic group was associated with more favorable overall survival than the laparotomic group, especially in UUM other than endometrial cancer ( p < 0.001). Conclusions: In women with UUM diagnosed after hysterectomy for presumed benign gynecological diseases, overall survival up to 7 years favors laparoscopic hysterectomy over laparotomic hysterectomy, and the incidence of UUM is relatively low. However, considering the devastating effect of intraperitoneal dissemination of UUM, surgeons should fully explain this issue to patients preoperatively and try to avoid intraperitoneal spread of tumor cells intraoperatively. [Table: see text]
A phase I trial of nab-paclitaxel/bevacizumab (AB160) nano-immunoconjugate therapy for metastatic gynecological malignancies: MC1371 (NCT02020707).
Authors: Kalogera Eleftheria , Suman Vera Jean , Nevala Wendy Kay , Finnes Heidi Diann , Schimke Jill , Strand Carrie , Glaser Gretchen , Grudem Megan , Jatoi Aminah , Klampe Carolyn , Kumar Amanika , Langstraat Carrie L , Wahner Hendrickson Andrea Elisabeth , Weroha Saravut John , Reid Joel M. , Markovic Svetomir , Block Matthew Stephen 
Published: May 2020

e18097 Background: AB160 is a 160 nm nano-immunoconjugate consisting of nab-paclitaxel (NP) nanoparticles non-covalently coated with bevacizumab (BEV) for targeted delivery into tissues expressing high levels of vascular-endothelial growth factor (VEGF). Both taxanes (GOG-0129C, GOG-0126R, GOG-0127V) and BEV (GOG-0229E, AURELIA, GOG-0227C) have demonstrated clinical activity in previously treated metastatic endometrial cancer (EC), ovarian cancer (OC), and cervical cancer (CC), respectively. Methods: A 3+3 phase I trial was conducted in patients with EC, platinum-resistant OC and CC who had prior systemic treatment for metastatic disease to determine the maximum tolerated dose of AB160 administered intravenously on days 1, 8 and 15 of a 28-day cycle. The starting dose level (DL1) was NP at 125 mg/m2 with BEV at 50 mg/m2. There were 2 higher dose levels: DL2 (NP at 150 mg/m2 with BEV at 60 mg/m2) and DL3 (NP at 175 mg/m2 with BEV at 70 mg/m2). Dose limiting toxicities (DLT) included grade (G) 4 neutropenia or anemia, PLT < 25,000, serum creatinine ≥2 times baseline, G2-4 neurologic toxicity or G3-4 non-hematologic toxicities. Disease evaluations were conducted after every 2 treatment cycles using RECIST criteria. Patients were treated until disease progression or intolerability. Samples were collected for pharmacokinetic (PK) studies. Results: Nine women 41 – 74 years of age (median 57) have enrolled (5 with EC and 4 with OC); data are available for the first 8. No DLTs have been observed among the 3 women enrolled on DL1, 3 women on DL2, and 2 women on DL3. All 3 patients on DL3 continue on treatment. The other 6 patients have discontinued due to adverse reactions (3), progression (2), and patient choice (1). The median number of cycles administered is 6 (4-14). The most common severe (G3/4) toxicities include neutropenia (37.5%) and leukopenia (25%). There have been 5 partial responses (62.5%): 1 on DL1 and 2 each on DL2 and DL3. PK evaluation is pending. Conclusions: AB160 therapy is safe and demonstrates promising clinical activity in patients with previously treated metastatic gynecologic malignancies. Further clinical testing is being pursued in this patient population. Clinical trial information: NCT02020707.
A Novel predictive probability algorithm to determine risk for malignancy between uterine fibroids versus uterine sarcoma.
Authors: Blackman Alexandra Michelle , Samborski Alexandra , Miller Michael Craig , Singh Rakesh , Kim Kyu Kwang , Turner Rachael , Messerlian Geralyn , Moore Richard G. 
Published: May 2020

e18098 Background: The combination of HE4 and CA125 can be used as a predictive probability algorithm to determine the risk of malignancy in women with a uterine mass. Many studies have been done looking at ways to differentiate between benign fibroids and uterine sarcomas with limited success. This study examined the utility of using a logistics regression algorithm containing biomarkers HE4 and CA 125 to predict risk of malignancy of a uterine mass. Methods: This was an IRB retrospective study using de-identified data form 5 pelvic mass studies. Patients were included if they were diagnosed with either uterine fibroids or uterine sarcoma on final pathology. Pre-operative serum levels of HE4 and CA125 were obtained for each patient. A logistics regression analysis was performed in a prior pelvic mass prospective trial and utilized in this analysis. The predictive probability algorithm was used to classify patients into high and low risk groups for sarcoma. Wilson’s score interval was used to determine confidence intervals. Results: There were 71 patients identified with a uterine mass. The mean age of study participants was 54 (range 22-85). There were 10 (14.1%) sarcomas and 61 fibroids (85.9%) identified. Six of the sarcomas were leiomyosarcomas (60.0%). There was 1 adenosarcoma (10%), 1 mixed sarcoma (10%) and 2 sarcomas which were not further characterized. A threshold of 13.1% was used to classify masses as low or high risk. The predictive probability algorithm was found to have a sensitivity of 90.9% (CI 55.5-99.7%), specificity of 60.7% (CI 47.3-72.9%), PPV of 27.3% (13.3-45.5%), and NPV of 97.4% (86.2-99.9%). An elevated risk of malignancy was noted in 9 (90%) sarcomas and 24 (39%) of fibroids. Conclusions: A predictive probability algorithm using HE4 and CA 125 had a high sensitivity for determining high and low risk of malignancy in patients with presumed uterine fibroids with a sensitivity of 90.9% for detecting sarcoma. This algorithm will be validated in a prospective clinical trial.
A single-center analysis of adjuvant sequential versus ‘sandwich’ chemoradiotherapy for patients with stage III endometrial cancer.
Authors: Shen Janice , Newman James , Hernandez Jennifer , Bloom Beatrice , Lee Jean Kyung , John Veena S. 
Published: May 2020

e18101 Background: To determine if the sequencing of chemotherapy with external beam radiotherapy (EBRT) in the adjuvant setting for FIGO stage III endometrial cancer impacts 2-year progression free survival (PFS). Methods: As part of our Gynecologic Oncology Multidisciplinary Group's initiative to establish an institutional guideline for the adjuvant treatment of Stage III endometrial cancer, we reviewed 144 cases identified by our cancer registry and departmental database. Treatment regimens were divided into three categories: sequential therapy with six cycles of carboplatin/taxane followed by EBRT, concurrent cisplatin for two cycles with EBRT followed by four cycles of carboplatin/taxane, or ‘sandwich’ therapy with three cycles of carboplatin/taxane followed by EBRT followed by three cycles of carboplatin/taxane. The published results of the phase III GOG-258 study called into question the efficacy of concurrent chemoradiation. Therefore, we only compared sequential versus ‘sandwich’ therapy using a Chi-Square analysis. We conducted a retrospective chart review to assess if patients were able to complete the prescribed six cycles and EBRT, and then measured their PFS at two years. We hypothesized that there would be no difference in PFS between the two groups. Results: There were no significant differences in clinical or pathologic factors between patients treated with either regimen. Ninety-four patients (65%) had stage IIIC disease. The majority of patients received six cycles of paclitaxel with carboplatin. Median EBRT dose was 45 Gy. There was no statistically significant difference in the estimated 2-year PFS between the sequential and ‘sandwich’ groups, which were 82% and 82.5%, respectively (p = 0.84). Conclusions: Adjuvant chemoradiation for FIGO stage III endometrial cancer given sequentially or in a ‘sandwich’ fashion appears to offer equally excellent early clinical patient outcomes.
Age-related clinicopathologic features and survival in papillary serous uterine cancer patients older and younger than 70: An exploratory analysis of a series of consecutive patients.
Authors: Lerner Jaren , Michel Miguel , Iskandar Andrew Samir , Kaur Jaspreet , Tuler Shahaf , Farrell Stephanie , Plaxe Steven C. , Dasanu Constantin 
Published: May 2020

e18104 Background: Papillary serous uterine cancer (PSUC) is a rare, clinically aggressive histotype accounting for 40% of uterine cancer deaths. Clinicopathologic characteristics and outcomes between older and younger PSUC patients may differ. Methods: With IRB approval, we conducted a retrospective analysis of 554 consecutive patients with uterine cancer treated at our institution from 2009-19. Consistent with findings from the SEER database, 28 patients (5%) had PSUC. Most PSUC patients were Caucasian; Latinas comprised 14.2%. Thirteen patients were seventy years of age or younger (≤70) and fifteen were older than seventy ( > 70). Clinicopathologic features, therapy and survival were compared between two cohorts. Statistical analysis: Significance of associations was assessed with Fishers' exact test. Survival analysis was performed with Cox proportional model with censoring to calculate hazard ratios (HR). Results: The two cohorts were well-balanced for stage (TNM stages I+II vs. TNM stages III+IV). More than 90% of patients in each group had surgical excision/debulking, and nearly half of patients in each group received systemic chemotherapy. The most frequently used chemotherapy regimen was carboplatin-paclitaxel. Compared to patients ≤70, patients > 70 were less likely to undergo postoperative radiation therapy (6% vs 61.5%; p = 0.001). Cancer-specific survival (CSS) was worse in patients > 70 as opposed to patients ≤70 (21.8 vs. 27.4 months; HR 0.61, p = 0.03). Four PSUC patients > 70 had a personal history of metachronous breast cancer; none ≤70 had a history of breast cancer. We identified five cases of breast cancer, two cases of colon cancer, and one case each of ovarian and uterine cancer in first-degree relatives of PSUC patients > 70. Conclusions: Older PSUC patients displayed significantly shorter CSS than their younger counterparts. They were also less likely to receive radiation therapy. As personal and family history of older PCUS patients identified an excess of other cancers, comprehensive germline mutation testing may be warranted. Final statistical analysis, comparison to SEER data and significance will be presented.