bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of diabetes and obesity on endometrial cancer outcomes.
Authors: Ko Emily Meichun , Walter Paige , Clark Leslie Horn , Jackson Amanda Lynn , Franasiak Jason , Havrilesky Laura Jean , Secord Angeles Alvarez , Moore Dominic T. , Gehrig Paola A. , Bae-Jump Victoria Lin 
Published: March 2020

5523 Background: Diabetes (DM) is a known risk factor for endometrial cancer (EC), yet its effect on cancer outcomes remains unclear. We sought to investigate of the relationship between DM, obesity, and anti-diabetic medication on EC recurrence and survival. Methods: An IRB approved multi-institution retrospective study included all EC patients diagnosed with carcinosarcoma as well as endometrioid, serous, and clear cell cancers between January 2005 to December 2010. Demographics, comorbidities, and medications were captured at the time of cancer diagnosis. Cohorts for comparison included women with and without DM; and diabetics treated with metformin-only (METFO) were compared to those not treated with METFO. Cox regression models were used to evaluate the effect of selected covariates on PFS and OS. Results: Of 1495 EC patients, 364 (24%) had DM. Diabetics were more likely to be African American (30 v 16%, p<0.0001) and have higher BMIs (median 37.0 v 31.2, p < 0.001). After adjusting for age, race, stage, and BMI, women with DM had a worse OS (HR 1.40, 95CI 1.03-1.79), but similar recurrence risk (HR 1.16, 95CI 0.91-1.48) to non-diabetics. In a subset analysis of women with endometrioid EC (n = 1144), those with DM were 1.6 times more likely to recur (95CI 1.01-1.89, p = 0.04) and 2.4 times more likely to die (95CI 1.6-3.46, p < 0.0001). METFO use was associated with a decreased risk of recurrence (PFS HR 0.54, 95CI 0.3-0.96, p = 0.04), and death (OS HR 0.43, 95CI 0.22-0.83, p = 0.01) compared to no METFO use. METFO users had a similar clinical outcome compared to non-diabetics (PFS HR 1.05, p = 0.82; OS HR 1.3, p = 0.46). Obese women with DM who were treated with non-METFO regimens had a 1.8-fold increased risk of recurrence (95CI 0.94-3.7, p = 0.07) and 2.7-fold increased risk of death (95CI 1.2-5.9, p = 0.01). No survival differences were seen in women with serous, clear cell, or carcinosarcoma. Conclusions: Our data demonstrates worse clinical outcomes for EC patients with DM and improved outcomes for METFO users, suggesting a link between tumor pathogenesis and insulin growth factor and mTOR pathways. Future investigation is required to elucidate the complex relationship between diabetes, anti-hyperglycemic agents, and cancer outcomes.
Outcome parameters in node-negative vulvar cancer: A subset analysis of the AGO Care 1 study.
Authors: Woelber Linn Lena , Jueckstock Julia Kathrin , Hilpert Felix , Neuser Petra , De Gregorio Nikolaus , Iborra Severine , Chen Frank , Habermann Anika , Hillemanns Peter , Fuerst Sophie , Strauss Hans-Georg , Baumann Klaus H. , Thiel Falk , Mustea Alexander , Meier Werner , Harter Philipp , Wimberger Pauline , Hanker Lars Christian , Schmalfeldt Barbara , Mahner Sven 
Published: March 2020

5531 Background: Prognosis of node-negative vulvar cancer is generally favorable compared to node positive disease. However, a small proportion of node-negative pts experience early recurrence with subsequent need for radical interventions. Aim of this analysis was to identify possible prognostic factors in this subset of pts. Methods: The AGO CaRE 1 study was designed as retrospective survey of treatment patterns and prognostic factors in vulvar cancer. Pts with primary squamous-cell vulvar cancer stage ≥1b treated at 29 gynecologic cancer centers in Germany 1998-2008 were included in a centralized database. Results: A total of 1618 pts were documented, 802 were node negative (pN0) after surgical staging and further analyzed. Median age was 66 yrs (21-94); 399 (49.8%) had pT1b, 365 (45.5%) pT2, 36 (4.5%) pT3 and 1 pT4 tumors; in 1 pt tumor stage was unknown. Median tumor size was 20 mm (1–345) and depth of invasion 4 mm (0.75–60). 703 (87.7%) pts had an R0 resection with a minimal margin of 5 mm (0.2–33); there were 46 R1 (5.7%) resections and 53 (6.6%) pts with unknown margin status. 692 pts (86.3%) received a full groin dissection (178 after sentinel node dissection) and in 85 pts (10.6%) only a sentinel node procedure was performed; surgery type was unknown in 25 pts (3.1%). 73 pts (9.1%) underwent adjuvant radiotherapy to the vulva. Median follow-up was 40 months. 169 pts (21.1 %) developed disease recurrence (thereof 111 (65.7%) at the vulva only and 53 (31.4%) at other locations, in 5 cases the localization was unknown) after a median of 17.7 months. 101 pts (12.6 %) died. To assess potential prognostic factors, multivariate analyses were performed including age, stage, tumor size, invasion depth, tumor grade, resection margin, adjuvant radiation, and mode of groin dissection [sentinel vs. full]) showing age as the only consistent prognostic factors for recurrence-free and overall survival. Conclusions: Even in the very large patient cohort of the AGO-CaRE database with more than 800 node-negative pts it was not possible to identify reliable clinicopathologic prognostic factors for node-negative disease. Identification of new biological markers will therefore be necessary to select high risk node negative pts for adjuvant treatment.
Malignant germ cell ovarian cancer (MGCOC) in the Cancer Registry of Norway (CRN): A long-term follow-up study of presentation, survival, and second cancers.
Authors: Solheim Olesya , Dahl Alv A. , Nesland Jahn M , Kaern Janne , Trope Claes , Rokkones Erik , Fossaa Sophie D 
Published: March 2020

5533 Background: Significant improvements in the management of MGCOC have been achieved during the past two decades. However, data on long term risk conferred by radiation and chemotherapy is scarce. This is a long-term follow-up study of presentation, survival and second cancers. Methods: 360 female patients with histologically confirmed MGCOC, recorded in the CRN between 1953 and 2009 were identified. Patients, diagnosed before 1980 were separated from those with a diagnosis 1980+, reflecting the introduction of cis-platin based chemotherapy. Data on survival and second cancer incidence were obtained by linkage to the CRN. Cox Hazards Models and Kaplan Meier estimates were used. Results: The annual incidence doubled during the observation time. Malignant teratoma was the most common histological subtype (n = 190 [53%]), followed by dysgerminoma (n = 113 [31%]) and other non - dysgerminoma tumors (n = 57 [16%]). Over two thirds of the patients (median age 34 years [range 2-92]) had localized disease with distant disease in 23%. Before 1980 70% of 159 patients received subdiaphragmatic radiotherapy, this percentage was reduced to 24% after 1980, while chemotherapy increased from 11% to 38%. The 10 years ovarian cancer specific survival (OvCSS) (median follow-up time of 9.8 years [range: 0 - 54]) increased significantly to 93% in women treated in 1980+ compared to 62% to those with an earlier diagnosis (p <0.001) . Significant period-related improvement in OvCSS was observed independently from the extent of the disease and for all histological subtypes. Women aged >50 years had a significantly poorer OvCSS than younger ones, (HR=5.98, 95%CI [3.39 to 10.57]) adjusted for histological type and stage. A second cancer was diagnosed in 27 women, 63% of these cancers were located below the diaphragm within or close to the radiation field. Conclusions: The incidence of MGCOC is rising in Norway. We observed significant improvement of ovarian cancer specific survival after the introduction of cisplatin-based chemotherapy. The development of second cancer after treatment for MGCOC seems to be related to abdominal radiotherapy.
A multiplex methylation-specific PCR assay for detection of early-stage ovarian cancer using cell-free serum DNA.
Authors: Kong Beihua , Zhang Qing , Hu Guohong , Yang Qifeng , Dong Ruifen , Xie Xing , Ma Ding , Shen Keng 
Published: March 2020

5535 Background: Epithelial ovarian cancer (EOC) remains the most lethal disease among gynecological malignancies. Prompt diagnosis is challenging because of the non-specific symptoms exhibited during the early stage of the disease. So there is an urgent need for better detection methods. Here we performed this work to build up a platform of multiplex methylation-specific PCR (MSP) assay to improve the early detection of ovarian cancer, via identifying the methylation status of cell-free serum DNA. Methods: After screening, we chose seven genes (APC, RASSF1A, CDH1, RUNX3, TFPI2, SFRP5 and OPCML) with a high frequency of methylation as candidate genes to construct the multiplex-MSP assay. When methylation of at least one of the seven genes was observed, the multiplex-MSP assay was considered positive. We performed the retrospective and screening study to verify its specificity and sensitivity in the detection of EOC. Results: The methylation status of cell-free serum DNA was examined in the preoperative serum of 202 patients, including 87 EOC cases (stage I, n=41, stage II-IV, n=46), 53 benign ovarian tumors and 62 healthy controls. As expected, multiplex MSP assay achieved a sensitivity of 85.3% and a specificity of 90.5% in stage I EOC, strikingly higher than that of single CA125, producing a sensitivity of 56.1% at 64.15% specificity [p=0.0036](Table). Conclusions: Multiplex MSP assay analyzing the methylation status of cell-free serum DNA is a suitable and reliable approach to improve the early detection of ovarian cancer, potentially benefiting a broad range of applications in clinical oncology. [Table: see text]
Surgical outcome score (SOS), a new algorithm based on HE4 and CA125, to predict surgical outcome in primary epithelial ovarian cancer (EOC) patients (pts).
Authors: Braicu Elena Ioana , van Gorp Toon , Richter Rolf , Chekerov Radoslav , Timmerman Dirk , Nassir Mani , Sehouli Jalid , Vergote Ignace 
Published: March 2020

5549 Background: There are no clinical or biomolecular algorithms to predict surgical outcome in EOC pts. Recently, we showed that the combination of HE4 and CA125 predict surgical outcome in advanced primary EOC (ASCO 2012). We validated the cut-off values in an independent cohort and developed a new algorithm to predict surgical outcome-SOS. Methods: Pts with primary EOC (n = 193) were selected for a retrospective study between 2003 and 2011. Preoperative serum HE4 and CA125 levels were measured. The predictive values of HE4 and CA125 were analyzed using the receiver operator characteristic (ROC) with the corresponding area under the curve (AUC). Separate logistic regression algorithms for pre- and postmenopausal women were utilized to categorize pts into low and high-risk for residual disease, using CA125 and HE4 within SOS algorithm. Furthermore we performed a multivariate analysis for prediction of progression free- (PFS) and overall survival (OS). Results: Maximal cytoreduction was achieved in 67.4% pts. Serum HE4 expression correlated with residual disease (p<0.001, RR: 2.74, 95%CI 1.65-4.54), reaching a 76.2% sensitivity (Se), 56.9% specificity (Sp) and 83.1% negative predictive value (NPV), with 235 pM cut-off value. CA125 correlated with residual disease in premenopausal pts (p=0.031, RR: 3.13, 95%CI 1.28-7.65). For a CA125 cut-off of 500 IU/l, the Se, Sp and NPV were 39.7%, 69.8%, and 70.3%, respectively. ROMA predicted surgical outcome (AUC = 0.70, p <0.001, 95% CI = 0.624-0.776, RR = 2.54), reaching a 76.2% Se, 53.5% Sp for 81% cut-off value. SOS algorithm performed better than HE4 or CA125 alone, and ROMA (AUC= 0.741, p < 0.001, 95% CI 0.670-0.812, RR = 4.98). The Se, Sp and NPV was 90.5%, 46.5% and 90.9%, respectively, for a SOS cut off value of 21.5%. FIGO stage and residual disease were the only prognostic factors for both PFS and OS. SOS was an independent prognostic for PFS (p = 0.009, HR = 1.014, 95% CI = 1.004-1.025), but not for OS. Conclusions: This independent validation study confirm the predictive value of CA124 and HE4 on surgical outcome. The combination of HE4 and CA125 within the SOS score improve the prediction of surgical outcome, and therefore of PFS.
Benefit of adjuvant chemotherapy for stage I epithelial ovarian cancer according to the histologic type.
Authors: Fujiwara Hiroyuki , Takei Yuji , Saga Yasushi , Machida Shizuo , Sato Naoto , Yoshida Chikako , Takahashi Suzuyo , Taneichi Akiyo , Suzuki Mitsuaki 
Published: March 2020

5552 Background: The benefit of adjuvant chemotherapy in stage I epithelial ovarian cancer (EOC) remains controversial. We retrospectively examined stage I EOC patients to clarify the benefits of adjuvant chemotherapy according to the histological type. Methods: The outcomes of 131 patients with stage I EOC that was diagnosed by exact staging laparotomy at the Jichi Medical University Hospital over a 22-year period from 1988 to 2009 were evaluated. Eighty-seven of the patients had received adjuvant chemotherapy (stage: IA 17, IC(intraoperative rupture;R) 27, IC(other) 43; histological type: clear cell adenocarcinoma(CCC) 38, mucinous adenocarcinoma(MC) 18, endometrioid adenocarcinoma(EC) 18, serous adenocarcinoma(SAC) 13), while 44 had undergone observation alone (stage: IA 31, IC(R) 12, IC(other) 1; histological type: CCC 11, MC 17, EC 11 and SAC 5). Outcomes for patients were compared between the two groups. Results: The overall recurrence rate in the adjuvant chemotherapy group was 18.4% (16/87). The rates of recurrence according to stage were IA 5.9% (1/17), IC(R) 14.8% (4/27), and IC (other) 25.6% (11/43). Recurrence by histological type were CCC 12, SAC 2(G1and G2), and one each for EC and MC. Recurrence was seen in all stages in CCC patients; however, there was no recurrence in stage IA in patients with non-CCC. The overall recurrence rate in the observation group was 11.4% (5/44). All five recurrences occurred in CCC patients, and no recurrence was observed in the 33 non-CCC patients (IA 26, IC(R) 7). In patients with IC(R) CCC, the recurrence rate was significantly higher in the observation group (80%;4/5) than in the adjuvant chemotherapy group (18.8%; 3/16) (p = 0.025). Conclusions: This retrospective study showed that the CCC is associated with recurrence in stage I EOC and adjuvant chemotherapy for these patients may improve outcomes. The recommended states for adjuvant chemotherapy in stage I EOC are as follow: 1) all subtype of stage I for CCC, and 2) IC(other) for non-CCC. Although further prospective studies are required, these results afford useful information with which to determine the adjuvant chemotherapy in stage I EOC.
Validation of urinary HE4 as a biomarker for ovarian cancer.
Authors: Li Zhong-Qian , Fermer Christian , Radwan Rachel R. , Hellman Maria , He Kuanglin , Falcone Katherine L. , Raju Savitha S. , Fegely Maryellen , Vucetic Zivjena , Dickson Diana L. , Kettlety Timothy R. , Moore Richard G. , Barnes Grady 
Published: March 2020

5563 Background: Urinary HE4 has been reported as a promising biomarker for ovarian cancer (OC). In the current study, a large validation was performed to evaluate urinary HE4 as a biomarker for the stratification of OC from benign pelvic masses. Methods: Normalized HE4 was obtained from the ratio of HE4 (pmol/L measured with HE4 EIA) and creatinine (mg/dL measured with a Jaffe Reaction) in single-point urine samples from female subjects with a pelvic mass (N = 809). The samples were from one case-control prospective study (Moore RG, 2008) and two prospective clinical trials (NCT00315692 and NCT00987649). R Package was used to randomly distribute the subjects into the Training and Testing Sets. Analyze-it was used to analyze the clinical performance. Results: Medians of Normalized HE4, sensitivities (SN) and likelihood ratios (LR) (+) of Normalized HE4 at two levels of specificity (SP) are presented in the Table. Conclusions: Urinary HE4 normalized with urinary creatinine appears to be a valid biomarker for the stratification of OC from a benign pelvic mass. [Table: see text]
Prognostic effect of EIF4EBP1 on ovarian cancer: A single gene biomarker for overall survival and platinum response.
Authors: Villalobos Victor Manuel , Wang Yan , Willis Scooter , Leyland-Jones Brian , Sikic Branimir I. 
Published: March 2020

5565 Background: Using a novel computational approach, Gene Set Outcome Analysis (GSOA), we were able to identify an area of amplification on chromosome 8p12 that leads to worse prognosis in high grade/high stage ovarian cancer. Located within this amplicon is EIF4EBP1, an effector of DNA translation that is activated by mTOR. Methods: We utilized the MSKCC CBIO cancer genetics portal and the ovarian TCGA clinical dataset, to detect variation in mRNA expression (EXP), (z-scores thresholds ± 2) and copy number variation (CNV), determined using GISTIC 2.0, that are associated with significant differences in PFS and overall survival in grade 3 and stage III/IV ovarian cancer. Results: 6.7% of tumors exhibited upregulation of EIF4EBP1 (CNV amplified and mRNA z > 2) and poorer prognosis with OS of 30.2 vs. 43.8 months (p = 0.0007, n = 445) in tumors not upregulated. Patients with upregulated vs. normal expression showed inferior PFS with first line, platinum based therapy, 10.0 vs. 15.2 months (p = 0.0406, n = 400), respectively. An additional 4.9% of cases had downregulation of EIF4EBP1, with homozygous deletion or mRNA expression z-scores < -2. Downregulation vs. normal expression also showed worse OS of 27.0 vs. 42.1 months (p = 0.0178) and PFS of 11.0 vs. 15.0 months (p = 0.028), respectively. As these groups are mutually exclusive and show a similar trend towards poor prognosis, when combined to compare aberrant vs. normal mRNA expression and copy number, we found an OS of 28.2 vs. 44.6 months (p = <0.0001) and PFS for first line platinum therapy of 10.2 vs. 15.3 months (p = 0.0024), respectively. Conclusions: In this dataset of 445 high-risk ovarian cancer patients, 11.8% exhibited aberrant expression of EIF4EBP1. While amplification of this region showed highly significant changes in OS and PFS, inclusion of both increased and decreased EIF4EBP1 mRNA expression achieved high statistical significance, demonstrating a “Goldilocks effect”, wherein normal expression leads to better outcomes. The potential relationship of gene expression levels of EIF4EBP1 to responsiveness to mTOR inhibitors should be explored in ovarian carcinomas.
Adverse event profile by therapy cycle for vintafolide plus pegylated liposomal doxorubicin (PLD) versus PLD alone in platinum-resistant ovarian cancer.
Authors: Symanowski James Thomas , Kutarska Elzbieta , Bidzinski Mariusz , Nguyen Binh , Rangwala Reshma A. , Naumann R. Wendel 
Published: March 2020

5572 Background: Vintafolide (EC145), a folic acid/desacetylvinblastine conjugate, binds with high affinity to folate receptors expressed in epithelial ovarian cancers. This analysis evaluated the incidence of adverse events (AEs) by treatment cycle and as a percent of total treatment cycles administered in the PRECEDENT trial, a randomized open-label study of subjects with platinum-resistant ovarian cancer receiving either vintafolide+PLD or PLD alone. Methods: Women ≥18 years old with ECOG status 0-2 and exposure to ≤2 prior systemic cytotoxic regimens were randomized 2:1 to vintafolide (2.5 mg IV tiw, weeks 1 and 3, q28 days)+PLD (50 mg/m2 IV day 1, q28 days) or PLD alone (same dose + schedule). AEs in the safety population (received at least 1 dose of study drug) were evaluated by cycle. Results: 157 patients received a total of 720 treatment cycles (518 vintafolide+PLD, 202 PLD alone). AEs (all grades, vintafolide+PLD vs PLD alone): 85.9% and 80.2% of cycles. Anemia, neutropenia, and thrombocytopenia were observed in 16.6% (vs 10.4% administered PLD alone), 19.1% (vs 10.4%), and 2.7% (vs 3.0%) of all cycles, respectively. Febrile neutropenia was observed in 0.2% (vs 0.5%) of cycles, respectively. Stomatitis and hand-foot syndrome (HFS) occurred in 16.6% (vs 22.8%) and 19.1% (vs 15.8%) of cycles, respectively. Peripheral sensory, motor, or sensorimotor neuropathy or polyneuropathy occurred in 10.1% (vs 2.5%) of cycles, and constipation and small intestinal obstruction/ileus were observed in 12.7% (vs 10.4%) and 2.9% (vs 4.0%) of cycles, respectively. Fatigue was similar between arms—15.8% of vintafolide+PLD vs 14.9% of PLD cycles. All AEs were noncumulative except for HFS, which for both arms increased in frequency through Cycle 6 compared with Cycles 1 and 2. Grade 3/4 AEs (vintafolide+PLD vs PLD alone): 29.3% vs 18.3% of cycles. Conclusions: After the number of treatment cycles was accounted for, anemia, neutropenia, and neuropathy were numerically greater in patients on vintafolide+PLD. Thrombocytopenia, constipation, small intestinal obstruction/ileus, fatigue, and HFS were similar. Stomatitis was numerically greater in patients administered PLD alone. Clinical trial information: NCT00722592.
Statin and aspirin use and risk of VTEs in ovarian cancer patients.
Authors: Rennert Hedy S , Rennert Gad , Lavie Ofer , Sagi Shlomi , Leviov Michele , Steiner Mariana , Shai Ayelet 
Published: March 2020

5576 Background: Deep vein thrombosis and pulmonary embolism - venous thromboembolic events (VTEs) - are associated with significant morbidity and increased risk of mortality in cancer patients. Ovarian cancer patients are at a particularly increased risk for VTEs. Statins and aspirin have been shown to reduce the risk of VTEs in the general population in randomized trials. However, the effect of these medications on the incidence of VTEs in ovarian cancer patients has not been studied. Methods: Patients diagnosed with ovarian cancer between years 2000 and 2011 were identified through the Israeli Cancer Registry (ICR). Patients insured by Clalit Health Services, the largest HMO in Israel, were included. Data regarding medication use, chronic diseases and VTE diagnosis were extracted from the computerized database. Patients taking Warfarin or Low Molecular Weight Heparin for 3 months or longer were excluded. Statistical analysis was performed using SPSS (v 18). Use of medications was analyzed as a time dependent covariate in a Cox regression model. Results: Of 1,886 patients 179 (9.5%) had a VTE during a median follow up of 3.13 years. 95 patients (5%) had a VTE 2 years after diagnosis of ovarian cancer. In a multivariate analysis use of chemotherapy and stage 3 or 4 at presentation were associated with an increased risk for VTE's 2 years after diagnosis. Age was associated with a trend for increased risk. Statins were used by 43.2% of the patients, and 31.9% used aspirin. Aspirin use was associated with a reduced incidence of a VTE, which was borderline statistically significant (p=0.054). Statin use did not affect the incidence of VTE's in the group of ovarian carcinoma patients. Conclusions: Our results suggest that in patients with ovarian cancer aspirin use is a possible protector from deep vein thrombosis and pulmonary embolism. Prospective trials are warranted to assess the benefit of aspirin and statins for prevention of VTE's in the high risk population of ovarian cancer patients. [Table: see text]