bluuebunny/crossref_metadata_2025_split huggingface dataset:
Utilizing propensity scores to determine the risk of recurrence and death in epithelial ovarian cancer.
Authors: Warner Lindsay Louise Morgenstern , Dowdy Sean Christopher , Martin Janice , Lemens Maureen , McGree Michaela , Weaver Amy , Podratz Karl C. , Bakkum-Gamez Jamie Nadine 
Published: March 2020

5577 Background: Perioperative red blood cell transfusion (PRBCT) may be a negative prognostic marker in surgical oncology. We assessed PRBCT as an independent risk factor for recurrence and death from epithelial ovarian cancer (EOC) in the largest cohort to date. Methods: Patient characteristics and process-of-care variables (NSQIP-defined, >130 variables) were retrospectively abstracted from 587 women who underwent primary staging and cytoreduction for EOC (1/1/03-12/29/08). Evaluated using propensity scoring with univariate logistic regression and odds ratios (OR) and Cox proportional hazards regression and hazard ratios (HR). Factors with p<0.1 used in multivariate models. Results: Rate of PRBCT was 77.0% (452/587). In univariable analysis, PRBCT was associated with older age (OR 1.25[95% CI 1.06, 1.48]/10yr increase), stage≥IIIa (4.66[3.04, 7.13]), splenectomy (26.63[3.67, 193.17]), higher surgical complexity (1.86[1.17, 2.95] score 2; 21.48 [7.37, 62.59] 3; referent 1), serous histology (2.36[1.57, 3.55]vs non-serous), longer operating time (1.58[1.36, 1.83]/hr increase), and residual disease (3.26[1.97, 5.41]≤1cm; 1.97[1.09, 3.56]>1cm), and lower preop hemoglobin (Hb) (1.89[1.59, 2.27]per 1g/dL decrease). In univariable analysis, PRBCT was associated with a higher risk of recurrence (HR 1.96[95% CI 1.43, 2.68]) and death (1.71[1.28, 2.28]). However, in multivariable analysis, stage≥IIIa (4.03[2.05, 6.49]), splenectomy (1.41[1.02, 1.95]), residual disease (1.86[1.41, 2.46]≤1cm; 2.91[2.02, 4.18]>1cm), and lower preop Hb (1.09[1.01, 1.19]) were associated with higher risk of recurrence. Older age (1.24[1.12, 1.37]), stage≥IIIa (3.07[1.93, 4.90]), albumin ≤3 g/dL (2.06[1.28, 3.31]), residual disease (1.63[1.22, 2.19]≤1cm; 3.03[2.19, 4.18]>1cm), and low Hb (1.08[1.00, 1.19]) were associated with higher risk of death. Serous histology (0.70[0.52, 0.95]) associated with lower risk of death. Conclusions: PRBCT does not appear to be directly associated with disease-free and overall survival in EOC. Lower preoperative Hb was associated with a higher risk of both recurrence and death. The need for PRBCT appears to be a stronger prognostic indicator than the receipt of PRBCT.
High-grade endometrial cancer: Revisiting tumor size and the lower uterine segment.
Authors: Doll Kemi M. , Denslow Sheri , Tseng Jill , Gehrig Paola A. , Nickles Fader Amanda 
Published: March 2020

5589 Background: Tumor size is an independent poor prognostic factor in endometrial cancer, while tumor location has shown mixed results, with few studies addressing high-grade disease. We aim to determine if tumor size (TS) or lower uterine segment involvement (LUS) is associated with nodal disease and recurrence in high-grade endometrial cancer. Methods: In an IRB-approved, multi-institutional cohort study of patients with clinically early-stage, high-grade endometrial cancer (grade 3 and all non-endometrioid histologies), records were reviewed for demographic, pathologic, and treatment data. Recurrence as a function of tumor size and location were analyzed using logistic regression and exact tests for significance. Hazard ratios were calculated. Results: 208 patients with high-grade histology were identified from Jan 2005 to Jan 2012 with 188 patients having tumor location identified and 183 having tumor size reported. Both pelvic and para-aortic lymphadenectomy were completed in 100% of patients. There were 75 endometrioid (36.1%), 35 papillary serous (16.8%), 12 clear cell (5.8%), 26 carcinosarcoma (12.5%), and 60 (28.8%) with undifferentiated or mixed histology. Median follow up time was 17.2 months (0.2 – 67.6 mo) with 55 recurrences. LUS tumors were more likely to have pelvic and para-aortic nodal disease (OR 3.83, 95%CI 1.70 – 8.60, OR 5.13, 95% CI 1.96 – 13.45) and increased recurrence rates (HR 2.21, 95% CI 1.16-4.20) on univariate analysis. Tumors size ≥2cm was associated with pelvic nodal disease (27.4% vs. 0%, p = 0.01; OR 10.00, p = 0.01). TS was not independently associated with recurrence and patterns of failure did not significantly differ with LUS involvement. Conclusions: In patients with clinically early stage, high-grade endometrial cancers, TS and LUS tumor location are significantly associated with lymph node metastasis and advanced stage disease at the time of comprehensive surgical staging. Tumor location in particular is strongly associated with distant nodal disease and is a poor prognostic indicator for recurrence. Studies evaluating the role of adjuvant therapy based on tumor size and tumor location would be helpful in improving patient related outcomes.
Statin use in uterine malignancies.
Authors: Spoozak Lori Ann , Girda Eugenia , Van Arsdale Anne , Einstein Mark H. , Goldberg Gary L. , Nevadunsky Nicole 
Published: March 2020

5592 Background: Statins, or 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors, are commonly used to manage hyperlipidemia. Epidemiologic studies have recently linked statins to improved cancer survival. Molecular pathways that explain this effect are not well defined, but may involve cell death and angiogenesis. Our aim was to determine the association between statin use and overall survival in a cohort of women with uterine malignancies. Methods: After IRB approval, a retrospective review of consecutive patients with uterine malignancies diagnosed between 01/2005 and 12/2009 at a single institution was performed. Age, race, diagnosis of hyperlipidemia, diabetes, hypertension, medication use including statins, beta-blockers, aspirin, pathology, and exposure to chemotherapy or radiation were abstracted from the time of initial diagnosis and treatment. Kaplan-Meier analysis, univariate, and multivariate Cox Proportional Hazard Regression were performed to assess the association between statin use, aspirin use, and survival. Results: Of 554 patients identified, 333 (60%) were not hyperlipidemic (NH), 165 (30%) were hyperlipidemic on statins (HS), and 56 (10%) were hyperlipidemic and not on statin therapy (HNS). The HS cohort was older, diabetic, hypertensive, used beta-blockers and aspirin. Stage, grade, and chemotherapy use were similar, but HS and HNS received more radiation (p<0.05). Both patients in the HS and HNS groups had improved overall survival compared to NH patients (p=0.04). Further stratifying our subgroups by aspirin use revealed that HS+aspirin users had significantly improved survival compared to other non-HS+aspirin users (p=0.01). In multivariate analysis, women who used statins had a 45% decreased hazard of death compared to NH women (HR = 0.55, 95% CI; 0.35, 0.87). Additionally, aspirin users had improved survival compared to non-users (HR = 0.47, 95% CI; 0.29, 0.76). Women using statins and aspirin had an 84% decreased hazard of death in comparison to other groups (HR = 0.16, 95% CI; 0.07,0.38, p<0.01). Conclusions: Statin and aspirin use are associated with improved overall survival in patients with uterine malignancy. Prospective evaluation of statin and aspirin use in uterine cancer is warranted.
Cridanimod and progestin therapy in hormone-resistant endometrial cancer.
Authors: Carlson Matthew J. , De Geest Koen , Wang Xiaofang , Leslie Kimberly K. , Dai Donghai 
Published: March 2020

5597 Background: Cridanimod is a novel small molecule that has been shown to increase progesterone receptor (PR) expression in rat endometrium. We hypothesize that cridanimod, in combination with progestin therapy, will increase PR expression and, thus improve survival in a mouse model of advanced, high grade endometrial cancer. Methods: Hec50co cells, established in our laboratory to represent genetically and phenotypically type II endometrial cancer, were injected into the peritoneal cavity of 96 athymic mice. These mice were randomly divided into 6 groups, receiving the following therapies: control (no therapy), medroxyprogesterone acetate (MPA) alone, cridanimod 1mg IM twice a week plus MPA, cridanimod 3mg plus MPA, cridanimod 6mg plus MPA, and adenovirus-mediated PR expression plus MPA. PR expression in tumor tissue and serum interferon (IFN) levels were assayed via Western blot and ELISA, respectively. Results: Kaplan-Meier survival analysis showed that the group receiving MPA plus 6 mg cridanimod twice a week had a significantly longer survival time than the control or MPA alone (62 ± 7.0 days vs 38 ± 5 or 33 ± 3, respectively, p < 0.05). The group with MPA plus 3 mg cridanimod had a significantly longer survival than the group with MPA alone (56 ± 8.0 days vs 33 ± 3, p < 0.05). Western blot analysis showed that PR proteins were substantially higher in xenograft tumors from animals treated with cridanimod at doses of 3mg and 6mg when comparing to the control and MPA alone groups, ELISA data showed significant increases in IFNα and -β in cridanimod-treated mice in a dose-dependent manner. Conclusions: Combined progestin and cridanimod therapy significantly improved survival of mice with high-grade, advanced endometrial cancer. Cridanimod significantly increased PR expression, suggesting that the therapeutic benefit of combined therapy is mediated by up-regulation of PR, which is likely to be mediated through cridanimod induction of IFNα and IFNβ expression. Further investigation is warranted to determine the utility of this promising agent.
Incidence, management, and resolution of noninfectious pneumonitis in BOLERO-2.
Authors: Ito Yoshinori , Noguchi Shinzaburo , Deleu Ines , Baselga José , Hortobagyi Gabriel N. , Bachelot Thomas Denis , Masuda Norikazu , Pistilli Barbara , Pritchard Kathleen I. , Iwata Hiroji , Gnant Michael , Eakle J F , Csõszi Tibor , Srimuninnimit Vichien , Puttawibul Puttisak , Roila Fausto , Panneerselvam Ashok , Taran Tanya , Sahmoud Tarek , Rugo Hope S. 
Published: March 2020

561 Background: The BOLERO-2 trial showed that adding everolimus (EVE) to exemestane (EXE) more than doubled progression-free survival (PFS) without reducing quality of life versus placebo (PBO) + EXE alone in postmenopausal women with hormone-receptor–positive (HR+), HER2-negative (HER2–) advanced breast cancer (ABC) progressing on/after nonsteroidal aromatase inhibitor (NSAI) therapy. Although generally well tolerated, mTOR inhibitors such as EVE have been associated with noninfectious pneumonitis (NIP). Methods: Patients (pts) were randomized 2:1 to receive EVE+EXE or PBO+EXE. Incidence and severity of NIP, consequent dose interruptions/adjustments, study drug discontinuations, and time to resolution were recorded. Results: Median duration of exposure to EVE was 24 weeks with median dose intensity of 8.6 mg/d. Pulmonary adverse events (AEs) of any grade (NIP, interstitial lung disease, lung infiltration, pneumonia, or pulmonary fibrosis) were recorded in 97 of 482 pts (20%) in the EVE+EXE arm versus 1 of 238 pts (<1%) in the PBO+EXE arm. Of these, 16% of pts (77 of 482) in the EVE+EXE arm versus 0 in the PBO+EXE arm had a diagnosis consistent with NIP. In the EVE+EXE arm, grade 1 (no symptoms), grade 2 and 3 NIP occurred in 7%, 6% and 3% of pts, respectively, and no grade 4 events were reported. Complete resolution of NIP to grade ≤1 was recorded for all but 4 pts for whom NIP was still observed at last follow-up before study discontinuation. Overall, in the EVE+EXE arm, NIP was recorded as the reason for dose interruption and treatment discontinuation in 7.5% and 5.6% of pts, respectively. Conclusions: Data from BOLERO-2 support the combination of EVE and EXE to significantly prolong PFS in postmenopausal women with HR+, HER2– ABC progressing on/after NSAI. The incidence of NIP in this study was generally consistent with reports from other oncology settings, was of mild to moderate severity, and was generally reversible with appropriate interventions and temporary dose modifications. Patient and healthcare provider education for early diagnosis and management of NIP are highly recommended. Clinical trial information: NCT00863655.
Initial results from the 21-gene breast cancer assay registry: A prospective observational study in patients (pts) with ER+, early-stage invasive breast cancer (EBC).
Authors: Vacirca Jeffrey L. , Tsai Michaela L. , Brufsky Adam , Michaelson Richard Alan , Smith Frederick P. , Schwartzberg Lee Steven , Butler Steven M , Jamshidian Farid , Sing Amy Pratt 
Published: March 2020

565 Background: Genomic assays such as the 21-gene breast cancer assay (Oncotype DX), have improved the ability to individualize pt treatment based on their individual tumor’s biology. Since 2004, when the 21-gene assay became commercially available, more than 300K assays have been ordered. While several studies have been conducted assessing the impact of having the Recurrence Score (Score) result on treatment decisions, most have been retrospective or evaluating the treatment recommendation. The Oncotype DX Breast Cancer Registry is a large prospective study conducted in clinical practices evaluating the types of pts having the assay ordered and the actual treatments delivered. We report here the first set of analyses. Methods: Pts with ER+ EBC were eligible to enroll. Data collected at baseline (BL) included age, size, grade, ER, PR and HER2 status. Data collected at the 6-month visit included Score and treatment given. Pt demographics, Score distribution, and associations with clinicopathologic (CP) factors are described. Results: A total of 890 pts were enrolled at 15 U.S. sites between 11/09-3/12. 803 eligible pts were included in the analyses. The Table shows BL characteristics, Score distribution and %CT given. Distribution of Score values across the CP factors was similar to the cohort overall. 30% of pts received CT. Among low Score patients, CT was given in 17% of pts <50y, 9% of Grade 3 tumors and 11% of tumors >2cm. Conclusions: A large, prospective registry for pts with EBC receiving the 21-gene breast cancer assay examined the application of the Score to treatment. The Score distribution is consistent with other retrospective cohorts. The association between the Score and the CP factors was modest. The CP factors did not predict the Score. In general, CT decisions followed the Score with the exception of younger pts; 17% received CT despite a low Score. These findings from a real-world cohort underscore the importance of understanding breast cancer biology in order to make more informed and individualized treatment decisions. [Table: see text]
Phase I clinical trial of bavituximab (Bavi) and paclitaxel (P) in patients (pts) with HER2-negative metastatic breast cancer (MBC).
Authors: Chalasani Pavani , Marron Marilyn , Clarke Kathryn , Schmidt Kathy , Powell Alisa , Iannone Maria , Stopeck Alison 
Published: March 2020

567 Background: Bavituximab is a novel tumor vascular targeting agent. It is an unconjugated, chimeric immunoglobulin G1 monoclonal antibody directed against phosphatidylserine (PS). PS is externally expressed on endothelial cells when exposed to hypoxia and/or other physiological stressors frequently observed in tumor-associated vasculature. On attaching to PS, Bavi triggers antitumor effects by inducing antibody-dependent cellular cytotoxicity and promoting antitumor immunity. Methods: We conducted a phase I clinical trial of Bavi in combination with P in pts with HER-2 negative MBC. Pts were treated with weekly P (80mg/m2 for 3/ 4 weeks) and weekly Bavi (3mg/kg for 4/ 4 wks). Microparticle generation, activation and circulating endothelial cell apoptotic markers were measured by flow cytometry. Results: 14 pts with MBC were enrolled. Median age at MBC diagnosis was 50yrs. Seven pts had triple negative MBC; 4 pts presented with de-novo metastatic disease. Prior treatments included chemotherapy in the adjuvant/neoadjuvant setting (8); metastatic setting (2); adjuvant hormonal therapy (3). Best responses to date include complete response (1), partial response (6), stable disease (1), progressive disease (2) and too early to evaluate (4). Bavi related toxicities include grade2/3 infusion related reactions in 2 pts (1 discontinued Bavi). Bone pain, fatigue, headache and neutropenia were the most common adverse effects. 1 pt had a catheter associated upper extremity thrombosis requiring anticoagulation. Laboratory correlative studies revealed no evidence of platelet activation of PAC-1 or P-Selectin. Median platelet and endothelial microparticles decreased from baseline in response to therapy. Conclusions: Bavi is a novel vascular targeting agent that is well tolerated in combination with P. Early results show promise in terms of clinical responses with 8 of 10 evaluable patients having clinical benefit. Early biomarker results suggest no effect of therapy on platelet activation but decreases in circulating microparticles is observed. Clinical trial information: NCT01288261.
Periodontal health in early-stage postmenopausal breast cancer survivors on aromatase inhibitors.
Authors: Taichman L. Susan , Inglehart Marita , Giannobile William , Braun Thomas , Kolenic Giselle , Van Poznak Catherine 
Published: March 2020

568 Background: Aromatase inhibitors (AIs) are associated with profound estrogen deprivation resulting in reduced bone mineral density (BMD). Periodontal diseases and tooth loss are associated with estrogen withdrawal and decreased systemic BMD. Little is known as to the impact of AIs on oral health. To investigate oral health as a breast cancer (BCA) survivorship concern, a prospective study was initiated to determine the prevalence of periodontal diseases in postmenopausal early stage (I-IIIA) BCA survivors on adjuvant AI therapy. Baseline assessments are presented here. Methods: Women within 6 months of initiating adjuvant AI for hormone receptor positive BCA were eligible to participate in this study of serial assessments of oral health. A control group of women without BCA and not on AI underwent parallel assessments. Periodontal status was evaluated by the following established dental techniques; (1) periodontal pocket depth (PD), (2) number of teeth with bleeding on probing (BOP), (3) the number of teeth with clinical attachment loss (CAL). Questionnaires regarding socio-demographic and dental utilization were administered to all participants. Linear regression modeling was used to analyze the outcomes. Results: The study met its target accrual of 58 postmenopausal women; 29 with BCA on AI and 29 controls. Demographics were similar regarding age, education, income level, frequency of dental visits, and dental insurance status across both groups. Baseline assessments demonstrated no differences in PD (2.0 mm vs. 2.0 mm; p < 0.95) or the number of teeth (26.6 vs 26.1; p< 0.39). Interestingly, the AI group had significantly more sites of BOP (27.9 vs 16.7; p < 0.02), and higher CAL (5.2 mm vs 4.0 mm; p < 0.01) than did controls. In linear regression analysis adjusted for income, AI use increased CAL by 1 mm (95% CI: 0.15 -1.88). There was also a trend for decreased CAL in subjects with incomes over $75,000 per year (p< 0.06). Conclusions: This first investigation of the periodontal status of women initiating adjuvant AI therpay identifies this population to have signs of increased risk for periodontal disease. Serial oral health assessments are being conducted to assess AI therapy and periodontal changes over time. Clinical trial information: NCT01693731.
Evaluation of microRNA-10b expression as a novel predictive marker of metastases development and patients’ survival in breast cancer.
Authors: Parrella Paola , Barbano Raffaela , Pasculli Barbara , Fontana Andrea , Copetti Massimiliano , Valori Vanna Maria , Poeta Maria Luana , Perrone Giuseppe , Castelvetere Marina , Coco Michelina , Balsamo Teresa , Pellegrini Fabio , Onetti-Muda Andrea , Maiello Evaristo , Murgo Roberto , Fazio Vito Michele 
Published: March 2020

576 Background: MicroRNA-10b was found highly expressed in metastatic breast cancer cell lines and able to generate metastases in mice models. The aim of this study is to evaluate the putative association between miR10b expression and disease progression. Methods: We selectedfrom our tumor bank 150 consecutive breast cancers with at least three years follow up. For each case frozen paired tumor and normal tissue and complete clinical data were available. Pathological examination was performed to ensure that each tumour sample contained more than 70% of cancer cells resulting in 114 samples suitable for RNA extraction. RNA quality was measured and only samples with RIN≥7.0 were analyzed (n=101) by a relative quantification method. Results: miR10b relative expression in tumor to normal samples (RERs) was significantly higher in the subgroup of patients with metastases (median 0.25 IQR 0.11-1.02) as compared with patients without metastases (median 0.09 IQR 0.04-0.29) (P=0.023 Mann Whitney Test). The association between miR-10b RERs and survival was evaluated in the group of patients without metastases at diagnosis (n=90). In univariate Cox regression model, patients with high miR-10b RERs had a higher risk of distant metastases development (HR 4.91, P=0.02) and disease related death (HR 6.02; P=0.01). In a multivariate Cox regression model adjusted for tumor size, lymph node metastases, grade, ER, PgR status, and Ki67 labeling index (n=79), higher miR-10b RERs were still associated with increased risk of distant metastases development (HR18.84; P<0.001) and disease related death (HR 13.39; P=0.003) (Table). Conclusions: We show that in breast cancer patients miR-10b expression is associated with worse prognosis on a short term follow up. These results suggest that miR-10b expression could be used for individual patient’s risk assessment and perhaps as potential therapeutical target. [Table: see text]