bluuebunny/crossref_metadata_2025_split huggingface dataset:
Surface-modified nanoparticle transport evaluated in a multistage model of ovarian cancer.
Authors: Winter Stephen , Miller Hunter , Frieboes Hermann , Steinbach-Rankins Jill 
Published: May 2020

e18057 Background: A novel multi-stage model composed of ovarian cancer (SKOV-3) and fibroblast (MRC-5) cells was developed to provide a physiologically relevant in vitro platform to assess nanoparticle (NP) transport and aid in the development of more targeted clinical therapies. This multicellular ovarian tumor spheroid model is customized to the stages of ovarian cancer progression. The model leverages knowledge of these distinct stages in vivo to simulate their respective microenvironment, and thus provide a more accurate platform for evaluation of nanoparticle transport and drug delivery into ovarian tumor tissue. We hypothesized that alterations to the tumor microenvironment (TME) along with inclusion of a peptide-based scaffold (Puramatrix, PMX) to represent the site of metastasis, would lead to enhanced cell growth, migration and altered NP transport, which may be more indicative of the challenging transport conditions encountered in clinical ovarian cancer. Methods: In order to validate the in vitro model, tumor spheroid growth and invasion were evaluated while exposed to stromal cell activation and tissue hypoxia. MRC-5 activation was achieved via the TGF-ß1 mediated pathway, while tissue hypoxia was induced via incubation at 5% oxygen. PEG and MPG surface-modified NP transport was assessed in both stages of the model via confocal microscopy. Results: Consistent with in vivo observations in the ascites and site of distal metastasis, spheroids exposed to an activated stromal microenvironment were denser, more contractile and more invasive than their unactivated counterparts (p < 0.05). Additionally, hypoxic conditions, like those observed in the low pH environment of the ascites, resulted in negative spheroid radial growth over 5 days, compared to an increase for those cultured in normoxic conditions (p < 0.005). MPG-modified NPs exhibited superior tissue penetration relative to PEG-modified NPs in the ascites stage of the model (p < 0.05). Alternatively, PEG NPs enhanced penetration relative to MPG NPs when evaluated under metastatic conditions. In this case, NP transport was attenuated regardless of surface modification, due to the PMX-induced ECM reorganization. Conclusions: A novel multi-stage model, representative of ovarian cancer, was developed to evaluate NP transport in tumor tissue. We evaluated critical conditions in the microenvironment of ascites and metastasis and how these conditions may affect nanotherapy. Future studies will evaluate NP treatments by encapsulating a chemotherapeutic and measuring IC-50 values.
Use of clinical classification software to differentiate good versus poor prognostic patients with ovarian cancer: A SEER-Medicare database analysis from the viera study.
Authors: Adeboyeje Gboyega , Desai Kaushal , Iqbal Shahed , He Jinghua , Monberg Matthew J. 
Published: May 2020

e18069 Background: Historically, recurrence in ovarian cancer (OC) following first-line (1L) chemotherapy (CT) occurs in up to 80% of patients within 2 years. The Clinical Classification Software (CCS) systematically classifies thousands of ICD-9 codes into a smaller number of clinically meaningful categories. We sought to use CCS and other routinely collected variables to differentiate the clinical and demographic profiles of patients with good prognosis (GP) versus poor prognosis (PP) in the United States (US). Methods: This was a retrospective cohort study of newly diagnosed (FIGO stage II - IV), treatment-naïve patients, ≥ 66 years, who received 4-10 cycles of platinum-based 1L CT between Jan 2009 - Dec 2015 using the SEER-Medicare database, a nationally representative cancer registry. Patient were assumed to have progressed to a subsequent line of therapy following a gap between consecutive CT cycles ≥ 63 days. Patients were classified as GP if alive ≥4 years with no further treatment following 1L CT; PP was defined as receipt of ≥2L CT within 12 months of initial 1L CT. Demographic and prognostic characteristics were assessed during a 6-month baseline period prior to initiation of 1L CT. We assessed clinically meaningful differences in baseline characteristics with absolute standardized differences (ASD) using a threshold of 0.1 (indicating negligible difference between two cohorts). Results: There were a total of 2,262 patients (mean age: 74.6 ±6.2 years) including 251 GP (11%) and 209 PP (9%) patients (table below). PP patients were significantly more likely to be older than 70 years, and present at stage IV, liver disease and ascites, and anemia at diagnosis. PP patients were also less likely to have primary debulking surgery. Conclusions: Approximately one tenth of OC patients received no further treatment 4 years after the initial treatment with contemporary standard of care. GP may be differentiated from PP on the basis of commonly used clinical characteristics such as stage and also specific comorbidities such as liver disease and ascites. [Table: see text]
Comparison of poly(ADP-ribose) polymerase inhibitors (PARPi's) as maintenance therapy for platinum-sensitive ovarian cancer: Systematic review and network meta-analysis.
Authors: Stemmer Amos , Tsoref Dalia , Stemmer Salomon M. 
Published: May 2020

e18070 Background: Over the past decade, 3 PARPi's (olaparib, niraparib and rucaparib) have been approved by the FDA as maintenance therapy for recurrent ovarian cancer. However, thus far, no trial compared the 3 approved PARPi's in the overall population, in patients with BRCA mutations (BRCAm), or in those with wild-type BRCA (BRCAwt). Methods: We performed a systematic review and identified relevant literature from Embase, Pubmed and Cochrane Library. To be included in the analysis, studies had to be phase 2 or 3 randomized controlled trials (RCT) of platinum-sensitive recurrent or newly diagnosed ovarian cancer, randomized to placebo or PARPi as maintenance therapy and where complete or partial response was documented. A frequentist network meta-analysis was used for indirect comparisons between the different PARPi's to assess superiority in terms of progression free survival (PFS), overall survival (OS), and adverse events. Results: Overall, 6 RCTs involving 2,770 patients, were included in the network meta-analysis. Results from the indirect comparisons revealed no statistically significant differences between the 3 different PARPi's with respect to OS. PFS results demonstrated a nonsignificant trend supporting superiority for niraparib in all patients as well as in BRCAm patients (Table). Only 2 studies reported OS results for niraparib and none reported OS results for rucaparib. Niraparib showed a statistically significant increased risk for all grade thrombocytopenia and neutropenia. Conclusions: Our analysis demonstrates no statistically significant differences between the 3 PARPi’s in any of the analyzed groups, and a trend supporting PFS superiority for niraparib in all patients and in BRCAm patients, while having greater risk for thrombocytopenia and neutropenia. Additional OS results are pending from current studies, and would be useful for elucidating the relative roles of the different PARPi's in platinum-sensitive ovarian cancer. [Table: see text]
Efficacy of platinum-based chemotherapy in platinum-resistant ovarian cancer: A systematic review with pooled analysis of outcomes.
Authors: Rumyantsev Alexey , Tyulyandina Alexandra , Fedyanin Mikhail , Pokataev Ilya , Glazkova Elena , Nikulin Vladislav , Tjulandin Sergei 
Published: May 2020

e18076 Background: Current management of recurrent ovarian cancer (OC) is based on the amount of time between the completion of penultimate platinum-based treatment and the detection of relapse. Patients with platinum-free interval (PFI) < 6 mo. are considered to be platinum-resistant (PROC) and to have low response rate (RR) probability to platinum-based chemotherapy. Methods: We searched PubMed database for all prospective and retrospective full-text articles and abstracts on the treatment of patients with PROC for all years between 01/01/2000 and 01/06/2019 in English language. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) tool was used to ensure transparent reporting of the results. Study inclusion criteria were: 1) morphologically confirmed epithelial ovarian cancer; 2) standard definition of PROC as a disease that recurred within 6 months after completion of platinum-based chemotherapy; 3) treatment with platinum- or non-platinum chemotherapy with agents that are routinely used for OC; 4) no concomitant therapy with targeted or investigational agents; 5) clearly defined RR for patients with PROC and criteria used for response assessment. Pooled analysis of outcomes and multiple linear regression analysis was conducted to assess the impact of platinum salts on probability of response. Results: We identified 7156 articles and screened them for title and abstract. After the review process we selected 197 studies for further analysis. Of them, 52 (n = 1320) and 145 (n = 6937) trials assessed efficacy of platinum- and non-platinum based chemotherapy respectively. Among patients treated with platinum-based and non-platinum chemotherapy RR was 36.04% (95% CI 33.45-38.63) and 14.85% (95% CI 14.01-15.68) respectively. Pooled median progression-free survival was 5.8 mo. and 3.75 mo. respectively. In multiple linear regression model administration of platinum-based chemotherapy was the strongest predictor of objective response with B value 0.503 (p < 0.001). Among platinum agents cisplatin (RR 39.9%: 95% CI 35.8-44.0%) and carboplatin (RR 42.3%; 95% CI 37.0-47.6%) were associated with better rates of objective response compared to oxaliplatin (RR 28.1%; 95% CI 23.9-32.3). Conclusions: This systematic review shows that patients with 'platinum-resistant' ovarian carcinoma may derive significant benefit from reintroduction of platinum agents and their value should be evaluated in further randomized trials.
Effect of bevacizumab in first-line chemotherapy on progression-free survival in advanced ovarian clear cell carcinoma.
Authors: Tate Shinichi , Nishikimi Kyoko , Matsuoka Ayumu , Shozu Makio 
Published: May 2020

e18086 Background: Advanced ovarian clear cell carcinoma (ACCC, stage III/IV disease) is a rare tumor characterized by chemoresistance. To evaluate the efficacy of bevacizumab (Bev) for ACCC, we investigated the survival outcome of first-line treatment before and after the approval of Bev for ovarian cancer treatment in November 2013 in Japan. Methods: We recruited 28 consecutive patients diagnosed with ACCC at our institution between 2007 and 2018. We performed cytoreductive surgery and administered paclitaxel-carboplatin chemotherapy (paclitaxel: 80 mg/m2 + carboplatin area under the curve 2.0–3.0 mg/mL/min, weekly without break) as first-line chemotherapy. Bev (15 mg/kg/3 weeks) was also administered after its approval. We compared progression-free survival (PFS) between Bev+ group (n = 18) and Bev- group (n = 10) using the Kaplan–Meier method and a Cox regression model. Results: Patients characteristics were similar between the Bev- and Bev+ groups. The median age was 54 years and 53 in the Bev- and Bev+ groups (p = 0.810), respectively. Three (30%) and 4 (22%) patients in the Bev- and Bev+ groups had stage IV disease (p = 0.674), respectively. The performance status (PS) was ≥2 in 1(10%) and 5 (28%) patients in the Bev- and Bev+ groups (p = 0.375), respectively. Peritoneal cancer index was 5.5 and 5.5 in the in Bev- and Bev+ groups (p = 0.727), respectively. Primary debulking surgery was performed in 10 (100%) and 11 (61%) patients in the Bev- and in Bev+ groups, respectively. Surgical complexity score was 9 and 9 in the Bev- and in Bev+ groups (p = 0.700), respectively. Completeness of resection was higher in the Bev- group (9/10, 90%) than in the Bev+ group (15/18, 83%) (p = 0.044). Eleven (61%) patients in the Bev+ group received ≥21 cycles of Bev. The median PFS increases from 12.0 months before Bev approval to 29.8 months after Bev approval (Wilcoxon test, p = 0.026). Multivariate analysis revealed that Bev use (p = 0.005) and PS < 2 (p = 0.035) were independent prognostic factors for PFS; however, completeness of resection was not a prognostic factor (p = 0.052). Conclusions: Bev in first-line chemotherapy improves the survival outcome of ACCC. [Table: see text]
Development of a personalized ex vivo drug screening test for patients with ovarian cancer.
Authors: Brückner Luzi , Reinshagen Annika , Aktas Bahriye , Bechmann Ingo , Nel Ivonne , Kallendrusch Sonja 
Published: May 2020

e18090 Background: The standard therapy of patients with ovarian cancer consists of primary surgery followed by chemotherapy. Initial response rates are very high, but recurrence occurs in 85% of the cases. Personalized ex vivo analyses of various anti-tumor compounds in a standardized tissue slice culture system (1) might be a very promising approach for individualized therapeutic decisions. In comparison to cell culture, tumor slice cultures maintain the direct tumor microenvironment which plays a role in resistance mechanisms and thus therapy response. Methods: Patient derived tumor cultures (1) are grown under standardized conditions and are analyzed semi-automated. Patient’s tumor samples were collected during surgery, cut into standardized slices and were cultivated in triplicates for 2, 4, 7 and 14 days and treated with standard therapy for 7 days. A baseline control was prepared at day 0. The cultured tissue is PFA-fixated and paraffin embedded. Hematoxylin eosin staining was performed for microscopic evaluation of morphologic structures. Subsequently, immunohistochemical staining against CD3 was applied to examine the immune setting of the tumor and its environment. Results: Ovarian tumor tissues remained their morphological properties over a period of 14 days. Parameters like cellular formation, proliferation and heterogeneity were adequately represented in the cultures.. Staining against CD3 revealed T-cells in ovarian tumor tissue slices up to 14 days ex vivo and individual response to treatment was observable. Conclusions: Correlation to clinical data is ongoing to analyze the tissue culture model of ovarian cancer for clinical usage. Different approaches, concerning mutational burden, immunological signature and histology are considered for decision of response and non-response.
Prognostic significance of hormone receptor (ER/PR) status in endometrial carcinoma in black women: Implications with lymph node metastasis.
Authors: Shah Manan , Jain Sanjay R , Oprea Gabriela , Shafi Saba 
Published: May 2020

e18099 Background: Histological examination of tumor tissues is necessary for deciding if endometrial surgery should include lymph node sampling. Studies have demonstrated that loss of estrogen and progesterone receptors (ER/ PR) independently predicts lymph node metastasis and poor prognosis. African American females in comparison to their Caucasian counterparts are diagnosed at a later stage, with higher grade, poorer prognostic histological types and worse outcomes. Our study aimed to investigate if the correlation between hormone receptor status and lymph node metastasis holds true in African American females which could aid in treatment strategies. Methods: We reviewed African American females (n = 70) diagnosed with Endometrial Cancer at our institution from 2015-2018 including endometrioid/non-endometrioid histology, FIGO stage I-IV, grade 1-3 for ER/PR receptors and presence or absence of pelvic lymph nodes based on preoperative endometrial curettage and post-surgical pathology specimens. Statistical analyses were performed using Fisher’s Exact test exploring associations between categorical variables (ER/PR and Lymph nodes Metastasis). All statistical tests were two-sided and considered significant if P value < 0.05. Results: The mean age of our sample was 61 ± 13 years. Mean BMI was 36±10kg/m2. Majority of our patients were postmenopausal (59 out of 70, 84%). FIGO Stage 1 and 2 constituted 72% (50 out of 70). Endometrioid histology constituted 39 out of 70 (55%) cases and non-endometrioid histology which includes serous, mixed and carcinosarcomas constituted 45% of the cases. Loss of estrogen receptor(ER-) was observed in 19 of 70 patients (27%) and loss of progesterone receptor(PR-) was seen in 22 patients (31%) which was significantly associated with lymph node metastasis (p value < 0.05).On subgroup analyses significant association was observed between PR+ and absence of lymph node metastasis in cases of endometrioid cancer (p value < 0.05) . Nevertheless, there was no statistical significant association (P value .10) between ER receptors and lymph node metastasis in patients with endometrioid cancer. In non-endometrioid histology both ER- and PR- were found to have statistical significant lymph node involvement. Conclusions: Loss of ER and PR receptors independently predicts lymph node metastasis in endometrial cancers in African American females.
Treatment and outcome of patients with uterine carcinosarcoma: Data from developing world.
Authors: Gulia Seema , Srikanth Anne , Adsul Dr Ketaki , Mahantshetty Umesh , Ghosh Jaya , Maheshwari Amita , Rath Sushmita , TS Shylasree , Chopra Supriya , Menon Santosh , Deodhar Kedar , Rekhi Bharat , Popat Palak , Gupta Sudeep 
Published: May 2020

e18102 Background: To evaluate the clinicopathological factors, outcome and prognostics factors of uterine carcinosarcoma. Methods: All patients of uterine carcinosarcoma treated between January 2013 and December 2018 were identified and their clinical, laboratory and imaging details were retrieved from electronic medical record. Details of the treatment received, toxicity profile and outcome were recorded and analyzed. Patients (including stage I) were considered for four cycles of chemotherapy (Paclitaxel +Carboplatin) followed by radiation (EBRT to pelvis with vaginal brachytherapy). Survival analysis was done using the Kaplan–Meier method and compared between treatment groups using the Log-rank test. Results: Of 81 cases, 48 % presented with early stage disease (FIGOI-II) and 52 % with late stage (FIGO III-IV) disease. Median age was 58 years (30-80 years). Most women (83%) were postmenopausal and 80% of them presented with postmenopausal bleeding. Six patients developed carcinosarcoma on adjuvant tamoxifen (given for breast cancer) after a median drug intake of 8 years. In early stage, 10% patients received only surgical treatment; 46% received both chemotherapy (CT) and radiation therapy (RT) while 33 % received RT alone. In advanced stage, 31% received only CT, 14 % received only RT and 33% received both CT and RT after surgery. About 8% of patients had myelosuppression(grade I/II), 10 % had peripheral neuropathy (grade I/II) and 11% had electrolyte imbalance. At a median follow up of 2 years (1- 80 months), median DFS and OS in early stage group was 28.5 months and 31.0 months while in advanced stage group it was 13.0 months and 15.0 months respectively. Distant metastasis (omentum, peritoneum and lung being the common site) were seen in 30% of patients while local relapse was seen in 5 % cases. On univariate analysis stage of disease and receipt of adjuvant therapy were the factors found to be significantly associated with improved OS (p < 0.001) and adjuvant RT alone was associated with improved DFS (p < 0.023). Conclusions: Adjuvant treatment (chemotherapy and or radiation therapy) is associated with improved overall survival in uterine carcinosarcoma, irrespective of stage at presentation.
The humanistic burden reported by first-line (1L) head and neck cancer patients diagnosed with recurrent/metastatic squamous cell carcinoma (R/M SCCHN) in europe: A real-world study.
Authors: Singh Prianka , Bennett Bryan , Bailey Tom , Taylor-Stokes Gavin , Rajkovic Ivana , Postema Roelien , Curtis Sharon , Curtis Chris 
Published: May 2020

e18514 Background: R/M SCCHN is associated with substantial humanistic burden and limited tolerable treatment options that are able to preserve heath-related quality of life (HRQoL). Real world evidence is lacking to characterize and quantify burden in these patients by geographic region and treatment. Methods: A cross-sectional study was conducted in France, Germany, Italy, Spain and the UK from Jan to May 2019. Physicians (n = 184) recruited patients to complete a survey assessing the impact of their SCCHN and completed medical charts for corresponding patients. Patient burden and HRQoL was captured through the patient survey, which included the Functional Assessment of Cancer Therapy Head and Neck Cancer (FACT H&N) (range: 0-148; sub scores physical/social/functional: 0-28, emotional 0-24). Higher scores for instruments indicate better HRQoL. Patients were identified as 1L platinum eligible according to clinical characteristics and treatments captured in the medical charts. Results: Physicians recruited 577 (99 UK, 114 France, 117 Germany, 117 Spain, and 130 Italy) 1L platinum eligible patients of mean age 62.8 years, most were male (72%) and had ECOG score 0-1 (79%) or 2 (21%). Over half (52%) received the EXTREME regimen, 9% received a separate cetuximab-based regimen. Patients experienced a high symptom burden, most commonly fatigue (43%), weight loss (40%), pain (35%), and difficulty swallowing (32%). Dry mouth and persistent sore throat were reported by 19% patients. Most patients reported at least some problems with performing usual activities (62%), at least moderate pain/discomfort (79%), and at least moderate anxiety/depression (71%). Patients had a diminished HRQoL in every FACT-H&N domain: total score, 73.2; physical, 15.0; social, 16.5; emotional, 11.7; functional well-being, 10.7. Conclusions: In Europe, patients treated for 1L R/M SCCHN experience considerable humanistic burden and diminished HRQoL. These data suggest an unmet need in this patient population for novel treatments that are able to maintain or even improve HRQoL.