bluuebunny/crossref_metadata_2025_split huggingface dataset:
On a possible mechanism of platinum resistance development in patients with advanced ovarian cancer.
Authors: Zhukova Galina V. , Ulianova Elena P. , Yakubova Darya Yu. , Sagakyants Aleksandr B. , Menshenina Anna P. , Moiseenko Tatiana I. , Verenikina Ekaterina V. , Zlatnik Elena Yu , Chalabova Tatiana G. , Pustovalova Alla V. , Kit Oleg I. 
Published: June 2022

e17549 Background: The question of the mechanisms of platinum resistance development in advanced ovarian cancer (OC) remains open. The aim of the study was to reveal the relationship between the proliferative activity of OC cells, the disruption of apoptosis processes and the changes in the activity of transporter proteins that provide the efflux of chemotherapy drugs. Methods: Patients with advanced OC (T3-4N0-3M0-1) of postmenopausal age, sensitive (SPtPs, n = 23) and resistant to platinum drugs (RPtPs, n = 17), operated on after 3-6 cycles of neoadjuvant chemotherapy, were retrospectively studied. The parameters of proliferative activity (ki67), apoptosis disturbances (p53), as well as the expression of BCRP and Pgp transporter proteins were evaluated in OC tissue using immunohistochemistry methods. Statistical analysis was performed using the Mann-Whitney and Pearson tests (χ2), as well as the Spearman's rank correlation coefficient (SC). Results: In total, the dominance of the RPtPs over the SPtPs was noted in terms of intensity of the studied indicators (p < 0.05-0.003), the most significant for Pgp expression. At the same time, moderate and high values of these indicators were observed in SPtPs in 42-61% of cases, which reduced the predictive value of the revealed differences. It was of interest that statistically significant correlations between the indicators in SPtPs differed from those in RPtPs. Thus, the following values of the SC were observed in SPtPs: +0.848 (ki67-p53), -0.675 (ki67-BCRP), -0.575 (p53-BCR). In RPtPs, another intensity and/or direction of these relations were noted: +0.521 (ki 67-p53), +0.500 (ki 67-BCRP), +0.705 (p53-BCR). There were no statistically significant relationships between ki67-Pgp expression in SPtPs and RPtPs. The direction and intensity of the studied relationships could indicate changes in cell regulation in primary OC in SPtPs compared to RPtPs. Thus, in SPtPs, they reflected a significant contribution of apoptotic disturbances to the enhancement of OC cell proliferation, which was limited by the negative feedback mechanism via BCRP activity suppression indicated by the presence of an inverse correlation ki67-BCRP. In RPtPs, this mechanism was apparently already lost, which resulted in a change in the direction of the statistical relationship ki67-BCRP from reverse to direct one. Under these conditions, the positive contribution of apoptosis disruption to the proliferative activity of OC cells could obviously be supplemented by a synergistic increase in the activity of the BCRP transporter protein, which removes platinum drugs from OC cells. Conclusions: Patients with advanced OC may develop platinum resistance due to discoordination of proliferation, apoptosis, and regulation of the activity of the BCRP transporter protein.
Chemotherapy and radiofrequency hyperthermia in advanced ovarian cancer.
Authors: Deniz Gulhan Ipek , Can Ayten , Tansan Sualp 
Published: June 2022

e17550 Background: Ovarian cancer (OC) is the the leading cause of cancer death in females. Most cases present at advanced stage. Standard treatment is cytoreductive surgery before or after paclitaxel and carboplatin chemotherapy (CT) followed by maintenance treatment. Weekly CT is at least as effective as three weekly CT in OC, and may overcome resistance in some patients. Hyperthermia has been used alone or in combination with radiotherapy and chemotherapy in the treatment of advanced cancer. Radiofrequency hyperthermia (Oncothermia-OT) is theoretically more effective and comfortable form of hyperthermia due to its selective effects on tumor cells. Since most advanced patients have disease limited to the abdominal cavity, OT can be applied with a single electrode to cover the whole abdomen. Immediately following CT, OT may result in aggregation of DNA repair ezymes secreted in response to CT in cancer cells. Methods: We used weekly CT with paclitaxel or nab-paclitaxel with carboplatin followed immediately by OT. (Oncotherm-EHY 3010) to the whole abdomen for one hour for eighteen weeks in 22 consecutive patients with advanced (III or IV) ovarian/primary peritoneal cancer between 2016 and 2021. 19 patients received bevacizumab every three weeks in addition to chemotherapy.All pts had ECOG PS 0-1. Maintenance treatment was bevacizumab (19 patients) or olaparib (3 patients) for one year. Patients were followed by periodic CT/MRI/PET-CT and CA-125 levels. Results: All patients completed eighteen weeks of planned treatment. No unexpected or grade III-IV toxicity was observed. Complete response was obtained in 21 patients and partial response in one patient. Median follow up is 30 months (range 8-73 months).18 patients are alive, with 12 patients in ongoing remission and 6 patients receiving palliative treatment. 4 patients have died of cancer. Conclusions: Although this is a single center retrospective observation, the combination of weekly paclitaxel/nab-paclitaxel and carboplatin CT in combination with immediate weekly OT appears tolerable and feasible. Despite all of the limitations of this observation, activity of CT and OT appears promising. These findings should be confirmed with prospective randomized trials.
Platinum vs non-platinum chemotherapy for platinum-resistant ovarian cancer: A meta-analysis.
Authors: Rumyantsev Alexey , Tyulyandina Alexandra , Fedyanin Mikhail , Pokataev Ilya , Glazkova Elena , Israelyan Edgar , Tjulandin Sergei 
Published: June 2022

e17551 Background: recurrent ovarian cancer (OC) patients with platinum-free interval (PFI) < 6 mo. are usually considered platinum-resistant and treated with non-platinum chemotherapy. However, this practice is not based on proper-conducted randomized trials. Methods: we queried the PubMed database for all full-text articles and abstracts on the treatment of patients with platinum-resistant ovarian cancer (PROC) in 01/01/2000-01/06/2019 timeframe. The PRISMA tool was used to ensure transparent reporting of the results. Inclusion criteria were: 1) histologically confirmed epithelial OC; 2) recurrent disease within 6 months after completion of platinum chemotherapy; 3) treatment with platinum- or non-platinum chemotherapy agents that are routinely used for OC; 4) no concomitant therapy with targeted or investigational agents; 5) defined response rate (RR) and assessment criteria. Proportion meta-analysis (random-effect model) and beta-regression were conducted to assess the impact of platinum agents on response rate as well as significance of other variables. In the beta-regression model response rate was a dependent variable, while platinum agents (yes or no), used non-platinum drugs and method of response assessment were independent variables. Statistical analysis was dose with meta and betareg packages of R software. Results: we identified 7156 articles and screened them for title and abstract, 157 studies for further analysis. Efficacy of non-platinum- and platinum-based therapy was assessed in 113 (n = 5272) and 44 (n = 1055) trials respectively. In meta-proportion random-effect model RR among patients treated with platinum-based and non-platinum chemotherapy RR was 36% (95% CI 30-41; I2 = 62%) and 16% (95% CI 14-19; I2= 70%) respectively. Multiple beta-regression model is presented in the Table below. For sensitivity analysis various regression models were made with different subsets of the trials and additional variables (including year of the trial, percentage of serous subtype of OC and median of prior therapy lines). Platinum was the strongest predictor of response in every developed model. Conclusions: this meta-analysis shows that patients with 'platinum-resistant' ovarian carcinoma may derive significant benefit from reintroduction of platinum agents. These results support recent ESMO-ESGO consensus on treatment of recurrent ovarian cancer and randomize trials are required to refine the role of platinum in early relapsed OC.[Table: see text]
Mechanisms of thrombosis pathogenesis and prevention vary in patients with ovarian and endometrial cancers.
Authors: Kaplieva Irina V. , Verenikina Ekaterina V. , Frantsiyants Elena M. , Myagkova Tatiana Yu. , Pogorelova Yulia A. , Surikova Ekaterina I. , Sheiko Elena A. , Trepitaki Lidia K. , Guskova Nailya K. , Zakharchenko Viktoria R. , Gusareva Marina A. , Atmachidi Dmitriy P. , Chernogorov Pavel V. , Moiseenko Tatiana I. , Kit Oleg I. 
Published: June 2022

e17554 Background: Thrombosis in patients with gynecologic cancers worsens the outcome of antitumor treatment and is one of the leading causes of their death. The kallikrein-kinin system (KKS) is involved in both the regulation of thrombus formation and the development of cancer. The purpose of this study was to analyze characteristics of the KKS components in the blood in patients with endometrial cancer (EM) and ovarian cancer (OC) with and without secondary thrombosis (VTEC). Methods: The study included 39 patients, mean age 58.0±4.2 years: main groups – patients with OC T1c-3cN0M0 (n = 10) or EC T1a-2N0M0 (n = 9) with VTEC; comparison groups - patients with OC (n = 10) or EC (n = 10) without VTEC. EC was represented by adenocarcinomas (G1-G3), OC by serous carcinomas (90%) and clear cell adenocarcinomas (10%). The control group included healthy women of the corresponding age (n = 10). Blood levels of kallikrein 1 (K1), kallikrein 14 (K14), and kininogen (KG) were measured by ELISA after the surgery. Results: EC patients with VTEC showed 1.5 times (p < 0.05) higher blood levels of K1, compared to donors, while other indices were unchanged. EC patients without VTEC had 4 times lower KG levels, compared to donors and EC+VTEC. In OC, regardless of the presence or absence of VTEC, levels of K1 in the blood increased, as well as in women with EC+VTEC, by 1.5 times (p < 0.05) compared with donors, which was combined with a twofold increase in KG in OC+VTEC and a decrease in KG by 1.4 times in OC patients without VTEC. Blood levels of K14 increased only in OC patients without VTEC by an average of 1.9 times (p < 0.05) compared with donors and OC+VTEC. Conclusions: The revealed changes in some KKS components in the blood demonstrate the similarity (K1 increase) and differences (KG increase only in OC) in the pathogenesis of thrombosis associated with gynecologic cancers. The mechanisms of protection against VTEC in the early postoperative period also showed common (KG decrease) and specific features associated with the characteristics of cancer (K14increase only in OC). The development of therapy aimed at correcting the identified disorders will allow an antitumor treatment program for this category of patients with maximum efficiency improving their quality of life and survival.
Data independent acquisition mass spectrometry in relation to potential diagnostic and prognostic biomarkers for high-grade serous ovarian cancer.
Authors: Huh Sunghyun , Kim Se Ik , Park Jieun , Choi Kyerim , Jang Hyunjee , Lee Sang-Won , Hwang Daehee , Yu Myeong-Hee , Chung Hyun Hoon , Kang Un-Beom 
Published: June 2022

e17564 Background: Ovarian cancer (OC) is one of the most common causes of cancer-related death among women worldwide. High-grade serous ovarian cancer (HGSOC) represents the major OC histological type, and challenges associated with its early detection and prediction of clinical outcomes significantly contribute to the high prevalence and poor prognosis of OC. Lack of reliable biomarkers further exacerbates the low survival rate of patients with HGSOC. Methods: In this study, we performed liquid chromatography data independent acquisition tandem-mass spectrometry (LC-DIA-MS/MS) experiments on depleted serum samples [26 HGSOC cases, 24 healthy controls (HCs)] to identify potential diagnostic and prognostic biomarkers for HGSOC. Results: A total of 1,148 proteins were identified in all samples combined, representing one of the largest quantifications in the serum proteome of OC to date. Among them, 122 proteins showed differential expressions between the serum proteome of HGSOC patients and HCs, including 109 up- and 14 down-regulated proteins in HGSOC. These potential diagnostic biomarkers were involved in the pathways related to immune response, TGF- β and IGF signaling, and lipid metabolism. Moreover, we performed Kaplan-Meier survival analysis on the HGSOC patients with and without recurrence, and identified several potential prognostic biomarkers highly associated with progression free survival (PFS). Using independent cohort samples, we validated the expression levels of HGSOC serum biomarker candidates using targeted proteomics approaches (MRM and PRM). In vitro functional assays revealed that some of these biomarkers may play an essential role in cancer cell migration and proliferation in HGSOC. Conclusions: In summary, our LC-DIA-MS/MS analysis of the HGSOC serum proteome successfully identified novel diagnostic and prognostic biomarkers for HGSOC, some of which were experimentally shown to have functional relevance to the pathophysiology of OC.
Brain metastases in ovarian cancer: Association of outcomes with timing of diagnosis.
Authors: Erfani Hadi , Mudgett Mudgett , Peterson Abigail , Seidman Benjamin , Nezhat Farr , Pejovic Tanja 
Published: June 2022

e17565 Background: Brain metastases (BM) in ovarian cancer (OC) are rare and late events during the disease course. We report our data on patients with OC who developed BM and compared the outcomes with subjects with evidence of BM at the time of diagnosis from the Surveillance, Epidemiologic, and End Results (SEER) national database. Methods: Retrospective chart review of all patients with brain metastasis in the setting of previously diagnosed ovarian cancer was performed in single NCI designated comprehensive cancer institute. Inclusion criteria were: primary cancer documented as ovarian or tubal, evidence of BM, treatment and follow up information. For comparison and due to rare nature of ovarian cancer cases with BM we utilized the SEER database. SEER data base reports only on patients with OC who had BM at the time of diagnosis. Study groups were: 1- BM at diagnosis 2- BM during disease course. Primary outcomes were overall death, and overall survival (OS) months. Secondary outcome was survival months after diagnosis of BM. Variables are reported as median and interquartile range (IQR) or number (%). Mean survival was calculated using Kaplan Meier analysis and Mantel-Cox rank test. Cox regression analysis was performed to calculate adjusted hazard ratios (HR). Results: 106 and 24 subjects were included with evidence of BM at diagnosis (Group 1, 2010-2016, SEER database) and during the disease (Group2, 1992-2017, institutional data), respectively. Age at diagnosis of OC was significantly higher in group 1 (64 year vs. 55 year, p = 0.002). In group 2, BM were diagnosed at median interval of 33.5 months. The median OS month was 3 [1, 10] months and 58 [21, 122] in group 1 and 2, respectively (p < 0.001). Although overall mortality rate was not statistically significantly different between the study groups, survival months after diagnosis of BM in group 2 was significantly higher than group 1 (14 months [4, 32] versus 3 months [1, 10], p = 0.002). Cox-regression analysis revealed 58% decrease in the hazard of overall death when the BM is diagnosed during the disease course. (Adjusted HR = 0.42, 95% CI: 0.19-0.91, p = 0.03). Conclusions: Outcomes of OC with BM is poor with high mortality rate regardless of timing of diagnosis of BM. Our study revealed that patients with diagnosis of BM during the disease course have statistically significantly longer survival after diagnosis of BM compared to those with BM at the time of diagnosis. In order to understand the occurrence of BM in OC and these differences, it is necessary to gain knowledge in the genetic and immune mechanisms that drive and allow the development of BM in ovarian cancer. This will allow for development of effective therapeutic strategies to treat BM, which is of critical importance now as we are gaining better control of peripheral disease in women with ovarian cancer.
Evaluating the use of machine learning use in ovarian cancer: A systematic review.
Authors: Piedimonte Sabrina , Rosa Gabriela , Gerstl Brigitte , Sopocado Mars , Coronel Ana , Llenno Salvador , Vicus Danielle 
Published: June 2022

e17570 Background: Ovarian cancer(OC) is the leading cause of death from gynecologic malignancy. Current challenges include lack of diagnostic tools, predictive biomarkers, and identifying appropriate surgical candidates. Machine learning(ML) is an emerging field that can make accurate projections by making inferences on data and may play a crucial role in OC.The objective of the current study was to review the literature on application of ML in OC and report the most commonly used algorithms and their performance in comparison to existing prediction tools and traditional regression models. Methods: This is a systematic review of published literature from January 1985 to March 2021 on the use of ML in OC. An extensive search of electronic library databases was conducted. Four independent reviewers screened the articles initially by title then full text. Quality was assessed using the MINORS criteria. P-values were generated using the Pearson’s Chi-squared(x2) test to compare performance of ML models with traditional statistics. No p-values were reported if only one study was available. Results: Among 4,295 articles screened, 88 studies on ML in OC were included. The mean age of OC patients was 54.7 years(11-90) and the most common stages at diagnosis were:Stage III (39.9%) and IV (34%). Applications of ML were in clinical datasets(33%, n = 29), preoperative diagnostics(30.7%, n = 27), serum biomarkers (21.6%, n = 19), genomics (12.5%, n = 11), and prediction of cytoreductive outcomes (2.3%, n = 2). The most commonly applied algorithms were Support Vector Machine [SVM](28%, n = 33)and Neural Networks[NN] (25.28%). Over the past decades, the number of publications on ML in OC increased three-fold from 20(1994-2010) to 67 (2011–2021). Only 9 (10%) studies compared ML techniques with existing prediction tools, or traditional regression models. Among 29 clinical dataset studies, 4 compared ML with traditional logistic regression(LR). Two studies reported better performance with ML compared to LR but not significant(accuracy: 0.88 vs 0.84, p = 0.15), one study performed comparably(accuracy: 0.1 vs 0.1) while one study performed worse(accuracy: 0.1 vs 0.97). Only one preoperative diagnostic study compared ML techniques with LR. SVM classifiers outperformed LR in classifying ovarian masses as benign or malignant(sensitivity: 0.88 vs. 0.70). One serum biomarker study compared LR with ML algorithms; LR performed better using two biomarkers for predicting OC(accuracy: 0.97 vs. 0.94). Among five studies reporting overall survival outcomes, only one study compared survival ML techniques using NN with LR and showed that NN classifiers outperformed LR in predicting overall survival(AUC: 0.72 vs. 0.62). Conclusions: This is the first systematic review exploring the literature on ML algorithms in OC. Most ML models outperformed traditional models. However, larger datasets would be required to validate findings.
Assessing homologous recombination deficiency (HRD) in ovarian cancer: Optimizing concordance of the regulatory-approved companion diagnostic and a next-generation sequencing (NGS) assay kit.
Authors: Weichert Wilko , Qiu Ping , Lunceford Jared , Wehn Amy , Yarunin Alexander , Cristescu Razvan , Liu Li , Roessler Kyria , Timms Kirsten , Marton Matthew John 
Published: June 2022

e17571 Background: Olaparib + bevacizumab is approved as first-line maintenance treatment of ovarian cancer that is HRD positive, defined as the presence of a deleterious/suspected deleterious BRCA mutation (BRCAm) and/or genomic instability. HRD genomic instability score (GIS) has been assessed in clinical trials using a regulatory-approved companion diagnostic, Myriad myChoice® CDx. We evaluated the performance of an in-development NGS assay kit that identifies BRCA variants based on genomic content from Illumina’s TruSight™ Oncology 500 research assay, and, with additional genomic content, measures HRD GIS in tumor tissue (Illumina test) in parallel. Analytic concordance of the Illumina test versus the Myriad myChoice® PLUS assay (Myriad test) under improved algorithms for calculating GIS scores is reported. Methods: Ovarian cancer tissue samples were analyzed with the Illumina (40 ng DNA; N = 227) and Myriad (200 ng DNA; N = 254) tests. Agreement rates for BRCA analysis, HRD GIS, and overall HRD status (includes BRCAm and HRD GIS [cutoff, 42]) were analyzed. For the overall and the non-BRCAm analysis cohorts, Pearson correlation between the continuous HRD GIS of the Illumina and Myriad tests was determined. Analytic sensitivity and specificity of the Illumina-derived HRD GIS to classify HRD GIS (cutoff, 42) were evaluated using AUROC. After initial concordance calculations, modifications were made to increase the quality of the Illumina preprocessing data (ie, reducing allele dosage noise and allele bias) upstream of the GIS calling algorithm. Reprocessing of the existing raw data led to further improvement in the point estimates of positive and negative percent agreement. Results: Prevalence using the Illumina and Myriad tests was 51.2% and 49.2% (overall HRD positive) and 27.6% and 25.5% (BRCAm), respectively. Agreement rates are reported in the Table. Correlation of the Illumina HRD GIS with Myriad HRD GIS was 0.980 (all samples) and 0.976 (non-BRCAm cohort); AUROCs were 0.995 and 0.992, respectively. Conclusions: Comparison between the Illumina and Myriad tests showed that overall HRD status, BRCA analysis, and HRD GIS detection results were > 90% concordant; HRD GIS was highly correlated (r > 0.98); and prevalence estimates were similar. These data suggest that a distributable kit solution, such as the Illumina test under development, will approach the performance of the Myriad myChoice HRD assay.[Table: see text]