bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinicopathological correlation of serum vascular endothelial growth factor and tissue carbonic anhydrase factor IX in stage IA to IIA carcinoma cervix.
Authors: Rajaram Shalini , Khan Musarrat Bahadur , Gupta Bindiya , Arora Vinod Kumar , Ahmed Rafat , Upreti Lalendra 
Published: May 2020

e18012 Background: VEGF initiates endothelial cell proliferation and angiogenesis in tumour cells while CA IX has an important role in pH regulation and elimination of hypoxia generated acid load during glycolysis.The present study was designed to identify these biomarkers and their correlation with tissue spread and behavior and eventually could lead to development of novel target therapies. The objective of this study was to correlate serum VEGF levels and tissue CA IX expression with clinicopathological features of carcinoma cervix stage IA to IIA. Methods: This exploratory case-control study included 19 cases with carcinoma cervix FIGO 2009 stage IA to IIA and 19 age matched controls. Out of the 19 cases, 12 underwent surgery and 7 received chemoradiation. Pre-therapy blood samples were collected for serum VEGF estimation from both cases and controls. For CA IX expression estimation, cervical tissue was taken for analysis. For cases, post-operative / post chemoradiation blood samples were taken for VEGF level estimation after 6 weeks. Results: The difference in mean serum VEGF levels between cases 1235.84 pg/ml (SD± 433.67) and controls 153.74 pg/ml (SD± 108.11) was statistically significant (p = 0.001). Mean serum VEGF level between pre and post-operative cases was 1108 pg/ml (SD± 407.62) and 391.42 pg/ml (SD± 270.71) while in pre and post chemoradiation cases it was 1455 pg/ml (SD± 413.38) and 623 pg/ml (SD± 238.41). This decrease was statistically significant (p = 0.00 & p = 0.018). VEGF positively correlated with histopathologic type (p = 0.016), grade (p = 0.012), and lymphovascular space invasion (p = 0.042).CA IX expression was seen in all cases while in controls no expression was seen. CA IX expression had a positive association with lymphnode metastasis (p = 0.041). Conclusions: Elevated pre-therapeutic serum VEGF suggests spread of tumor and can be used as a prognostic marker for cancer cervix. CA IX immunostaining in cervical biopsy samples can be used as a surrogate marker for tumor aggressiveness and distant spread.
Impact of leucocyte modifications in patients with locally advanced cervical treated by chemoradiotherapy.
Authors: Gennigens Christine , de Cuypere Marjolein , Barbeaux Annelore , Forget Frederic , Hermesse Johanne , Gonne Elodie , Jerusalem Guy Heinrich Maria , Kridelka Frederic 
Published: May 2020

e18014 Background: Concomitant cisplatin-based chemoradiotherapy (CCRT), followed by image guided-adaptive brachytherapy (IGABT) is the recommended treatment for patients suffering from locally advanced cervical cancer (LACC). Methods: Between January 2010 and May 2017, 103 patients with LACC (FIGO 2009-stages IB2-IVA) received CCRT followed by IGABT. The objectives of this study were to evaluate the impact of white blood cells (WBC) and polymorphonuclear neutrophils (PMN) counts variations on outcomes. This variable was calculated by substraction between WBC or PMN levels at the first cycle (CB) and the last cycle (CL) of chemotherapy (CT)(DCB-CL). The data were reviewed retrospectively, with Cox regression for univariate and multivariate analysis. Results: The median age at diagnosis was 50 years. The median tumor size at diagnosis was 47mm. The majority of the patients had FIGO stage II (60.2%) or stage I (21.4%) disease with squamous histology (88.3%). Patients received a median dose of external-beam radiotherapy (EBRT) of 45 Gy (range 40-50.4 Gy) by 1.8-2 Gy fractions, with a median cumulative dose of all the radiotherapy of 85 Gy. The median duration of EBRT+IGABT was 51 days (range 31-94). All patients received at least one cycle of cisplatin, but the majority received 5 (40.4%) or 6 (39.4%) cycles. The median follow-up time for all patients was 30.1 months. The overall survival (OS) and recurrence-free survival (RFS) at 3 years was 81,4% and 76,8% respectively. Univariate analysis associated higher DCB-CL WBC and DCB-CL PMN with better OS and RFS. Multivariate analysis confirmed that DCB-CL WBC (HR, 0.856; 95% CI, 0.737-0.986; p = 0.018) and DCB-CL PMN (HR, 0.863; 95% CI, 0.750-0.994; p = 0.041) were associated with better OS and RFS respectively. A linear regression analysis was performed to cross the DCB-CL WBC/PMN and the number of CT cycles. This analysis reveals that an increasing number of CT cycles is linked to an increased DCB-CL WBC/PMN. Conclusions: Our study reveals the impact of DCB-CL WBC and PMN on outcomes. These two tests could become biomarkers during CCRT to discuss adjuvant treatments, but also to adapt our follow-up.
Efficacy and safety of PEGylated recombinant human granulocyte stimulating factor in the prevention of neutropenia during concurrent chemoradiotherapy.
Authors: Zou Dongling , Zhou Qi , Guo Mingfang 
Published: May 2020

e18018 Background: This randomized controlled prospective study aims to explore the efficacy and safety of using PEG-rhG-CSF to prevent neutropenia during concurrent chemoradiotherapy of paclitaxel and cisplatin (TP) regimen for cervical cancer. Methods: Patients who met the eligibility criteria were divided into two groups according to the randomized principle of 2:1: the experimental group (patients used 6 mg PEG-rhG-CSF prophylactically after chemotherapy) and the control group (patients did not use PEG-rhG-CSF for prevention and were given 5 ug / kg rhG-CSF when ANC < 1✕109). TP combination regimen was used for concurrent chemotherapy, specifically as follows: paclitaxel 150mg / m2 (day 1), cisplatin 35mg / m2 (day 1-2), repeated every three weeks. The PTV dose was 45 Gy in 1.8 Gy daily fractions, with five fractions per week. SPSS 25.0 software was used for statistical analysis of the data, t-test was used for measurement data, and χ2 test Fisher exact test was used for enumeration data. P < 0.05 was considered statistically significant. Results: As of September 2019, 30 patients were enrolled into this study, including 18 in the experimental group and 12 in the control group. One of the 18 patients in the test group (5.6%) had a Grade 3/4 neutropenia. Ten of the 12 patients in the control group (83.3%) developed Grade 3/4 neutropenia. The incidence of Grade 3/4 neutropenia in the two groups was statistically significant (P < 0.001, Table 1). The incidence of FN was 5.6% in the experimental group and 8.3% in the control group (P = 1.000). The incidence of delayed chemotherapy course was 11.1% in the experimental group and 58.3% in the control group (P = 0.013). The incidence of delayed chemotherapy course in the two groups was statistically significant (Table 1). As shown in Figure 4, the experimental group had a completion time of radiotherapy for 46.7 days, while the control group had 49.0 days (P = 0.278). Conclusions: Although the results of bone marrow function and overall survival are still to be obtained, it can be initially seen from the intermediate-term data that the use of PEG-rhG-CSF primary prevention reduced the granulocytopenia and the delay of the chemotherapy course during the concurrent chemoradiotherapy TP regimen for cervical cancer, which has the value of further completing this study. [Table: see text]
Treatment patterns among newly diagnosed women with cervical cancer in the United States.
Authors: Shah Anuj , Kebede Nehemiah , Shah Ruchit , Corman Shelby , Nwankwo Chizoba 
Published: May 2020

e18019 Background: To address the gap in US-based real-world data, this analysis described the real-world treatment patterns among newly diagnosed cervical cancer patients. Methods: Women newly diagnosed with cervical cancer between Jan 2015 – June 2018, with a confirmatory diagnosis or treatment within 2 months, and continuous enrollment for 12 months prior and 6 months post diagnosis were identified in the Optum Clinformatics DataMart database. Surgeries (hysterectomy, conization, lymphadenectomy and trachelectomy), radiation (external beam radiotherapy [EBRT]/brachytherapy) and systemic therapies (chemotherapy/immunotherapy) received after diagnosis were described by line of therapy (LOT). The start of the first LOT was the date of the first treatment. All treatments initiated within 90 days of a surgery or the end of radiotherapy, and all systemic treatment started within 28 days of any previous treatment were a part of the same LOT. Most frequently received treatments in LOT1 and 2 and time to treatment initiation were described. Results: Out of 1,004 newly diagnosed women, 655 (65.2%) received at least LOT1 and 162 (16.14%) received LOT2. Median time to first LOT was 1.5 (1.4 – 1.7) months from diagnosis. Surgery was the most common treatment in LOT1 (58.0%). Among patients receiving radiation, the majority received a combination of EBRT and brachytherapy (LOT1: 66.9%, LOT2: 58.0%). The use of chemotherapy increased with subsequent LOTs (LOT1: 53.3%, LOT2: 61.1%). Treatments received in LOT1 and LOT2 are described in the table. Conclusions: This analysis shows that newly diagnosed cervical cancer patients are primarily receiving guideline recommended treatment with surgery or chemoradiation as primary treatment. Radiation therapy includes EBRT and brachytherapy. Counts ≤ 10 are not reported (NR). [Table: see text]
A retrospective study of carboplatin and liposomal doxorubicin in patients with locally advanced or recurrent squamous cell carcinoma of the cervix.
Authors: Chang LEI , Yuan Zhongfu , Tian Wanjia 
Published: May 2020

e18021 Background: The efficacy and safety of the combination of carboplatin and liposomal doxorubicin was tested in in patients with locally advanced or recurrent cervical cancer. Methods: The combination of carboplatin (area under the concentration curve AUC = 5) and liposomal doxorubicin (starting dose, 40 mg/m2) was administered intravenously every 28 days to 75 patients with locally advanced or recurrent cervical cancer to determine the drug efficacy and safety. Results: During the observation, all patients were received surgery or radiation before combination chemotherapy. 58 patients were assessable for response, and 12 patients were assessable for toxicity. During therapy, none patients required discontinuation of chemotherapy while only 2 patients needed dose reduction, because of side effect. The overall response rate was 77.3%, the median time to response was 8 weeks, the median duration of response was 24 weeks, and the median survival was 37 weeks. The most common adverse events with these patients included myelosuppression (69.0%), neutropenia (31.0%), anemia (23.0%), thrombocytopenia (21.0%) and neutropenic fever (11.0%). Conclusions: The combination of carboplatin and liposomal doxorubicin shows clinical efficacy and acceptable safety in patients with locally advanced or recurrent cervical carcinoma. It might provide a noval treatment for late stage cervical cancer.
Quality of life of cervical cancer patients after specialized treatment in Kazakhstan.
Authors: Kaidarova Dilyara , Pak Roza , Chingissova Zhanna 
Published: May 2020

e18024 Background: In Kazakhstan cervical cancer (CC) ranks 2nd in morbidity and mortality among women with malignant neoplasms. 88% of women are diagnosed in stages 1-2. Age range of patients with cervical cancer is becoming younger with women age 35-55 years old. This urges implementation of an effective system for assessing and maintaining the quality of life of people with CC who undergo special treatment. Methods: During study we used The EORTC quality of life questionnaire (QLQ C-30) Version 3.0 on 157 patients with stage 1-2 CC, 1+ year after chemoradiotherapy (CRT, n = 65) and surgical treatment (ST, n = 92). For statistical analysis, we used the Wilcoxon rank-sum test and the chi-square test using SPSS version 22.0. Results: When analyzing limitations in everyday activities (work etc) (sign 1), 13.8% -18.5% of patients with cervical cancer noted “significant” and “very strong” impact on quality of life after CRT compared with 1.1% - 3.3% of patients after ST (p < 0.001). Study showed that there is a strong correlation between treatment method and quality of life (table 1). 35.4% of patients after CRT have noted “significant” difficulties in carrying out work requiring a higher level of physical effort (sign 2). In contrast, only 16.3% of patients after ST noted “significant” difficulties, which is 2.2 times less (p < 0.006). Assessment revealed a moderate quantitative correlation (table 1). 16.9% of patients after CRT noted severe pain (sign 3) compared with 2.2% of patients who received ST (p < 0.001). Assessment revealed a moderate quantitative correlation (table 1). Absence of feeling of weakness (sign 4) was greater among patients from the ST group - 21.7% compared with CRT - 9.2% (p < 0.03). Assessment revealed a strong quantitative correlation (table). 15.4% of patients after CRT, compared with 2.2% of patients who received ST (p < 0.001) have noted that their physical condition and treatment had a “very strong” impact on their personal life (sign 5). Conclusions: Assessment revealed that CC patients who received CRT showed lower physical and social indicators of quality of life. [Table: see text]
Relative gene copy numbers in various patterns of cervical cancer growth.
Authors: Timoshkina Natalya N. , Petrusenko Natalia A. , Nikitina Vera P. , Spiridonova Diana A. , Verenikina Ekaterina V. , Nikitin Ivan S. , Zhenilo Oksana E. , Vladimirova Liubov Yu , Kit Oleg I. 
Published: May 2020

e18029 Background: Numerous studies on cervical cancer confirm an important role of specific genomic changes in the onset and development of cervical intraepithelial neoplasia and their effect on the progression of cervical cancer. Solid tumors are characterized by genomic changes leading to a change in the DNA sequence copy number. The purpose of the study was to reveal changes in the relative copy number of the ESR1, ESR2, GPER1, STS, SULT1A1, SULT1E1, CYP1A1, CYP1A2 genes responsible for the reception and metabolism of estrogens in cervical tissues in endophytic and exophytic patterns of tumor growth in order to find predictive markers of malignancy. Methods: The study included 40 patients aged 28-65 years with cervical cancer of endophytic (n = 20) and exophytic (n = 20) growth patterns. Eligibility criteria included a morphologically confirmed cervical squamous cell cancer T1b-2aN0M0, stage I-II. The Thermo Scientific GeneJET FFPE DNA Purification Kit was used for the DNA extraction from FFPE blocks of tumor and healthy tissues. DNA concentrations were measured on the Qubit 2.0 fluorimeter (Invitrogen, USA) using the Quant-iT dsDNA High-Sensitivity (HS) Assay Kit (Invitrogen, USA). Results: The relative copy number of the GPER1, SULT1A1, CYP1A1 genes in tumor samples increased (p < 0.05) compared with normal tissues in the total sample of patients diagnosed with cervical cancer. In contrast to the total sample, an increase in the SULT1A1 gene dosage did not reach a statistically significant level in any group (p = 0.242 and p = 0.157); the copy number of the GPER1 locus significantly increased only in the group with the endophytic growth pattern (p = 0.040), as well as the CYP1A2 gene dosage (p = 0.025). Patients of 36-55 years with endophytic tumors showed a statistically significant (p < 0.05) increase in the GPER1 and CYP1A1 gene copy numbers with the rates of 41.7% and 66.7%, respectively, as well as an increased amplification of the CYP1A2 gene in 41.67% of patients. In women of 56-75 years with endophytic tumors, an increase in the copy numbers of the ESR2, GPER1, SULT1A1 genes was observed with a frequency of 50%, 100% and 75%, respectively. Patients aged 20-35 and 36-55 years with exophytic tumors showed a statistically significant (p < 0.05) increase in the CYP1A1 gene copy numbers in 33.33% and 45.45%, respectively. Conclusions: The results suggest the use of the GPER1, SULT1A1 and CYP1A1 gene copy numbers as biomarkers of cervical tumors.
Treatment patterns of advanced or recurrent endometrial cancer following platinum-based therapy in the US real-world setting.
Authors: Klink Andrew J. , DeMars Leslie , Huang Joice , Maiese Eric M. , Feinberg Bruce A. , Hurteau Jean 
Published: May 2020

e18036 Background: Following disease progression on or after primary (1L) platinum-based therapy (PBT) for advanced/recurrent (A/R) endometrial cancer (EC), patient (pt) prognosis is poor and no consensus on standard second-line therapy exists. This retrospective analysis aimed to understand real-world (RW) treatment patterns of pts with A/R mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) EC who progressed after 1L PBT. Methods: Physicians in Cardinal Health’s Oncology Provider Extended Network submitted retrospective data by abstracting outpatient electronic medical records of pts who received systemic treatment for A/R EC following PBT from 2016 to 2018. Demographics, clinical characteristics, treatments received, and outcomes were summarized descriptively. Results: This study included 84 pts with A/R dMMR/MSI-H EC (table). The majority of participating physicians were hematologists/medical oncologists (80%) and practiced in the community setting (70%). Median duration of therapy (mDOT) in 1L was 4.9 months (95% CI, 4.47–5.57); 64% of pts discontinued treatment due to therapy completion and 35% due to disease progression. In contrast, mDOT in 2L was 6.2 months (95% CI, 5.40–6.37); 37% of pts discontinued treatment due to therapy completion and 44% due to disease progression. The most common MMR/MSI testing modalities were next-generation sequencing (NGS) only, immunohistochemistry (IHC) only, and polymerase chain reaction (PCR) only (table). Conclusions: RW treatment patterns in pts with A/R dMMR/MSI-H EC show that most will undergo PBT retreatment. However, progression is the main reason for discontinuation during retreatment. An urgent need exists for durable therapies that improve prognosis. Opportunities to improve timely testing of MMR/MSI exist. [Table: see text]
Is there a high risk of renal dysfunction and the need for its prevention in patients with gynecological cancers after surgery?
Authors: Tumanyan Sergey V. , Moiseenko Tatiana I. , Verenikina Ekaterina V. , Frantsiyants Elena M. , Menshenina Anna P. , Oros Oksana V. , Sugak Elizaveta Yu. 
Published: May 2020

e18037 Background: Renal dysfunction in cancer patients is an urgent problem of clinical practice in oncology which can often challenge the efficacy of anticancer treatment and the disease prognosis. The purpose of the study was to reveal risk factors for renal dysfunction in oncogynecological patients. Methods: A prospective randomized study of the renal function included 174 patients aged 54-82 years with reproductive tumors. The control group included 34 patients with benign uterine tumors. Glomerular filtration rate (GFR) was estimated using the CKD-EPI equation. Results: GFR in the main group was 71.6±2.3 mL/min/1.73m2. Renal dysfunction was found in 42.5%. The majority of patients (115 patients, 66.1%) had concomitant diseases classified as modifiable risk factors for the development and progression of chronic kidney disease (KDIGO, 2017), including hypertonic disease in 46.6% (χ2= 4.4, p < 0.05), diabetes in 39.1% (χ2= 7.9, p < 0.05), cardiovascular diseases in 27.6% (χ2= 3.9, p < 0.05), and morbid obesity in 68.9%. This confirmed the decisive importance of hypercholesterolemia, hyperglycemia and hypertension as risk factors for reduced GFR. 52.9% of patients had a combination of these factors, which together with the initial renal dysfunction suggested a high probability of acute renal failure in the perioperative period. Conclusions: The assessment of kidney function in patients with gynecological cancers is required to determine the intensity of treatment in the perioperative period, the general disease prognosis and risks of possible complications.
Utilizing porcupine (PORCN) and DKK1 inhibition to improve anti-tumor immunity in a murine model of ovarian cancer.
Authors: Wall Jaclyn , Katre Ashwini A. , Meza-Perez Selene , Londono Angelina , Norian Lyse , Arend Rebecca Christian 
Published: May 2020

e18041 Background: Epithelial ovarian cancers (EOC) are immunologically “cold” tumors and consequently have seen limited success with immunotherapy. Wnt-beta/catenin signaling is dysregulated in multiple cancers, including EOC, and is characterized by immune exclusion. Porcupine (PORCN) is the enzyme necessary for secretion of Wnt ligands, which is required for activation of Wnt/beta-catenin signaling. Up-regulation of the Wnt/beta-catenin pathway leads to increased levels of the target gene DKK1, which plays a role in immune exclusion. Our goal is to improve the tumor immune response via targeting Wnt-signaling in EOC. Methods: We utilized a syngeneic murine model (ID8 cell line) deficient in p53 (ID8p53−/−) with and without the addition of a Luciferase tag (Luc+/-) to assess the effect of treatment with a PORCN inhibitor, CGX-1321, with and without DKN-01, a monoclonal antibody targeting DKK1. Mice were treated with vehicle/control, CGX-1321, DKN-01, or CGX-1321/DKN-01. Treatment was given for either 14 or 31 days. In Luc+ mice, bioluminescence imaging was performed weekly. Following mouse sacrifice, omental weights and ascites volume were measured. Omental tumor was used for flow cytometry and representative samples were sent for NanoString analysis. Results: Treatment with CGX-1321 for 14 days reduced omental weight and ascites volume in Luc- mice only (p = 0.02); however, earlier and extended treatment with CGX-1321 and CGX-1321/DKN-01 in Luc+ mice decreased omental weight (p = 0.008 and 0.0025); mice treated with CGX did not develop any ascites with the same treatment schedule. While treatment with DKN-01 alone did not decrease omental weight, treatment with DKN-01 and combination CGX-1321/DKN-01 increased total percentage of NK cells (p = 0.0192 and 0.0070). CGX-1321 and DKN-01 alone and in combination increased the total percentage of CD8+ T cells in omental tumors (p = 0.0238, 0.037, and 0.0127). Conclusions: CGX-1321 decreased omental weight and ascites volume, while DKN-01 increased the cellular percentage of NK cells. Both DKN-01 and CGX-1321 increased CD8+ T cells. Wnt-inhibition is therapeutically promising in EOC, and the combination of a PORCN inhibitor with DKN-01 could improve the response to immune checkpoint blockage and further investigation is warranted.