bluuebunny/crossref_metadata_2025_split huggingface dataset:
Morbidity and mortality of pelvic exenteration for cervical cancer at a German referral center.
Authors: Boekhoff Jelena , terGlane Luisa , Wagner Uwe , Hegele Axel 
Published: June 2021

e17505 Background: The purpose of this study was to evaluate data regarding the outcome of pelvic exenteration (PE) when performed for advanced or recurring cervical cancer. Methods: A total of 24 patients underwent PE for cervical cancer at the University Hospital Marburg between 2011 and 2016. Their data were retrospectively assessed and statistically analyzed. Survival was evaluated using the Kaplan-Meyer method. Results: Mean age was 52.2 years (29.7 to 72.6 years), mean BMI was 23.4 kg/m2. Most common indication was squamous cell carcinoma, whereas 3 patients underwent PE for adenocarcinoma. The majority of the tumors (62.5%) were stage pT4. Negative margins could be achieved in 70.8%. Lymph nodes could be assessed in 55% and were tumor-afflicted in 20.8%. 45.8% were treated for recurrent cancer; median recurrence free time between previous treatment and PE was 16 months. Up-front PE was performed in 20.8%. Another 79.2% received treatment prior to PE: 20.8% received all 3 treatment modalities whereas 37.5% had two treatments before (29.2% underwent chemo- and radiotherapy, 8.3% had surgery and radiotherapy) and 20.8% underwent one type of treatment. Anterior PE (APE) and total PE (TPE) were performed in 62.5% and 37.5%, respectively. Median operation time was 324min. Blood products were administered perioperatively in 75%; 37.5% needed 2 or more. Median hospital stay was 25 days. Major complications (Clavien Dindo≥3) were observed in 41.7% and 16.7% had no complications. Overall Survival (OS) was 29.2%; median overall survival was 19.1 months. 2- and 3-year survival rates for curative PE were 50% and 35% respectively. 4 patients underwent PE with palliative intent. Overall survival correlated significantly with R1- (p = 0.012), N1- (p = 0.047) and M1-status p < 0.01), TPE (p = 0.034) and surgical time > 6 h (p = 0.003). Conclusions: In cases of advanced or recurrent cervical cancer gynecologists struggle to find suitable therapeutic options, especially since most patients have already received radio- and/or chemotherapy. PE is a valid option for selected patients that may represent a cure with tolerable complication rates.
A retrospective study of anlotinib in patients with cervical cancer after chemoradiotherapy.
Authors: Tan Liu , Chu Alan , Yang Yu , Yuan Jinjin , Hou Ge , Song Rui , Wang Cheng , Xiao Chenhu , Chai Ting , Liu Shijia , Zhang Pan , Liu Zongwen 
Published: June 2021

e17509 Background: Anlotinib is a novel small molecule antiangiogenic drug, which can inhibit multiple tyrosine kinase receptor activity. Its antitumor activity has been proved in various cancers, including gynecological tumors. This retrospective study explored the efficacy and safety of anlotinib monotherapy or anlotinib combined chemotherapy in cervical cancer patients who have disease progressed or metastasis after chemoradiotherapy. Methods: 28 patients with cervical cancer admitted to the Second Affiliated Hospital of Zhengzhou University were enrolled. These patients who had received radiotherapy and at least one line chemotherapy had tumor progression or metastasis. 13 patients received anlotinib monotherapy (12mg/d from day 1 to day 14 in a 21-day cycle) and 15 patients received chemotherapy combined with the anlotinib. Treatment was continued until disease progression or death or intolerable adverse events. The primary endpoint was the objective response rate (ORR), and the secondary endpoints were disease control rate (DCR), progression-free survival (PFS) and safety. Results: As of Dec 31 2020, no one was lost follow up. 2 patients were still under treatment, and 26 patients were evaluable. 1 CR, 6 PR, 13 SD, 6 PD, yielding the ORR of 26.92%, and the DCR of 76.92%. The median PFS for receiving anlotinib monotherapy was 4.57 (95% CI, 3.85-5.29) months, and 8.47 (95% CI, 5.09-11.85) months for combination group. The most common adverse events (AEs)were grade 1, including hypertension (46.43%), anemia (42.85%) and fatigue (39.29%). Grade 3 AEs were hypertension(10.71%) and anemia(7.14%). No higher grade AEs occurred. Conclusions: Anlotinib is safe and effective for patients with advanced cervical cancer after chemoradiotherapy, and it is well tolerated.
Dynamics of oxidative blood status and activity of antioxidant system of erythrocytes in patients with cervical cancer receiving combination therapy with dendritic cell vaccine.
Authors: Goroshinskaya Irina A. , Menshenina Anna P. , Frantsiyants Elena M. , Moiseenko Tatiana I. , Verenikina Ekaterina V. , Nemashkalova Ludmila A. , Chudilova Anastasia V. , Cherkasova Anna A. , Chalabova Tatiana G. 
Published: June 2021

e17516 Background: The combination treatment with plasmapheresis and non-specific immunotherapy for locally advanced cervical cancer (CC) is shown to be effective. We studied the effect of immunotherapy with dendritic cell vaccine (DCV) as a part of combination therapy on the intensity of the lipid peroxidation (LPO) and activity of antioxidant enzymes. Methods: Plasma and erythrocyte content of malondialdehyde (MDA), the activity of superoxide dismutase (SOD), catalase, glutathione dependent enzymes and the content of reduced glutathione (GSH) in erythrocytes were determined in 24 patients with CC of T2a-2bN0-1M0 stages and in 25 women without cancer. The patients underwent neoadjuvant chemotherapy (CT) with cisplatin and bleomycin, followed by 2 cycles of DCV, for a total of 6 courses of CT and 12 cycles of DCV. Results: Initially, patients demonstrated intensification of free radical processes enhancing after PCT and the first two DCV: MDA in erythrocytes elevated by 52.2-111.7%, in the blood plasma by 2.2-3.5 times. Subsequent DCV cycles normalized the LPO. MDA levels after 4 DCV cycles were lower than the initial values in erythrocytes by 30.4% (p = 0.04), in plasma by 55.6% (p = 0.007), i.e. were similar to the levels in healthy women. The SOD activity was decreased by 16.7-27.3% (p < 0.005) after 4-6 DCV cycles and normalized after the 7th cycle. The catalase activity in erythrocytes was decreased before treatment and after PCT by 42.4% (p = 0.000000), during vaccine therapy by 20.5-37.7% (p < 0.0005). In reduced catalase activity, inactivation of hydrogen peroxide was realized, apparently, by glutathione peroxidase (GPO), and its increased activity (by 37-102.3%, p≤0.00005) was supported by a high GSH content - by 11.6-52.4% (p < 0.02) above the norm at all stages after the 2nd DCV cycle. And only with the complete normalization of the erythrocyte MDA content, the GPO activity after the 7th DCV cycle decreased by 46.7% (p = 0.000000) relative to the levels before the treatment and did not differ significantly from the values in donors. Conclusions: Vaccine therapy helped to enhance the activity of the glutathione system becoming the most important component of antioxidant protection in the blood of CC patients. Already 3-4 DCV cycles normalized the LPO sharply increased in CC patients during CT. Multi-course vaccine therapy allowed maintaining the optimal oxidative status of the blood.
A multicenter analysis of treatment and outcomes in neuroendocrine carcinoma of the uterine cervix (NCUC).
Authors: Hickman Ashley Deanelle , McGarrah Patrick Walsh , Glaser Gretchen , Naraev Boris , Wahner Hendrickson Andrea Elisabeth , Halfdanarson Thorvardur Ragnar 
Published: June 2021

e17518 Background: Morbidity and mortality for patients with cervical cancer has improved significantly over the past few decades with modern multimodal therapy. However, neuroendocrine carcinoma of the uterine cervix (NCUC), which accounts for 1-2% of cervical cancers, remains a deadly subtype. In this study, we combine data from Mayo Clinic (MC) and the University of Iowa Hospitals and Clinics (UIHC) to provide information on tumor characteristics, treatment, and outcomes. Methods: The electronic medical record was reviewed for patients with NCUC from MC and UIHC. Data on diagnosis, treatment, and outcomes were collected through chart review. Primary endpoints included progression-free survival (PFS) and overall survival (OS). Secondary endpoints included median survival, survival at 1 year after surgery, and survival at 1 year by first line chemotherapy agent. Kaplan-Meier survival analysis was used to estimate median PFS, median survival, and OS. Fisher’s test analysis was used to calculate survival at 1 year after surgery and by first line chemotherapy agent. Results: There were 62 patients (MC: 26, UIHCC: 36) with NCUC stage I-IV (stage I: 29, stage II: 9, stage III: 7, stage IV: 14, unknown: 3). Median age of diagnosis was 47 years (range 21-77 years). By subtype, 47 were small cell (76%), 9 were large cell (15%), and 6 were unknown/undetermined (9%). The initial treatment modalities for each patient are outlined in the table. 28 patients had complete/partial response or stable disease from first line treatment, while 10 patients had disease progression. Of the patients who initially responded or had stable disease, 16 later progressed (57%) with a median time to progression of 15 months. Median follow up was 65.1 months with a median OS of 28.5 months. Median survival for those with stage I was 40.9 months, stage II: 54.6 months, stage III: 8.75 months, and stage IV: 11.7 months. There was a significant difference in overall survival at 1 year between those who received surgery and those who did not in stage I/II ( p = 0.01). There was no significant difference in overall survival at 1 year for those who received surgery in stage III/IV. There was no statistical difference in survival at 1 year for carboplatin or cisplatin in combination with etoposide as first line chemotherapy agent. Conclusions: NCUC is an aggressive malignancy that is usually progressive despite multimodal therapy. Our study demonstrated a median overall survival of 28.5 months and 5-year survival rate of 21%. Our study showed a survival benefit at 1 year for those who receive surgery with stage I/II NCUC. There was no significant survival benefit at 1 year between carboplatin or cisplatin in combination with etoposide as first line agent.[Table: see text]
Cervical cancer screening: Twelve years experience of the Kazakhstan National Screening program.
Authors: Bolatbekova Raikhan , Kaidarova Dilyara , Zhylkaidarova Alma , Sadykova Tolkyn , Kukubassov Yerlan , Satanova Alima , Aidarov Askar 
Published: June 2021

e17520 Background: Cervical cancer (CC) is the most common gynecological cancer in Kazakhstan (KZ). Standardized incidence rate of CC was 16.7 per 100, 000, while the mortality rate was 5, 9 per 100, 000, in 2020. The National Cervical Screening program in KZ uses cytology (Pap test) from 2008, which is free of charge for women aged 30 to 70 years of age with an interval of 4 years. In 2017 Experts from ImPact Mission and analyzed existing CC screening revealed a number of recommendations aimed at reducing the screening interval and increasing the coverage. The purpose of this study was to analyze results of CC screening in KZ and his impact on CC incidence and mortality. Methods: Coverage, the number of screened women, the level of pre-cancer detection and cervical cancer during screening have been obtained from specific reports (form № 025, № 08) for 2008-2020. Results: The total number of screened women for 2008 were 554 283 women. There is a decrease in screening coverage to 45.9% in 2017 due to a decrease in funding. in this regard, in 2017, a number of changes were made to the existing screening program. In 2020 after the CC screening improvement 786 690 women were examined during the screening program, coverage rate was 66, 2%, . Analysis of screening results showed a marked increase in the detection of precancerous lesion from 0, 136 in 2008 to 0, 87 with an increasing by 37%. The analysis of CC incidence revealed significant changes: after the introduction of screening, an increase in the incidence rate is noted from 15.5 in 2008 to 20.1 per 100, 000 female population in 2015. Since 2015, there has been a significant decrease to 16.7 per 100, 000 women. Conclusions: Despite the positive results of screening, an increse the screening coverage, improvement in the detection of the initial stage of CC, mortality rate from CC and a one-year mortality remain high, which makes it necessary to improve the screening of CC in KZ through the introduction of HPV-screening
Investigating reasons for discontinuation of first-line adjuvant chemotherapy among ovarian cancer patients in the midwestern United States.
Authors: Weeks Kristin S. , Stewart Sherri L. , West Michele , Carnahan Ryan , Oleson Jacob , Lynch Charles F. 
Published: June 2021

e17523 Background: Receipt of surgery and adjuvant chemotherapy greatly impact survival outcomes for ovarian cancer, the deadliest gynecologic malignancy with a high recurrence/progression rate. Most patients receive first-line, platinum-based chemotherapy. Platinum-based chemotherapy causes severe side effects, including nephrotoxicity and myelosuppression. Evidence for other chemotherapeutic agents is lacking and options are limited for women who cannot tolerate first-line chemotherapy. We aimed to determine the prevalence of premature first-line chemotherapy discontinuation and to detail reasons for discontinuation. Methods: We used the population-based cohort, Patterns of Ovarian Cancer Care and Survival in the Midwestern Region of the United States—a CDC Investigation, comprised of women diagnosed with histologically confirmed, stage IB-IV ovarian cancer in 2010-2012 in the Midwestern United States (i.e., Iowa, Kansas and Missouri) between the ages of 18 and 89 years. We limited the cohort to patients who received cancer-directed surgery and initiated adjuvant chemotherapy. Chemotherapy lines, completion, and reasons for discontinuation were abstracted from patient medical records by cancer registrars using standardized protocols. Results: Nineteen percent (N= 107/559) of ovarian cancer patients who initiated adjuvant chemotherapy did not complete first-line treatment. Reasons for chemotherapy discontinuation included toxicity or other kinds of intolerance (39%), poor quality of life or comorbid conditions (19%) or exhibited no response (17%) (Table). No significant differences were observed between gynecologic oncologists and non-gynecologic oncologist chemotherapy providers (p=0.109). Conclusions: One in 5 women who initiated did not complete first-line chemotherapy. Reasons were varied and suggested that lack of tolerance is not the only factor in discontinuation. Lack of response and the presence of comorbid conditions are considerations that can be taken into account during decision-making processes for treatment. More clinical research into additional chemotherapy options that may be useful in these patients is necessary.[Table: see text]
Anlotinib in patients with recurrent platinum-resistant or refractory ovarian carcinoma: A prospective, single-arm, single-center, phase II clinical study.
Authors: Wang Huaying , Shen Wenbin , Shan Boer 
Published: June 2021

e17524 Background: Anlotinib is a new multi-target tyrosine kinase inhibitor (TKI) and its anti-tumor targets include vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptor (PDGFR), and c-kit. This phase II study aims to evaluate the safety and efficacy of anlotinib monotherapy in patients with recurrent or refractory ovarian carcinoma. We have previously reported primary results (objective response rate (ORR) 35.7%, 95%CI: 12.8-64.9; and disease control rate (DCR) 85.7%, 95%CI: 57.2-98.2) in 14 patients), and we now present the updated ORR, DCR and safety data in more patients. Methods: Patients who have previously received second-line or more chemotherapy, with histopathologically confirmed ovarian high-grade serous gonadal ovarian carcer (including salpingocarcinoma and peritoneal carcinoma), ECOG 0-2 were considered eligible for enrollment. Anlotinib was administered orally (12 mg qd, d1-14; 21 days per cycle) till disease progression, death or intolerant toxicity. Therapeutic effects are evaluated every 6 weeks. The primary endpoint was ORR and the secondary endpoints included DCR, progression-free survival (PFS), overall survival (OS), safety and quality of life (QoL). Results: Between March 2019 and January 2021, 31 patients (female) with FIGO histopathological stage IC (1, 3.2%), IIC (1, 3.2%), IIIC (23, 74.2%) and IV (6, 19.4%) were enrolled and 24 patients were evaluable with a median age of 59 years (range: 37-73). The median treatment period was 4.96 months (95% CI: 4.50-7.56). Therapeutic evaluation showed the incidence of complete response, partial response, stable disease and progression disease was 4.2%, 25%, 45.8% and 25% respectively, yielding the ORR of 29.2% (7/24; 95% CI: 14.6-57.0) and the DCR of 75.0% (18/24; 95% CI: 53.3-90.2). The median PFS was 6.34 months (95% CI: 3.14-9.54). The median OS was not reached. Most of the occurring adverse events (AEs) were grade 1 and grade 2, and ≥10% grade 1 AEs included hypertention (45.83%), fatigue (29.17%), hand-foot syndrome (33.33%) and hoarseness (12.50%). Grade 2 AEs only included gingival bleeding (4.2%), hand-foot syndrome (4.2%), renal dysfunction (4.2%) and cancer pain (4.2%). No higher grade AEs were observed. Neither unexpected safety signals nor treatment related death occurred. Conclusions: Anlotinib showed a promising efficacy with an acceptable safety profile for patients with recurrent platinum-resistant or refractory ovarian carcinoma. Further evaluation of PFS and OS is ongoing. Clinical trial information: ChiCTR2000029654.
Impact of pleural effusion in ovarian cancer: A retrospective study in Lleida, Spain.
Authors: Murata Eleonor Paola , Bielsa Silvia , Pardina Marina , Salud Salvia Antonieta , Porcel Laura , Porcel Jm 
Published: June 2021

e17534 Background: The presence of pleural effusion in the evolution of patients with ovarian cancer is not uncommon. In one series of 123 patients, malignant pleural effusion at the diagnoses was observed in 29%, and 70% during the course of the disease. Methods: This observational, retrospective study included patients with ovarian cancer and pleural effusion between July 2007 and December 2019 in Lleida, province of Catalonia, Spain. Data were collected from electronic medical reports. This study analyzed the clinical features of ovarian cancer patients with pleural effusion and its impact on their survival. Results: Data from 189 patients with ovarian cancer were collected. The median age was 63 years old. Pleural effusion was observed in 81 patients, 55 at the diagnosis and 26 in the disease evolution. Fifty five percent were confirmed as malignant etiology. Most of the patients were diagnosed with an advanced stage (38.3% stage IIIC, 12.3% stage IVA, 40.7% stage IVB), and 74.1% were high-grade serous carcinoma. When the pleural effusion was observed at the diagnosis, the median overall survival was 20.8 vs 69.3 months in the absence of it (p < 0.001). When the pleural effusion was observed at any time of the disease, the median overall survival was 26.7 vs 90.4 months without it (p < 0.001). Conclusions: In this study, patients with ovarian cancer and pleural effusion, at diagnosis or in the course of the disease, experienced reduced survival compared with the absence of it.
Variance of HRD score from primary to recurrent in high-grade serous ovarian cancer.
Authors: Chen Xiaoxiang , Ni Jing , Xu Xia , Guo Wenwen , Zhao Qian , Cheng Xianzhong , Zhou Rui , Gu Hongyuan , Chen Chen 
Published: June 2021

e17540 Background: Homologous recombination deficiency (HRD) is an important biomarker of poly (ADP-ribose) polymerase inhibitor (PARPi) in patients with high-grade serous ovarian cancer (HGSOC). The stability of HRD in the recurrent HGSOC and its primary pair from Jiangsu Institute of Cancer Hospital was investigated. Methods: A total of paired 18 samples from 9 HGSOC patients were analyzed. HRD score was evaluated by loss of heterozygosity(LOH) and genetic mutations were also detected from next-generation sequencing.The student t-test evaluated the difference of HRD score between matched tumors. The functional annotation and clustering of affected genes in the recurrent tumor cells were analyzed by the KEGG Orthology (KO) database. Results: The HRD score of recurrent HGSOC tumors was significantly higher than that of the paired primary ones (p = 0.004). A total of 30 new somatic sequence variants at 27 genes presented in the recurrent tumors, were not found in any matched primary tumors. Of which, 19 (63.3%) were copy number variants (CNVs), 3 (10%) variants were rearrangement, and 8 (26.7%) were somatic point mutation. In these17 genes with CNVs, 14 genes had gene amplification variants, among them 50% (7/14) genes associated with the positive regulation of cell proliferation and cellular response to DNA damage stimulus. Four somatic point mutations involved in tumor suppressor pathway. Conclusions: Our data shed first light on the statistically significant changes of HRD score in paired recurrent HGSOC. The HRD score changes over time may imply further instantaneity assay strategy.
Identification of signal transduction pathway activity with potential clinical target in high-grade serous ovarian and tubal carcinoma.
Authors: van der Ploeg Phyllis , van Lieshout Laura A.M. , Wesseling-Rozendaal Yvonne J.W. , Van De Stolpe Anja , Bosch Steven L. , Lentjes-Beer Marjolein H.F.M. , van Diest Paul J. , Vos M.Caroline , De Hullu Joanne , Bekkers Ruud L.M. , Piek Jurgen M.J. 
Published: June 2021

e17541 Background: High-grade serous carcinoma (HGSC) is the most common subtype of epithelial ovarian and tubal cancer. It has a high mortality rate, even after successful first-line treatment with debulking surgery and chemotherapy. Although therapeutic options for targeted therapy are rapidly expanding, identification of patients who respond to these therapies remains a challenge. In recognition of the importance of the functional phenotype of cancer cells, Verhaegh et al. (Cancer Res 2014) developed assays to measure functional activity of signal transduction pathways (STPs) based on mRNA expression levels of pathway-specific target genes. In this study, we aimed to identify HGSCs with STP activity with potential clinical target by comparing their activity assessment with STP activity in normal Fallopian tube epithelium (FTE), the tissue of origin of most HGSCs. Methods: We included 67 primary tumor samples taken prior to start of chemotherapy of postmenopausal patients diagnosed with advanced stage HGSC and 8 morphologically normal FTE samples of healthy postmenopausal women. Using OncoSignal pathway assays, we assessed functional pathway activity of the androgen receptor (AR), estrogen receptor (ER), PI3K, Hedgehog, TGF-𝛽 and Wnt pathways. Differences in STP activity between groups were compared with Mann-Whitney U tests. Cut-off value for aberrant STP activity was defined as two standard deviations above the mean value of STP activity measured in FTE samples. Results: In the HGSC group we observed lower median ER (p < 0.001) and Wnt (p = 0.046) pathway activity and higher median PI3K (p = 0.025) and TGF-𝛽 pathway (p = 0.030) activity as compared to the normal FTE group. In individual HGSC samples, aberrant activity was identified for the AR (n = 14), PI3K (n = 16), Hedgehog (n = 4), TGF-𝛽 (n = 36) and Wnt (n = 10) pathways. Frequently observed combinations of aberrant STP activity were AR/TGF-𝛽 (n = 8), TGF-𝛽/Wnt (n = 6) and PI3K/Hedgehog (n = 3). In total, we identified at least one STP with potential clinical target in 52 of the 67 HGSC samples. Conclusions: Our analysis enabled the identification of STP activity with potential clinical target in 78% of the analyzed HGSC samples. Differentiation between normal and aberrant STP activity could have clinical utility in the selection of HGSC patients for targeted therapy.