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Summary: Background: Front-line maintenance therapy with bevacizumab demonstrates high efficacy and safety in epithelial ovarian cancer, as already shown in large phase III trials; however, the corresponding study populations are often not fully representative of patients in clinical routine. In this Austria-based multicenter study, we aimed to explore the real-world outcomes of bevacizumab use in front-line treatment of ovarian cancer, including patients with comorbidities and poor performance status. Patients: This study is an open label single arm multicenter noninterventional trial and included patients with newly diagnosed advanced epithelial ovarian cancer, who were treated with platinum-based chemotherapy and were candidates for receiving bevacizumab according to the product label. Data collection started in the third quarter of 2012 and ended in the third quarter of 2018. Results: In this study 50 patients were included and 575 adverse events were reported for 90% of the patients. The majority of the adverse events were mild (47%) or moderate (37%). The most common adverse events were hypertension (60%), anemia (48%), leukopenia (42%), thrombocytopenia (36%), neutropenia (36%) and proteinuria (26%). A relation to bevacizumab was documented only for 10.3% of all adverse events. In almost 50% of all adverse events, no intervention was needed and bevacizumab treatment had to be interrupted only in 3.3% of all adverse events. The median progression-free survival was 1.3 years (95% CI 1.1–1.8). Conclusion: The routine use of front-line bevacizumab for advanced ovarian cancer is associated with high efficacy comparable with that obtained in randomized phase III clinical trials; however, hypertension and proteinuria were reported significantly more often in our Austria-based real-world population. [ABSTRACT FROM AUTHOR]

The therapeutic potential of immune checkpoint inhibitors is currently being investigated in epithelial ovarian cancer (EOC), but immunological effects of the programmed cell death protein 1 (PD-1)/programmed cell death 1 ligand 1 (PD-L1) axis in EOC still remain poorly understood. The aim of this study was thus to compare infiltration rates of PD-1 and PD-L1 expressing tumor infiltrating leucocytes (TILs) in primary ovarian tumor tissue and metastatic intraperitoneal implants and to investigate its impact on overall survival (OS). Tumor specimens (ovarian tumor tissues and intraperitoneal metastases) of 111 patients were used to investigate the PD-1, PD-L1 and CD8 expression rates on TILs and PD-L1 expression rate of tumor cells. The percentages of CD8, PD-1, and PD-L1 expressing subpopulations of TILs differ in primary ovarian tumor tissues and metastatic intraperitoneal implants. High PD-1 among TILs in peritoneal metastases were associated with favorable OS. High PD-L1 expression in TILs was associated with poor OS. Combining both factors in peritoneal metastases revealed an unfavorable prognosis. Primary ovarian tumor tissue and intraperitoneal metastatic tissues in EOC might have different strategies to evade immune control. Those findings are of importance for the process of biomarker assessment to predict patients' response to immunotherapy. [ABSTRACT FROM AUTHOR]

Purpose: To assess the impact of frailty on compliance of standard therapy, complication, rate and survival in patients with gynecological malignancy aged 80 years and older. Methods: In total, 83 women with gynecological malignancy (vulva, endometrial, ovarian or cervical cancer) who underwent primary treatment between 2007 and 2017 were retrospectively analyzed. Frailty index was calculated and its association with compliance of standard treatment, peri- and postoperative mortality and morbidity, and survival was evaluated. Results: Frailty was observed in 24.1% of cases. Both frail and non-frail patients were able to receive standard therapy in most cases − 75.0% and 85.7%, respectively (p = 0.27). Frail patients did not show an increased postoperative complication rate. Frail patients had shorter 3 years overall survival rates (28%) when compared to non-frail patients (55%) (p = 0.02). In multivariable analysis high frailty index (Hazard Ratio [HR] 12.15 [1.39–106.05], p = 0.02) and advanced tumor stage (HR 1.33 [1.00–1.76], p = 0.05) were associated with poor overall survival, but not age, histologic grading, performance status, and compliance of standard therapy. Conclusion: Majority of patients was able to receive standard therapy, as suggested by the tumor board, irrespective of age and frailty. Nonetheless, frailty is a common finding in patients with gynecological malignancy aged 80 years and older. Frail patients show shorter progression-free, and overall survival within this cohort. [ABSTRACT FROM AUTHOR]

Objective: Hypoalbuminemia, a known marker for malnutrition, has been associated with an increased risk for perioperative morbidity and poor prognosis in patients with solid tumors. The aim of this study was to investigate the prognostic and predictive value of pre-treatment serum albumin levels for survival and postoperative complications in patients with vulvar cancer undergoing surgery.Methods: Within in this retrospective study, we assessed data of 103 consecutive patients with vulvar cancer undergoing primary surgery into this study. Pre-treatment serum albumin levels were correlated with clinico-pathological parameters and complications. We performed univariate log-rank test and multivariable Cox regression models to evaluate the association between pre-treatment serum albumin and survival.Results: We found hypoalbuminemia (< 35 mg/dl) in 9 of 103 (8.7%) patients. No difference in tumor characteristics was observed between patients with hypoalbuminemia and normal serum albumin levels. Difference in postoperative complications (55.6% and 37.8% of patients with hypoalbuminemia and normal serum albumin levels, respectively) was not statistically significant (p = 0.345). Shorter overall survival (OS) was observed in patients with hypoalbuminemia (5-year OS rate 17.1%) when compared to patients with normal serum albumin levels (5-year OS rate 58.6%, p = 0.004). In multivariable analysis, age (p = 0.017), FIGO stage (p = 0.011) and serum albumin levels (p = 0.013) were independently associated with OS.Conclusion: Pre-treatment hypoalbuminemia is an independent prognostic biomarker for OS in patients with vulvar cancer. We did not find an association between pre-treatment hypoalbuminemia and a higher risk for postoperative complications. [ABSTRACT FROM AUTHOR]

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Purpose: The aim of the present study was to assess the value of the Glasgow Prognostic Score (GPS) as a prognostic tool for predicting post-relapse survival (PRS) in patients with recurrent cervical cancer.Methods: We retrospectively evaluated the data of 116 patients with recurrent cervical cancer in whom serologic biomarkers had been assessed at the time of relapse. The GPS was calculated as follows: patients with elevated serum C-reactive protein levels and hypoalbuminemia were allocated a score of 2, and those with 1 or no abnormal value were allocated a score of 1 and 0, respectively. To assess the association between factors including the GPS and PRS, we performed uni- and multivariate survival analyzes.Results: After a median follow-up of 20.9 months from recurrence, a 5-year PRS rate of 25% (SE 4.7%) was observed. Only in 29.8% of the patients, recurrence was limited to the pelvis. In uni- and multivariate survival analyzes, the GPS [HR 1.6 (95% CI 0.9-2.4), p = 0.01], a history of radiation therapy as part of initial treatment [HR 2.7 (95% CI 1.1-6.9), p = 0.03], and the presence of peritoneal carcinomatosis or multiple sites of relapse [HR 4.2 (95% CI 1.9-9.3), p < 0.001] were associated with shorter PRS. The GPS correlated with higher squamous cell carcinoma antigen levels (p = 0.001), shorter median PRS (p = 0.009), and less intensive treatment for relapse (p = 0.02).Conclusions: A higher GPS at the time of relapse, a history of radiation therapy, and the presence of peritoneal carcinomatosis or multiple sites of relapse are independently associated with shorter PRS in patients with recurrent cervical cancer. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the risk for endometrial cancer (EC) in a large series of asymptomatic patients with thickened endometrium at ultrasound examination based on previously published data of a theoretical cohort.Methods: In a prospective register study, a total of 1024 women with thickened endometrium in ultrasound examination undergoing histological diagnosis by dilation, hysteroscopy and curettage were evaluated. 124 patients were excluded due to current medication with tamoxifen and/or presence of HNPCC leaving 900 patients for further analysis.Results: Mean [standard deviation (SD)] age of patients was 65.6 (8.6) years. Mean (SD) endometrial thickness was 11.9 (5.8) mm. 32 and 6 cases of EC and complex endometrial hyperplasia with atypia were found, respectively. In the univariate analysis, a statistically significant association between endometrial thickness, current use of antihypertensive medication, number of deliveries, and the presence of endometrial fluid in preoperative vaginal ultrasound (p < 0.05) with EC was found. A multivariate logistic regression model incorporating these parameters showed a statistically significant independent association of endometrial thickness, number of deliveries, and the presence of endometrial fluid in preoperative vaginal ultrasound (p < 0.05), but not current use of antihypertensive medication, with EC. Using a cut-off of the endometrial thickness of > 11 mm, the risk for "EC alone" and "EC and complex endometrial hyperplasia with atypia combined" was found to be 6.7% and 7.9%, respectively.Conclusions: Our data compare favorably to a theoretical cohort suggesting a clinically reasonable cut-off of > 11 mm endometrial thickness to discriminate between "normal" and "pathological". The data regarding "risk for endometrial cancer" can be used for counseling affected women. [ABSTRACT FROM AUTHOR]

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Purpose: This manuscript reports the consensus recommendations on screening and diagnosis of Lynch syndrome (LS) in patients with endometrial or ovarian cancer as well as on possible preventive measures in effectively LS-diagnosed women. The recommendations are issued by the Austrian Arbeitsgemeinschaft für Gynäkologische Onkologie (AGO) of the Österreichischen Gesellschaft für Gynäkologie und Geburtshilfe (OEGGG) after consultation of the most recent and relevant literature and following deliberation by the Genetic Task-Force convoked May, 2015 by the AGO Council.Results and Conclusion: The Austrian AGO recommends immunohistochemical tissue screening for type-I and type-II endometrial cancers in all patients below the age of 70 years, and for all endometrioid and clear-cell ovarian cancers independently of the patient's age. If needed immunohistochemistry should be complemented by tissue MLH1 promotor hypermethylation testing and/or microsatellite instability (MSI) analysis. The diagnosis LS requires confirmation through identification of a germline mutation by a molecular genetic examination in the mismatch repair genes using the patient's blood. This should be performed without preceding tissue screening when in LS-associated cancer patients the family history fulfills the Amsterdam II or the revised Bethesda criteria. In LS-diagnosed women, the age for prophylactic surgery should be set flexibly based on an informed consent. Regarding the monitoring of these women, chemo-preventive measures as well as screening procedures either to avoid or to early detect LS-related tumors are discussed with a special light on their specific limitations. [ABSTRACT FROM AUTHOR]

Angiogenesis plays a pivotal role in normal ovarian physiology as well as in the formation and progression of ovarian cancer. Several well-designed phase II and III trials studied the efficacy of antiangiogenic agents in advanced ovarian cancer. The results of these trials demonstrated significantly prolonged progression-free survival when antiangiogenic agents were used as a maintenance therapy. To date, no effect on overall survival could be ascertained. The most widely studied antiangiogenic agent, bevacizumab - a monoclonal humanized antibody against vascular endothelial growth factor - was effective in all phases of the disease (first-line therapy, platinum-sensitive and platinum-resistant recurrence). These results led to regulatory approval in many countries including the European Union. Other anti-VEGF agents such as tyrosine kinase inhibitors have not shown increased activity but increased toxicity relative to bevacizumab. Agents targeting angiopoietin-1 and -2 are in development and new combinations with PARP inhibitors and immune checkpoint inhibitors are studied. This review summarizes the current data and knowledge on the clinical use of antiangiogenic agents in advanced ovarian cancer. [ABSTRACT FROM AUTHOR]

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Myeloperoxidase (MPO) is an oxidant generating enzyme normally restricted to myeloid cells, however aberrant MPO expression has been found to occur in non-myeloid cells in some disease states. The functional -463GA promoter polymorphism alters MPO expression levels. The -463G is within an SP1 binding site and is associated with higher gene expression. The G allele is most frequent with ~62 % of European populations being GG homozygotes. The GA polymorphism has been associated with risk or survival in a variety of cancers including lung and breast cancer. In this study we determined the frequency of the -463G/A polymorphism in 230 ovarian cancer patients, 75 patients with borderline ovarian tumors, and 299 healthy controls. The GG genotype was found to be overrepresented in patients with early stage ovarian cancer (83.3 % GG, p = 0.008) as compared to healthy controls (62 % GG), suggesting that MPO oxidants may increase risk. Immunohistochemical analysis revealed MPO expression in a subset of columnar ovarian epithelial carcinoma cells in early stage carcinomas. [ABSTRACT FROM AUTHOR]

Purpose: The extent of conization seems to influence the risk of preterm birth. The aim of this study was to compare the cone volume after surgical resection with large loop excision of the transformation zone (LLETZ) and cold knife conization (CKC). Methods: The present retrospective multi-center study comprises 804 consecutive women, who underwent LLETZ ( n = 412) or CKC ( n = 392) between 2004 and 2009. Univariate and multivariable analyses were performed to compare cone volumes removed by LLETZ and CKC and identify independent risk factors for large cone volume. Results: The median resected cone volume after LLETZ was significantly smaller [1.6 cm (0.8-2.9)] than after CKC [2.1 cm (1.4-3.5)] (<0.0001). Complete resection rates were comparable in both groups. Conization method, cone depth, and institution type were independent risk factors for removal of a large cone volume. Conclusion: CKC removes larger cone volumes than LLETZ without the advantage of higher complete resection rates. [ABSTRACT FROM AUTHOR]

Copyright of Wiener Klinische Wochenschrift is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Wiener Klinische Wochenschrift is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective:Besides its important role in immune response and inflammatory processes the cytokine interleukin-6 (IL-6) is crucially involved in carcinogenesis. A common polymorphism within the gene encoding IL-6 (IL6) is known to alter IL-6 protein expression and has been associated with patients' prognosis in various malignancies. No data are available with respect to vulvar cancer. Therefore, we determined the prognostic potential of the common -174(G→C) single nucleotide polymorphism in the promoter region of IL6 in a series of patients with this disease.Methods:The IL6 promoter polymorphism was investigated in 81 Caucasian patients with surgically treated squamous cell vulvar cancer using pyrosequencing. Results were correlated with clinical data.Results:No association was ascertained between the IL6 promoter polymorphism and the investigated clinicopathologic parameters, ie, tumor stage, lymph node involvement, tumor grade, and patient's age at diagnosis. In an univariate analysis, lymph node involvement and patients' age at diagnosis were associated with patient prognosis. In a multivariate analysis, including tumor stage and lymph node involvement as established prognostic factors and the IL6 promoter polymorphism, lymph node involvement, and the presence of at least one mutant allele, but not tumor stage, were associated with increased disease-free and overall survival.Conclusion:Our data suggest that the IL6 - 174(G→C) promoter polymorphism might serve as an additional prognostic parameter in patients with vulvar cancer. [ABSTRACT FROM PUBLISHER]

The aim of our study was to determine the prevalence of tumor anemia and thrombocytosis in patients with vulvar cancer, and to evaluate the prognostic value or pretreatment hemoglobin (Hb) and platelet count regarding disease-free and overall survival of patients with vulvar cancer. We measured pretreatment Hb and platelet count in 62 patients with squamous cell vulvar cancer. The results were correlated to clinical data. Median Hb and platelet count in patients with vulvar cancer were 13.1 g/dl (range 8.3-16.2) and 268,500/μl (range 88,000-778,000), respectively. Cut-off levels of 12 g/dl and 300,000/μl were selected for tumor anemia and tumor thrombocytosis, respectively according to published criteria. Tumor anemia and tumor thrombocytosis were present in 30.6 and 27.4% of patients with vulvar cancer, respectively. In a univariate analysis tumor stage and tumor thrombocytosis were significantly associated with a shortened disease-free (log-rank test, p < 0.001 and p = 0.003, respectively) and overall survival (log-rank test, p < 0.001 and p < 0.001, respectively). Tumor anemia was not associated with a shortened disease-free, but with a shortened overall survival of patients with vulvar cancer (log-rank test, p = 0.1 and p = 0.002, respectively). A multivariate Cox regression model considering tumor stage, tumor anemia, and tumor thrombocytosis showed, however, that pretreatment Hb and platelet count did not confer additional prognostic information to that already obtained by the established prognosticator tumor stage on disease free (multivariate Cox regression model, p = 0.8, p = 0.2, and p = 0.003, respectively) and overall survival (multivariate Cox regression model, p = 0.4, p = 0.5, and p = 0.04, respectively). Pretreatment tumor anemia and tumor thrombocytosis were associated with a poor prognosis, but were not an independent predictor of outcome in patients with vulvar cancer. Copyright © 2000 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The aim of the present study was to evaluate the clinical usefulness of the cytokeratin tumor marker tissue polypeptide antigen (TPA) in patients with vulvar cancer. This retrospective study comprises 41 patients with vulvar cancer FIGO stages I-III, 17 patients with vulvar intraepithelial neoplasia (VIN) III, and 40 healthy female controls. Serum concentrations of TPA were measured using a microparticle enzyme immunoassay. Results were correlated to clinical data. Median serum concentrations of TPA in healthy female controls, patients with VIN III, and patients with vulvar cancer were 42 U/l (range 12-192), 53 U/l (range 17-127.9) and 57 U/l (range 4.2-423), respectively (Mann-Whitney U test, p = 0.8). Serum concentrations of TPA were not associated with stage of disease, histological grade, and age at the time of diagnosis. In vulvar cancer patients, elevated serum concentrations of TPA prior to therapy were not associated with a shortened disease-free or overall survival (log-rank test: p = 0.5 and p = 0.9, respectively). In a multivariate Cox regression model comprising tumor stage and TPA, tumor stage, but not TPA revealed a statistically significant influence on disease-free (Cox proportional hazard regression model, p = 0.05 and p = 0.6, respectively) and overall (Cox proportional hazard regression model, p = 0.04 and p = 0.8, respectively) survival of patients with vulvar cancer. We conclude that cytokeratin expression, as reflected by serum concentrations of TPA, does not play a role in the natural history of vulvar cancer. The evaluation of serum concentrations of TPA prior to therapy is not recommended. Copyright © 2000 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

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Vulvar cancer is a rare malignancy with poor prognosis that generally occurs in elderly patients. The individual prognosis is difficult to assess. Serum creatinine levels are frequently elevated in elderly patients. Recent evidence have shown shown that - besides indicating kidney impairment - serum creatinine levels may be used to predict the survival in cancer patients. Several studies observed an association between elevated serum creatinine levels and poor prognosis in patients with solid tumors. In this retrospective cohort study, serum creatinine levels were evaluated in 170 patients with invasive vulvar cancer. Serum creatinine levels were correlated to established clinicopathologic factors. Univariate and multivariate survival analysis were performed. Elevated serum creatinine levels (>1.2 mg/dl) were significantly associated with both poor disease specific and overall survival. Three year overall survival rates were 74.8% and 32.5% for patients with serum creatinine levels of ≤ and >1.2 mg/dl, respectively. In a multivariate survival model, serum creatinine levels were significantly associated with overall survival independent of tumor stage and patients' age. In conclusion, pretherapeutic serum creatinine levels may be useful as an independent prognostic parameter in patients with vulvar cancer. [ABSTRACT FROM AUTHOR]

A correction to the article "Austrian Arbeitsgemeinschaft für Gynäkologische Onkologie (AGO) guideline for prophylaxis with granulocyte colony-stimulating factors (G-CSF) in gynecologic malignancies, including breast cancer," that was published in the June 2012 issue is presented.