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1.
Gynecol Oncol Rep ; 37: 100817, 2021 Aug.
Article En | MEDLINE | ID: mdl-34258357

•Checkpoint inhibitor therapy affecting PD-L1 as treatment for advanced solid tumors.•Success in trial pembrolizumab therapy in multiresistant metastatic choriocarcinoma.•Long-term remission after pembrolizumab therapy in multiresistant choriocarcinoma.•Only six reported cases, one with comparable follow-up and outcome.

3.
Gynecol Oncol ; 152(2): 235-242, 2019 02.
Article En | MEDLINE | ID: mdl-30466805

OBJECTIVE: Surgical assessment of residual tumor provides the strongest prognostic information in advanced ovarian cancer (AOC), with the best outcome observed after complete resection. Postoperative radiological assessment before initiation of chemotherapy can supplement the information obtained by surgical assessment; however, it may also reveal conflicting findings. METHODS: Patients with AOC enrolled in the AGO-OVAR 12 trial underwent baseline imaging before the first chemotherapy cycle. The findings from surgical and radiologic assessment for disease extend were compared. Additionally, an integrated approach was assessed. RESULTS: Complete data from all 3 assessment methods were available for 1345 patients. Of 689 patients with complete resection, tumor was observed in 28% and 22% of patients undergoing radiologic and integrated assessment, respectively. Patients with surgical- radiological and surgical-integrated concordant findings showed a 5-year overall survival (5Y-OS) of 72% and 71%, whereas patients with surgical-radiological and surgical-integrated discordant results showed inferior 5Y-OS of 47% and 49%, respectively. Patients with surgically assessed residual disease had a 5-YOS of 37%. The interval between surgery and baseline assessment was independently associated with discordance between assessment methods, which might reflect early tumor regrowth. CONCLUSIONS: Baseline tumor assessment before chemotherapy provides information that stratifies patients with complete resection into different prognostic groups. Integrating the data from different assessment methods might lead to improved definitions of prognostic groups. Further investigation to determine if earlier initiation of chemotherapy after debulking surgery could increase survival of patients with early tumor regrowth is warranted.


Carcinoma, Ovarian Epithelial/pathology , Carcinoma, Ovarian Epithelial/surgery , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carboplatin/administration & dosage , Carcinoma, Ovarian Epithelial/drug therapy , Carcinoma, Ovarian Epithelial/mortality , Double-Blind Method , Female , Humans , Indoles/administration & dosage , Middle Aged , Neoplasm Staging , Neoplasm, Residual/pathology , Paclitaxel/administration & dosage , Prognosis , Young Adult
4.
Ann Oncol ; 29(8): 1784-1792, 2018 08 01.
Article En | MEDLINE | ID: mdl-29767688

Background: Niraparib is a poly(ADP-ribose) polymerase inhibitor approved in the USA and Europe for maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy. In the pivotal ENGOT-OV16/NOVA trial, the dose reduction rate due to treatment-emergent adverse event (TEAE) was 68.9%, and the discontinuation rate due to TEAE was 14.7%, including 3.3% due to thrombocytopenia. A retrospective analysis was carried out to identify clinical parameters that predict dose reductions. Patients and methods: All analyses were carried out on the safety population, comprising all patients who received at least one dose of study drug. Patients were analyzed according to the study drug consumed (i.e., as treated). A predictive modeling method (decision trees) was used to identify important variables for predicting the likelihood of developing grade ≥3 thrombocytopenia within 30 days after the first dose of niraparib and determine cut-off points for chosen variables. Results: Following dose modification, 200 mg was the most commonly administered dose in the ENGOT-OV16/NOVA trial. Baseline platelet count and baseline body weight were identified as risk factors for increased incidence of grade ≥3 thrombocytopenia. Patients with a baseline body weight <77 kg or a baseline platelet count <150 000/µl in effect received an average daily dose ∼200 mg (median = 207 mg) due to dose interruption and reduction. Progression-free survival in patients who were dose reduced to either 200 or 100 mg was consistent with that of patients who remained at the 300 mg starting dose. Conclusions: The analysis presented suggests that patients with baseline body weight of <77 kg or baseline platelets of <150 000/µl may benefit from a starting dose of 200 mg/day. ClinicalTrials.gov ID: NCT01847274.


Indazoles/administration & dosage , Neoplasm Recurrence, Local/drug therapy , Ovarian Neoplasms/drug therapy , Piperidines/administration & dosage , Poly(ADP-ribose) Polymerase Inhibitors/administration & dosage , Thrombocytopenia/epidemiology , Administration, Oral , Adult , Body Weight , Dose-Response Relationship, Drug , Female , Humans , Incidence , Indazoles/adverse effects , Maintenance Chemotherapy/adverse effects , Maintenance Chemotherapy/methods , Neoplasm Recurrence, Local/blood , Neoplasm Recurrence, Local/mortality , Ovarian Neoplasms/blood , Ovarian Neoplasms/mortality , Piperidines/adverse effects , Platelet Count , Poly(ADP-ribose) Polymerase Inhibitors/adverse effects , Progression-Free Survival , Retrospective Studies , Risk Factors , Thrombocytopenia/blood , Thrombocytopenia/chemically induced
6.
Arch Gynecol Obstet ; 297(4): 837-846, 2018 04.
Article En | MEDLINE | ID: mdl-29356953

BACKGROUND: Ovarian, tubal, and peritoneal carcinomas primarily affect the peritoneal cavity, and they are typically diagnosed at an advanced tumor stage (Foley, Rauh-Hain, del Carmen in Oncology (Williston Park) 27:288-294, 2013). In the course of primary surgery, postoperative tumor residuals are, apart from the tumor stage, the strongest independent factors of prognosis (du Bois, Reuss, Pujade-Lauraine, Harter, Ray-Coquard, Pfisterer in Cancer 115:1234-1244, 2009). Due to improved surgical techniques, including the use of multi-visceral procedures, macroscopic tumor clearance can be achieved in oncological centers, in most cases (Harter, Muallem, Buhrmann et al in Gynecol Oncol 121:615-619, 2011). However, to date, it has not been shown that peritoneal carcinomatosis is, per se, an independent factor of prognosis or that it excludes the achievement of tumor clearance. Several studies have shown that a preceding drug therapy in peritoneal carcinomatosis could positively influence the overall prognosis (Trimbos, Trimbos, Vergote et al in J Natl Cancer Inst 95:105-112, 2003). In relapses of ovarian carcinoma, studies have shown that peritoneal carcinomatosis is a negative predictor of complete tumor resection; however, when it is possible to resect the tumor completely, peritoneal carcinomatosis does not play a role in the prognosis (Harter, Hahmann, Lueck et al in Ann Surg Oncol 16:1324-1330, 2009). RESULTS: PIPAC is a highly experimental method for treating patients with ovarian, tubal, and peritoneal cancer. To date, only three studies have investigated a total of 184 patients with peritoneal carcinomatosis (Grass, Vuagniaux, Teixeira-Farinha, Lehmann, Demartines, Hubner in Br J Surg 104:669-678, 2017). Only some of those studies were phase I/II studies that included PIPAC for patients with different indications and different cancer entities. It is important to keep in mind that the PIPAC approach is associated with relatively high toxicity. To date, no systematic dose-finding studies have been reported. Moreover, no studies have reported improvements in progression-free or overall survival associated with PIPAC therapy. CONCLUSIONS: Randomized phase III studies are required to evaluate the effect of this therapy compared to other standard treatments (sequential or simultaneous applications with systemic chemotherapy). In cases of ovarian, tubal, and peritoneal cancer, PIPAC should not be performed outside the framework of prospective, controlled studies.


Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma/drug therapy , Fallopian Tube Neoplasms/drug therapy , Ovarian Neoplasms/drug therapy , Peritoneal Neoplasms/drug therapy , Administration, Inhalation , Aerosols , Austria , Cisplatin/administration & dosage , Doxorubicin/administration & dosage , Fallopian Tube Neoplasms/pathology , Female , Humans , Neoplasm Recurrence, Local/drug therapy , Neoplasm, Residual , Ovarian Neoplasms/pathology , Peritoneal Neoplasms/pathology , Prognosis , Prospective Studies , Treatment Outcome
7.
Ann Oncol ; 27(12): 2236-2241, 2016 12.
Article En | MEDLINE | ID: mdl-27789470

BACKGROUND: Randomized, phase III trial to evaluate safety and efficacy of topotecan and carboplatin (TC) compared with standard platinum-based combinations in platinum-sensitive recurrent ovarian cancer (ROC). PATIENTS AND METHODS: Patients were randomly assigned in a 1:1 ratio to the experimental TC arm (topotecan 0.75 mg/m2/ days 1-3 and carboplatin AUC 5 on day 3 every 3 weeks) or to one of the standard regimes [(PC) paclitaxel plus carboplatin; (GC) gemcitabine plus carboplatin; (PLDC) pegylated liposomal doxorubicin and carboplatin] which could be chosen by individual preference but before randomization. The primary end point was progression-free survival (PFS) after 12 months. Overall survival (OS), response rate, toxicity, quality of life and treatment preference regarding standard treatment were defined as secondary end points. RESULTS: A total of 550 patients were recruited. The PFS rate after 12 months was 37.0% for TC compared with 40.2% in the standard combinations (P = 0.470). The overall response rate was 73.1% for TC versus 75.1% for standard combinations (P = 0.149). After a median follow-up of 20 months, the median PFS was 10 months [95% confidence interval (CI) 9.4-10.6] and did not differ between both arms (P = 0.414). The median OS was 25 months in the TC arm versus 31 months in the standard arm (95% CI: 22.4-27.6 resp. 26.0-36.0; P = 0.163). Severe hematologic toxicities (grade 3/4) were rare in the experimental arm (P < 0.001), with 17.4% leucopenia, 27.8% neutropenia and 15.9% thrombopenia. CONCLUSION: The combination of carboplatin and topotecan was well tolerated with significant lower rates of severe hematological toxicities but did not improve PFS or OS in platinum-sensitive relapsed ovarian cancer compared with established standard regimens.


Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Carboplatin/administration & dosage , Neoplasm Recurrence, Local/drug therapy , Ovarian Neoplasms/drug therapy , Topotecan/administration & dosage , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Austria , Carboplatin/adverse effects , Deoxycytidine/administration & dosage , Deoxycytidine/adverse effects , Deoxycytidine/analogs & derivatives , Disease-Free Survival , Doxorubicin/administration & dosage , Doxorubicin/adverse effects , Doxorubicin/analogs & derivatives , Female , Humans , Middle Aged , Neoplasm Recurrence, Local/pathology , Ovarian Neoplasms/pathology , Paclitaxel/administration & dosage , Paclitaxel/adverse effects , Polyethylene Glycols/administration & dosage , Polyethylene Glycols/adverse effects , Quality of Life , Topotecan/adverse effects , Gemcitabine
8.
Br J Cancer ; 111(8): 1519-25, 2014 Oct 14.
Article En | MEDLINE | ID: mdl-25225907

BACKGROUND: This is the first study investigating the safety and efficacy of the trifunctional antibody catumaxomab administered i.p. at the end of cytoreductive surgery and postoperatively prior to standard chemotherapy in patients with primary epithelial ovarian cancer (EOC). METHODS: Patients received i.p. catumaxomab 10 µg intraoperatively and 10, 20, 50 and 150 µg on days 7, 10, 13 and 16, respectively, postoperatively. After the study, patients received standard chemotherapy and were followed for 23 months. The primary endpoint was the rate of postoperative complications. RESULTS: Forty-one patients entered the study and were evaluable for safety and 34 were alive at 24 months. Complete tumour resection rate was 68%. Postoperative complications were observed in 51%, the most common anastomotic leakage (7%) and wound infections (5%). The most common catumaxomab-related adverse events were abdominal pain, nausea, vomiting and pyrexia. Thirty-nine percent discontinued catumaxomab therapy, and 98% received chemotherapy post study. Kaplan-Meier estimates of disease-free and overall survival after 24 months were 56% and 85%, respectively. CONCLUSIONS: Intra- and close postoperative catumaxomab seems feasible, but efficacy and safety were limited by postsurgical complications. In the future prospective trials are needed to investigate the best schedule of integration of catumaxomab into current treatment strategies for EOC.


Antibodies, Bispecific/therapeutic use , Neoplasms, Glandular and Epithelial/drug therapy , Ovarian Neoplasms/drug therapy , Adult , Aged , Antibodies, Bispecific/administration & dosage , Carcinoma, Ovarian Epithelial , Female , Humans , Intraoperative Care , Middle Aged , Neoplasms, Glandular and Epithelial/surgery , Ovarian Neoplasms/surgery , Postoperative Care
9.
Br J Cancer ; 109(3): 610-4, 2013 Aug 06.
Article En | MEDLINE | ID: mdl-23921280

BACKGROUND: Gamma-glutamyltransferase (GGT) - a membrane-bound enzyme crucially involved in the cell's detoxification pathway and apoptotic balance - is involved in tumour development, progression and chemotherapy resistance. Elevated GGT serum levels are associated with increased cancer risk in women and worse prognosis in gynaecologic cancers. The present study investigated the prognostic role of GGT in ovarian cancer patients. METHODS: In this multicenter study, pre-therapeutic GGT levels were ascertained in 634 consecutive patients with epithelial ovarian cancer (EOC, n=567) and borderline tumour of the ovary (BTO, n=67). Gamma-glutamyltransferase serum levels were associated with clinicopathological parameters and uni- and multivariate survival analyses were performed. Immunohistochemistry of GGT was performed in ovarian cancer tissue and correlated with GGT serum levels. RESULTS: Pre-therapeutic GGT serum levels were higher in patients with EOC (28.56 (38.24) U l(-1)) than in patients with BTO (20.01 (12.78) U l(-1), P=0.01). High GGT serum levels were associated with advanced FIGO stage (P<0.001) and with worse overall survival in univariate (P<0.001) and multivariable analysis (P=0.02, HR 1.2 (1.1-1.5)). We further investigated the association between systemic GGT serum levels and local GGT expression in EOC tumour tissue and observed an association between these two parameters (P=0.03). CONCLUSION: High pre-therapeutic GGT serum levels are associated with advanced tumour stage and serve as an independent prognostic marker for worse overall survival in patients with EOC. Gamma-glutamyltransferase expression in ovarian cancer tissue is reflected in GGT serum levels.


Neoplasms, Glandular and Epithelial/enzymology , Ovarian Neoplasms/enzymology , gamma-Glutamyltransferase/blood , Carcinoma, Ovarian Epithelial , Female , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Middle Aged , Neoplasm Staging , Neoplasms, Glandular and Epithelial/pathology , Ovarian Neoplasms/pathology , Prognosis , Severity of Illness Index
10.
Br J Cancer ; 109(1): 215-8, 2013 Jul 09.
Article En | MEDLINE | ID: mdl-23764750

BACKGROUND: Thyroid function has been suggested to interfere with tumour biology and prognosis in different cancers. The present study was performed to investigate the impact of pre-therapeutic serum thyroid-stimulating hormone (TSH) levels on the prognosis of patients with endometrial cancer. METHODS: Pre-therapeutic serum TSH was investigated in 199 patients with endometrial cancer. After stratification in TSH risk groups, univariate and multivariable survival analyses were performed. RESULTS: Elevated TSH was independently associated with poor disease-specific survival in univariate/multivariable survival analyses (P=0.01 and P=0.03, respectively). CONCLUSION: Thyroid-stimulating hormone may serve as a novel and independent prognostic parameter for disease-specific survival in patients with endometrial cancer.


Endometrial Neoplasms/blood , Endometrial Neoplasms/mortality , Thyrotropin/blood , Aged , Endometrial Neoplasms/metabolism , Female , Humans , Kaplan-Meier Estimate , Prognosis , Thyroid Gland/physiology
11.
Br J Cancer ; 107(6): 918-24, 2012 Sep 04.
Article En | MEDLINE | ID: mdl-22871885

BACKGROUND: Nomograms are predictive tools that are widely used for estimating cancer prognosis. The aim of this study was to develop a nomogram for the prediction of overall survival (OS) in patients diagnosed with cervical cancer. METHODS: Cervical cancer databases of two large institutions were analysed. Overall survival was defined as the clinical endpoint and OS probabilities were estimated using the Kaplan-Meier method. Based on the results of survival analyses and previous studies, relevant covariates were identified, a nomogram was constructed and validated using bootstrap cross-validation. Discrimination of the nomogram was quantified with the concordance probability. RESULTS: In total, 528 consecutive patients with invasive cervical cancer, who had all nomogram variables available, were identified. Mean 5-year OS rates for patients with International Federation of Gynecologists and Obstetricians (FIGO) stage IA, IB, II, III, and IV were 99.0%, 88.6%, 65.8%, 58.7%, and 41.5%, respectively. Seventy-six cancer-related deaths were observed during the follow-up period. FIGO stage, tumour size, age, histologic subtype, lymph node ratio, and parametrial involvement were selected as nomogram covariates. The prognostic performance of the model exceeded that of FIGO stage alone and the model's estimated optimism-corrected concordance probability was 0.723, indicating accurate prediction of OS. We present the prediction model as nomogram and provide a web-based risk calculator (http://www.ccc.ac.at/gcu). CONCLUSION: Based on six easily available parameters, a novel statistical model to predict OS of patients diagnosed with cervical cancer was constructed and validated. The model was implemented in a nomogram and provides accurate prediction of individual patients' prognosis useful for patient counselling and deciding on follow-up strategies.


Nomograms , Uterine Cervical Neoplasms/mortality , Uterine Cervical Neoplasms/pathology , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adult , Aged , Area Under Curve , Austria/epidemiology , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Cohort Studies , Female , Humans , Kaplan-Meier Estimate , Lymphatic Metastasis , Middle Aged , Neoplasm Staging , Predictive Value of Tests , Prognosis , ROC Curve , Uterine Cervical Neoplasms/surgery , White People/statistics & numerical data
12.
Br J Cancer ; 106(9): 1551-5, 2012 Apr 24.
Article En | MEDLINE | ID: mdl-22315051

BACKGROUND: Gamma-glutamyltransferase (GTT), a known marker for apoptotic balance, seems to promote tumour progression, invasion and drug resistance. Recently, high GGT serum levels were shown to be associated with impaired prognosis in patients with cervical cancer. The aim of this study was to investigate the value of pre-therapeutic serum GGT levels as prognostic parameter in patients with endometrial cancer. METHODS: Within the present multi-centre trial, clinical-pathological parameters and pre-therapeutic serum GGT levels were evaluated in 874 consecutive patients with endometrial cancer. Patients were stratified in GGT risk groups, and univariate and multivariable survival analyses were performed. RESULTS: Mean pre-therapeutic serum GGT level was 30.8 (41.5) U l(-1). Elevated and highly elevated serum GGT levels (P=0.03 and P=0.005), tumour stage (P<0.001 and P<0.001), grade (P<0.001 and P=0.02) and age (P<0.001 and P<0.001) were independently associated with progression-free survival in univariate and multivariable survival analyses. Pre-therapeutic GGT was not associated with advanced tumour stage (P=0.6), higher histological grade (P=0.6) or unfavourable histological subtype (P=0.3). CONCLUSION: Pre-therapeutic serum GGT is a novel and independent prognostic parameter for progression-free survival of patients with endometrial cancer. Stratifying patients into prognostic subgroups could be used for patient counselling and individualised treatment planning.


Biomarkers, Tumor/blood , Endometrial Neoplasms/blood , Endometrial Neoplasms/enzymology , Neoplasm Recurrence, Local/blood , Neoplasm Recurrence, Local/enzymology , gamma-Glutamyltransferase/blood , Aged , Endometrial Neoplasms/mortality , Enzyme-Linked Immunosorbent Assay , Female , Humans , Neoplasm Recurrence, Local/mortality , Prognosis , Survival Rate
13.
Ann Oncol ; 23(5): 1185-1189, 2012 May.
Article En | MEDLINE | ID: mdl-21976386

BACKGROUND: To perform a subset analysis of patients with partially platinum-sensitive recurrent ovarian cancer (ROC) who received either CD [carboplatin-pegylated liposomal doxorubicin (PLD)] or CP (carboplatin-paclitaxel) in the CALYPSO trial. PATIENTS AND METHODS: CALYPSO, an international phase III, non-inferiority trial, enrolled women with ROC that relapsed >6 months following first- or second-line therapy. Patients were randomized to CD or CP. Patients with a treatment-free interval of >6 and ≤ 12 months were evaluated for progression-free survival (PFS), the primary end point of CALYPSO trial, and safety. RESULTS: A total of 344 partially platinum-sensitive patients were included (N = 161, CD and N = 183, CP). The hazard ratio for PFS was 0.73 (95% confidence interval: 0.58-0.90; P = 0.004 for superiority) in favor of CD. Median PFS times were 9.4 months (CD) and 8.8 months (CP). Toxicities more common with CP versus CD included grade 3/4 neutropenia (50% versus 39%; P = 0.015), grade 2 alopecia (86% versus 9%; P < 0.001), neuropathy and hypersensitivity reactions. Hand-foot syndrome was more common with CD; however, grade 3/4 reactions were low (one patient in each arm). CONCLUSION: Carboplatin-PLD has a more favorable risk-benefit profile than CP in patients with partially platinum-sensitive ROC and should be considered an effective treatment option for these patients.


Adenocarcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carboplatin/administration & dosage , Doxorubicin/analogs & derivatives , Ovarian Neoplasms/drug therapy , Paclitaxel/administration & dosage , Polyethylene Glycols/administration & dosage , Adenocarcinoma/pathology , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carboplatin/adverse effects , Disease-Free Survival , Doxorubicin/administration & dosage , Doxorubicin/adverse effects , Drug Resistance, Neoplasm/drug effects , Female , Humans , Middle Aged , Ovarian Neoplasms/pathology , Paclitaxel/adverse effects , Platinum Compounds/therapeutic use , Polyethylene Glycols/adverse effects , Recurrence , Treatment Outcome , Young Adult
14.
Br J Cancer ; 103(5): 613-6, 2010 Aug 24.
Article En | MEDLINE | ID: mdl-20628380

BACKGROUND: To evaluate the prognostic value of lymph node density (LND) in patients with lymph node-positive cervical cancer. METHODS: A total of 88 consecutive patients were included in our study. Patients were treated with cisplatin-based concomitant chemoradiotherapy after surgical staging was performed at the Medical University of Vienna. Lymph node density, that is, the ratio of positive lymph nodes to the total number of lymph nodes removed, was assessed pathologically. Patients were stratified into two groups according to LND: patients with LND 10%. Lymph node density was correlated with clinicopathological parameters by chi(2)-tests. Univariate log-rank tests and multivariate Cox regression models were used to evaluate the association between LND and survival. RESULTS: A significant correlation between LND and FIGO stage (P=0.03), but not patients' age (P=0.2), histological grade (P=0.8), and histological type (P=0.5), was observed. In a univariate survival analysis, LND (P=0.01; P=0.01), FIGO stage (P=0.01; P=0.008), and histological grade (P=0.03; P=0.04) were associated with disease-free and overall survival, respectively. Patients with LND >10% had impaired disease-free and overall survival rates compared with patients with LND 10% is associated with an impaired disease-free and overall survival. Lymph node density may be used as an independent prognostic parameter in patients with lymph node-positive cervical cancer.


Lymph Nodes/pathology , Uterine Cervical Neoplasms/pathology , Adult , Female , Humans , Lymphatic Metastasis/pathology , Middle Aged , Prognosis , Uterine Cervical Neoplasms/mortality
15.
Br J Cancer ; 102(6): 952-6, 2010 Mar 16.
Article En | MEDLINE | ID: mdl-20160724

BACKGROUND: To analyse the correlation between pre-treatment plasma fibrinogen levels and clinical-pathological parameters in patients with endometrial cancer and to assess the value of plasma fibrinogen as a prognostic parameter. METHODS: Within a retrospective multi-centre study, the records of 436 patients with endometrial cancer were reviewed and pre-treatment plasma fibrinogen levels were correlated with clinical-pathological parameters and patients' survival. RESULTS: The mean (s.d.) pre-treatment plasma fibrinogen level was 388.9 (102.4) mg per 100 ml. Higher plasma fibrinogen levels were associated with advanced tumour stage (FIGO I vs II vs III and IV, P=0.002), unfavourable histological subtype (endometrioid vs non-endometrioid histology, P=0.03), and higher patients' age (< or =67 years vs >67 years, P=0.04), but not with higher histological grade (G1 vs G2 vs G3, P=0.2). In a multivariate analysis, tumour stage (P<0.001 and P<0.001), histological grade (P=0.009 and P=0.002), patients' age (P=0.001 and P<0.001), and pre-treatment plasma fibrinogen levels (P=0.04 and P=0.02) were associated with disease-free and overall survival, respectively. CONCLUSION: Plasma fibrinogen levels can be used as an independent prognostic parameter for the disease-free and overall survival of patients with endometrial cancer.


Carcinoma, Endometrioid/diagnosis , Endometrial Neoplasms/diagnosis , Fibrinogen/analysis , Aged , Carcinoma, Endometrioid/blood , Carcinoma, Endometrioid/mortality , Carcinoma, Endometrioid/pathology , Endometrial Neoplasms/blood , Endometrial Neoplasms/mortality , Endometrial Neoplasms/pathology , Female , Humans , Middle Aged , Neoplasm Staging , Predictive Value of Tests , Prognosis , Retrospective Studies , Survival Analysis
16.
Br J Cancer ; 96(3): 485-91, 2007 Feb 12.
Article En | MEDLINE | ID: mdl-17245339

HER2/neu overexpression is a driving force in the carcinogenesis of several human cancers. In breast cancer the prognostic influence of HER2/neu was shown to be at least partly based on increased metastatic potential mediated by the chemokine-chemokine receptor pair SDF-1(CXCL12)/CXCR4. We wanted to evaluate the influence of HER2/neu on ovarian cancer prognosis and to investigate whether compromised survival would correlate with CXCR4 expression and/or SDF-1 abundance. Therefore, we analysed HER2/neu, CXCR4, and SDF-1 in 148 ovarian tumour samples by means of immunohistochemistry on tissue microarrays. Overexpression of HER2/neu was found in 27.6% of ovarian cancer tissues and in 15% of ovarian borderline tumours. In ovarian cancer patients, overexpression of HER2/neu correlated closely with overall survival (univariate hazard ratio (HR) 2.59, P=0.005; multiple corrected HR 1.92, P=0.074). In contrast, CXCR4 expression and SDF-1 abundance had no impact on overall survival, and both parameters were not correlated with HER2/neu expression. As expected, cytoplasmic CXCR4 expression and SDF-1 abundance correlated closely (P<0.0001). Our results confirm a univariate influence of HER2/neu expression on overall survival, which was completely independent of the expression of CXCR4 and the abundance of SDF-1, implying significant differences between the HER2/neu downstream pathways in ovarian cancer compared with breast cancer.


Chemokines, CXC/physiology , Ovarian Neoplasms/mortality , Receptor, ErbB-2/analysis , Receptors, CXCR4/physiology , Signal Transduction , Adult , Aged , Aged, 80 and over , Chemokine CXCL12 , Chemokines, CXC/analysis , Female , Humans , Middle Aged , Ovarian Neoplasms/chemistry , Prognosis , Receptors, CXCR4/analysis
17.
Gynecol Oncol ; 102(2): 226-9, 2006 Aug.
Article En | MEDLINE | ID: mdl-16443259

OBJECTIVES: Platinum resistance is a significant problem in patients with ovarian cancer. The aim of this phase II study was to define the response rates, the progression-free survival and the toxicity profile of the combination of PEG liposomal doxorubicin (L-DXR) and gemcitabine (GEM). MATERIAL AND METHODS: Thirty one patients with histologically confirmed platinum-refractory or -resistant epithelial ovarian cancer were scheduled to receive 6 cycles of L-DXR 30 mg/m(2) on day 1 as well as GEM 650 mg/m(2) on days 1 and 8 every 28 days. RESULTS: The median number of chemotherapy cycles given was 4. The mean dose intensity for L-DXR and GEM on day 1 was 96% and 97%, respectively. The mean dose intensity for GEM on day 8 was 93%. The overall response rate was 33% (10 of 30 evaluable patients; 20% complete responses). The median progression-free survival was 3.8 months, and the median overall survival was 15.8 months, respectively. Toxicity was acceptable. One quarter of patients developed grade 3 or 4 neutropenia, but none developed febrile neutropenia. Palmoplantar erythrodysesthesia (PPE) grades 2 and 3 occurred in 13% and 3% only, respectively, and no grade 4 PPE was observed. Grades 1 to 3 stomatitis was found in 58% of patients (10% grade 3). CONCLUSION: The combination of L-DXR and GEM is an active and acceptably tolerated option in the treatment of patients with platinum-resistant and -refractory ovarian cancer. Dose reductions seem advisable in the case of > or =grade 2 stomatitis and/or PPE > or =grade 2.


Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Neoplasm Recurrence, Local/drug therapy , Ovarian Neoplasms/drug therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Deoxycytidine/administration & dosage , Deoxycytidine/adverse effects , Deoxycytidine/analogs & derivatives , Disease-Free Survival , Doxorubicin/administration & dosage , Doxorubicin/adverse effects , Doxorubicin/analogs & derivatives , Female , Humans , Middle Aged , Polyethylene Glycols/administration & dosage , Polyethylene Glycols/adverse effects , Quality of Life , Gemcitabine
18.
Gynecol Oncol ; 84(3): 449-52, 2002 Mar.
Article En | MEDLINE | ID: mdl-11855886

OBJECTIVE: The aim of the study was to determine the diagnostic accuracy and feasibility of sentinel lymph node (SLN) detection using a gamma probe in patients suffering from vulvar cancer. METHODS: From May 1998 to November 2000, 26 patients with early vulvar cancer, planned for local wide excision or vulvectomy including groin dissection, were eligible for the study. Two to 3 h before the planned procedure we injected technetium(99) m-labeled microcolloid intradermally at four locations around the tumor. Dynamic and static images were recorded using a gamma camera. SLN locations were marked on the overlying skin. In the operating theater SLNs were identified at the beginning of the procedure using a handheld gamma-detection probe. After resection of suspected SLNs a standard unilateral or bilateral groin dissection was performed, subsequently followed by local wide excision or, if indicated, radical vulvectomy. Sentinel node detection using technetium(99) m-labeled microcolloid was compared with final histopathological and immunohistochemical results. RESULTS: Scintigraphy showed focal uptake in all 26 patients. Intraoperatively we detected all sentinel nodes by handheld gamma probe. In 20 patients, one sentinel node was identified unilaterally, while in 6 patients two or more nodes were identified bilaterally. Histologically positive SLNs were found in 9 patients. In our preliminary series we did not find any false-negative SLN. CONCLUSION: Identification of sentinel nodes in vulvar cancer is feasible with preoperatively administered technetium(99)m-labeled microcolloid. We confirm the results of previous studies and improve the evidence that the SLN procedure could be implemented in future therapy concepts.


Lymph Nodes/diagnostic imaging , Sentinel Lymph Node Biopsy/methods , Vulvar Neoplasms/diagnostic imaging , Adult , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/diagnostic imaging , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathology , Colloids/administration & dosage , Colloids/pharmacokinetics , Female , Humans , Lymph Nodes/metabolism , Lymph Nodes/pathology , Middle Aged , Radionuclide Imaging , Radiopharmaceuticals/pharmacokinetics , Technetium/pharmacokinetics , Vulvar Neoplasms/metabolism , Vulvar Neoplasms/pathology
19.
Eur J Obstet Gynecol Reprod Biol ; 100(1): 72-6, 2001 Dec 10.
Article En | MEDLINE | ID: mdl-11728661

OBJECTIVE: To investigate whether high-risk HPV infection associated with cervical intraepithelial neoplasia (CIN) was successfully eliminated after electrosurgical conization by large-loop excision of the transformation zone (LLETZ). STUDY DESIGN: 142 women, who were admitted for conization of CIN 1-3 were recruited into a prospective follow-up study of HPV infection, including cervical sampling for HPV DNA before, and then 3, 6 and 12 months after surgery. We examined whether there were any differences in the rate of HPV DNA positivity after LLETZ between specific risk groups, such as patients with primary (i.e. before surgical treatment) high-risk HPV infection, CIN of different grades, and positive margins. RESULTS: We did not detect statistically significant differences between specific risk groups. According to the assay used (hybrid capture II) at the last follow-up visit 94% of primarily infected patients were completely free from infection with high-risk HPV types, while 6% had persisting HPV infection. CONCLUSIONS: With a detection limit of 5000 genomes/ml HPV DNA the hybrid capture II results revealed, that after electrosurgical removal of CIN in 94% of patients testing positive for high-risk HPV DNA prior to surgery were negative 12 months post-surgery.


Conization , Papillomaviridae , Papillomavirus Infections/surgery , Tumor Virus Infections/surgery , Uterine Cervical Dysplasia/virology , Cervix Uteri/surgery , Cervix Uteri/virology , Colposcopy , DNA, Viral/analysis , Female , Humans , Papillomaviridae/genetics , Risk Factors
20.
J Am Assoc Gynecol Laparosc ; 8(4): 591-3, 2001 Nov.
Article En | MEDLINE | ID: mdl-11677343

The literature revealed only six cases of cervical carcinoma metastatic to a port site after laparoscopic lymphadenectomy. A woman with a poorly differentiated squamous cell carcinoma of the cervix had port site metastases after laparoscopic lymph node staging. The frequency of this event might be higher than expected. Therefore, surgeons should reduce mechanical irritation of port sites and spillage of tumor cells.


Abdominal Neoplasms/secondary , Carcinoma, Squamous Cell/secondary , Carcinoma, Squamous Cell/surgery , Laparoscopy/adverse effects , Lymph Nodes/pathology , Uterine Cervical Neoplasms/pathology , Abdominal Neoplasms/pathology , Abdominal Neoplasms/surgery , Adult , Carcinoma, Squamous Cell/pathology , Female , Follow-Up Studies , Humans , Laparoscopy/methods , Neoplasm Seeding , Neoplasm Staging/adverse effects , Risk Assessment , Treatment Outcome , Uterine Cervical Neoplasms/surgery
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