Zurich Consensus: German Expert Opinion on the St. Gallen Votes on 15 March 2009 (11th International Conference at St. Gallen: Primary Therapy of Early Breast Cancer)

A German working group of 23 breast cancer experts discussed the results from the vote at this year's St. Gallen Consensus Conference on Primary Therapy for Early Breast Cancer ( March 11-14, 2009) and came up with some concrete recommendations for day-to-day therapeutic decisions in Germany. Due the fact that the concept of the St. Gallen Consensus Conference merely allows for a minimal consensus, the objective of the working group was to provide practice-related recommendations for day-to-day clinical decisions in Germany. One area of emphasis at St. Gallen was tumor biology as a starting point for reaching individual therapeutic decisions. Intensive discussion was necessary with respect to the clinical relevance of predictive and prognostic factors. A new addition to the area of systemic therapy was a first-ever discussion of the adjuvant administration of bisphosponates and the fact that therapy with trastuzumab in HER2 overexpressing breast cancer has been defined as the standard for neoadjuvant therapy. The value of taxanes as a component of (neo) adjuvant chemotherapy as well as the value of aromatase inhibitors for the endocrine adjuvant treatment of postmenopausal patients were affirmed

Prospective evaluation of prognostic factors uPA/PAI-1 in node-negative breast cancer: Phase III NNBC3-Europe trial (AGO, GBG, EORTC-PBG) comparing 6 × FEC versus 3 × FEC/3 × Docetaxel

Contains fulltext : 98255.pdf (publisher's version ) (Open Access)BACKGROUND: Today, more than 70% of patients with primary node-negative breast cancer are cured by local therapy alone. Many patients receive overtreatment by adjuvant chemotherapy due to inadequate risk assessment. So far, few clinical trials have prospectively evaluated tumor biology based prognostic factors. Risk assessment by a biological algorithm including invasion factors urokinase-type plasminogen activator (uPA) and its inhibitor plasminogen activator inhibitor type 1 (PAI-1) will assess up to 35-55% of node-negative patients as low-risk and thus avoid chemotherapy. In contrast, a clinical-pathological algorithm will only classify 20-40% of patients as low-risk. High-risk node-negative patients should receive chemotherapy. Anthracycline-based regimens are accepted as a standard, the additional benefit of taxanes remains an open question. METHODS/DESIGN: The international NNBC3 ("Node Negative Breast Cancer 3-Europe") trial compares biological risk assessment (UP) using invasion factors uPA/PAI-1 with a clinical-pathological algorithm (CP). In this trial, the type of risk assessment (CP or UP) was chosen upfront by each center for its patients. Fresh frozen tissue was obtained to determine uPA/PAI-1 using an enzyme-linked immunosorbent assay (ELISA). Patients assessed as high-risk were stratified by human epidermal growth factor receptor 2 (HER2) status and then randomised to receive anthracycline-containing chemotherapy 5-Fluorouracil (F)/Epirubicin (E)/Cyclophosphymide (C) or an anthracycline-taxane sequence (FE(100)C*6 versus FE(100)C*3 followed by Docetaxel(100)*3). DISCUSSION: In this trial, 4,149 node-negative patients with operable breast cancer from 153 centers in Germany and France were included since 2002. Measurement of uPA/PAI-1 by ELISA was performed with standardised central quality assurance for 2,497 patients (60%) from 56 "UP"-centers. The NNBC 3-Europe trial showed that inclusion of patients into a clinical phase III trial is feasible based on biological testing of fresh frozen tumor material. In addition, 2,661 patients were classified as high-risk and thus received chemotherapy. As adjuvant chemotherapy, 1,334 high-risk patients received FE(100)C-Docetaxel(100), and 1,327 received French FE(100)C. No unexpected toxicities were observed. Chemotherapy efficacy and comparison of UP with CP will be evaluated after longer follow-up. TRIAL REGISTRATION: clinical Trials.gov NCT01222052

Momentum-Dependent Mean Field Based Upon the Dirac-Brueckner Approach for Nuclear Matter

A momentum-dependent mean field potential, suitable for application in the transport-model description of nucleus-nucleus collisions, is derived in a microscopic way. The derivation is based upon the Bonn meson-exchange model for the nucleon-nucleon interaction and the Dirac-Brueckner approach for nuclear matter. The properties of the microscopic mean field are examined and compared with phenomenological parametrizations which are commonly used in transport-model calculations.Comment: 15 pages text (RevTex) and 4 figures (postscript in a separate uuencoded file), UI-NTH-930

TIMP-1 and VEGF-165 serum concentration during first-line therapy of ovarian cancer patients

<p>Abstract</p> <p>Background</p> <p>Angiogenesis appears to play an important role in ovarian cancer. Vascular endothelial growth factor (VEGF) has recently been implicated as a therapeutic target in ovarian cancer. The tissue inhibitor of metalloproteinase 1 (TIMP-1) is involved in tissue invasion and angiogenesis. The application of serum TIMP-1 and VEGF to monitor primary therapy and predict clinical outcome of patients with ovarian cancer is unclear.</p> <p>Methods</p> <p>Patients with epithelial ovarian cancer who presented for primary surgery were included in this study. A total of 148 serum samples from 37 patients were analyzed. Samples were prospectively collected at 4 predefined time points: 1. before radical debulking surgery, 2. after surgery and before platinum/taxane based chemotherapy, 3. during chemotherapy, 4. after chemotherapy. Serum VEGF-165 and TIMP-1 as well as CA-125 were quantified by ELISA or ECLIA and correlation with response and long-term clinical outcome was analyzed.</p> <p>Results</p> <p>Serum levels of all markers changed substantially during first-line therapy. High CA-125 (p = 0.002), TIMP-1 (p = 0.007) and VEGF-165 (p = 0.02) after chemotherapy were associated with reduced overall survival. In addition, elevated CA-125 (p < 0.001) and VEGF-165 (p = 0.006) at this time point predicted poor progression-free survival. TIMP-1 and VEGF-165 were closely correlated at all time-points during therapy.</p> <p>Conclusions</p> <p>TIMP-1 and VEGF serum levels changed significantly during first-line therapy of ovarian cancer patients and predicted prognosis. These findings support the role of angiogenesis in ovarian cancer progression and the use of antiangiogenic therapy.</p

Poguttke erzählt : Lustige Abenteuer und gemütliche Danziger Geschichten

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Poguttke auf Tourchen! : Mochumsche Moppchen vom Danziger Mottlaustrand

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Stämmtischgespräche des Rentiers und Maurerpoliers a. D. Franz Poguttke nebst fröhlichen Danziger Versen und bilderlosen Stacheldraht-Kriegsfilmen seines Freundes Adolf Schaweiter

21 cm

Prognostic and predictive relevance of CA-125 at primary surgery of ovarian cancer

Despite radical surgery and chemotherapy, most patients with ovarian cancer develop recurrence and die due to progressive disease. To stratify patients for optimal therapy, prognostic and predictive factors are needed. We examined the role of pre- and postoperative CA-125 in this context. A total of 231 patients with primary ovarian cancer who presented for surgery at our institution between 1996 and 2004 were included in this study (25% FIGO stage I/II and 75% FIGO stage III/IV). The prognostic and predictive values of CA-125 serum concentrations before and after surgery as well as their correlation with clinicopathological variables were analyzed. Median preoperative CA-125 was 61.6 kU/l (9-1,867 kU/l) in stage I/II patients and 533.15 kU/l (10-22,617 kU/l) in stage III/IV patients. Before surgery, 67% of stage I/II patients and 96% of stage III/IV patients had elevated CA-125 (> 35 kU/l). There was a significant decrease in CA-125 after surgery in both patient cohorts (61.6-43.4 kU/l, P = 0.001 and 533.15-92.3 kU/l, P <0.001, respectively). Furthermore, in stage III/IV patients with complete or so-called optimal (<1 cm residual disease) debulking, preoperative CA-125 levels were significantly lower than in patients with residual disease > 1 cm (P = 0.01, P = 0.009, respectively). Neither CA-125 concentration before surgery nor its decrease was prognostically relevant for recurrence and survival at any stage. However, in stage III/IV patients, a high postoperative CA-125 was associated with shorter progression-free survival (P = 0.024). Although CA-125 serum levels differ significantly before and after surgery in early and advanced-stage ovarian cancer and preoperative CA-125 values correlate with surgical outcome in advanced-stage disease, we could not determine a preoperative cutoff value for prediction of the surgical result. A prognostic relevance was only observed for postoperative CA-125 in stage III/IV patients