Cost-effectiveness of the addition of early hormonal therapy in locally advanced prostate cancer: results decisively determined by the cut-off time-point chosen for the analysis

We present a retrospective cost-effectiveness analysis using data from a randomised controlled trial (EORTC 22863) of the addition of early hormonal therapy with a luteinising hormone-releasing horn-tone (LHRH) analogue to radiotherapy in the treatment of patients with locally advanced prostate cancer. Data on the use of medical resources were extracted from the hospital charts of 90 patients recruited into the trial by one French hospital. Costs are assessed from the viewpoint of the French healthcare financing system and adjusted for censoring. Expected costs per patient of each treatment is related to the expected outcome, mean survival time, estimated by a restricted means analysis. The time point of restriction is determined by statistical criteria. In the base case analysis with a cut-off time point at 8.58 years, the combined therapy group (COMB) had a gain in mean survival time of 1.06 years (7.05 versus 5.99 years) and a reduction of average total costs of 12 700 French francs (FF) (58 300 FF versus 71 000 FF). The analysis of uncertainty uses bootstrap techniques with 5000 replicates to examine the joint distribution of cost and survival outcomes. In 76% of the cases, COMB results in longer mean survival time and lower costs than the radiotherapy group (RT). In cases where COMB therapy raises costs (13% of the cases), it is rarely by more than 20 000 FF per patient, no matter the size of the associated survival gain. It is thus highly likely that COMB should be considered a cost-effective option compared with RT for these patients. The exact result of the economic evaluation is decisively determined by the restriction time point selected for the determination of mean survival time, partly also because the average total costs of the two treatments develop entirely differently as a function of the survival time. (C) 2001 Elsevier Science Ltd. All rights reserved

An experimental study of the electronic absorption and fluorescence spectral properties of new p-substituted-N-phenylpyrroles and their electrosynthesized polymers

International audienc

Behaviour of bovine phosphatidylethanolamine-binding protein with model membranes. Evidence of affinity for negatively charged membranes.

International audienceThe ability of phosphatidylethanolamine-binding protein (PEBP) to bind membranes was tested by using small and large unilamellar vesicles and monolayers composed of l-alpha-1,2-dimyristoylphosphatidylcholine, l-alpha-1,2-dimyristoylphosphatidylglycerol and l-alpha-1,2-dimyristoylphosphatidylethanolamine. PEBP only bound to model membranes containing l-alpha-1,2-dimyristoylphosphatidylglycerol; the interaction was primarily due to electrostatic forces between the basic protein and the acidic phospholipids. Further experiments indicated that the interaction was not dependent on the length and unsaturation of the phospholipid acyl chains and was not modified by the presence of cholesterol in the membrane. PEBP affinity for negatively charged membranes is puzzling considering the previous identification of the protein as a phosphatidylethanolamine-binding protein, and suggests that the association of PEBP with phospholipid membranes is driven by a mechanism other than its binding to solubilized phosphatidylethanolamine. An explanation was suggested by its three-dimensional structure: a small cavity at the protein surface has been reported to be the binding site of the polar head of phosphatidylethanolamine, while the N-terminal and C-terminal parts of PEBP, exposed at the protein surface, appear to be involved in the interaction with membranes. To test this hypothesis, we synthesized the two PEBP terminal regions and tested them with model membranes in parallel with the whole protein. Both peptides displayed the same behaviour as whole PEBP, indicating that they could participate in the binding of PEBP to membranes. Our results strongly suggest that PEBP directly interacts with negatively charged membrane microdomains in living cells

Radiothérapie à visée Curative dans les adénocarcinomes de prostate localisés survenant après 80 ans. Une étude du Rare Cancer Network

info:eu-repo/semantics/publishe

Curative external beam radiotherapy in patients over 80 years of age with localized prostate cancer: a retrospective rare cancer network study

PURPOSE: To analyse tolerance and outcome of patients over 80 years of age who choose external beam radiation therapy to the prostate as a curative treatment. METHODS AND MATERIAL: We evaluated acute and late side effects, biological DFS (bDFS) and actuarial survival as well as causes of death in relation to the clinical status including co-morbidity, PSA value, Gleason score and modalities of external radiotherapy in patients with localised prostate cancer >80 years of age. RESULTS: From January 1990 to December 2000, 65 eligible cases (median age: 81) were treated by 12 different participating institutions in the Rare Cancer Network. Tumour stage was T1N0M0, T2N0M0 and T3N0M0 for 10, 40, and 15 patients, respectively. Median follow-up was 65 months (range 22-177). Five-year overall survival rate was 77% with a 5-year bDFS rate of 73%. The incidence of grade 3 early toxicity was 12% and 9% for urinary and digestive tract, respectively. CONCLUSIONS: Radiation therapy given with curative intent is well tolerated in this selected group of patients aged over 80 years with localised prostate cancer. Results in terms of survival do not suggest a deleterious impact of this treatment. Therefore the authors recommend that radiation therapy with curative intent should not be withheld in selected elderly patients with localised prostate cancer

Improved size-tunable preparation of polymeric nanoparticles by microfluidic nanoprecipitation

International audienceSize-tunable polymeric nanoparticles have been successfully produced by a microfluidic-assisted nanoprecipitation process. A multilamination micromixer has been chosen to fabricate continuously nanoparticles of methacrylic polymers. Various operating conditions, such as the polymer concentration, the amount of non-solvent and the characteristics of the raw polymer (molecular weight and architecture: linear vs. branched) have been investigated. Their influences on the final particle size, ranging from 76 to 217 nm, have been correlated to the mechanisms leading to the formation of nanoparticles. In this type of microfluidic device, mixing mainly operates by diffusion mass transfer, helped by hydrodynamic focusing. The effect of micromixing on the size of particles has also been shown experimentally and supported by a computational fluid dynamics (CFD) study. A mixing criterion has been defined and numerically calculated to corroborate the effect of the flow rate of polymer solution on the particles size. An increase in the polymer solution flow rate increases the value of this mixing criterion, resulting in smaller nanoparticles