Clinicians' adherence versus non adherence to practice guidelines in the management of patients with sarcoma: a cost-effectiveness assessment in two European regions

International audienceABSTRACT: BACKGROUND: Although the management of sarcoma is improving, non adherence to clinical practice guidelines (CPGs) remains high, mainly because of the low incidence of the disease and the variety of histological subtypes. Since little is known about the health economics of sarcoma, we undertook a cost-effectiveness analysis (within the CONnective TIssue CAncer NETwork, CONTICANET) comparing costs and outcomes when clinicians adhered to CPGs and when they did not. METHODS: Patients studied had a histological diagnosis of sarcoma, were older than 15 years, and had been treated in the Rhone-Alpes region of France (in 2005/2006) or in the Veneto region of Italy (in 2007). Data collected retrospectively for the three years after diagnosis were used to determine relapse free survival and health costs (adopting the hospital's perspective and a microcosting approach). All costs were expressed in euros at their 2009 value. A 4% annual discount rate was applied to both costs and effects. The incremental cost-effectiveness ratio (ICER) was expressed as cost per relapse-free year gained when management was compliant with CPGs compared with when it was not. To capture uncertainty surrounding ICER, a probabilistic sensitivity analysis was performed based on a non-parametric bootstrap method. RESULTS: A total of 219 patients were included in the study. Compliance with CPGs was observed for 118 patients (54%). Average total costs reached 23,571 euros when treatment was in accordance with CPGs and 27,313 euros when it was not. In relation to relapse-free survival, compliance with CPGs strictly dominates non compliance, i.e. it is both less costly and more effective. Taking uncertainty into account, the probability that compliance with CPGs still strictly dominates was 75%. CONCLUSIONS: Our findings should encourage physicians to increase their compliance with CPGs and healthcare administrators to invest in the implementation of CPGs in the management of sarcoma

Stratégie de prise en charge des déficiences liées à la filariose lymphatique dans le cadre du programme d'élimination de la maladie

LYON1-BU Santé (693882101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Traitement locorégional des séreuses carcinomateuses abdominales et thoraciques (du modèle expérimental à la recherche clinique)

Le but de ce travail a été d'améliorer la prise en charge thérapeutique, locorégionale et ciblée des carcinoses péritonéales (CP) et pleurales. Sur le plan expérimental, après la mise au point d'un modèle animal de CP, fiable, reproductible et évaluable, ce travail rapporte les résultats encourageants de l'administration intrapéritonéale d'une nouvelle molécule inductrice d'apoptose, le DIMATE, sur le développement d'une CP microscopique et en association à une chirurgie de cytoréduction au stade de CP macroscopique. Sur le plan clinique, après avoir fait le point sur la physiopathologie, l'histoire naturelle et les différentes approches thérapeutiques disponibles pour le traitement des carcinoses pleurales, il précise le rationnel d'une approche locorégionale ainsi que les moyens de sa mise en oeuvre et il rapporte les résultats carcinologiques d'une cohorte de patients présentant une carcinose pleurale et traité par chimiohyperthermie intrathoraciqueLYON1-BU.Sciences (692662101) / SudocSudocFranceF

Développement du radiomarquage des protéines à l'aide de technétium et de gallium (mise au point sur des immunoglobulines et application à l'annexine A5 en vue de détecter la mort)

Le présent travail a consisté à développer des méthodes de marquage de protéines à l aide de technétium 99m et de gallium. Les techniques ont été mises au point sur des -globulines puis appliquées à l annexine A5, marqueur de mort cellulaire in vivo. Le marquage au 99mTc a consisté à dériver les protéines à l aide de 2-iminothiolane afin de générer des groupements thiols libre servant de point d ancrage au cœur 99mTc-tricarbonyl. Cette méthode originale s est révélée particulièrement efficace, notamment en comparaison de la stratégie de référence utilisant le groupement HYNIC. Le marquage au gallium a été réalisé à l aide de 67Ga, après dérivation des protéines à l aide d anhydride de DTPA. D intéressant résultats ont été obtenus et devront être confirmés ultérieurement à l aide de 68Ga, émetteur de positronsThe aim of this study was to develop new radiolabeling methods of proteins with technetium 99m and gallium. Proteins of interest like immunoglobulins or annexin A5, which can be used to detect cell death in vivo, were used. Free thiols groups were first generated on their surfaces after reaction with 2-iminothiolane. Derivatized proteins were then radiolabeled with 99mTc-tricarbonyl. This new strategy permited to obtain very encouraging results in comparison to the HYNIC method, considered as the reference Radiolabelings with gallium were performed using 67Ga after derivatization of proteins in presence of DTPA anhydride. The interesting results obtained have now to be confirmed with 68Ga, a positron emitterLYON1-BU.Sciences (692662101) / SudocSudocFranceF

Selection of patients and staging of peritoneal surface malignancies

Peritoneal carcinomatosis (PC) is a common evolution of cancer of the gastrointestinal tract, and has been traditionally regarded as a terminal disease with short median survival. During the last 20 years, thanks to its favourable oncologic results, a new loco-regional therapeutic approach, combining cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC), has an important development. Due to its significant, but acceptable, morbidity and mortality, and high cost, this comprehensive management plan requires knowledgeable patient selection. Quantitative prognostic indicators are required to assess a patient’s eligibility. Large multicenter studies have identified several prognostic factors, which can be used for a better selection of patients who would benefit from the combination of cytoreductive surgery with HIPEC. Indications for treatment of PC with cytoreduction and HIPEC are now validated for several diseases: peritoneal mesothelioma, pseudomyxoma peritonei, PC from the appendix, and colorectal cancer. Indications are still under discussion for gastric and ovarian carcinomatosis. Computed tomography is the best radiological for staging the disease. The extent of peritoneal carcinomatosis is, however, difficult to evaluate preoperatively, and precise evaluation is most often performed during surgical exploration. Cytoreductive surgery associated with HIPEC for the treatment of peritoneal carcinomatosis should be performed for young patients with limited and resectable carcinomatosis, in specialized institutions involved in the management of peritoneal surface malignancies

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Objectifs : Présenter un panorama général des MD-PhD programs, les doubles cursus américains permettant l’obtention d’un doctorat en science et d’un diplôme d’exercice de la médecine, et proposer le développement d’une filière pilote au sein de l’Université de Lyon. Exégèse : Les MD-PhD programs permettent la formation de médecins chercheurs tout en réduisant la durée globale d’études. Ils ont atteint les objectifs initialement fixés aux États-Unis et dans les pays où ils se sont exportés. L’Université de Lyon dispose des structures d’enseignement et de recherche, notamment l’École Normale Supérieure de Lyon et les facultés de médecine, pour accueillir une filière pilote

Impact of hyperthermic intraperitoneal chemotherapy on Hsp27 protein expression in serum of patients with peritoneal carcinomatosis

International audienceDespite the strong rationale for combining cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with peritoneal carcinomatosis, thermotolerance and chemoresistance might result from heat shock protein overexpression. The aim of the present study was thus to determine whether the heat shock protein 27 (Hsp27), a potential factor in resistance to treatment, could have a higher level in serum from patients under this combined therapy. Patients receiving CRS plus HIPEC for peritoneal carcinomatosis (group 1), patients with cancer or a history of cancer undergoing abdominal surgery (group 2), and patients without malignancies undergoing abdominal surgery (group 3) were included. Hsp27 serum levels were determined before and at different times following CRS and HIPEC using enzyme-linked immunosorbent assay. In group 1 (n = 25), the high Hsp27 levels, observed at the end of surgery compared with before (p < 0.0001), decreased during HIPEC, but remained significantly higher than before surgery (p < 0.0005). In groups 2 (n = 11) and 3 (n = 15), surgery did not significantly increase Hsp27 levels. A targeted molecular strategy, inhibiting Hsp27 expression in tumor tissue, could significantly reduce resistance to the combined CRS plus HIPEC treatment. This approach should be further assessed in a clinical phase I trial