[ISO 9001 certification of innovation and clinical research departments: Extending the scope of health assessment]. / Certification ISO 9001 des Directions de la recherche clinique et de l'innovation : vers une extension du périmètre aux évaluations économiques.

BACKGROUND: The International organization for standardization (ISO) is the world leader in providing industrial and commercial standards and certifications. Beyond medical devices, four French clinical research and innovation departments have received an ISO 9001 certification (the standard for quality management). Simultaneously, medico-economic studies have become increasingly important in the public decision process. Using the clinical research and innovation department from the Léon-Bérard Cancer Center as an example, the purpose of this article is to show how the scope of the ISO 9001 certification has been extended to cover medico-economic studies. METHOD: All of the processes, procedures, operating modes, documents, and indicators used by the clinical research and innovation department of the Léon-Bérard center were investigated. Literature searches were conducted using Medline keywords. The recommendations from the French national authority for health and other organizations, such as the International society for pharmacoeconomics and outcomes research (ISPOR), were also considered, as well as the recommendations of the General inspectorate of social affairs. RESULTS: In accordance with the national and international recommendations, two procedures were created and four procedures were revised at this center. Five indicators of quality and an evaluation chart were developed. CONCLUSION: By adopting the ISO 9001 certification into its medico-economic studies, the clinical research and innovation department of the Léon-Bérard center has used an innovative approach in the context of the growing importance of economic studies in decision-making.

Immune cell dysfunctions in breast cancer patients detected through whole blood multi-parametric flow cytometry assay.

Monitoring functional competence of immune cell populations in clinical routine represents a major challenge. We developed a whole-blood assay to monitor functional competence of peripheral innate immune cells including NK cells, dendritic and monocyte cell subsets through their ability to produce specific cytokines after short-term stimulation, detected through intra-cytoplasmic staining and multi-parametric flow-cytometry. A PMA/ionomycin T cell activation assay complemented this analysis. Comparing cohorts of healthy women and breast cancer (BC) patients at different stages, we identified significant functional alteration of circulating immune cells during BC progression prior to initiation of treatment. Of upmost importance, as early as the localized primary tumor (PT) stage, we observed functional alterations in several innate immune populations and T cells i.e. (i) reduced TNFα production by BDCA-1+ DC and non-classical monocytes in response to Type-I IFN, (ii) a strong drop in IFNγ production by NK cells in response to either Type-I IFN or TLR7/8 ligand, and (iii) a coordinated impairment of cytokine (IL-2, IFNγ, IL-21) production by T cell subpopulations. Overall, these alterations are further accentuated according to the stage of the disease in first-line metastatic patients. Finally, whereas we did not detect functional modification of DC subsets in response to TLR7/8 ligand, we highlighted increased IL-12p40 production by monocytes specifically at first relapse (FR). Our results reinforce the importance of monitoring both innate and adaptive immunity to better evaluate dysfunctions in cancer patients and suggest that our whole-blood assay will be useful to monitor response to treatment, particularly for immunotherapeutic strategies.

Design of a randomised controlled trial of adapted physical activity during adjuvant treatment for localised breast cancer: the PASAPAS feasibility study.

INTRODUCTION: After a diagnosis of localised breast cancer, overweight, obesity and weight gain are negatively associated with prognosis. In contrast, maintaining an optimal weight through a balanced diet combined with regular physical activity appears to be effective protective behaviour against comorbidity or mortality after a breast cancer diagnosis. The primary aim of the Programme pour une Alimentation Saine et une Activité Physique Adaptée pour les patientes atteintes d'un cancer du Sein (PASAPAS) randomised controlled trial is to evaluate the feasibility of implementing an intervention of adapted physical activity (APA) for 6 months concomitant with the prescription of a first line of adjuvant chemotherapy. Secondary aims include assessing the acceptability of the intervention, compliance to the programme, process implementation, patients' satisfaction, evolution of biological parameters and the medicoeconomic impact of the intervention. METHODS AND ANALYSIS: The study population consists of 60 women eligible for adjuvant chemotherapy after a diagnosis of localised invasive breast cancer. They will be recruited during a 2-year inclusion period and randomly allocated between an APA intervention arm and a control arm following a 2:1 ratio. All participants should benefit from personalised dietetic counselling and patients allocated to the intervention arm will be offered an APA programme of two to three weekly sessions of Nordic walking and aerobic fitness. During the 6-month intervention and 6-month follow-up, four assessments will be performed including blood draw, anthropometrics and body composition measurements, and questionnaires about physical activity level, diet, lifestyle factors, psychological criteria, satisfaction with the intervention and medical data. ETHICS AND DISSEMINATION: The study was approved by the French Ethics Committee (Comité de Protection des Personnes Sud-Est IV) and the national agencies for biomedical studies and for privacy. All participants will give written informed consent. The study findings will be disseminated through the scientific public and serve as a foundation for future randomised controlled trials of efficacy.

Sequential high-dose chemotherapy protocol for relapsed poor prognosis germ cell tumors combining two mobilization and cytoreductive treatments followed by three high-dose chemotherapy regimens supported by autologous stem cell transplantation. Results of the phase II multicentric TAXIF trial.

BACKGROUND: High-dose chemotherapy (HD-CT) is able to circumvent platinum resistance of resistant/refractory germ-cell tumors (GCTs), but expectancy of cure remains low. New strategies are needed with new drugs and a sequential approach. MATERIALS AND METHODS: Patients with relapsed poor-prognosis GCTs were scheduled to receive two cycles combining epirubicin and paclitaxel (Taxol) followed by three consecutive HD-CT supported by stem cell transplantation [one course combining cyclophosphamide, 3 g/m(2) + thiotepa, 400 mg/m(2), followed by two ICE regimens (ifosfamide, 10 g/m(2), carboplatin, AUC 20, etoposide, 1500 mg/m(2))]. RESULTS: From March 1998 to September 2001 (median follow-up, 31.8 months), 45 patients (median age, 28 years) were enrolled in this phase II study. Twenty-two patients received the complete course. Twenty-five patients died from progression and five from toxicity. The overall response rate was 37.7%, including an 8.9% complete response rate. The median overall survival was 11.8 months. The 3-year survival and progression-free survival rate was 23.5%. The 'Beyer' prognostic score predicted the outcome after HD-CT. CONCLUSION: Although our results warrant further studies on HD-CT in relapsed poor prognosis GCTs, patients with a Beyer score >2 did not benefit from this approach and should not be enrolled in HD-CT trials. Better selection criteria have to be fulfilled in forthcoming studies.