Amélioration de la survie globale des patients porteurs de cancer du rein métastatique grâce aux thérapies ciblées (revue monocentrique depuis 2000)

Contexte : les thérapies ciblées ont radicalement modifiés la prise en charge thérapeutique des patients atteints de cancer du rein métastatique. Le but de ce travail est de déterminer dans la pratique clinique quotidienne l impact de ces nouvelles thérapies sur la survie globale. Methodes : Etude retrospective, mono-centrique, non interventionnelle incluant les cancers du rein métastatiques à cellules claires diagnostiqués depuis 2000 sur le Centre Hospitalier Universitaire de Grenoble. Les 2 cohortes ont été déterminées en fonction de la première ligne thérapeutique reçue (thérapies ciblées ou autres traitements). Résultats : Quatre-vingt dix-huit patients ont été inclus entre le 1er Janvier 2000 et le 31 Decembre 2010. Les 2 cohortes étaient comparables, en particulier la distribution des profils pronostiques. En premiere ligne, 58 patients ont reçus une thérapie ciblée dont 21% ont été traités par bevacizumab, 71% par sunitinib et 8% par temsirolimus. Dans l autre cohorte (n=40), 37,5% des patients ont reçus des cytokines, 15% une chimiothérapie cytotoxique ou une hormonothérapie. La médiane de survie globale des patients traités par thérapie ciblée est significativement augmentée (30 mois contre 13 mois; p<.003, log-rank test). Le Hazard Ratio (HR) de décès à 3 ans est de 0.53 (intervalle de confiance 95%, 0.33-0.85; p=.008, log-rank test). Le HR de décès à 3 ans ajusté sur le profil pronostique est de 0.43 (IC95%,0.27-0.71). Conclusion : Cette étude retrospective objective l amélioraton de survie globale des patients atteints de cancer du rein métastatique, quelque soit le groupe pronostique, grâce à l apport des thérapies ciblées.Introduction: Anti-angiogenic treatment had radically modified therapeutic strategy in metastatic renal cell carcinoma (mRCC). This study is aimed to determine the overall survival (OS) improvement in clinical practice. Patients and methods: Retrospective, monocentric and non-interventional study in mRCC diagnosed since 2000 with 2 cohorts of patients determined according to the first line treatment (targeted therapy or others treatment). Results: Between 1 January 2000 and 31 December 2010, 98 patients were included. The 2 cohorts were balanced with regard to baseline disease and demographic characteristics in particular for prognosis profiles distribution. As first line, 58 patients received targeted therapy whose 21% were treated by bevacizumab, 71% by sunitinib and 8% by temsirolimus. In non-targeted therapy cohort (n=40), 37.5% were treated by cytokines, 15% by cytotoxic chemotherapy or hormonal therapy. Patients treated with targeted therapy had a significantly longer median OS (30 months vs 13 months; p<.003, log-rank test). The Hazard Ratio (HR) of death at 3 years was 0.53 (95% Confidence Interval, 0.33-0.85; p=.008, log-rank test). When adjusted to the prognosis profile, the HR of death was 0.43 (95%CI, 0.27-0.71). Conclusions: This retrospective study demonstrated the improvement of OS due to targeted treatments, for all prognostic risk groups. This result supported the complete change of care of mRCC patients with extension of therapeutic indications and efficient therapeutic lines.GRENOBLE1-BU Médecine pharm. (385162101) / SudocSudocFranceF

Short-Term cost impact of compliance with clinical practice guidelines for initial sarcoma treatment

Background: The impact of compliance to clinical practice guidelines (CPG) on outcomes and/or costs of care has not been completely clarified.Objective: To estimate relationships between medical expenditures and compliance to CPG for initial sarcoma treatment.Research design: Selected cohorts of patients diagnosed with sarcoma in 2005 and 2006, and treated at the University hospital and/or the cancer centre of the Rhône-Alpes region, France (n=90). Main outcome measurements were: patient characteristics, compliance with CPG, health outcomes, and costs. Data were mainly extracted from patient records. The logarithm of treatment costs was modelled using linear and Tobit regressions.Results: Rates of compliance with CPG were 86%, 66%, 88%, 89%, and 95% for initial diagnosis, primary surgical excision, wide surgical excision, chemotherapy, and radiotherapy, respectively. Total average costs reached €24,439, with €1,784, €11,225, €10,360, and €1,016 for diagnosis, surgery (primary and wide surgical excisions), chemotherapy, and radiotherapy, respectively. Compliance of diagnosis with CPG decreased the cost of diagnosis, whereas compliance of primary surgical excision increased the cost of chemotherapy. Compliance of chemotherapy with CPG decreased the cost of radiotherapy.Conclusion: Since chemotherapy is one of the major cost drivers, these results support that compliance with guidelines increases medical care expenditures in short term.Oncology; Sarcoma; Cost; Clinical guidelines; Efficacy; Medical Practices; Government Policy; Regulation; Public Health

La protéine kinase ck2 (corrélation de la surexpression de la sous-unité catalytique a en immuno-histochimie à des facteurs de mauvais pronostic sur une série de 111 adénocarcinomes de prostate)

La protéine CK2 est une sérine-thréonine kinase ubiquitaire et conservée au cours de l'évolution. Elle est composée d'un dimère de 2 sous-unités régulatrices b sur lequel s'associent 2 sous-unités catalytiques a. Dans ce travail, l'expression de la CK2a a été étudiée rétrospectivement par immuno-histochimie (IHC) sur cent onze adénocarcinomes de prostate (72 du CU de Grenoble et 39 sur une puce à tissus du commerce). Les patients ont été répartis dans 3 groupes : 0/1+ (expression faible), 2+ (expression modérée) et 3+ et plus (surexpression). La CK2a est plus exprimée dans les glandes prostatiques tumorales que dans les glandes normales et son expression est majoritairement cytoplasmique (p<0.001). Le groupe surexpression (3+) regroupe 43.3% des cancers et les facteurs pronostiques y sont péjoratifs : 85% des tumeurs 3+ ont un score de Gleason supérieur ou égal à 7, 48% correspondent à des stades pT3-T4 et 63,6% présentent des emboles péri-nerveux et/ou lymphatiques. Les tumeurs des groupes 0/1+ et 2+ rassemblés ont 55.5% de score de Gleason supérieur ou égal à 7, 16% sont des pT3-T4 et 38% comportent des emboles. Ces différences sont statistiquement significatives (p<0.001 à 0.05). Il n'y a pas de données de survie disponibles pour étudier l'impact du statut CK2a sur le devenir des patients. Des études complémentaires sont nécessaires.CK2 is an ubiquitinous and highly conserved serine/threonine protein kinase. Potential substrates are >300. Its role in human cancerogenesis remains unclear, but data showed that it promotes proliferation and protect cancer cells against apoptosis. Cristallography depict an heterotetramere, with 2 regulatory subunits (CK2b) associated with 2 catalytic subunits (CK2a). In this study, we performed immunochemistry with a specific anti-CK2a polyclonal antibody. Analysis of 111 samples of human prostate adenocarcinoma showed an overexpression in 43.3% of cases. Patients in this subgroup ( overexpression group ) have bad prognostic factors: 85% with Gleason score up to 6, 48% are pT3-T4 tumors and 63.6% show perineural invasion. By comparison, these percentages are respectively 55.5%, 16% and 38% in the remaining group. Differences are statistically significant (p<0.001 to 0.05). Then, overexpression group seems to be clinically relevant, but survival data are lacking. Furthers investigations are needed to explore the exact role of CK2a in prostate cancer, and to establish if this protein represent a new biomarker.GRENOBLE1-BU Médecine pharm. (385162101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

La protéine kinase ck2 (corrélation de la surexpression de la sous-unité catalytique a en immuno-histochimie à des facteurs de mauvais pronostic sur une série de 111 adénocarcinomes de prostate)

La protéine CK2 est une sérine-thréonine kinase ubiquitaire et conservée au cours de l'évolution. Elle est composée d'un dimère de 2 sous-unités régulatrices b sur lequel s'associent 2 sous-unités catalytiques a. Dans ce travail, l'expression de la CK2a a été étudiée rétrospectivement par immuno-histochimie (IHC) sur cent onze adénocarcinomes de prostate (72 du CU de Grenoble et 39 sur une puce à tissus du commerce). Les patients ont été répartis dans 3 groupes : 0/1+ (expression faible), 2+ (expression modérée) et 3+ et plus (surexpression). La CK2a est plus exprimée dans les glandes prostatiques tumorales que dans les glandes normales et son expression est majoritairement cytoplasmique (p300. Its role in human cancerogenesis remains unclear, but data showed that it promotes proliferation and protect cancer cells against apoptosis. Cristallography depict an heterotetramere, with 2 regulatory subunits (CK2b) associated with 2 catalytic subunits (CK2a). In this study, we performed immunochemistry with a specific anti-CK2a polyclonal antibody. Analysis of 111 samples of human prostate adenocarcinoma showed an overexpression in 43.3% of cases. Patients in this subgroup ( overexpression group ) have bad prognostic factors: 85% with Gleason score up to 6, 48% are pT3-T4 tumors and 63.6% show perineural invasion. By comparison, these percentages are respectively 55.5%, 16% and 38% in the remaining group. Differences are statistically significant (p<0.001 to 0.05). Then, overexpression group seems to be clinically relevant, but survival data are lacking. Furthers investigations are needed to explore the exact role of CK2a in prostate cancer, and to establish if this protein represent a new biomarker.GRENOBLE1-BU Médecine pharm. (385162101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

An impressive response with larotrectinib in a patient with a papillary thyroid carcinoma harboring an SQSTM1-NTRK1 fusion

NTRK rearrangements represent a very rare genomic abnormality among all cancers but can be detected in thyroid cancer with a non-negligible frequency of 2%. Dramatic clinical responses to therapies targeting NTRK chimeric proteins are now well described in the literature. SQSTM1-NTRK1 fusions have not yet been described in a full clinical case report. We report a patient with a papillary thyroid carcinoma harboring this unique rearrangement, with an impressive clinical and radiologic response to larotrectinib, a highly specific inhibitor

Nuclear localization of protein kinase CK2 catalytic subunit (CK2alpha) is associated with poor prognostic factors in human prostate cancer.

International audienceMany genomic abnormalities have been identified in various subsets of prostate cancer, but until now, few genes have been associated with the progression of this cancer. High activity of protein serine/threonine kinase CK2 has been observed in various solid tumours and this alteration has been linked both to growth-related functions and to suppression of cellular apoptosis. Here, we provide the first evidence for a strong association between a nuclear localization of CK2alpha, evaluated by immunohistochemistry, and poor prognostic factors in a retrospective cohort of 131 human prostate adenocarcinomas. Nuclear CK2alpha localization is significantly correlated with higher Gleason score, more locally advanced disease (cT3-T4) and more perineural or lymphatic invasion (p<0.0019 to 0.046). In contrast, despite a strong trend, no significant relationship was found between higher initial PSA and nuclear CK2alpha localization. Thus, this previously undescribed molecular heterogeneity is the first step in defining CK2 as both a potential biomarker and a promising target in human prostate cancer

Cluster analysis and principal component analysis to access the variability of data in cost evaluations: methods and applications in oncology

International audienc

Cluster analysis and principal component analysis to access the variability of data in cost evaluations: methods and applications in oncology

International audienc

Short-Term cost impact of compliance with clinical practice guidelines for initial sarcoma treatment

Working paper GATE 08-22Background: The impact of compliance to clinical practice guidelines (CPG) on outcomes and/or costs of care has not been completely clarified.Objective: To estimate relationships between medical expenditures and compliance to CPG for initial sarcoma treatment.Research design: Selected cohorts of patients diagnosed with sarcoma in 2005 and 2006, and treated at the University hospital and/or the cancer centre of the Rhône-Alpes region, France (n=90). Main outcome measurements were: patient characteristics, compliance with CPG, health outcomes, and costs. Data were mainly extracted from patient records. The logarithm of treatment costs was modelled using linear and Tobit regressions.Results: Rates of compliance with CPG were 86%, 66%, 88%, 89%, and 95% for initial diagnosis, primary surgical excision, wide surgical excision, chemotherapy, and radiotherapy, respectively. Total average costs reached €24,439, with €1,784, €11,225, €10,360, and €1,016 for diagnosis, surgery (primary and wide surgical excisions), chemotherapy, and radiotherapy, respectively. Compliance of diagnosis with CPG decreased the cost of diagnosis, whereas compliance of primary surgical excision increased the cost of chemotherapy. Compliance of chemotherapy with CPG decreased the cost of radiotherapy.Conclusion: Since chemotherapy is one of the major cost drivers, these results support that compliance with guidelines increases medical care expenditures in short term