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Le but de cet article est de présenter la validation en français d'une échelle de sentiment d'efficacité personnelle. Nous avons créé une échelle de neuf items que nous avons fait passer à 170 étudiants (25 femmes et 145 hommes d'âge moyen 19,46 ans) scolarisés en France en première ou deuxième année de classes préparatoires aux grandes écoles (CPGE) scientifiques. Les résultats sont en faveur d'une solution factorielle hiérarchique avec un facteur général de second ordre et deux facteurs de premier ordre. L'analyse de validité prédictive réplique des résultats déjà présents dans la littérature lorsque l'on établit des liens entre variables conatives et performances académiques. Les estimations de cohérence interne sont élevées et correspondent aux recommandations de la littérature. Nos résultats donnent suffisamment de preuves de validité et de fidélité. Au vu des bonnes qualités psychométriques de l'échelle, nous la recommandons pour une utilisation appliquée et dans la recherche, par exemple dans le cadre d'un protocole d'accompagnement des étudiants. The aim of this study is to present the validation in French of a self-efficacy scale. We created nine items and proposed this scale to 170 French (25 women and 145 men, average age 19.46) students in first and second year in scientific preparatory classes for selective postgraduate schools. A hierarchical factor solution with one common factor and two primary factors was retained. The analysis of predictive validity replicates results observed in the literature when the paths between conative variables and academic performance are investigated. Internal consistency coefficients are high and correspond to the recommended values in the literature. Our research provides sufficient evidence of validity and fidelity. Given the good psychometric qualities of the scale, we recommend it for applied use and research in particular to build support protocols for students. [ABSTRACT FROM AUTHOR]

Abstract Purpose Increased baseline carcinoembryonic antigen (CEA) serum level is associated with inferior overall survival (OS) in metastatic colorectal cancer (mCRC). However, limited data exist on its predictive relevance for targeted therapies. Therefore, we analysed its relevance in FIRE-3, a randomised phase III study. Experimental design FIRE-3 evaluated first-line FOLFIRI plus cetuximab (FOLFIRI/Cet) versus FOLFIRI plus bevacizumab (FOLFIRI/Bev) in mCRC patients with RAS -WT tumour (i.e. wild-type in KRAS and NRAS exons 2–4). Herein, the impact of CEA on patient outcome was investigated. Results Of 400 patients, 356 (89.0%) were evaluable for CEA. High CEA (>10 ng/ml; N = 237) compared to low CEA (≤10 ng/ml; N = 119) was associated with shorter OS in the FOLFIRI/Bev arm (hazard ratio [HR] = 1.50; P = 0.036), while no significant OS difference was observed in the FOLFIRI/Cet arm (HR = 1.07; P = 0.74). In patients with high CEA, FOLFIRI/Cet compared to FOLFIRI/Bev showed a greater OS benefit (HR = 0.56; P < 0.001) than in patients with low CEA (HR = 0.78; P = 0.30). Furthermore, FOLFIRI/Cet exhibited significantly superior objective response rate in patients with high CEA (odds ratio = 2.21; P = 0.006) in contrast to patients with low CEA (odds ratio = 0.90; P = 0.85). Conclusion In patients with RAS -WT mCRC receiving first-line chemotherapy with FOLFIRI/Cet versus FOLFIRI/Bev, elevated CEA was associated with inferior survival in the bevacizumab arm, while this was not the case when cetuximab was applied. Comparison of OS and objective response rate according to treatment arms indicated that cetuximab was greatly superior to bevacizumab in patients with elevated CEA, while this effect was markedly lower and lost statistical significance in patients with low CEA. Highlights • High baseline CEA impacts survival in patients with metastatic colorectal cancer. • In FIRE-3, high baseline CEA led to shorter survival in FOLFIRI+bevacizumab arm. • Contrary, high baseline CEA did not show shorter survival in FOLFIRI+cetuximab arm. • Survival benefit of FOLFIRI+cetuximab over FOLFIRI+bevacizumab depended on CEA. • High baseline CEA may predict benefit from FOLFIRI+cetuximab over FOLFIRI+bevacizumab. [ABSTRACT FROM AUTHOR]

Background We explored the impacts of sequential application of various treatment lines on survival kinetics. Therefore, differences in overall survival (OS) observed in FIRE-3 were investigated in the context of time and exposure to applied treatment. Patients and methods OS analyses (stratified by treatment with FOLFIRI plus either cetuximab or bevacizumab) were performed according to time intervals as well as using a Cox model to define changes of hazard ratio (HR) over time. Results The fraction of patients with systemic treatment and time on treatment markedly decreases over treatment lines and time. OS evaluation by a Cox model indicated a trend towards a non-proportional hazard between treatment arms (P = 0.12/P = 0.09 for KRAS –intention-to-treat (ITT)/all- RAS wild-type populations, respectively). To improve the fit of the model, a change-point (point of curve separation) was estimated at 22.6 months (day 687) after randomisation. The HR between the two arms before 22.6 months was not significantly different from one. However, markedly different survival kinetics in favour of the cetuximab arm were apparent after the change-point ( KRAS -ITT: P = 0.0018; HR, 0.60 [95% confidence interval [CI], 0.44–0.83] and RAS : P = 0.0006; HR, 0.51 [95% CI, 0.35–0.75]). Conclusion The differences in OS favouring the cetuximab arm become apparent about 22.6 months after randomisation, indicating that only those patients who survive 22.6 months after randomisation benefit from the superiority of the cetuximab arm. When OS curves separate, only few patients receive active systemic treatment in short courses, suggesting that earlier treatment effects are responsible for later kinetics of survival curves. [ABSTRACT FROM AUTHOR]

Background: To explore the impact of KRAS, NRAS and BRAF mutations as well as KRAS mutation variants in patients with metastatic colorectal cancer (mCRC) receiving first-line therapy. Patients and methods: A total of 1239 patients from five randomized trials (FIRE-1, FIRE-3, AIOKRK0207, AIOKRK0604, RO91) were included into the analysis. Outcome was evaluated by the Kaplan-Meier method, log-rank tests and Cox models. Results: In 664 tumors, no mutation was detected, 462 tumors were diagnosed with KRAS-, 39 patients with NRAS- and 74 patients with BRAF-mutation. Mutations in KRAS were associated with inferior progression-free survival (PFS) and overall survival (OS) [multivariate hazard ratio (HR) for PFS: 1.20 (1.02-1.42), P = 0.03; multivariate HR for OS: 1.41 (1.17-1.70), P < 0.001]. BRAF mutation was also associated with inferior PFS [multivariate HR: 2.19 (1.59-3.02), P<0.001] and OS [multivariate HR: 2.99 (2.10-4.25), P < 0.001]. Among specific KRAS mutation variants, the KRAS G12C-variant (n= 28) correlated with inferior OS compared with unmutated tumors [multivariate HR 2.26 (1.25-4.1), P = 0.001]. A similar trend for OS was seen in the KRAS G13D-variant [n = 71, multivariate HR 1.46 (0.96-2.22), P=0.10]. More frequent KRAS exon 2 variants like G12D [n = 152, multivariate HR 1.17 (0.86-1.6), P=0.81] and G12V [n = 92, multivariate HR 1.27 (0.87-1.86), P = 0.57] did not have significant impact on OS. Conclusion: Mutations in KRAS and BRAF were associated with inferior PFS and OS of mCRC patients compared with patients with non-mutated tumors. KRAS exon 2 mutation variants were associated with heterogeneous outcome compared with unmutated tumors with KRAS G12C and G13D (trend) being associated with rather poor survival. [ABSTRACT FROM AUTHOR]

Background The FIRE-3 trial investigated combination chemotherapy plus either cetuximab or bevacizumab in patients with untreated metastatic colorectal cancer (mCRC) not scheduled for upfront surgery. We aimed to determine the number of patients who present with potentially resectable disease during systemic first-line therapy and to compare the findings with study reports concerning resections and outcome. Patients and methods This evaluation of 448 patients was performed as central review blinded for treatment, other reviewers' evaluations and conducted interventions. Resectability was defined if at least 50% of the reviewers recommended surgical-based intervention. Overall survival was assessed by Kaplan–Meier method. Results Resectability increased from 22% (97/448) at baseline before treatment to 53% (238/448) at best response ( P < 0.001), compared with an actual secondary resection rate for metastases of 16% (72/448). At baseline (23% versus 20%) and best response (53% versus 53%), potential resectability of metastases in this molecular unselected population was similar in cetuximab-treated patients versus bevacizumab-treated patients and not limited to patients with one-organ disease. The actual resection rate of metastases was significantly associated with treatment setting ( P = 0.02; university hospital versus hospital/practice). Overall survival was 51.3 months (95% confidence interval [CI] 35.9–66.7) in patients with resectable disease who received surgery, 30.8 months (95% CI 26.6–34.9) in patients with resectable disease without surgery and 18.6 months (95% CI 15.8–21.3) in patients with unresectable disease ( P < 0.001). Conclusions Our findings illustrate the potential for conversion to resectability in mCRC, certain reluctance towards metastatic resections in clinical practice and the need for pre-planned and continuous evaluation for metastatic resection in high-volume centres. ClinicalTrials.gov-identifier NCT00433927. [ABSTRACT FROM AUTHOR]