Guidelines for time-to-event end point definitions in sarcomas and gastrointestinal stromal tumors (GIST) trials: results of the DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials)†.

BACKGROUND: The use of potential surrogate end points for overall survival, such as disease-free survival (DFS) or time-to-treatment failure (TTF) is increasingly common in randomized controlled trials (RCTs) in cancer. However, the definition of time-to-event (TTE) end points is rarely precise and lacks uniformity across trials. End point definition can impact trial results by affecting estimation of treatment effect and statistical power. The DATECAN initiative (Definition for the Assessment of Time-to-event End points in CANcer trials) aims to provide recommendations for definitions of TTE end points. We report guidelines for RCT in sarcomas and gastrointestinal stromal tumors (GIST). METHODS: We first carried out a literature review to identify TTE end points (primary or secondary) reported in publications of RCT. An international multidisciplinary panel of experts proposed recommendations for the definitions of these end points. Recommendations were developed through a validated consensus method formalizing the degree of agreement among experts. RESULTS: Recommended guidelines for the definition of TTE end points commonly used in RCT for sarcomas and GIST are provided for adjuvant and metastatic settings, including DFS, TTF, time to progression and others. CONCLUSION: Use of standardized definitions should facilitate comparison of trials' results, and improve the quality of trial design and reporting. These guidelines could be of particular interest to research scientists involved in the design, conduct, reporting or assessment of RCT such as investigators, statisticians, reviewers, editors or regulatory authorities.

Growth modulation index as metric of clinical benefit assessment among advanced soft tissue sarcoma patients receiving trabectedin as a salvage therapy.

BACKGROUND: The growth modulation index (GMI) is the ratio of time to progression with the nth line (TTP(n)) of therapy to the TTP(n)(-1) with the n-1th line. GMI >1.33 is considered as a sign of activity in phase II trials. PATIENTS AND METHODS: This retrospective analysis evaluated the concordance between the GMI and the efficacy outcomes in 279 patients with advanced soft tissue sarcoma (ASTS) treated with trabectedin 1.5 mg/m² (24-h infusion every 3 weeks) in four phase II trials. RESULTS: One hundred and forty-two (51%) patients received one prior line and 137 ≥ 2 lines. The median TTP(n) was 2.8 months (range 0.2-26.8), whereas the median TTP(n)(-1) was 4.0 months (0.3-79.5). The median GMI was 0.6 (0.0-14.4). Overall, 177 patients (63%) had a GMI <1; 21 (8%) a GMI equal to 1-1.33 and 81 (29%) a GMI >1.33, which correlated with the median overall survival in those patients (9.1, 13.9 and 23.8 months, respectively, P = 0.0005). A high concordance rate between the GMI and response rate (P < 0.0001) and progression-free survival (PFS, P < 0.0001) was observed. Good performance status (PS) was the only factor associated with GMI >1.33 (PS = 0; P < 0.04). CONCLUSIONS: A high GMI was associated with favorable efficacy outcomes in patients treated with trabectedin. Further research is needed to assess GMI as an indicator in this setting.

[Phases 0, 1 and 2 oncology clinical trials: current questions]. / Etudes cliniques de phases 0, 1 et 2 en cancérologie: questions d'actualité.

We propose here a general review of current questions related to early trials, including the choice of the primary endpoint, role of bayesian designs, role of stratification and randomization for phase 2 trials, patient selection, and new designs for phase 1 and phase 0 trials. We also discuss the difficulties to apply such methodologies to molecular targeted therapies development.

Additional direct medical costs associated with nosocomial infections after head and neck cancer surgery: a hospital-perspective analysis.

The clinical impact of surgical site infections (SSI) and postoperative pneumonia (PP) after head and neck cancer surgery has been assessed in the past, but little is known about their economic impact. The present study was designed to evaluate costs related to SSI and PP after head and neck cancer surgery with opening of mucosa. The incidence of SSI and PP was measured in a prospective cohort of 261 patients who had undergone head and neck cancer surgery. The additional direct medical costs related to these infections from the hospital perspective were determined based on postoperative length of stay. The mean direct hospital costs for patients with and without SSI or PP were compared. Of the 261 patients, 81 (31%), 21 (8%) and 13 (5%) developed SSI, PP or both, respectively. The additional lengths of stay attributable to SSI, PP or both were 16, 17 and 31 days, respectively, and additional direct medical costs related to these conditions were 17,000, 19,000 and 35,000 Euros. Nosocomial infections after head and neck cancer surgery significantly increase patients' length of stay and therefore generate additional direct medical costs. These results support the application of preventive interventions to reduce nosocomial infections in this setting.

[Analysis of the factors influencing the internal reporting of nosocomial infections. A review of 108 notifications]. / Analyse des facteurs influençant la démarche de signalement interne d'infection nosocomiale. A propos de 108 signalements.

INTRODUCTION: Since July 26, 2001, the external reporting to the regional office of health and social affairs (Direction départementale des affaires sanitaires et sociales--Ddass) and the coordination centre (Comité de lutte contre les infections nosocomiales--Cclin) for the fight against nosocomial infections (NI) is mandatory. However, the modalities of internal reporting to the Clin are unknown. METHOD: We performed a retrospective analysis of 108 cases of NI reported over 23 months in 4 medical-surgical departments (MSD) with 14 to 35 NI reported/MSD. The distribution of the bacteria responsible was compared with that of the local epidemiological state (chi2 test). A correlation analysis was performed between the number of NI reported in each MSD and the structural characteristics and activity index of these MSD (Spearmann's correlation test). RESULTS: The NI were predominantly infections related to a catheter (43), lower respiratory tract (25) and infection of the site of surgery (19). Ninety were documented biologically, among which 10 implied multi-resistant bacteria. Ninety-four NI were associated with the prescription of an antibiotic. Compared with the local epidemiological state, the NI reported generally implied multi-resistant bacteria (p=0.009). The other microbiological data had little implication. In each of the MSD, the number of cases reported was independent of: the global activity, the number of interventions, the mean duration of hospitalisation, the number of beds, the number of clinicians, the number of new patients managed and the chemotherapy outpatient activity. Conversely, there was a strong correlation between the global consumption of antibiotics (r=0.78), and the number of the Clin members in each MSD DMC (r=0.82). CONCLUSION: In each MSD, the internal reporting of NI relies on the discovery of multi-resistant bacteria, but above all on the implication of those involved in the fight against nosocomial infections.