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.

Radiologic assessment of earliest, best, and plateau response of gastrointestinal stromal tumors to neoadjuvant imatinib prior to successful surgical resection.

BACKGROUND: To determine the timing of earliest, best and plateau response to neoadjuvant imatinib in patients with GIST. MATERIALS AND METHODS: In this IRB-approved retrospective study, we included all 20 patients (10 women; mean age 61 years, range 30-83 years) with KIT-positive primary GIST who received neoadjuvant imatinib and underwent surgery between January 2001 and December 2012. Earliest (earliest time to partial response), best (percentage reduction in longest axial diameter [LAD] and volume correlated with RECIST 1.1 and volumetric criteria) and plateau (time point when there was <10% change in treatment response between two consecutive scans beyond best response) responses were analyzed on review of imaging. RESULTS: Median tumor size at baseline was 7.2 cm (range, 3.0-31.4 cm). Median duration of neoadjuvant imatinib was 32 weeks (IQR, 16-36 weeks). Partial response was noted in 16/20 patients (median interval = 16 weeks; IQR, 7-26 weeks); 4/20 had stable disease. Median time to earliest PR was 16 weeks (IQR, 7-26 weeks). At best response, median decrease in LAD and volume were 43% (IQR, 31-48%) and 83% (IQR, 63-87%), (median interval = 28 weeks; IQR, 18-37 weeks), at which point 10 tumors were resected. Plateau response (45% [IQR, 35-45%] LAD reduction) was noted in the remaining 10 patients (median interval = 34 weeks; IQR, 26-41 weeks) before resection. Tumor size, location or risk category did not correlate with best response or time to best response. CONCLUSION: Best response to neoadjuvant imatinib was seen at 28 weeks irrespective of tumor size and location. Plateau response was seen at 34 weeks, beyond which further treatment may not be beneficial.