| Added by | mollevi |
|---|---|
| Group name | EquipeMY |
| Item Type | Journal Article |
| Title | Disease-free survival as a surrogate for overall survival in neoadjuvant trials of gastroesophageal adenocarcinoma: Pooled analysis of individual patient data from randomised controlled trials |
| Creator | Ronellenfitsch et al. |
| Author | Ulrich Ronellenfitsch |
| Author | Katrin Jensen |
| Author | Svenja Seide |
| Author | Meinhard Kieser |
| Author | Matthias Schwarzbach |
| Author | Tracy E. Slanger |
| Author | Bryan Burmeister |
| Author | David Kelsen |
| Author | Donna Niedzwiecki |
| Author | Guillaume Piessen |
| Author | Christoph Schuhmacher |
| Author | Susan Urba |
| Author | Cornelis van de Velde |
| Author | Marc Ychou |
| Author | Ralf Hofheinz |
| Author | Sylvie Lorenzen |
| Abstract | INTRODUCTION: Disease-free survival (DFS) is increasingly being used as surrogate end-point for overall survival (OS) in cancer trials. So far, there has been no validation of the surrogacy of DFS for OS for neoadjuvant treatment of gastroesophageal adenocarcinoma. METHODS: The study uses individual patient data (IPD) from eight randomised controlled trials (RCTs) (n = 1126 patients) comparing neoadjuvant therapy followed by surgery with surgery alone for gastroesophageal adenocarcinoma. Correlation between OS time and DFS time was calculated to evaluate individual-level surrogacy. For each trial, survival curves using the Kaplan-Meier method were plotted and hazard ratios (HRs) on the treatment effects were calculated for OS and DFS separately. Those HRs were pooled in a random-effects meta-analysis. Observed HRs were compared with predicted HRs for OS using results from an error-in-variables linear regression model accounting for the uncertainty about the estimated effect. The strength of the association was quantified by the coefficient of determination to assess trial-level surrogacy. The surrogate threshold effect was calculated to determine the minimum treatment effect on DFS necessary to predict a non-zero treatment effect on OS. RESULTS: A strong correlation between OS time and DFS time was observed, indicating a high individual-level surrogacy. For all RCTs, estimated HRs for OS and DFS were highly similar. In the meta-analysis, the overall HR for OS was virtually identical to that for DFS. The estimated coefficient of determination r2 for the association between HRs for OS and DFS was 0.912 (95% confidence interval: 0.75-1.0), indicating a very good fit of the regression model and thus a strong trial-level surrogacy between OS and DFS. The surrogate threshold effect based on the regression analysis was 0.79. DISCUSSION: Based on strong correlations between DFS and OS, as well as a strong correlation of the treatment effects of the two end-points in the error-in-variable regression, DFS seems an appropriate surrogate marker for OS in randomised trials of neoadjuvant chemotherapy or chemoradiotherapy for gastroesophageal adenocarcinoma. |
| Publication | European Journal of Cancer (Oxford, England: 1990) |
| Volume | 123 |
| Pages | 101-111 |
| Date | Dec 2019 |
| Journal Abbr | Eur. J. Cancer |
| Language | eng |
| DOI | 10.1016/j.ejca.2019.10.001 |
| ISSN | 1879-0852 |
| Short Title | Disease-free survival as a surrogate for overall survival in neoadjuvant trials of gastroesophageal adenocarcinoma |
| Library Catalog | PubMed |
| Extra | 00000 PMID: 31678767 |
| Tags | Adenocarcinoma, Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Biomarkers, Chemoradiotherapy, Digestive System Surgical Procedures, Disease-Free Survival, Esophageal Neoplasms, Female, Gastroesophageal adenocarcinoma, Humans, Individual patient data meta-analysis, Male, Middle Aged, Neoadjuvant chemoradiotherapy, Neoadjuvant chemotherapy, Neoadjuvant Therapy, Proportional Hazards Models, Stomach Neoplasms, Survival Rate, Treatment Outcome, Young Adult |
| Date Added | 2019/12/10 - 16:58:09 |
| Date Modified | 2020/07/24 - 16:15:10 |
| Notes and Attachments | PubMed entry (Attachment) PubMed entry (Attachment) |
Institut de Recherche en Cancérologie de
