Disease-free survival as a surrogate for overall survival in early-stage pancreatic cancer trials: a correlation meta-analysis
Bibliographic record
Abstract
Objective: Disease-free survival (DFS) is frequently used as the primary endpoint in trials of adjuvant and neoadjuvant therapies for early-stage pancreatic cancer (PC), but its validity as a surrogate for overall survival (OS) remains uncertain. This study evaluates the strength and consistency of DFS as a surrogate for OS in early-stage PC trials. Methods and analysis: This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Trials of early-stage PC involving drug therapy were identified through PubMed, Embase and Cochrane CENTRAL databases, and data on DFS and OS with HR and CIs were extracted. Trial-level surrogacy of DFS for OS was assessed using weighted linear regression, calculating the coefficient of determination (R²) and surrogate threshold effect (STE). Results: 29 trials involving 6777 patients were included. In adjuvant trials, HR of DFS strongly correlated with HR of OS (R²=0.70) at trial-level, with the STE of 0.94 indicating the maximum DFS HR beyond which OS benefit was unlikely. The correlation strength differed between phase III (R²=0.71) versus phase II (R²=0.67) trials. This correlation was stronger in trials including radiation therapy (R²=0.81) and trials in the neoadjuvant setting (R²=0.90). No trial in our study was a registration trial of a new molecule and all involved chemotherapy. Conclusion: Treatment effects on DFS had a strong correlation with treatment effects on OS, making DFS a potential surrogate endpoint for OS in early-stage PC trials of cytotoxic chemotherapies, but its use in registration trials requires careful consideration due to variability across treatment settings and trial designs. PROSPERO registration number: CRD42024595441.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.008 | 0.011 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.005 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".