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Research article
Yuan-Fang Li
Corresponding Author
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The most recent version of this article is available here.
Background: We aimed to assess whether disease-free survival (DFS) could serve as a reliable surrogate endpoint for overall survival (OS) in adjuvant trials of pancreatic cancer.
Methods: We systematically reviewed adjuvant randomized trials for non-metastatic pancreatic cancer after curative resection that reported a hazard ratio (HR) for DFS and OS. We assessed the correlation between treatment effect (HR) on DFS and OS, weighted by sample size or precision of hazard ratio estimate, assuming fixed and random effects, and calculated the surrogate threshold effect (STE). We also performed sensitivity analyses and a leave-one-out cross validation approach to evaluate the robustness of our findings.
Results: After screening 450 relevant articles, we identified a total of 20 qualifying trails comprising 5170 patients for quantitative analysis. We noted a strong correlation between the treatment effects for DFS and OS, with coefficient of determination of 0.82 in the random effect model, 0.82 in the fixed effect model, and 0.80 in the sample size weighting; the robustness of this finding was further verified by the leave-one-out cross-validation approach. Sensitivity analyses with restriction to phase 3 trials, large trials, trials with mature follow-up periods, and trials with adjuvant therapy versus adjuvant therapy strengthened the correlation (0.75 to 0.88) between DFS and OS. The STE was 0.96 for DFS.
Conclusions: Therefore, DFS could be regarded as a surrogate endpoint for OS in adjuvant trials of pancreatic cancer. In future similar adjuvant trials, a hazard ratio for DFS of 0.96 or less would predict a treatment impact on OS.
Keywords
pancreatic cancer; disease-free survival; overall survival; surrogate
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Editorial decision: Major revision
On 23 Mar, 2020
Reviewer #2 agreed
On 16 Dec, 2019
Review #2 received
Received 16 Dec, 2019
Review #1 received
Received 16 Dec, 2019
Reviewer #1 agreed
On 07 Dec, 2019
Reviewers invited
Invitations sent on 11 Oct, 2019
Editor assigned
On 16 Sep, 2019
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On 27 Aug, 2019
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On 27 Aug, 2019
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This preprint is under consideration at BMC Cancer. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Yuan-Fang Li
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
No community comments so far
Version 3
Posted 04 May, 2020
No comments provided
Editorial decision: Minor revision
On 27 Apr, 2020
No comments provided
Editorial decision: Minor revision
On 23 Apr, 2020
Editor assigned
On 20 Apr, 2020
Submission checks complete
On 19 Apr, 2020
Editor invited
On 19 Apr, 2020
No comments provided
Editorial decision: Major revision
On 23 Mar, 2020
Reviewer #2 agreed
On 16 Dec, 2019
Review #2 received
Received 16 Dec, 2019
Review #1 received
Received 16 Dec, 2019
Reviewer #1 agreed
On 07 Dec, 2019
Reviewers invited
Invitations sent on 11 Oct, 2019
Editor assigned
On 16 Sep, 2019
Submission checks complete
On 27 Aug, 2019
Editor invited
On 27 Aug, 2019
First submitted
On 08 Aug, 2019
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
The most recent version of this article is available here.
Background: We aimed to assess whether disease-free survival (DFS) could serve as a reliable surrogate endpoint for overall survival (OS) in adjuvant trials of pancreatic cancer.
Methods: We systematically reviewed adjuvant randomized trials for non-metastatic pancreatic cancer after curative resection that reported a hazard ratio (HR) for DFS and OS. We assessed the correlation between treatment effect (HR) on DFS and OS, weighted by sample size or precision of hazard ratio estimate, assuming fixed and random effects, and calculated the surrogate threshold effect (STE). We also performed sensitivity analyses and a leave-one-out cross validation approach to evaluate the robustness of our findings.
Results: After screening 450 relevant articles, we identified a total of 20 qualifying trails comprising 5170 patients for quantitative analysis. We noted a strong correlation between the treatment effects for DFS and OS, with coefficient of determination of 0.82 in the random effect model, 0.82 in the fixed effect model, and 0.80 in the sample size weighting; the robustness of this finding was further verified by the leave-one-out cross-validation approach. Sensitivity analyses with restriction to phase 3 trials, large trials, trials with mature follow-up periods, and trials with adjuvant therapy versus adjuvant therapy strengthened the correlation (0.75 to 0.88) between DFS and OS. The STE was 0.96 for DFS.
Conclusions: Therefore, DFS could be regarded as a surrogate endpoint for OS in adjuvant trials of pancreatic cancer. In future similar adjuvant trials, a hazard ratio for DFS of 0.96 or less would predict a treatment impact on OS.
Figure 1
Figure 2
Figure 3
Figure 4
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