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Evaluation of progression-free survival as a surrogate endpoint for overall survival in locally advanced or metastatic differentiated thyroid cancer: a systematic review

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Abstract

Purpose

Patients with locally advanced or metastatic differentiated thyroid cancer (DTC) have a variable prognosis, and the development of more effective treatment strategies is an important research topic. Overall survival (OS) is the gold standard for research endpoints in randomized controlled trials (RCTs), but observing an OS benefit requires the inclusion of a large number of patients and a long follow-up period. In this study, we aimed to investigate whether progression-free survival (PFS) could be used as a surrogate endpoint for OS in locally advanced or metastatic DTC clinical trials.

Materials and methods

We conducted a search in the PubMed and EMBASE databases to include all RCTs of locally advanced or metastatic DTC and extracted survival data. A weighted linear regression analysis was performed to explore the correlation between PFS benefit and OS benefit by taking the logarithm of the hazard ratios (HRs) of PFS and OS for each trial with a base of 10 and weighted by the number of patients in each RCT.

Results

Seven RCTs, including 1410 patients, were included. At the trial level, PFS benefit was weakly correlated with OS benefit (R2 = 0.210, 95% CI: 0.000–0.811) and did not meet the statistical criteria for the surrogate endpoint.

Conclusion

This study does not support PFS as a surrogate endpoint for OS in locally advanced or metastatic DTC clinical trials.

Trial registration

PROSPERO Identifier: CRD42022334898

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Data availability

All datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Author contributions

Conceptualization: X.X.; Methodology: S.Y., J.Z.; Formal analysis and investigation: S.Y., J.Z.; Writing - original draft preparation: S.Y., J.Z.; Writing - review and editing: X.X.

Funding

This study is supported by the National Natural Science Foundation of China (32071436) and the Beijing Municipal Natural Science Foundation (7222127).

Author information

Author notes

  1. These author contributed equally: Shijie Yang, Jing Zhan

Authors and Affiliations

  1. Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

    Shijie Yang & Xiequn Xu

  2. Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

    Shijie Yang

  3. Department of Anesthesiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

    Jing Zhan

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  1. Shijie Yang
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Correspondence to Xiequn Xu.

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Yang, S., Zhan, J. & Xu, X. Evaluation of progression-free survival as a surrogate endpoint for overall survival in locally advanced or metastatic differentiated thyroid cancer: a systematic review. Endocrine 82, 491–497 (2023). https://doi.org/10.1007/s12020-023-03507-3

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  • DOI: https://doi.org/10.1007/s12020-023-03507-3

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