{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T09:15:37Z","timestamp":1793697337693,"version":"4.5.1"},"reference-count":59,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T00:00:00Z","timestamp":1746489600000},"content-version":"unspecified","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["bmjonc"],"accepted":{"date-parts":[[2025,4,23]]},"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and analysis<\/jats:title>\n                  <jats:p>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 (R\u00b2) and surrogate threshold effect (STE).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>29 trials involving 6777 patients were included. In adjuvant trials, HR of DFS strongly correlated with HR of OS (R\u00b2=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 (R\u00b2=0.71) versus phase II (R\u00b2=0.67) trials. This correlation was stronger in trials including radiation therapy (R\u00b2=0.81) and trials in the neoadjuvant setting (R\u00b2=0.90). No trial in our study was a registration trial of a new molecule and all involved chemotherapy.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>PROSPERO registration number<\/jats:title>\n                  <jats:p>CRD42024595441.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/bmjonc-2025-000766","type":"journal-article","created":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T07:10:17Z","timestamp":1746601817000},"page":"e000766","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":6,"title":["Disease-free survival as a surrogate for overall survival in early-stage pancreatic cancer trials: a correlation meta-analysis"],"prefix":"10.1136","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-8347-1212","authenticated-orcid":false,"given":"Lu\u00eds Felipe","family":"Leite","sequence":"first","affiliation":[{"name":"Department of Medical Sciences, Federal Fluminense University, Niter\u00f3i, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luiz F","family":"Costa de Almeida","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Federal Fluminense University, Niter\u00f3i, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas","family":"Diniz da Concei\u00e7\u00e3o","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Federal Fluminense University, Niter\u00f3i, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana","family":"Macambira Noronha","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Universidade Federal do Cear\u00e1, Fortaleza, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcos","family":"Belotto","sequence":"additional","affiliation":[{"name":"Department of Surgical Oncology, Hospital 9 de Julho, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erick F","family":"Saldanha","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology and Haematology, Department of Medicine, Princess Margaret Hospital Cancer Centre, University of Toronto, Toronto, Ontario, Canada"},{"name":"Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thais Baccili Cury","family":"Megid","sequence":"additional","affiliation":[{"name":"Dr Georges-L-Dumont University Hospital Centre, Moncton, New Brunswick, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata","family":"D\u2019Alpino Peixoto","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, BC Cancer Agency, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bishal","family":"Gyawali","sequence":"additional","affiliation":[{"name":"Department of Oncology, Queen\u2019s University, Kingston, Ontario, Canada"},{"name":"Division of Cancer Care and Epidemiology, Sinclair Cancer Research Institute, Queen' University, Kingston, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2025,5,6]]},"reference":[{"key":"2025090109112640000_4.1.e000766.1","first-page":"1121","article-title":"Clinical endpoints in oncology - a primer","volume":"11","author":"Delgado","year":"2021","journal-title":"Am J Cancer Res"},{"key":"2025090109112640000_4.1.e000766.2","unstructured":"FDA . 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