Cited by 171Gastric Cancer Management and OutcomesStatistical Methods in Clinical TrialsMeta-analysis and systematic reviews

Disease-free survival as a surrogate for overall survival in adjuvant trials of gastric cancer: a meta-analysis

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Oba, Koji, Paoletti, Xavier, Alberts, Steven, Bang, Yung-Jue, Benedetti, Jacqueline, Bleiberg, Harry, Catalano, Paul, Lordick, Florian +12 more·2013·JNCI Journal of the National Cancer Institute

Abstract

BACKGROUND: In investigations of the effectiveness of surgery and adjuvant chemotherapy for gastric cancers, overall survival (OS) is considered the gold standard endpoint. However, the disadvantage of using OS as the endpoint is that it requires an extended follow-up period. We sought to investigate whether disease-free survival (DFS) is a valid surrogate for OS in trials of adjuvant chemotherapy for gastric cancer. METHODS: The GASTRIC group initiated a meta-analysis of individual patient data collected in randomized clinical trials comparing adjuvant chemotherapy vs surgery alone for patients with curatively resected gastric cancer. Surrogacy of DFS was assessed through the correlation between the endpoints as well as through the correlation between the treatment effects on the endpoints. External validation of the prediction based on DFS was also evaluated. RESULTS: Individual patient data from 14 randomized clinical trials that included a total of 3288 patients were analyzed. The rank correlation coefficient between DFS and OS was 0.974 (95% confidence interval [CI] = 0.971 to 0.976). The coefficient of determination between the treatment effects on DFS and on OS was as high as 0.964 (95% CI = 0.926 to 1.000), and the surrogate threshold effect based on adjusted regression analysis was 0.92. In external validation, the six hazard ratios for OS predicted according to DFS were in very good agreement with those actually observed for OS. CONCLUSIONS: DFS is an acceptable surrogate for OS in trials of cytotoxic agents for gastric cancer in the adjuvant setting.

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  1. The Gastrointestinal Tumor Study Group. Controlled trial of adju- vant chemotherapy following curative resection for gastric cancer. The Gastrointestinal Tumor Study Group. Cancer. 1982;49(6):1116-1122.
  2. Krook JE, O'Connell MJ, Wieand HS, et al. A prospective, rand- omized evaluation of intensive-course 5-fluorouracil plus doxorubicin as surgical adjuvant chemotherapy for resected gastric cancer. Cancer. 1991;67(10):2454-2458.

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Authors
Oba, K., Paoletti, X., Alberts, S., Bang, Y.-J., Benedetti, J., Bleiberg, H., Catalano, P., Lordick, F., Michiels, S., Morita, S., Ohashi, Y., Pignon, J.-P., Rougier, P., Sasako, M., Sakamoto, J., Sargent, D., Shitara, K., Cutsem, E. V., Buyse, M., & Burzykowski, T.
Affiliations
Mayo Clinic (US)
Venue
JNCI Journal of the National Cancer Institute
Published
2013-10-09
Volume
105
Issue
21
Pages
1600-1607
ISSN
  • 0027-8874 (ISSN-L)
  • 1460-2105
OpenAlex
W2168202113
Cited by
168
References
33
Citations by year
2026: 5 · 2025: 14 · 2024: 11 · 2023: 15 · 2022: 12 · 2021: 22 · 2020: 12 · 2019: 16 · 2018: 7 · 2017: 19 · 2016: 12 · 2015: 12 · 2014: 8 · 2013: 3
FWCI
1.86
Type
journal article
Language
en
Open access
Locations
  • JNCI Journal of the National Cancer Institute (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Document Server@UHasselt (UHasselt) (submittedVersion, other-oa)
  • HighWire Press Open Archive (submittedVersion)
  • Seoul National University Open Repository (Seoul National University) (submittedVersion)
Funders
  • GlaxoSmithKline
  • Institut National Du Cancer
  • Japan Society for the Promotion of Science (25461577)
  • National Cancer Institute (U10CA021115, P30CA015083)
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Gastric Cancer Management and Outcomes
  • Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
  • Social Sciences › Decision Sciences › Statistics, Probability and Uncertainty › Meta-analysis and systematic reviews
Keywords
gastric cancer, disease-free survival, overall survival, surrogate endpoints, adjuvant chemotherapy, curative resection, endpoint correlation, external validation, individual patient data, cytotoxic drugs
MeSH terms
Antineoplastic Combined Chemotherapy Protocols, Cost-Benefit Analysis, Drug Administration Schedule, Gastrectomy, Humans, Stomach Neoplasms, Time Factors, Linear Models, Odds Ratio, Randomized Controlled Trials as Topic, Treatment Outcome, Chemotherapy, Adjuvant, Disease-Free Survival, Kaplan-Meier Estimate

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