ArticleJAMA network open2019
Evaluation of Continuous Tumor-Size-Based End Points as Surrogates for Overall Survival in Randomized Clinical Trials in Metastatic Colorectal Cancer.
Article in JAMA network open, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
11 citing papers in PubMed, 12 citations in OpenAlex.
- Modified FOLFOXIRI plus cetuximab versus bevacizumab in RAS wild-type metastatic colorectal cancer: a randomized phase II DEEPER trial.Nature communications · 2024Trial
- Quantitative dual-layer spectral CT parameters associated with a continuous improvement response pattern to CAPTEM in advanced gastroenteropancreatic neuroendocrine neoplasms.Abdominal radiology (New York) · 2026Article
- A framework to evaluate surrogate endpoints at the trial level: analysis in colorectal cancer.Journal of the National Cancer Institute · 2026Article
- Early Tumor Shrinkage and Depth of Response as Predictive Markers of Treatment Response and Prognosis in Solid Tumors.Cancer medicine · 2025Review
- Associations between early tumor shrinkage/depth of response and survival from the ARCAD database.JNCI cancer spectrum · 2025Article
- Variability of HCC Tumor Diameter and Density Measurements on Dynamic Contrast-Enhanced Computed Tomography.Tomography (Ann Arbor, Mich.) · 2025Article
- Tumor Response Predicts Survival Time of Nivolumab Monotherapy for Advanced Gastric Cancer: A Subgroup Analysis of the DELIVER Trial (JACCRO GC-08).The oncologist · 2024Observational
- Support to early clinical decisions in drug development and personalised medicine with checkpoint inhibitors using dynamic biomarker-overall survival models.British journal of cancer · 2023Review
- Clinicopathologic and prognostic factors of patients with T3/T4 colorectal signet ring cell carcinoma: a population-based study.Journal of cancer research and clinical oncology · 2023Article
- Clinical Trial Endpoints in Metastatic Cancer: Using Individual Participant Data to Inform Future Trials Methodology.Journal of the National Cancer Institute · 2022Review
- Evaluation of Surrogate Endpoints Using Information-Theoretic Measure of Association Based on Havrda and Charvat Entropy.Mathematics (Basel, Switzerland) · 2022Article
Corrections and comments
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Authors and funding
28 authors at 20 institutions in 10 countries.
Funding
Abstract
Importance: Tumor measurements can be used to estimate time to nadir and depth of nadir as potential surrogates for overall survival (OS). Objective: To assess time to nadir and depth of nadir as surrogates for OS in metastatic colorectal cancer. Design, Setting, and Participants: Pooled analysis of 20 randomized clinical trials within the Aide et Recherche en Cancerologie Digestive database, which contains academic and industry-sponsored trials, was conducted. Three sets of comparisons were performed: chemotherapy alone, antiangiogenic agents, and anti-epidermal growth factor receptor agents in first-line treatment for patients with metastatic colorectal cancer. Main Outcomes and Measures: Surrogacy of time to nadir and depth of nadir was assessed at the trial level based on joint modeling of relative tumor-size change vs baseline and OS. Treatment effects on time to nadir and on depth of nadir were defined in terms of between-arm differences in time to nadir and in depth of nadir, and both were assessed in linear regressions for their correlation with treatment effects (hazard ratios) on OS within each set. The strengths of association were quantified using sample-size-weighted coefficients of determination (R2), with values closer to 1.00 indicating stronger association. At the patient level, the correlation was assessed between modeled relative tumor-size change and OS. Results: For 14 chemotherapy comparisons in 4289 patients, the R2 value was 0.63 (95% CI, 0.30-0.96) for the association between treatment effects on time to nadir and OS and 0.08 (95% CI, 0-0.37) for depth of nadir and OS. For 11 antiangiogenic agent comparisons (4854 patients), corresponding values of R2 were 0.25 (95% CI, 0-0.72) and 0.06 (95% CI, 0-0.35). For 8 anti-epidermal growth factor receptor comparisons (2684 patients), corresponding values of R2 were 0.24 (95% CI, 0-0.83) and 0.21 (95% CI, 0-0.78). Conclusions and Relevance: In contrast with early reports favoring depth of response as a surrogate, these results suggest that neither time to nadir nor depth of nadir is an acceptable surrogate for OS in the first-line treatment of metastatic colorectal cancer.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.