Comparison of continuous versus categorical tumor measurement-based metrics to predict overall survival in cancer treatment trials

Ming Wen An, Sumithra J. Mandrekar, Megan E. Branda, Shauna L. Hillman, Alex A. Adjei, Henry C. Pitot, Richard M. Goldberg, Daniel J. Sargent

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


Purpose: The categorical definition of response assessed via the Response Evaluation Criteria in Solid Tumors has documented limitations. We sought to identify alternative metrics for tumor response that improve prediction of overall survival. Experimental Design: Individual patient data from three North Central Cancer Treatment Group trials (N0026, n = 117; N9741, n = 1,109; and N9841, n = 332) were used. Continuous metrics of tumor size based on longitudinal tumor measurements were considered in addition to a trichotomized response [TriTR: response (complete or partial) vs. stable disease vs. progression). Cox proportional hazards models, adjusted for treatment arm and baseline tumor burden, were used to assess the impact of the metrics on subsequent overall survival, using a landmark analysis approach at 12, 16, and 24 weeks postbaseline. Model discrimination was evaluated by the concordance (c) index. Results: The overall best response rates for the three trials were 26%, 45%, and 25%, respectively. Although nearly all metrics were statistically significantly associated with overall survival at the different landmark time points, the concordance indices (c-index) for the traditional response metrics ranged from 0.59 to 0.65; for the continuous metrics from 0.60 to 0.66; and for the TriTR metrics from 0.64 to 0.69. The c-indices for TriTR at 12 weeks were comparable with those at 16 and 24 weeks. Conclusions: Continuous tumor measurement-based metrics provided no predictive improvement over traditional response-based metrics or TriTR; TriTR had better predictive ability than best TriTR or confirmed response. If confirmed, TriTR represents a promising endpoint for future phase II trials.

Original languageEnglish (US)
Pages (from-to)6592-6599
Number of pages8
JournalClinical Cancer Research
Issue number20
StatePublished - Oct 15 2011

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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