title: Comparison of continuous versus categorical tumor measurement-based metrics to predict overall survival in cancer treatment trials.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors: Department of Mathematics, Vassar College, Poughkeepsie, New York, USA.
authors: Ming-Wen
authors: MW
authors: An
authors: Sumithra J
authors: SJ
authors: Mandrekar
authors: Megan E
authors: ME
authors: Branda
authors: Shauna L
authors: SL
authors: Hillman
authors: Alex A
authors: AA
authors: Adjei
authors: Henry C
authors: HC
authors: Pitot
authors: Richard M
authors: RM
authors: Goldberg
authors: Daniel J
authors: DJ
authors: Sargent
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001699:Biometry; D002986:Clinical Trials as Topic; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000401:mortality* / Q000473:pathology* / Q000628:therapy; D011379:Prognosis; D016016:Proportional Hazards Models; D012680:Sensitivity and Specificity; D016896:Treatment Outcome; D047368:Tumor Burden