title: Evaluating Continuous Tumor Measurement-Based Metrics as Phase II Endpoints for Predicting Overall Survival.
abstract: BACKGROUND
  We sought to develop and validate clinically relevant, early assessment continuous tumor measurement-based metrics for predicting overall survival (OS) using the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 data warehouse.
  
  
  METHODS
  Data from 13 trials representing 2096 patients with breast cancer, non-small cell lung cancer (NSCLC), or colorectal cancer were used in a complete case analysis. Tumor measurements from weeks 0-6-12 assessments were used to evaluate the ability of slope (absolute change in tumor size from 0-6 and 6-12 weeks) and percent change (relative change in tumor size from 0-6 and 6-12 weeks) metrics to predict OS using Cox models, adjusted for average baseline tumor size. Metrics were evaluated by discrimination (via concordance or c-index), calibration (goodness-of-fit type statistics), association (hazard ratios), and likelihood (Bayesian Information Criteria), with primary focus on the c-index. All statistical tests were two-sided.
  
  
  RESULTS
  Comparison of c-indices suggests slight improvement in predictive ability for the continuous tumor measurement-based metrics vs categorical RECIST response metrics, with slope metrics performing better than percent change metrics for breast cancer and NSCLC. However, these differences were not statistically significant. The goodness-of-fit statistics for the RECIST metrics were as good as or better than those for the continuous metrics. In general, all the metrics performed poorly in breast cancer, compared with NSCLC and colorectal cancer.
  
  
  CONCLUSIONS
  Absolute and relative change in tumor measurements do not demonstrate convincingly improved overall survival predictive ability over the RECIST model. Continued work is necessary to address issues of missing tumor measurements and model selection in identifying improved tumor measurement-based metrics.
authors: Department of Mathematics, Vassar College, Poughkeepsie, NY (MWA); Department of Biostatistics, Analytical Science, Takeda Pharmaceuticals, Deerfield, IL (XD); Department of Health Sciences Research, Mayo Clinic, Rochester, MN (JM, DJS, SJM); Biometrics and Data Management Department, Novartis Pharmaceuticals Corporation, East Hanover, NJ (YH); Department of Oncology, Mayo Clinic, Rochester, MN (AG); European Organisation for Research and Treatment of Cancer (EORTC), Brussels, Belgium (JB). mian@vassar.edu.
authors: Ming-Wen
authors: MW
authors: An
authors: Department of Mathematics, Vassar College, Poughkeepsie, NY (MWA); Department of Biostatistics, Analytical Science, Takeda Pharmaceuticals, Deerfield, IL (XD); Department of Health Sciences Research, Mayo Clinic, Rochester, MN (JM, DJS, SJM); Biometrics and Data Management Department, Novartis Pharmaceuticals Corporation, East Hanover, NJ (YH); Department of Oncology, Mayo Clinic, Rochester, MN (AG); European Organisation for Research and Treatment of Cancer (EORTC), Brussels, Belgium (JB).
authors: Xinxin
authors: X
authors: Dong
authors: Department of Mathematics, Vassar College, Poughkeepsie, NY (MWA); Department of Biostatistics, Analytical Science, Takeda Pharmaceuticals, Deerfield, IL (XD); Department of Health Sciences Research, Mayo Clinic, Rochester, MN (JM, DJS, SJM); Biometrics and Data Management Department, Novartis Pharmaceuticals Corporation, East Hanover, NJ (YH); Department of Oncology, Mayo Clinic, Rochester, MN (AG); European Organisation for Research and Treatment of Cancer (EORTC), Brussels, Belgium (JB).
authors: Jeffrey
authors: J
authors: Meyers
authors: Department of Mathematics, Vassar College, Poughkeepsie, NY (MWA); Department of Biostatistics, Analytical Science, Takeda Pharmaceuticals, Deerfield, IL (XD); Department of Health Sciences Research, Mayo Clinic, Rochester, MN (JM, DJS, SJM); Biometrics and Data Management Department, Novartis Pharmaceuticals Corporation, East Hanover, NJ (YH); Department of Oncology, Mayo Clinic, Rochester, MN (AG); European Organisation for Research and Treatment of Cancer (EORTC), Brussels, Belgium (JB).
authors: Yu
authors: Y
authors: Han
authors: Department of Mathematics, Vassar College, Poughkeepsie, NY (MWA); Department of Biostatistics, Analytical Science, Takeda Pharmaceuticals, Deerfield, IL (XD); Department of Health Sciences Research, Mayo Clinic, Rochester, MN (JM, DJS, SJM); Biometrics and Data Management Department, Novartis Pharmaceuticals Corporation, East Hanover, NJ (YH); Department of Oncology, Mayo Clinic, Rochester, MN (AG); European Organisation for Research and Treatment of Cancer (EORTC), Brussels, Belgium (JB).
authors: Axel
authors: A
authors: Grothey
authors: Department of Mathematics, Vassar College, Poughkeepsie, NY (MWA); Department of Biostatistics, Analytical Science, Takeda Pharmaceuticals, Deerfield, IL (XD); Department of Health Sciences Research, Mayo Clinic, Rochester, MN (JM, DJS, SJM); Biometrics and Data Management Department, Novartis Pharmaceuticals Corporation, East Hanover, NJ (YH); Department of Oncology, Mayo Clinic, Rochester, MN (AG); European Organisation for Research and Treatment of Cancer (EORTC), Brussels, Belgium (JB).
authors: Jan
authors: J
authors: Bogaerts
authors: Department of Mathematics, Vassar College, Poughkeepsie, NY (MWA); Department of Biostatistics, Analytical Science, Takeda Pharmaceuticals, Deerfield, IL (XD); Department of Health Sciences Research, Mayo Clinic, Rochester, MN (JM, DJS, SJM); Biometrics and Data Management Department, Novartis Pharmaceuticals Corporation, East Hanover, NJ (YH); Department of Oncology, Mayo Clinic, Rochester, MN (AG); European Organisation for Research and Treatment of Cancer (EORTC), Brussels, Belgium (JB).
authors: Daniel J
authors: DJ
authors: Sargent
authors: Department of Mathematics, Vassar College, Poughkeepsie, NY (MWA); Department of Biostatistics, Analytical Science, Takeda Pharmaceuticals, Deerfield, IL (XD); Department of Health Sciences Research, Mayo Clinic, Rochester, MN (JM, DJS, SJM); Biometrics and Data Management Department, Novartis Pharmaceuticals Corporation, East Hanover, NJ (YH); Department of Oncology, Mayo Clinic, Rochester, MN (AG); European Organisation for Research and Treatment of Cancer (EORTC), Brussels, Belgium (JB).
authors: Sumithra J
authors: SJ
authors: Mandrekar
mesh_terms: D001499:Bayes Theorem; D001943:Breast Neoplasms / Q000401:mortality / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality / Q000473:pathology; D017322:Clinical Trials, Phase II as Topic; D015179:Colorectal Neoplasms / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000401:mortality / Q000473:pathology; D008297:Male; D015233:Models, Statistical; D009369:Neoplasms / Q000401:mortality* / Q000473:pathology*; D016017:Odds Ratio; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D047368:Tumor Burden