ACCENT-Based Nomograms to Predict Recurrence and Overall Survival in Stage III Colon Cancer Lindsay A. Renfro 1 , Axel Grothey 2 , Leonard B. Saltz 3 , Thierry Andr é 4 , Roberto Labianca 5 , Steven R. Alberts 2 , Charles L. Loprinzi 2 , Greg Yothers 6 , Daniel J. Sargent 1
ACCENT-Based Nomograms to Predict Recurrence and Overall Survival in Stage III Colon Cancer
Lindsay A. Renfro1, Axel Grothey2, Leonard B. Saltz3, Thierry André4, Roberto Labianca5, Steven R. Alberts2, Charles L. Loprinzi2, Greg Yothers6, Daniel J. Sargent1
for the Adjuvant Colon Cancer Endpoints (ACCENT) Group
1Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN; 2Department of Oncology, Mayo Clinic, Rochester, MN; 3Gastrointestinal Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, NY;
4Hôpital Saint Antoine, Paris, France; 5Oncology Unit, Ospedali Riuniti di Bergamo, Bergamo, Italy; 6National Surgical Adjuvant Breast and Bowel (NSABP) Project Biostatistical Center, Pittsburgh, PA
Comparison with AJCC Staging
Background:Current prognostic tools and staging systems in colon cancer (CC) use relatively few patient attributes; including additional covariates may improve prediction. Using the large ACCENT database, we constructed clinically based nomograms for overall survival (OS) and time to recurrence (TTR) in stage III CC that better separate patients into risk groups compared to AJCC v7 staging.
Methods:15,995 stage III patients accrued to phase III clinical trials since 1989 were used to construct Cox models for TTR and OS, stratified by study. Variables included age, sex, race, BMI, performance status, tumor grade, tumor stage, ratio of positive lymph nodes to nodes examined, number/location of primary tumors, and treatment class. Missing data (<18%) were imputed, continuous variables modeled with splines, and clinically relevant pairwise interactions included if p < 0.001. Final models were internally validated via bootstrapping for corrected calibration and C-indices for survival data. Nomogram-defined risk tertiles were compared to AJCC v7 stage III for observed 3-year TTR and 5-year OS for a subset of 7400 patients with complete data.
Results:All variables were statistically and clinically significant for OS; age and race did not predict TTR. No meaningful interactions existed. Nomograms for OS and TTR were well calibrated and associated with C-indices of 0.66 and 0.65, respectively, vs. 0.58 and 0.59 for AJCC. Nomogram risk tertiles were better separated than AJCC groups. Removing treatment from the nomograms did not hurt performance (C=0.66 for OS and 0.65 for TTR).
Conclusions:The proposed ACCENT nomgrams are internally valid and have the potential to aid prognostication, patient/physician communication, and decision making in patients with stage III colon cancer.
Continuous Predictor Effects