Contribution of immunoscore and molecular features to survival prediction in stage III colon cancer

Frank A. Sinicrope, Qian Shi, Fabienne Hermitte, Tyler J. Zemla, Bernhard Mlecnik, Al B. Benson, Sharlene Gill, Richard M. Goldberg, Morton S. Kahlenberg, Suresh G. Nair, Anthony F. Shields, Thomas C. Smyrk, Jerome Galon, Steven R. Alberts

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Background: The American Joint Committee on Cancer staging and other prognostic tools fail to account for stageindependent variability in outcome. We developed a prognostic classifier adding Immunoscore to clinicopathological and molecular features in patients with stage III colon cancer. Methods: Patient (n=559) data from the FOLFOX arm of adjuvant trial NCCTG N0147 were used to construct Cox models for predicting disease-free survival (DFS). Variables included age, sex, T stage, positive lymph nodes (+LNs), N stage, performance status, histologic grade, sidedness, KRAS/BRAF, mismatch repair, and Immunoscore (CD3+, CD8+ T-cell densities). After determining optimal functional form (continuous or categorical) and within Cox models, backward selection was performed to analyze all variables as candidate predictors. All statistical tests were two-sided. Results: Poorer DFS was found for tumors that were T4 vs T3 (hazard ratio [HR] = 1.76, 95% confidence interval [CI] = 1.19 to 2.60; P=.004), right- vs left-sided (HR = 1.52, 95% CI = 1.14 to 2.04; P=.005), BRAF V600E (HR = 1.74, 95% CI = 1.26 to 2.40; P<.001), mutant KRAS (HR = 1.66, 95% CI = 1.08 to 2.55; P=.02), and low vs high Immunoscore (HR = 1.69, 95% CI = 1.22 to 2.33; P =.001) (all P<.02). Increasing numbers of +LNs and lower continuous Immunoscore were associated with poorer DFS that achieved significance (both Ps<.0001). After number of pLNs, T stage, and BRAF/KRAS, Immunoscore was the most informative predictor of DFS shown multivariately. Among T1-3 N1 tumors, Immunoscore was the only variable associated with DFS that achieved statistical significance. A nomogram was generated to determine the likelihood of being recurrence-free at 3 years. Conclusions: The Immunoscore can enhance the accuracy of survival prediction among patients with stage III colon cancer.

Original languageEnglish (US)
JournalJNCI Cancer Spectrum
Issue number3
StatePublished - 2020

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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