Contribution of Immunoscore and Molecular Features to Survival Prediction in Stage lll Colon Cancer
Menée à partir de données portant sur 559 patients atteints d'un cancer du côlon de stade III et inclus dans un essai évaluant un traitement adjuvant, cette étude évalue l'intérêt des caractéristiques moléculaires de la tumeur et d'un système de score, basé sur l'infiltration de la tumeur par les lymphocytes (CD3+, CD8+, concentration lymphocytaire), pour prédire avec précision la survie des patients
Background : AJCC staging and other prognostic tools fail to account for stage-independent 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, gender, T stage, positive lymph nodes (+LNs), N stage, performance status, histologic grade, sidedness, KRAS/BRAF, mismatch repair, 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 [HR 1.76, 95% CI 1.19, 2.60, p = 0.004], right vs left sided [HR 1.52, 95% CI 1.14, 2.04, p = 0.005], BRAF V600E[HR 1.74, 95% CI 1.26, 2.40, p < 0.001], mutant KRAS [HR 1.66, 95% CI 1.08, 2.55, p = 0.02], and low vs high Immunoscore [HR 1.69, 95% CI 1.22 to 2.33, p = 0.001] (all p ≤ 0.02). Increasing number of +LNs and lower continuous Immunoscore were associated with poorer DFS that achieved significance (both p <0.0001). After number of +LNs, T stage and BRAF/KRAS, Immunoscore was the most informative predictor of DFS shown multivariately. Among T 1-3 N 1 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 wthe stage III colon cancer.
JNCI Cancer Spectrum , article en libre accès, 2019