Prognostic variables in low and high risk stage III colon cancers treated in two adjuvant chemotherapy trials. (February 2021)

• Record Type: Journal Article
• Authors: Sinicrope, Frank A.; Chakrabarti, Sakti; Laurent-Puig, Pierre; Huebner, Luke; Smyrk, Thomas C.; Tabernero, Josep; Mini, Enrico; Goldberg, Richard M.; Zaanan, Aziz; Folprecht, Gunnar; Van Laethem, Jean Luc; Le Malicot, Karine; Shi, Qian; Alberts, Steven R.; Taieb, Julien
• Is Part Of: European journal of cancer. Volume 144(2021)
• Page Start: 101
• Page End: 112
• Publication Date: 2021-02
• Subjects: Colon cancer -- Stage III -- Adjuvant therapy -- Risk groups -- Microsatellite instability -- Deficient mismatch repair -- Prognosis -- Recurrence; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2020.11.016
• Languages: English
• ISSNs: 0959-8049

Abstract

Abstract: Background: Stratification of patients with stage III colon cancer into low (T1-3 N1 ) and high (T4 and/or N2 ) risk groups is used to guide the duration of adjuvant chemotherapy. We determined the relative contribution of clinical and molecular features to survival by risk group. Materials & methods: Stage III colon cancer (N = 5337) patients from two adjuvant trials of FOLFOX ± cetuximab [N0147 (Alliance), PETACC-8] were risk grouped, then subgrouped by clinical features and molecular variables [ KRAS and BRAF/ mismatch repair (MMR) combined variable]. Distributions of disease-free survival (DFS), overall survival (OS), and survival after recurrence (SAR) were estimated. In multivariable Cox models, backward elimination was performed for analysis of candidate predictors of outcomes. Relative contributions of model-selected variables to outcomes by risk group were calculated using χ2. Results: Among low risk tumours, mutant KRAS and male gender were significantly associated with poorer OS multivariately. In high risk tumours, significantly poorer OS was observed for right sidedness and for mutant KRAS and BRAF V600E /pMMR, subgroups. Specifically, BRAF V600E /pMMR (OS: HR = 1.75; 95% CI: 1.36–2.24; P adj <.0001) and right- versus left-sidedness were associated with significantly poorer DFS, OS (HR = 1.56; 95% CI: 1.31–1.83; P adj <.0001), and SAR (HR = 1.64; 95% CI: 1.37–1.95; P adj <.0001). Poor prognosis of mutant KRAS for DFS and OS was similar among risk groups. BRAF /MMR and sidedness were associated with poorer SAR in both low and high risk tumours. Age, gender, and KRAS were the top three relative contributors to DFS and OS among low risk tumours; sidedness ranked first for DFS and OS, and second to BRAF /MMR for SAR among high risk tumours. Conclusion: Sidedness and BRAF/ MMR contributed the most to survival outcomes among high risk tumours and should be interpreted in the context of risk group. Highlights: Sidedness, KRAS, and BRAFV600E are related with poorer survival in high and low risk tumours. Sidedness and BRAF /MMR contributed the most to survival among high risk tumours. Age, gender, and KRAS were the top relative contributors to survival in low risk tumours.