Department of Oncology, Mayo Clinic and Mayo Comprehensive Cancer Center, Rochester, MN, USA.
Department of Oncology, Mayo Clinic and Mayo Comprehensive Cancer Center, Rochester, MN, USA.
Eur J Cancer. 2021 Feb;144:101-112. doi: 10.1016/j.ejca.2020.11.016. Epub 2020 Dec 17.
Stratification of patients with stage III colon cancer into low (TN) and high (T and/or N) 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.
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/pMMR, subgroups. Specifically, BRAF/pMMR (OS: HR = 1.75; 95% CI: 1.36-2.24; P<.0001) and right- versus left-sidedness were associated with significantly poorer DFS, OS (HR = 1.56; 95% CI: 1.31-1.83; P<.0001), and SAR (HR = 1.64; 95% CI: 1.37-1.95; P<.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.
Sidedness and BRAF/MMR contributed the most to survival outcomes among high risk tumours and should be interpreted in the context of risk group.
将 III 期结肠癌患者分层为低危（TN）和高危（T 和/或 N）组，以指导辅助化疗的持续时间。我们通过风险组确定了临床和分子特征对生存的相对贡献。
来自两项 FOLFOX ± 西妥昔单抗辅助试验（N0147[Alliance]，PETACC-8）的 III 期结肠癌（N=5337）患者进行风险分组，然后根据临床特征和分子变量（KRAS 和 BRAF/错配修复（MMR）联合变量）进行亚组分组。估计无病生存（DFS）、总生存（OS）和复发后生存（SAR）的分布。在多变量 Cox 模型中，采用后向消除法对候选预测结局的因素进行分析。使用 χ2 计算模型选择变量对风险组结局的相对贡献。
在低危肿瘤中，KRAS 突变和男性在多变量分析中与 OS 显著相关。在高危肿瘤中，右侧肿瘤和 KRAS 和 BRAF/MMR 突变亚组的 OS 明显较差。具体而言，BRAF/MMR（OS：HR=1.75；95%CI：1.36-2.24；P<.0001）和右侧与左侧相比，DFS、OS（HR=1.56；95%CI：1.31-1.83；P<.0001）和 SAR（HR=1.64；95%CI：1.37-1.95；P<.0001）的预后明显较差。KRAS 突变对 DFS 和 OS 的不良预后在各风险组中相似。BRAF/MMR 和侧别与低危和高危肿瘤中的 SAR 较差相关。年龄、性别和 KRAS 是低危肿瘤 DFS 和 OS 的前三个相对贡献因素；侧别对 DFS 和 OS 的影响最大，其次是高危肿瘤的 BRAF/MMR 对 SAR 的影响。
侧别和 BRAF/MMR 对高危肿瘤的生存结局贡献最大，应结合风险组进行解释。
