Sinicrope Frank A, Shi Qian, Hermitte Fabienne, Zemla Tyler J, Mlecnik Bernhard, Benson Al B, Gill Sharlene, Goldberg Richard M, Kahlenberg Morton S, Nair Suresh G, Shields Anthony F, Smyrk Thomas C, Galon Jerome, Alberts Steven R
Division of Oncology, Department of Medicine, Mayo Clinic, Rochester, MN, USA.
Alliance Statistics and Data Center, Rochester, MN, USA.
JNCI Cancer Spectr. 2020 Apr 5;4(3):pkaa023. doi: 10.1093/jncics/pkaa023. eCollection 2020 Jun.
The American Joint Committee on Cancer 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.
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, , 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.
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; = .004), right- vs left-sided (HR = 1.52, 95% CI = 1.14 to 2.04; = .005), (HR = 1.74, 95% CI = 1.26 to 2.40; < .001), mutant (HR = 1.66, 95% CI = 1.08 to 2.55; = .02), and low vs high Immunoscore (HR = 1.69, 95% CI = 1.22 to 2.33; = .001) (all <.02). Increasing numbers of +LNs and lower continuous Immunoscore were associated with poorer DFS that achieved significance (both s<.0001). After number of +LNs, T stage, and , Immunoscore was the most informative predictor of DFS shown multivariately. Among T N 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.
The Immunoscore can enhance the accuracy of survival prediction among patients with stage III colon cancer.
美国癌症联合委员会分期系统及其他预后评估工具未能考虑到与分期无关的预后差异。我们开发了一种预后分类器，将免疫评分纳入III期结肠癌患者的临床病理和分子特征中。
使用辅助试验NCCTG N0147中FOLFOX组的患者（n = 559）数据构建Cox模型，以预测无病生存期（DFS）。变量包括年龄、性别、T分期、阳性淋巴结（+LNs）、N分期、体能状态、组织学分级、肿瘤位置、错配修复以及免疫评分（CD3、CD8 T细胞密度）。在确定最佳函数形式（连续型或分类型）后，在Cox模型内进行向后选择，以分析所有变量作为候选预测因子。所有统计检验均为双侧检验。
T4期肿瘤与T3期肿瘤相比，DFS较差（风险比[HR]=1.76，95%置信区间[CI]=1.19至2.60；P =.004）；右侧肿瘤与左侧肿瘤相比（HR = 1.52，95% CI = 1.14至2.04；P =.005），（HR = 1.74，95% CI = 1.26至2.40；P <.001），错配修复缺陷（dMMR）（HR = 1.66，95% CI = 1.08至2.55；P =.02），以及低免疫评分与高免疫评分相比（HR = 1.69，95% CI = 1.22至2.33；P =.001）（所有P <.02）。+LNs数量增加和免疫评分连续降低与较差的DFS相关，差异具有统计学意义（均P <.0001）。在考虑+LNs数量、T分期和后，多变量分析显示免疫评分是DFS最具信息量的预测因子。在T N肿瘤中，免疫评分是与DFS相关且具有统计学意义的唯一变量。生成了一个列线图来确定患者3年无复发的可能性。
免疫评分可提高III期结肠癌患者生存预测的准确性。
