International validation of the consensus Immunoscore for the classification of colon cancer: a prognostic and accuracy study
International validation of the consensus Immunoscore for the classification of colon cancer: a prognostic and accuracy study
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DOI：
10.1016/s0140-6736(18)30789-x
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发表时间：
2018-05-26
期刊：
影响因子：
168.9
通讯作者：
Galon, Jerome
中科院分区：
文献类型：
--
作者：
Pages, Franck;Mlecnik, Bernhard;Galon, Jerome
背景结肠癌患者复发风险的估计必须改进。需要稳健的免疫评分量化来将免疫参数引入癌症分类中。该研究的目的是评估的预后价值的肿瘤浸润性T细胞计数和细胞毒性肿瘤浸润性T细胞计数与共识Immunoscore检测在I-III期结肠cancer.Methods的患者在13个国家的14个中心的国际财团，由癌症免疫治疗学会领导，评估了TNM分期I-III结肠癌患者的Immunoscore检测。患者被随机分配到训练集、内部验证集或外部验证集。通过免疫组织化学处理来自每个患者的结肠肿瘤和浸润性边缘的石蜡切片，并且通过数字病理学定量肿瘤和浸润性边缘中的CD 3+和细胞毒性CD 8 + T细胞的密度。每个患者的免疫评分来源于四个密度梯度的平均值。主要终点是评估免疫评分对复发时间的预后价值，复发时间定义为从手术到疾病复发的时间。分层多变量考克斯模型用于评估免疫评分和结果之间的关联，调整潜在的混杂因素。Harrell的C-统计量被用来评估模型performance.Findings组织样本从3539例患者进行了处理，并从2681例患者的样本被纳入质量控制后的分析（700例患者的训练集，636例患者的内部验证集，和1345例患者的外部验证集）。Immunoscore检测显示观察者和中心之间的重复性很高（结肠肿瘤r=0.97;浸润性边缘r=0.97; p
Background The estimation of risk of recurrence for patients with colon carcinoma must be improved. A robust immune score quantification is needed to introduce immune parameters into cancer classification. The aim of the study was to assess the prognostic value of total tumour-infiltrating T-cell counts and cytotoxic tumour-infiltrating T-cells counts with the consensus Immunoscore assay in patients with stage I-III colon cancer.Methods An international consortium of 14 centres in 13 countries, led by the Society for Immunotherapy of Cancer, assessed the Immunoscore assay in patients with TNM stage I-III colon cancer. Patients were randomly assigned to a training set, an internal validation set, or an external validation set. Paraffin sections of the colon tumour and invasive margin from each patient were processed by immunohistochemistry, and the densities of CD3+ and cytotoxic CD8+ T cells in the tumour and in the invasive margin were quantified by digital pathology. An Immunoscore for each patient was derived from the mean of four density percentiles. The primary endpoint was to evaluate the prognostic value of the Immunoscore for time to recurrence, defined as time from surgery to disease recurrence. Stratified multivariable Cox models were used to assess the associations between Immunoscore and outcomes, adjusting for potential confounders. Harrell's C-statistics was used to assess model performance.Findings Tissue samples from 3539 patients were processed, and samples from 2681 patients were included in the analyses after quality controls (700 patients in the training set, 636 patients in the internal validation set, and 1345 patients in the external validation set). The Immunoscore assay showed a high level of reproducibility between observers and centres (r=0.97 for colon tumour; r=0.97 for invasive margin; p