Spatial Architecture and Arrangement of Tumor-Infiltrating Lymphocytes for Predicting Likelihood of Recurrence in Early-Stage Non-Small Cell Lung Cancer.
Spatial Architecture and Arrangement of Tumor-Infiltrating Lymphocytes for Predicting Likelihood of Recurrence in Early-Stage Non-Small Cell Lung Cancer.
复制标题
空间结构和肿瘤浸润淋巴细胞的排列，以预测早期非小细胞肺癌中复发的可能性。
DOI：
10.1158/1078-0432.ccr-18-2013
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发表时间：
2019-03-01
期刊：
影响因子：
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通讯作者：
Madabhushi A
中科院分区：
文献类型：
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作者：
Corredor G;Wang X;Zhou Y;Lu C;Fu P;Syrigos K;Rimm DL;Yang M;Romero E;Schalper KA;Velcheti V;Madabhushi A
高度肿瘤浸润淋巴细胞（TILs）的存在已被证明与非小细胞肺癌（NSCLC）患者的预后相关。然而，近期证据表明组织结构对疾病特异性生存和复发也有预后意义。我们展示了一组描述符（SpaTIL），其通过数字图像捕捉TILs和肿瘤细胞的密度及空间共定位，能够预测早期NSCLC复发的可能性。
在四个不同队列的301名患者中探究了早期NSCLC复发与SpaTIL特征之间的关联。队列D1（n = 70）用于确定最具预后价值的SpaTIL特征，并训练一个分类器来预测复发的可能性。在队列D2（n = 119）、D3（n = 112）和D4（n = 112）中评估分类器的性能。两名病理学家对D1和D2的每个样本进行分级；分析了观察者内一致性以及人工分级与复发可能性之间的关联。
SpaTIL与所有测试组的复发可能性相关（对数秩检验p < 0.02）。一项多变量Cox比例风险分析显示风险比为3.08（95%置信区间为2.1 - 4.5，p = 7.3×10⁻⁵）。相比之下，专家病理学家使用肿瘤分级的一致性为中等（κ = 0.5），并且在D2中人工TIL分级仅对一名判读者有预后价值（p = 8.0×10⁻³）。
发现一组与TILs的密度和空间结构相关的特征与早期NSCLC的复发可能性相关。该信息可能潜在地用于辅助早期NSCLC的治疗计划和管理。
Presence of a high degree of tumor-infiltrating lymphocytes (TILs) has proven to be associated with outcome in patients with non-small cell lung cancer (NSCLC). However, recent evidence indicate that tissue architecture is also prognostic of disease specific survival and recurrence. We show a set of descriptors (SpaTIL) that capture density and spatial co-localization of TILs and tumor cells across digital images can predict likelihood of recurrence in early-stage NSCLC. The association between recurrence in early-stage NSCLC and SpaTIL features was explored on 301 patients across four different cohorts. Cohort D1 (n=70) was used to identify the most prognostic SpaTIL features and to train a classifier to predict the likelihood of recurrence. The classifier performance was evaluated in cohorts D2 (n=119), D3 (n=112), and D4 (n=112). Two pathologists graded each sample of D1 and D2; intra-observer agreement and association between manual grading and likelihood of recurrence were analyzed. SpaTIL was associated with likelihood of recurrence in all test sets (log rank p<0.02). A multivariate Cox Proportional Hazards analysis revealed a HR of 3.08 (95% confidence interval, 2.1–4.5, p=7.3×10−5). In contrast, agreement among expert pathologists using tumor grade was moderate (Kappa=0.5), and the manual TIL grading was only prognostic for one reader in D2 (p=8.0×10−3). A set of features related to density and spatial architecture of TILs was found to be associated with a likelihood of recurrence of early-stage NSCLC. This information could potentially be used for helping in treatment planning and management of early-stage NSCLC.