Table S1. List of all SpaTIL features. Table S2. List of the most discriminating spaTIL features for predicting recurrence in NSCLC. In this study, density is defined as the ratio of the number of cells within the cluster to the cluster pixel area, betweenness centrality is a measure of centrality in a graph based on shortest paths, and closeness centrality is a measure of centrality calculated as the sum of the length of the shortest paths between the node and all other nodes in the graph. Table S3: Summary of clinical and pathological features of the studied NSCLC cohorts. Table S4: Multivariable survival analysis on the test sets including SpaTIL. Table S5. Treatment information for the datasets included in this study.
ARTICLE ABSTRACT
The presence of a high degree of tumor-infiltrating lymphocytes (TIL) has been proven to be associated with outcome in patients with non–small cell lung cancer (NSCLC). However, recent evidence indicates that tissue architecture is also prognostic of disease-specific survival and recurrence. We show a set of descriptors (spatial TIL, SpaTIL) that capture density, and spatial colocalization of TILs and tumor cells across digital images that 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; intraobserver 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 an 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.See related commentary by Peled et al., p. 1449
