Prognostic Significance of Tumor-Infiltrating Lymphocytes Determined Using LinkNet on Colorectal Cancer Pathology Images

PURPOSETumor-infiltrating lymphocytes (TILs) have a significant prognostic value in cancers. However, very few automated, deep learning-based TIL scoring algorithms have been developed for colorectal cancer (CRC).MATERIALS AND METHODSWe developed an automated, multiscale LinkNet workflow for quantifying TILs at the cellular level in CRC tumors using H&E-stained images from the Lizard data set with annotations of lymphocytes. The predictive performance of the automatic TIL scores (TILsLink) for disease progression and overall survival (OS) was evaluated using two international data sets, including 554 patients with CRC from The Cancer Genome Atlas (TCGA) and 1,130 patients with CRC from Molecular and Cellular Oncology (MCO).RESULTSThe LinkNet model provided outstanding precision (0.9508), recall (0.9185), and overall F1 score (0.9347). Clear continuous TIL-hazard relationships were observed between TILsLink and the risk of disease progression or death in both TCGA and MCO cohorts. Both univariate and multivariate Cox regression analyses for the TCGA data demonstrated that patients with high TIL abundance had a significant (approximately 75%) reduction in risk for disease progression. In both the MCO and TCGA cohorts, the TIL-high group was significantly associated with improved OS in univariate analysis (30% and 54% reduction in risk, respectively). The favorable effects of high TIL levels were consistently observed in different subgroups (classified according to known risk factors).CONCLUSIONThe proposed deep-learning workflow for automatic TIL quantification on the basis of LinkNet can be a useful tool for CRC. TILsLink is likely an independent risk factor for disease progression and carries predictive information of disease progression beyond the current clinical risk factors and biomarkers. The prognostic significance of TILsLink for OS is also evident.