Spatial architecture and arrangement of tumor-infiltrating lymphocytes for predicting likelihood of recurrence in early-stage non-small cell lung cancer

Purpose: 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. Experimental design: 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. Results: 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=7.3x10^-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=8.0x10^-3). Conclusion: 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.

https://ift.tt/2x3vgEX