Journal
CLINICAL CANCER RESEARCH
Volume 25, Issue 5, Pages 1526-1534Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-18-2013
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Funding
- NCI of the NIH [1U24CA199374-01, R01CA202752-01A1, R01CA208236-01A1, R01 CA216579-01A1, R01 CA220581-01A1]
- National Center for Research Resources [1 C06 RR12463-01]
- Department of Defense (DOD) Prostate Cancer Idea Development Award
- DOD Lung Cancer Idea Development Award
- DOD Peer Reviewed Cancer Research Program [W81XWH-16-1-0329]
- Ohio Third Frontier Technology Validation Fund
- Wallace H. Coulter Foundation Program in the Department of Biomedical Engineering
- Clinical and Translational Science Award Program (CTSA) at Case Western Reserve University
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Purpose: 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. 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), andD4 (n = 112). Two pathologists graded each sample ofD1 andD2; intraobserver 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 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)). Conclusions: 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.
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