A prognostic and predictive computational pathology image signature for added benefit of adjuvant chemotherapy in early stage non-small-cell lung cancer

Abstract

Background: We developed and validated a prognostic and predictive computational pathology risk score (CoRiS) using H&E stained tissue images from patients with early-stage non-small cell lung cancer (ES-NSCLC).

Methods: 1330 patients with ES-NSCLC were acquired from 3 independent sources and divided into four cohorts D_1-4. D₁ comprised 100 surgery treated patients and was used to identify prognostic features via an elastic-net Cox model to predict overall and disease-free survival. CoRiS was constructed using the Cox model coefficients for the top features. The prognostic performance of CoRiS was evaluated on D₂ (N=331), D₃ (N=657) and D₄ (N=242). Patients from D₂ and D₃ which comprised surgery + chemotherapy were used to validate CoRiS as predictive of added benefit to adjuvant chemotherapy (ACT) by comparing survival between different CoRiS defined risk groups.

Findings: CoRiS was found to be prognostic on univariable analysis, D₂ (hazard ratio (HR) = 1.41, adjusted (adj.) P = .01) and D₃ (HR = 1.35, adj. P < .001). Multivariable analysis showed CoRiS was independently prognostic, D₂ (HR = 1.41, adj. P < .001) and D₃ (HR = 1.35, adj. P < .001), after adjusting for clinico-pathologic factors. CoRiS was also able to identify high-risk patients who derived survival benefit from ACT D₂ (HR = 0.42, adj. P = .006) and D₃ (HR = 0.46, adj. P = .08).

Interpretation: CoRiS is a tissue non-destructive, quantitative and low-cost tool that could potentially help guide management of ES-NSCLC patients.

Funding: Data collection, anlaysis, and computation resources of the research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under award numbers: 1U24CA199374-01, R01CA202752-01A1, R01CA208236-01A1, R01 CA216579-01A1, R01 CA220581-01A1, 1U01 CA239055-01. National Center for Research Resources under award number 1 C06 RR12463-01. VA Merit Review Award IBX004121A from the United States Department of Veterans Affairs Biomedical Laboratory Research and Development Service, the DOD Prostate Cancer Idea Development Award (W81XWH-15-1-0558), the DOD Lung Cancer Investigator-Initiated Translational Research Award (W81XWH-18-1-0440), the DOD Peer Reviewed Cancer Research Program (W81XWH-16-1-0329), the Ohio Third Frontier Technology Validation Fund, the Wallace H. Coulter Foundation Program in the Department of Biomedical Engineering and the Clinical and Translational Science Award Program (CTSA) at Case Western Reserve University.

Keywords: Computational pathology; Early-stage non-small cell lung cancer; Prognostic and predictive.