• Quantitative Biomedical Research Center, Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas, 75390, USA.
• Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
• Department of Thoracic Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS), Beijing, China.
• Department of Pathology, Division of Pathology/Lab Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
• Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
• Quantitative Biomedical Research Center, Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas, 75390, USA. Guanghua.Xiao@UTSouthwestern.edu.

Prediction of disease prognosis is essential for improving cancer patient care. Previously, we have demonstrated the feasibility of using quantitative morphological features of tumor pathology images to predict the prognosis of lung cancer patients in a single cohort. In this study, we developed and validated a pathology image-based predictive model for the prognosis of lung adenocarcinoma (ADC) patients across multiple independent cohorts. Using quantitative pathology image analysis, we extracted morphological features from H&E stained sections of formalin fixed paraffin embedded (FFPE) tumor tissues. A prediction model for patient prognosis was developed using tumor tissue pathology images from a cohort of 91 stage I lung ADC patients from the Chinese Academy of Medical Sciences (CAMS), and validated in ADC patients from the National Lung Screening Trial (NLST), and the UT Special Program of Research Excellence (SPORE) cohort. The morphological features that are associated with patient survival in the training dataset from the CAMS cohort were used to develop a prognostic model, which was independently validated in both the NLST (n = 185) and the SPORE (n = 111) cohorts. The association between predicted risk and overall survival was significant for both the NLST (Hazard Ratio (HR) = 2.20, pv = 0.01) and the SPORE cohorts (HR = 2.15 and pv = 0.044), respectively, after adjusting for key clinical variables. Furthermore, the model also predicted the prognosis of patients with stage I ADC in both the NLST (n = 123, pv = 0.0089) and SPORE (n = 68, pv = 0.032) cohorts. The results indicate that the pathology image-based model predicts the prognosis of ADC patients across independent cohorts.