BackgroundTo establish a machine-learning-derived nomogram based on radiomic features and clinical factors to predict post-surgical 2-year progression-free survival (PFS) in patients with lung adenocarcinoma.MethodsPatients with >2 years post-surgical prognosis results of lung adenocarcinoma were included in Hospital-1 for model training (n = 100) and internal validation (n = 50), and in Hospital-2 for external testing (n = 50). A total of 1,672 radiomic features were extracted from 3D segmented CT images. The Rad-score was established using random survival forest by accumulating and weighting the top-20 imaging features contributive to PFS. A nomogram for predicting PFS was established, which comprised the Rad-score and clinical factors highly relevant to PFS.ResultsIn the training, internal validation, and external test groups, 69/100 (69%), 37/50 (74%) and 36/50 (72%) patients were progression-free at two years, respectively. According to the Rad-score, the integral of area under the curve (iAUC) for discriminating high and low risk of progression was 0.92 (95%CI: 0.77-1.0), 0.70 (0.41-0.98) and 0.90 (0.65-1.0), respectively. The C-index of Rad-score was 0.781 and 0.860 in the training and external test groups, higher than 0.707 and 0.606 for TNM stage, respectively. The nomogram integrating Rad-score and clinical factors (lung nodule type, cM stage and histological type) achieved a C-index of 0.845 and 0.837 to predict 2-year PFS, respectively, significantly higher than by only radiomic features (all p < 0.01).ConclusionThe nomogram comprising CT-derived radiomic features and risk factors showed a high performance in predicting post-surgical 2-year PFS of patients with lung adenocarcinoma, which may help personalize the treatment decisions.