Development and Validation of a Combined Model for Preoperative Prediction of Lymph Node Metastasis in Peripheral Lung Adenocarcinoma

BACKGROUND: Based on the “seed and soil” theory proposed by previous studies, we aimed to develop and validate a combined model of machine learning for predicting lymph node metastasis (LNM) in patients with peripheral lung adenocarcinoma (PLADC). METHODS: Radiomics models were developed in a primary cohort of 390 patients (training cohort) with pathologically confirmed PLADC from January 2016 to August 2018. The patients were divided into the LNM (−) and LNM (+) groups. Thereafter, the patients were subdivided according to TNM stages N0, N1, N2, and N3. Radiomic features from unenhanced computed tomography (CT) were extracted. Radiomic signatures of the primary tumor (R1) and adjacent pleura (R2) were built as predictors of LNM. CT morphological features and clinical characteristics were compared between both groups. A combined model incorporating R1, R2, and CT morphological features, and clinical risk factors was developed by multivariate analysis. The combined model’s performance was assessed by receiver operating characteristic (ROC) curve. An internal validation cohort containing 166 consecutive patients from September 2018 to November 2019 was also assessed. RESULTS: Thirty-one radiomic features of R1 and R2 were significant predictors of LNM (all P < 0.05). Sex, smoking history, tumor size, density, air bronchogram, spiculation, lobulation, necrosis, pleural effusion, and pleural involvement also differed significantly between the groups (all P < 0.05). R1, R2, tumor size, and spiculation in the combined model were independent risk factors for predicting LNM in patients with PLADC, with area under the ROC curves (AUCs) of 0.897 and 0.883 in the training and validation cohorts, respectively. The combined model identified N0, N1, N2, and N3, with AUCs ranging from 0.691–0.927 in the training cohort and 0.700–0.951 in the validation cohort, respectively, thereby indicating good performance. CONCLUSION: CT phenotypes of the primary tumor and adjacent pleura were significantly associated with LNM. A combined model incorporating radiomic signatures, CT morphological features, and clinical risk factors can assess LNM of patients with PLADC accurately and non-invasively.