Abstract

To determine the added value of combining intratumoral and peritumoral CT radiomics for the prediction of epidermal growth factor receptor (EGFR) gene mutations in primary lung cancer (PLC). This study included 478 patients with PLC (348 adenocarcinomas and 130 other histological types) who underwent surgical resection and EGFR gene testing. Two radiologists performed segmentation of tumors and peritumoral regions using precontrast high-resolution CT images, and 398 radiomic features (212 intra- and 186 peritumoral features) were extracted. The peritumoral region was defined as the lung parenchyma within a distance of 3 mm from the tumor border. Model performance was estimated using Random Forest, a machine-learning algorithm. EGFR mutations were found in 162 tumors; 161 adenocarcinomas, and one pleomorphic carcinoma. After exclusion of poorly reproducible and redundant features, 32 radiomic features remained (14 intra- and 18 peritumoral features) and were included in the model building. For predicting EGFR mutations, combining intra- and peritumoral radiomics significantly improved the performance compared to intratumoral radiomics alone (AUC [area under the receiver operating characteristic curve], 0.774 vs 0.730; p < 0.001). Even in adenocarcinomas only, adding peritumoral radiomics significantly increased performance (AUC, 0.687 vs 0.630; p < 0.001). The predictive performance using radiomics and clinical features was significantly higher than that of clinical features alone (AUC, 0.826 vs 0.777; p = 0.005). Combining intra- and peritumoral radiomics improves the predictive accuracy of EGFR mutations and could be used to aid in decision-making of whether to perform biopsy for gene tests. Adding peritumoral to intratumoral radiomics yields greater accuracy than intratumoral radiomics alone in predicting EGFR mutations and may serve as a non-invasive method of predicting of the gene status in PLC.

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