We evaluated whether the optimal selection of CT reconstruction settings enables the construction of a radiomics model to predict epidermal growth factor receptor (EGFR) mutation status in primary lung adenocarcinoma (LAC) using standard of care CT images. Fifty-one patients (EGFR:wildtype = 23:28) with LACs of clinical stage I/II/IIIA were included in the analysis. The LACs were segmented in four conditions, two slice thicknesses (Thin: 1 mm; Thick: 5 mm) and two convolution kernels (Sharp: B70f/B70s; Smooth: B30f/B31f/B31s), which constituted four groups: (1) Thin-Sharp, (2) Thin-Smooth, (3) Thick-Sharp, and (4) Thick-Smooth. Machine learning algorithms selected and combined 1,695 quantitative image features to build prediction models. The performance of prediction models was assessed by calculating the area under the curve (AUC). The best prediction model yielded AUC (95%CI) = 0.83 (0.68, 0.92) using the Thin-Smooth reconstruction setting. The AUC of models using thick slices was significantly lower than that of thin slices (P < 10−3), whereas the impact of reconstruction kernel was not significant. Our study showed that the optimal prediction of EGFR mutational status in early stage LACs was achieved by using thin CT-scan slices, independently of convolution kernels. Results from the prediction model suggest that tumor heterogeneity is associated with EGFR mutation.

Achieving high feature reproducibility while preserving biological information is one of the main challenges for the generalizability of current radiomics studies. Non-clinical imaging variables, such as reconstruction kernels, have shown to significantly impact radiomics features. In this study, we retrain an open-source convolutional neural network (CNN) to harmonize computerized tomography (CT) images with various reconstruction kernels to improve feature reproducibility and radiomic model performance using epidermal growth factor receptor (EGFR) mutation prediction in lung cancer as a paradigm. In the training phase, the CNN was retrained and tested on 32 lung cancer patients’ CT images between two different groups of reconstruction kernels (smooth and sharp). In the validation phase, the retrained CNN was validated on an external cohort of 223 lung cancer patients’ CT images acquired using different CT scanners and kernels. The results showed that the retrained CNN could be successfully applied to external datasets with different CT scanner parameters, and harmonization of reconstruction kernels from sharp to smooth could significantly improve the performance of radiomics model in predicting EGFR mutation status in lung cancer. In conclusion, the CNN based method showed great potential in improving feature reproducibility and generalizability by harmonizing medical images with heterogeneous reconstruction kernels.