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The complex pathobiology of lung cancer, and its spread worldwide, has prompted research studies that combine radiomic and genomic approaches. Indeed, the early identification of genetic alterations and driver mutations affecting the tumor is fundamental for correctly formulating the prognosis and therapeutic response. In this work, we propose a radiogenomic workflow to detect the presence of KRAS and EGFR mutations using radiomic features extracted from computed tomography images of patients affected by lung adenocarcinoma. To this aim, we investigated several feature selection algorithms to identify the most significant and uncorrelated sets of radiomic features and different classification models to reveal the mutational status. Then, we employed the SHAP (SHapley Additive exPlanations) technique to increase the understanding of the contribution given by specific radiomic features to the identification of the investigated mutations. Two cohorts of patients with lung adenocarcinoma were used for the study. The first one, obtained from the Cancer Imaging Archive (TCIA), consisted of 60 cases (25% EGFR, 23% KRAS); the second one, provided by the Azienda Ospedaliero-Universitaria ’Ospedali Riuniti’ of Foggia, was composed of 55 cases (16% EGFR, 28% KRAS). The best-performing models proposed in our study achieved an AUC of 0.69 and 0.82 on the validation set for predicting the mutational status of EGFR and KRAS, respectively. The Multi-layer Perceptron model emerged as the top-performing model for both oncogenes, in some cases outperforming the state of the art. This study showed that radiomic features can be associated with EGFR and KRAS mutational status in patients with lung adenocarcinoma.

Lung cancer is one of the deadliest diseases worldwide. Computed Tomography (CT) images are a powerful tool for investigating the structure and texture of lung nodules. For a long time, trained radiologists have performed the grading and staging of cancer severity by relying on radiographic images. Recently, radiomics has been changing the traditional workflow for lung cancer staging by providing the technical and methodological means to analytically quantify lesions so that more accurate predictions could be performed while reducing the time required from each specialist to perform such tasks. In this work, we implemented a pipeline for identifying a radiomic signature composed of a reduced number of features to discriminate between adenocarcinomas and other cancer types. In addition, we also investigated the reproducibility of this radiomic study analysing the performances of the classification models on external validation data. In detail, we first considered two publicly available datasets, namely D1 and D2, composed of n = 262 and n = 89 samples, respectively. Ten significant features, according to univariate AUC evaluated on D1, were retained. Mann–Whitney U tests recognised three of these features to have a statistically different distribution, with a p-value < 0.05. Then, we collected n = 51 CT images from patients with lung nodules at the Azienda Ospedaliero—Universitaria “Policlinico Riuniti” in Foggia. Resident radiologists manually annotated the lung lesions in images to allow the subsequent analysis of the malignancy regions. We designed a pipeline for feature extraction from the Volumes of Interest in order to generate a third dataset, i.e., D3. Several experiments have been performed showing that the selected radiomic signature not only allowed the discrimination of lung adenocarcinoma from other cancer types independently from the input dataset used for training the models, but also allowed reaching good classification performances also on external validation data; in fact, the radiomic signature computed on D1 and evaluated on the local cohort allowed reaching an AUC of 0.70 (p<0.001) for the task of predicting the histological subtype.