Comparing Modelling Architectures in the context of EGFR Status Classification in Non Small Cell Lung Cancer

Radiogenomics enables the non-invasive characterisation of the genomic and molecular properties of tumours, with epidermal growth factor receptor (EGFR) mutations in non–small cell lung cancer (NSCLC) being one of the most investigated applications. In this study, we evaluate radiomics, contrastive learning, and convolutional deep learning approaches to predict the EGFR mutation status from chest Computed Tomography (CT) images using the TCIA Radiogenomics dataset (n=115). Our results, using 10-fold cross validation, demonstrate the capacity of imaging models to predict mutation status from CT data in a manner consistent with existing literature. Among the evaluated methods, models integrating radiomic with clinical features achieved the best performance, with an AUC of 0.790 and AUPRC of 0.517, outperforming both contrastive learning (AUC=0.787) and convolutional architectures (AUC=0.763). Beyond methodological comparisons, we discuss the challenges related to clinical translation. Specifically, we contrast radiogenomics with conventional tissue biopsies, and identify scenarios where radiogenomics might be useful, either independently or in conjunction with other existing diagnostic technologies. Together these findings evidence the potential utility of radiogenomics EGFR models and provide direct architecture comparisons on the same dataset.