Sparse Regularized Autoencoders-Based Radiomics Data Augmentation for Improved EGFR Mutation Prediction in NSCLC

Lung cancer (LC) remains a leading cause of cancer mortality worldwide, where accurate and early identification of gene mutations such as epidermal growth factor receptor (EGFR) is critical for precision treatment. However, machine learning-based radiomics approaches often face challenges due to the small and imbalanced nature of the datasets. This study proposes a comprehensive framework based on Generic Sparse Regularized Autoencoders with Kullback–Leibler divergence (GSRA-KL) to generate high-quality synthetic radiomics data and overcome these limitations. A systematic approach generated 63 synthetic radiomics datasets by tuning a novel kl_weight regularization hyperparameter across three hidden-layer sizes, optimized using Optuna for computational efficiency. A rigorous assessment was conducted to evaluate the impact of hyperparameter tuning across 63 synthetic datasets, with a focus on the EGFR gene mutation. This evaluation utilized resemblance-dimension scores (RDS), novel utility-dimension scores (UDS), and t-SNE visualizations to ensure the validation of data quality, revealing that GSRA-KL achieves excellent performance (RDS > 0.45, UDS > 0.7), especially when class distribution is balanced, while remaining competitive with the Tabular Variational Autoencoder (TVAE). Additionally, a comprehensive statistical correlation analysis demonstrated strong and significant monotonic relationships among resemblance-based performance metrics up to moderate scaling (≤1.0*), confirming the robustness and stability of inter-metric associations under varying configurations. Complementary computational cost evaluation further indicated that moderate kl_weight values yield an optimal balance between reconstruction accuracy and resource utilization, with Spearman correlations revealing improved reconstruction quality (MSE ρ=−0.78, p<0.001) at reduced computational overhead. The ablation-style analysis confirmed that including the KL divergence term meaningfully enhances the generative capacity of GSRA-KL over its baseline counterpart. Furthermore, the GSRA-KL framework achieved substantial improvements in computational efficiency compared to prior PSO-based optimization methods, resulting in reduced memory usage and training time. Overall, GSRA-KL represents an incremental yet practical advancement for augmenting small and imbalanced high-dimensional radiomics datasets, showing promise for improved mutation prediction and downstream precision oncology studies.