Radiomic Feature Selection Using Gradient Loss of Deep Neural Network for Lung Cancer Stage Detection

Radiomics is the established approach for CT-based lung cancer phenotyping, yet comparisons with foundation models rarely isolate contributions of feature extractor, classification head, and segmentation choice, or test cross-cohort robustness. We benchmark five feature extractors (Curia, Curia-2, DINOv3, Radiomics2D, Radiomics3D), seven classification heads (TabPFN, TabICL, XGBoost, CatBoost, Random Forest, logistic regression, Ridge), and three segmentation regimes on five tasks: tumor volume and stage classification, 2-year survival prediction, histology classification, and age prediction. Models are trained on LUNG1 (n=338) and evaluated on an internal test set (n=84) and the external LUNG2 cohort (n=211), with worst-case cross-cohort performance as the primary metric. The dominant design factor is task-dependent: segmentation drives volume and stage classification, while classifier choice drives survival, histology, and age prediction. Radiomics is competitive for tumor volume, tumor stage and survival (partly due to label-derivation effects for the former); Curia variants reach comparable peak scores for survival; DINOv3 falls slightly short across tasks. Patch and slice aggregation have negligible impact. We recommend Curia with tumor segmentation and a CatBoost head as a safe default, achieving the best mean rank across the three primary clinical tasks, though task-specific selection consistently outperforms any cross-task default. When tumor delineations are unavailable, Curia-2 with lung segmentation and logistic regression offers a competitive alternative. All pipelines use a two-stage design suited to small cohort sizes where end-to-end fine-tuning would risk overfitting.

Imaging signatures are quantitative features extracted from medical images that provide clinically meaningful information for tumor diagnosis, characterization, prognosis, and treatment planning. Although deep learning has shown great potential for imaging signature discovery, its limited interpretability remains a major barrier to clinical adoption. Existing approaches often achieve high predictive performance but provide little biological insight into the identified signatures. We propose a unified framework for interpretable imaging signature discovery by integrating deep learning based segmentation, explainable classification, and radiomic analysis. A robust segmentation model is first used to accurately delineate tumors, followed by a Grad-CAM guided pipeline that identifies diagnostically important regions as candidate imaging signatures. A mutual information based adaptive thresholding strategy enables patient-specific signature extraction. The resulting signatures are validated using a downstream deep learning classification model, while radiomic features extracted from the signature regions are evaluated with traditional machine learning models and interpreted using SHAP to identify the most discriminative biomarkers. The proposed framework is evaluated on the public BUSI breast ultrasound, KiTS renal CT, and BraTS brain tumor datasets, as well as a private UF Health renal CT cohort. Compared with conventional whole-tumor radiomics, the proposed signature-based approach achieves improved discriminative performance while providing greater biological interpretability. By converting deep learning attention into reproducible quantitative imaging biomarkers, this framework offers an interpretable and reproducible solution for non-invasive tumor characterization and imaging biomarker discovery.

Lung cancer causes more deaths than any other malignancy, and low-dose CT screening is the main pathway to early diagnosis. That pathway hinges on the smallest lesions, yet nodules below six millimeters remain hard to detect, because most methods treat a nodule as a generic object and ignore the imaging physics behind its appearance. We show that this appearance is highly regular. Intensity peaks at the geometric center of a nodule and decays radially in a Gaussian pattern, and a fit to 18,218 annotated lesions from three public benchmarks yields a mean radial coefficient of determination above 0.86 in every dataset and size stratum. A square convolution samples both axes uniformly and is mismatched to this radial signal, most severely for small nodules. Guided by this evidence, we propose GRIPNet (Gaussian Radial Intensity Prior Network), a detector in which every module maps to a measurable property of the intensity distribution. Pinwheel convolutions decompose radial gradients, a dual-frequency module separates boundary detail from structural context, dilated masked attention matches the decay extent, and an adaptive loss reweights samples by conspicuity. GRIPNet raises mAP@0.5 to 95.3, 91.6 and 97.9 percent on KanserSet, LUNA16 and Lung-PET-CT-Dx while sharpening high-IoU localization at real-time speed.