Evaluating Multi-Task Morphological Concept Learning for Pulmonary Nodule Malignancy Assessment in 3D CT

Foundation models provide transferable CT representations, but predictions based directly on these embeddings are difficult to interpret. We developed concept bottleneck models that map two frozen CT foundation-model representations to eight radiologist-defined pulmonary-nodule attributes and predict malignancy from the estimated concepts and nodule size. The models included CT-FM, a whole-CT self-supervised encoder using a 96^3-voxel nodule-centered patch, and FMCIB, a nodule-focused contrastive encoder using a 50-mm crop. Eight ridge-regression concept heads were trained on 2,610 LIDC-IDRI nodules. Malignancy models were trained on LUNA25 and evaluated on a held-out internal test set and the external DLCS cohort. Concept fidelity was assessed using five-fold cross-validated R^2, and malignancy discrimination was assessed using AUROC with 95% confidence intervals estimated by patient-grouped bootstrap resampling. Concept fidelity was modest but higher for FMCIB than CT-FM for subtlety (R2, 0.24 vs. 0.11), spiculation (0.17 vs. 0.08), texture (0.17 vs. 0.07), and lobulation (0.15 vs. 0.05). Internally, the CT-FM and FMCIB concept+size models achieved AUROCs of 0.86 (95% CI, 0.80-0.92) and 0.86 (0.79-0.92), respectively. Externally, AUROCs were 0.72 (0.68-0.75) and 0.73 (0.70-0.76), compared with 0.73 for nodule size alone and 0.60 and 0.67 for the corresponding embedding only probes. Additive predictions could be decomposed into feature-level contributions and modified through controlled concept interventions. Concept bottlenecks provided transparent malignancy predictions with discrimination similar to nodule size alone, while differences in concept fidelity suggest that concept recovery depends on the underlying foundation-model representation.

The accurate classification of benign and malignant pulmonary nodules in CT scans is critical for early lung cancer screening, yet remains challenging due to the multi-scale and heterogeneous nature of pulmonary nodules. While deep learning offers potential for auxiliary diagnosis, most existing models act as "black boxes", lacking the transparency and explainability required for trustworthy clinical integration. To address this issue, we propose M3Net, a novel 3D network for pulmonary nodule classification inspired by the hierarchical diagnostic workflow of radiologists, which integrates multi-scale contextual information from fine-grained structures to global anatomical relationships. Our framework constructs a progressive multi-scale input, from fine-grained nodule structures to local semantics and global spatial relationships. M3Net employs scale-specific encoders and ensures cross-scale semantic consistency through latent space projection and mutual information maximization. Extensive experiments on the public LIDC-IDRI dataset and a self-collected clinical dataset (USTC-FHLN) demonstrate that our method achieves state-of-the-art performance, with accuracies of 86.96% and 84.24% respectively, outperforming the best baseline by 3.26% and 2.17%. The results validate that M3Net provides a more robust and clinically relevant solution for pulmonary nodule classification. The code is available at https://github.com/jylEcho/M3-Net.

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.