From Adult Renal Masses to Pediatric Wilms Tumors: Evaluating Cross-Domain Generalization of Kidney Lesion Segmentation on MRI

Deep learning-based organs/structures-at-risk(OARs) auto-contouring models can improve radiotherapy workflows, but models trained on adult data often underperform in pediatric patients. Developing robust pediatric-specific models is hindered by data scarcity and fragmentation across centers. Federated learning (FL) enables privacy-preserving collaborative training without the need for data sharing. We evaluated the feasibility and performance of FL for developing pediatric-specific OAR segmentation models across two European medical centers. Computed tomography (CT) images from pediatric patients from Utrecht and Heidelberg with a renal tumor or abdominal neuroblastoma were retrospectively collected and locally processed. An nnU-Net-based framework segmented 19 OARs using local and FL schemes. FL was implemented with secure weight exchange on a cloud storage across institutional firewalls. Performance was assessed using the Dice similarity coefficient (DSC), 95th percentile Hausdorff distance, and mean surface distance. Robustness to patient orientation, false-positive segmentation of surgically removed kidneys, and failure cases were identified. A total of 310 postoperative CTs from 272 patients (105 renal tumors, 167 neuroblastomas) were included. Local models performed well on their respective center data but showed significantly reduced cross-center performance for four to seven of the nine evaluated OARs (DSC). In contrast, the FL model matched local performance for at least seven of nine OARs and achieved the best cross-center results across three metrics, with DSC gains of 0.003-0.007 over local models. FL also maintained stable performance across patient orientations and reduced false-positive kidney segmentations. Real-world FL improves cross-center robustness of CT-based OAR segmentation models in pediatric upper abdominal tumors.

The rapid proliferation of open-source medical foundation models (FMs) raises a practical question: how well do their pre-trained representations transfer to clinically relevant but data-scarce classification tasks? Particularly in CT-based renal lesion classification, a push toward greater generalizability would be meaningful, as the field is constrained by inherently limited training data. We addressed this through a benchmark of three medical FMs on this specific task. This six-class problem spans common entities like cysts and clear cell renal cell carcinoma, alongside rare subtypes. Using a frozen feature-probing protocol, we compared FM embeddings against a handcrafted radiomics classifier and a 3D ResNet-50 trained from scratch. Models were trained on a composite dataset of 2,854 lesions and evaluated on an external test set of 234 lesions from The Cancer Imaging Archive. Our results reveal two key findings. First, FM performance (AUC 0.70-0.77) matched the from-scratch ResNet (AUC 0.72) while drastically reducing hardware demand, requiring only seconds on a CPU after feature extraction. However, the conventional radiomics baseline significantly outperformed all deep learning approaches, achieving an AUC of 0.88 (all p $\leq$ 0.002). This suggests that current generalist FM embeddings do not yet capture the fine-grained texture and shape heterogeneity driving histological subtype discrimination. Despite their potential in data-scarce settings, medical FMs did not surpass established models for renal lesion stratification, leaving radiomics as the current state-of-the-art.

Reliable clinical deployment of machine learning requires models that know when they are likely to fail, particularly for subgroups underrepresented in training data. A common case is pediatric care, where models trained on adult cohorts can silently under-perform on children with no indication that something has gone wrong. As retraining with labeled pediatric data is often infeasible, detecting such failures at inference time is a critical clinical need. Building on the VIDS (Variational Inference under Distribution Shifts) framework, we introduce VIDS-Seg, which applies amortized variational inference over a lightweight prediction head to make this adaptive, OOD-aware prior tractable for dense image segmentation. We evaluate VIDS-Seg on left ventricular segmentation in echocardiography, a setting where pediatric anatomy differs systematically from the adult population most segmentation models are trained on, training on an adult cohort (EchoNet-Dynamic) and evaluating zero-shot on a pediatric cohort (EchoNet-Pediatric). Across all age strata, VIDS-Seg matches competitive baselines in segmentation accuracy while producing substantially higher spatial correspondence between predicted uncertainty and segmentation error, an advantage that persists even after applying temperature scaling to all baselines. Downstream, it yields more accurate and stable ejection fraction estimates and more reliable detection of cardiac malfunction in the infant subgroup. Our results indicate that OOD-aware uncertainty quantification can serve as a practical safety layer for deployed segmentation models, enabling detection of silent failures in underrepresented subgroups without retraining or additional labeled data.