Toward Scalable Early Cancer Detection: Evaluating EHR-Based Predictive Models Against Traditional Screening Criteria

Current cancer screening guidelines cover only a few cancer types and rely on narrowly defined criteria such as age or a single risk factor like smoking history, to identify high-risk individuals. Predictive models using electronic health records (EHRs), which capture large-scale longitudinal patient-level health information, may provide a more effective tool for identifying high-risk groups by detecting subtle prediagnostic signals of cancer. Recent advances in large language and foundation models have further expanded this potential, yet evidence remains limited on how useful HER-based models are compared with traditional risk factors currently used in screening guidelines. We systematically evaluated the clinical utility of EHR-based predictive models against traditional risk factors, including gene mutations and family history of cancer, for identifying high-risk individuals across eight major cancers (breast, lung, colorectal, prostate, ovarian, liver, pancreatic, and stomach), using data from the All of Us Research Program, which integrates EHR, genomic, and survey data from over 865,000 participants. Even with a baseline modeling approach, EHR-based models achieved a 3- to 6-fold higher enrichment of true cancer cases among individuals identified as high risk compared with traditional risk factors alone, whether used as a standalone or complementary tool. The EHR foundation model, a state-of-the-art approach trained on comprehensive patient trajectories, further improved predictive performance across 26 cancer types, demonstrating the clinical potential of EHR-based predictive modeling to support more precise and scalable early detection strategies.

On the Role of Calibration in Benchmarking Algorithmic Fairness for Skin Cancer Detection

Artificial Intelligence (AI) models have demonstrated expert-level performance in melanoma detection, yet their clinical adoption is hindered by performance disparities across demographic subgroups such as gender, race, and age. Previous efforts to benchmark the performance of AI models have primarily focused on assessing model performance using group fairness metrics that rely on the Area Under the Receiver Operating Characteristic curve (AUROC), which does not provide insights into a model's ability to provide accurate estimates. In line with clinical assessments, this paper addresses this gap by incorporating calibration as a complementary benchmarking metric to AUROC-based fairness metrics. Calibration evaluates the alignment between predicted probabilities and observed event rates, offering deeper insights into subgroup biases. We assess the performance of the leading skin cancer detection algorithm of the ISIC 2020 Challenge on the ISIC 2020 Challenge dataset and the PROVE-AI dataset, and compare it with the second and third place models, focusing on subgroups defined by sex, race (Fitzpatrick Skin Tone), and age. Our findings reveal that while existing models enhance discriminative accuracy, they often over-diagnose risk and exhibit calibration issues when applied to new datasets. This study underscores the necessity for comprehensive model auditing strategies and extensive metadata collection to achieve equitable AI-driven healthcare solutions. All code is publicly available at https://github.com/bdominique/testing_strong_calibration.

Real-time prediction of breast cancer sites using deformation-aware graph neural network

Early diagnosis of breast cancer is crucial, enabling the establishment of appropriate treatment plans and markedly enhancing patient prognosis. While direct magnetic resonance imaging-guided biopsy demonstrates promising performance in detecting cancer lesions, its practical application is limited by prolonged procedure times and high costs. To overcome these issues, an indirect MRI-guided biopsy that allows the procedure to be performed outside of the MRI room has been proposed, but it still faces challenges in creating an accurate real-time deformable breast model. In our study, we tackled this issue by developing a graph neural network (GNN)-based model capable of accurately predicting deformed breast cancer sites in real time during biopsy procedures. An individual-specific finite element (FE) model was developed by incorporating magnetic resonance (MR) image-derived structural information of the breast and tumor to simulate deformation behaviors. A GNN model was then employed, designed to process surface displacement and distance-based graph data, enabling accurate prediction of overall tissue displacement, including the deformation of the tumor region. The model was validated using phantom and real patient datasets, achieving an accuracy within 0.2 millimeters (mm) for cancer node displacement (RMSE) and a dice similarity coefficient (DSC) of 0.977 for spatial overlap with actual cancerous regions. Additionally, the model enabled real-time inference and achieved a speed-up of over 4,000 times in computational cost compared to conventional FE simulations. The proposed deformation-aware GNN model offers a promising solution for real-time tumor displacement prediction in breast biopsy, with high accuracy and real-time capability. Its integration with clinical procedures could significantly enhance the precision and efficiency of breast cancer diagnosis.

Anatomy-Aware Lymphoma Lesion Detection in Whole-Body PET/CT

Early cancer detection is crucial for improving patient outcomes, and 18F FDG PET/CT imaging plays a vital role by combining metabolic and anatomical information. Accurate lesion detection remains challenging due to the need to identify multiple lesions of varying sizes. In this study, we investigate the effect of adding anatomy prior information to deep learning-based lesion detection models. In particular, we add organ segmentation masks from the TotalSegmentator tool as auxiliary inputs to provide anatomical context to nnDetection, which is the state-of-the-art for lesion detection, and Swin Transformer. The latter is trained in two stages that combine self-supervised pre-training and supervised fine-tuning. The method is tested in the AutoPET and Karolinska lymphoma datasets. The results indicate that the inclusion of anatomical priors substantially improves the detection performance within the nnDetection framework, while it has almost no impact on the performance of the vision transformer. Moreover, we observe that Swin Transformer does not offer clear advantages over conventional convolutional neural network (CNN) encoders used in nnDetection. These findings highlight the critical role of the anatomical context in cancer lesion detection, especially in CNN-based models.

nnMIL: A generalizable multiple instance learning framework for computational pathology

Computational pathology holds substantial promise for improving diagnosis and guiding treatment decisions. Recent pathology foundation models enable the extraction of rich patch-level representations from large-scale whole-slide images (WSIs), but current approaches for aggregating these features into slide-level predictions remain constrained by design limitations that hinder generalizability and reliability. Here, we developed nnMIL, a simple yet broadly applicable multiple-instance learning framework that connects patch-level foundation models to robust slide-level clinical inference. nnMIL introduces random sampling at both the patch and feature levels, enabling large-batch optimization, task-aware sampling strategies, and efficient and scalable training across datasets and model architectures. A lightweight aggregator performs sliding-window inference to generate ensemble slide-level predictions and supports principled uncertainty estimation. Across 40,000 WSIs encompassing 35 clinical tasks and four pathology foundation models, nnMIL consistently outperformed existing MIL methods for disease diagnosis, histologic subtyping, molecular biomarker detection, and pan- cancer prognosis prediction. It further demonstrated strong cross-model generalization, reliable uncertainty quantification, and robust survival stratification in multiple external cohorts. In conclusion, nnMIL offers a practical and generalizable solution for translating pathology foundation models into clinically meaningful predictions, advancing the development and deployment of reliable AI systems in real-world settings.

The Impact of Longitudinal Mammogram Alignment on Breast Cancer Risk Assessment

Regular mammography screening is crucial for early breast cancer detection. By leveraging deep learning-based risk models, screening intervals can be personalized, especially for high-risk individuals. While recent methods increasingly incorporate longitudinal information from prior mammograms, accurate spatial alignment across time points remains a key challenge. Misalignment can obscure meaningful tissue changes and degrade model performance. In this study, we provide insights into various alignment strategies, image-based registration, feature-level (representation space) alignment with and without regularization, and implicit alignment methods, for their effectiveness in longitudinal deep learning-based risk modeling. Using two large-scale mammography datasets, we assess each method across key metrics, including predictive accuracy, precision, recall, and deformation field quality. Our results show that image-based registration consistently outperforms the more recently favored feature-based and implicit approaches across all metrics, enabling more accurate, temporally consistent predictions and generating smooth, anatomically plausible deformation fields. Although regularizing the deformation field improves deformation quality, it reduces the risk prediction performance of feature-level alignment. Applying image-based deformation fields within the feature space yields the best risk prediction performance. These findings underscore the importance of image-based deformation fields for spatial alignment in longitudinal risk modeling, offering improved prediction accuracy and robustness. This approach has strong potential to enhance personalized screening and enable earlier interventions for high-risk individuals. The code is available at https://github.com/sot176/Mammogram_Alignment_Study_Risk_Prediction.git, allowing full reproducibility of the results.

Multimodal RGB-HSI Feature Fusion with Patient-Aware Incremental Heuristic Meta-Learning for Oral Lesion Classification

Early detection of oral cancer and potentially malignant disorders is challenging in low-resource settings due to limited annotated data. We present a unified four-class oral lesion classifier that integrates deep RGB embeddings, hyperspectral reconstruction, handcrafted spectral-textural descriptors, and demographic metadata. A pathologist-verified subset of oral cavity images was curated and processed using a fine-tuned ConvNeXt-v2 encoder, followed by RGB-to-HSI reconstruction into 31-band hyperspectral cubes. Haemoglobin-sensitive indices, texture features, and spectral-shape measures were extracted and fused with deep and clinical features. Multiple machine-learning models were assessed with patient-wise validation. We further introduce an incremental heuristic meta-learner (IHML) that combines calibrated base classifiers through probabilistic stacking and patient-level posterior smoothing. On an unseen patient split, the proposed framework achieved a macro F1 of 66.23% and an accuracy of 64.56%. Results demonstrate that hyperspectral reconstruction and uncertainty-aware meta-learning substantially improve robustness for real-world oral lesion screening.

A Second-Order Attention Mechanism For Prostate Cancer Segmentation and Detection in Bi-Parametric MRI

The detection of clinically significant prostate cancer lesions (csPCa) from biparametric magnetic resonance imaging (bp-MRI) has emerged as a noninvasive imaging technique for improving accurate diagnosis. Nevertheless, the analysis of such images remains highly dependent on the subjective expert interpretation. Deep learning approaches have been proposed for csPCa lesions detection and segmentation, but they remain limited due to their reliance on extensively annotated datasets. Moreover, the high lesion variability across prostate zones poses additional challenges, even for expert radiologists. This work introduces a second-order geometric attention (SOGA) mechanism that guides a dedicated segmentation network, through skip connections, to detect csPCa lesions. The proposed attention is modeled on the Riemannian manifold, learning from symmetric positive definitive (SPD) representations. The proposed mechanism was integrated into standard U-Net and nnU-Net backbones, and was validated on the publicly available PI-CAI dataset, achieving an Average Precision (AP) of 0.37 and an Area Under the ROC Curve (AUC-ROC) of 0.83, outperforming baseline networks and attention-based methods. Furthermore, the approach was evaluated on the Prostate158 dataset as an independent test cohort, achieving an AP of 0.37 and an AUC-ROC of 0.75, confirming robust generalization and suggesting discriminative learned representations.

EndoSight AI: Deep Learning-Driven Real-Time Gastrointestinal Polyp Detection and Segmentation for Enhanced Endoscopic Diagnostics

Precise and real-time detection of gastrointestinal polyps during endoscopic procedures is crucial for early diagnosis and prevention of colorectal cancer. This work presents EndoSight AI, a deep learning architecture developed and evaluated independently to enable accurate polyp localization and detailed boundary delineation. Leveraging the publicly available Hyper-Kvasir dataset, the system achieves a mean Average Precision (mAP) of 88.3% for polyp detection and a Dice coefficient of up to 69% for segmentation, alongside real-time inference speeds exceeding 35 frames per second on GPU hardware. The training incorporates clinically relevant performance metrics and a novel thermal-aware procedure to ensure model robustness and efficiency. This integrated AI solution is designed for seamless deployment in endoscopy workflows, promising to advance diagnostic accuracy and clinical decision-making in gastrointestinal healthcare.

ProstNFound+: A Prospective Study using Medical Foundation Models for Prostate Cancer Detection

Purpose: Medical foundation models (FMs) offer a path to build high-performance diagnostic systems. However, their application to prostate cancer (PCa) detection from micro-ultrasound ({\mu}US) remains untested in clinical settings. We present ProstNFound+, an adaptation of FMs for PCa detection from {\mu}US, along with its first prospective validation. Methods: ProstNFound+ incorporates a medical FM, adapter tuning, and a custom prompt encoder that embeds PCa-specific clinical biomarkers. The model generates a cancer heatmap and a risk score for clinically significant PCa. Following training on multi-center retrospective data, the model is prospectively evaluated on data acquired five years later from a new clinical site. Model predictions are benchmarked against standard clinical scoring protocols (PRI-MUS and PI-RADS). Results: ProstNFound+ shows strong generalization to the prospective data, with no performance degradation compared to retrospective evaluation. It aligns closely with clinical scores and produces interpretable heatmaps consistent with biopsy-confirmed lesions. Conclusion: The results highlight its potential for clinical deployment, offering a scalable and interpretable alternative to expert-driven protocols.