TrajOnco: a multi-agent framework for temporal reasoning over longitudinal EHR for multi-cancer early detection

Accurate estimation of cancer risk from longitudinal electronic health records (EHRs) could support earlier detection and improved care, but modeling such complex patient trajectories remains challenging. We present TrajOnco, a training-free, multi-agent large language model (LLM) framework designed for scalable multi-cancer early detection. Using a chain-of-agents architecture with long-term memory, TrajOnco performs temporal reasoning over sequential clinical events to generate patient-level summaries, evidence-linked rationales, and predicted risk scores. We evaluated TrajOnco on de-identified Truveta EHR data across 15 cancer types using matched case-control cohorts, predicting risk of cancer diagnosis at 1 year. In zero-shot evaluation, TrajOnco achieved AUROCs of 0.64-0.80, performing comparably to supervised machine learning in a lung cancer benchmark while demonstrating better temporal reasoning than single-agent LLMs. The multi-agent design also enabled effective temporal reasoning with smaller-capacity models such as GPT-4.1-mini. The fidelity of TrajOnco's output was validated through human evaluation. Furthermore, TrajOnco's interpretable reasoning outputs can be aggregated to reveal population-level risk patterns that align with established clinical knowledge. These findings highlight the potential of multi-agent LLMs to execute interpretable temporal reasoning over longitudinal EHRs, advancing both scalable multi-cancer early detection and clinical insight generation.

PC-MIL: Decoupling Feature Resolution from Supervision Scale in Whole-Slide Learning

Whole-slide image (WSI) classification in computational pathology is commonly formulated as slide-level Multiple Instance Learning (MIL) with a single global bag representation. However, slide-level MIL is fundamentally underconstrained: optimizing only global labels encourages models to aggregate features without learning anatomically meaningful localization. This creates a mismatch between the scale of supervision and the scale of clinical reasoning. Clinicians assess tumor burden, focal lesions, and architectural patterns within millimeter-scale regions, whereas standard MIL is trained only to predict whether "somewhere in the slide there is cancer." As a result, the model's inductive bias effectively erases anatomical structure. We propose Progressive-Context MIL (PC-MIL), a framework that treats the spatial extent of supervision as a first-class design dimension. Rather than altering magnification, patch size, or introducing pixel-level segmentation, we decouple feature resolution from supervision scale. Using fixed 20x features, we vary MIL bag extent in millimeter units and anchor supervision at a clinically motivated 2mm scale to preserve comparable tumor burden and avoid confounding scale with lesion density. PC-MIL progressively mixes slide- and region-level supervision in controlled proportions, enabling explicit train-context x test-context analysis. On 1,476 prostate WSIs from five public datasets for binary cancer detection, we show that anatomical context is an independent axis of generalization in MIL, orthogonal to feature resolution: modest regional supervision improves cross-context performance, and balanced multi-context training stabilizes accuracy across slide and regional evaluation without sacrificing global performance. These results demonstrate that supervision extent shapes MIL inductive bias and support anatomically grounded WSI generalization.

Architecture-Agnostic Modality-Isolated Gated Fusion for Robust Multi-Modal Prostate MRI Segmentation

Multi-parametric prostate MRI -- combining T2-weighted, apparent diffusion coefficient, and high b-value diffusion-weighted sequences -- is central to non-invasive detection of clinically significant prostate cancer, yet in routine practice individual sequences may be missing or degraded by motion, artifacts, or abbreviated protocols. Existing multi-modal fusion strategies typically assume complete inputs and entangle modality-specific information at early layers, offering limited resilience when one channel is corrupted or absent. We propose Modality-Isolated Gated Fusion (MIGF), an architecture-agnostic module that maintains separate modality-specific encoding streams before a learned gating stage, combined with modality dropout training to enforce compensation behavior under incomplete inputs. We benchmark six bare backbones and assess MIGF-equipped models under seven missing-modality and artifact scenarios on the PI-CAI dataset (1,500 studies, fold-0 split, five random seeds). Among bare backbones, nnUNet provided the strongest balance of performance and stability. MIGF improved ideal-scenario Ranking Score for UNet, nnUNet, and Mamba by 2.8%, 4.6%, and 13.4%, respectively; the best model, MIGFNet-nnUNet (gating + ModDrop, no deep supervision), achieved 0.7304 +/- 0.056. Mechanistic analysis reveals that robustness gains arise from strict modality isolation and dropout-driven compensation rather than adaptive per-sample quality routing: the gate converged to a stable modality prior, and deep supervision was beneficial only for the largest backbone while degrading lighter models. These findings support a simpler design principle for robust multi-modal segmentation: structurally contain corrupted inputs first, then train explicitly for incomplete-input compensation.

Inferring High-Level Events from Timestamped Data: Complexity and Medical Applications

In this paper, we develop a novel logic-based approach to detecting high-level temporally extended events from timestamped data and background knowledge. Our framework employs logical rules to capture existence and termination conditions for simple temporal events and to combine these into meta-events. In the medical domain, for example, disease episodes and therapies are inferred from timestamped clinical observations, such as diagnoses and drug administrations stored in patient records, and can be further combined into higher-level disease events. As some incorrect events might be inferred, we use constraints to identify incompatible combinations of events and propose a repair mechanism to select preferred consistent sets of events. While reasoning in the full framework is intractable, we identify relevant restrictions that ensure polynomial-time data complexity. Our prototype system implements core components of the approach using answer set programming. An evaluation on a lung cancer use case supports the interest of the approach, both in terms of computational feasibility and positive alignment of our results with medical expert opinions. While strongly motivated by the needs of the healthcare domain, our framework is purposely generic, enabling its reuse in other areas.

OpenTME: An Open Dataset of AI-powered H&E Tumor Microenvironment Profiles from TCGA

The tumor microenvironment (TME) plays a central role in cancer progression, treatment response, and patient outcomes, yet large-scale, consistent, and quantitative TME characterization from routine hematoxylin and eosin (H&E)-stained histopathology remains scarce. We introduce OpenTME, an open-access dataset of pre-computed TME profiles derived from 3,634 H&E-stained whole-slide images across five cancer types (bladder, breast, colorectal, liver, and lung cancer) from The Cancer Genome Atlas (TCGA). All outputs were generated using Atlas H&E-TME, an AI-powered application built on the Atlas family of pathology foundation models, which performs tissue quality control, tissue segmentation, cell detection and classification, and spatial neighborhood analysis, yielding over 4,500 quantitative readouts per slide at cell-level resolution. OpenTME is available for non-commercial academic research on Hugging Face. We will continue to expand OpenTME over time and anticipate it will serve as a resource for biomarker discovery, spatial biology research, and the development of computational methods for TME analysis.

Interpretable Prostate Cancer Detection using a Small Cohort of MRI Images

Prostate cancer is a leading cause of mortality in men, yet interpretation of T2-weighted prostate MRI remains challenging due to subtle and heterogeneous lesions. We developed an interpretable framework for automatic cancer detection using a small dataset of 162 T2-weighted images (102 cancer, 60 normal), addressing data scarcity through transfer learning and augmentation. We performed a comprehensive comparison of Vision Transformers (ViT, Swin), CNNs (ResNet18), and classical methods (Logistic Regression, SVM, HOG+SVM). Transfer-learned ResNet18 achieved the best performance (90.9% accuracy, 95.2% sensitivity, AUC 0.905) with only 11M parameters, while Vision Transformers showed lower performance despite substantially higher complexity. Notably, HOG+SVM achieved comparable accuracy (AUC 0.917), highlighting the effectiveness of handcrafted features in small datasets. Unlike state-of-the-art approaches relying on biparametric MRI (T2+DWI) and large cohorts, our method achieves competitive performance using only T2-weighted images, reducing acquisition complexity and computational cost. In a reader study of 22 cases, five radiologists achieved a mean sensitivity of 67.5% (Fleiss Kappa = 0.524), compared to 95.2% for the AI model, suggesting potential for AI-assisted screening to reduce missed cancers and improve consistency. Code and data are publicly available.

Needle in a Haystack -- One-Class Representation Learning for Detecting Rare Malignant Cells in Computational Cytology

In computational cytology, detecting malignancy on whole-slide images is difficult because malignant cells are morphologically diverse yet vanishingly rare amid a vast background of normal cells. Accurate detection of these extremely rare malignant cells remains challenging due to large class imbalance and limited annotations. Conventional weakly supervised approaches, such as multiple instance learning (MIL), often fail to generalize at the instance level, especially when the fraction of malignant cells (witness rate) is exceedingly low. In this study, we explore the use of one-class representation learning techniques for detecting malignant cells in low-witness-rate scenarios. These methods are trained exclusively on slide-negative patches, without requiring any instance-level supervision. Specifically, we evaluate two OCC approaches, DSVDD and DROC, and compare them with FS-SIL, WS-SIL, and the recent ItS2CLR method. The one-class methods learn compact representations of normality and detect deviations at test time. Experiments on a publicly available bone marrow cytomorphology dataset (TCIA) and an in-house oral cancer cytology dataset show that DSVDD achieves state-of-the-art performance in instance-level abnormality ranking, particularly in ultra-low witness-rate regimes ($\leq 1\%$) and, in some cases, even outperforming fully supervised learning, which is typically not a practical option in whole-slide cytology due to the infeasibility of exhaustive instance-level annotations. DROC is also competitive under extreme rarity, benefiting from distribution-augmented contrastive learning. These findings highlight one-class representation learning as a robust and interpretable superior choice to MIL for malignant cell detection under extreme rarity.

Maximizing T2-Only Prostate Cancer Localization from Expected Diffusion Weighted Imaging

Multiparametric MRI is increasingly recommended as a first-line noninvasive approach to detect and localize prostate cancer, requiring at minimum diffusion-weighted (DWI) and T2-weighted (T2w) MR sequences. Early machine learning attempts using only T2w images have shown promising diagnostic performance in segmenting radiologist-annotated lesions. Such uni-modal T2-only approaches deliver substantial clinical benefits by reducing costs and expertise required to acquire other sequences. This work investigates an arguably more challenging application using only T2w at inference, but to localize individual cancers based on independent histopathology labels. We formulate DWI images as a latent modality (readily available during training) to classify cancer presence at local Barzell zones, given only T2w images as input. In the resulting expectation-maximization algorithm, a latent modality generator (implemented using a flow matching-based generative model) approximates the latent DWI image posterior distribution in the E-steps, while in M-steps a cancer localizer is simultaneously optimized with the generative model to maximize the expected likelihood of cancer presence. The proposed approach provides a novel theoretical framework for learning from a privileged DWI modality, yielding superior cancer localization performance compared to approaches that lack training DWI images or existing frameworks for privileged learning and incomplete modalities. The proposed T2-only methods perform competitively or better than baseline methods using multiple input sequences (e.g., improving the patient-level F1 score by 14.4\% and zone-level QWK by 5.3\% over the T2w+DWI baseline). We present quantitative evaluations using internal and external datasets from 4,133 prostate cancer patients with histopathology-verified labels.

Detection and Classification of (Pre)Cancerous Cells in Pap Smears: An Ensemble Strategy for the RIVA Cervical Cytology Challenge

Automated detection and classification of cervical cells in conventional Pap smear images can strengthen cervical cancer screening at scale by reducing manual workload, improving triage, and increasing consistency across readers. However, it is challenged by severe class imbalance and frequent nuclear overlap. We present our approach to the RIVA Cervical Cytology Challenge (ISBI 2026), which requires multi-class detection of eight Bethesda cell categories under these conditions. Using YOLOv11m as the base architecture, we systematically evaluate three strategies to improve detection performance: loss reweighting, data resampling and transfer learning. We build an ensemble by combining models trained under each strategy, promoting complementary detection behavior and combining them through Weighted Boxes Fusion (WBF). The ensemble achieves a mAP50-95 of 0.201 on the preliminary test set and 0.147 on the final test set, representing a 29% improvement over the best individual model on the final test set and demonstrating the effectiveness of combining complementary imbalance mitigation strategies.

Center-Aware Detection with Swin-based Co-DETR Framework for Cervical Cytology

Automated analysis of Pap smear images is critical for cervical cancer screening but remains challenging due to dense cell distribution and complex morphology. In this paper, we present our winning solution for the RIVA Cervical Cytology Challenge, achieving 1st place in Track B and 2nd place in Track A. Our approach leverages a powerful baseline, integrating the Co-DINO framework with a Swin-Large backbone for robust multi-scale feature extraction. To address the dataset's unique fixed-size bounding box annotations, we formulate the detection task as a center-point prediction problem. Tailoring our approach to this formulation, we introduce a center-preserving data augmentation strategy and an analytical geometric box optimization to effectively absorb localization jitter. Finally, we apply track-specific loss tuning to adapt the loss weights for each task. Experiments demonstrate that our targeted optimizations improve detection performance, providing an effective pipeline for cytology image analysis. Our code is available at https://github.com/YanKong0408/Center-DETR.