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.

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.

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.

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.

Improving Deep Learning-Based Target Volume Auto-Delineation for Adaptive MR-Guided Radiotherapy in Head and Neck Cancer: Impact of a Volume-Aware Dice Loss

Background: Manual delineation of target volumes in head and neck cancer (HNC) remains a significant bottleneck in radiotherapy planning, characterized by high inter-observer variability and time consumption. This study evaluates the integration of a Volume-Aware (VA) Dice loss function into a self-configuring deep learning framework to enhance the auto-segmentation of primary tumors (PT) and metastatic lymph nodes (LN) for adaptive MR-guided radiotherapy. We investigate how volume-sensitive weighting affects the detection of small, anatomically complex nodal metastases compared to conventional loss functions. Methods: Utilizing the HNTS-MRG 2024 dataset, we implemented an nnU-Net ResEnc M architecture. We conducted a multi-label segmentation task, comparing a standard Dice loss baseline against two Volume-Aware configurations: a "Dual Mask" setup (VA loss on both PT and LN) and a "Selective LN Mask" setup (VA loss on LN only). Evaluation metrics included volumetric Dice scores, surface-based metrics (SDS, MSD, HD95), and lesion-wise binary detection sensitivity and precision. Results: The Selective LN Mask configuration achieved the highest LN Volumetric Dice Score (0.758 vs. 0.734 baseline) and significantly improved LN Lesion-Wise Detection Sensitivity (84.93% vs. 81.80%). However, a critical trade-off was observed; PT detection precision declined significantly in the selective setup (63.65% vs. 81.27%). The Dual Mask configuration provided the most balanced performance across both targets, maintaining primary tumor precision at 82.04% while improving LN sensitivity to 83.46%. Conclusions: A volume-sensitive loss function mitigated the under-representation of small metastatic lesions in HNC. While selective weighting yielded the best nodal detection, a dual-mask approach is required in multi-label tasks to maintain segmentation accuracy for larger primary tumor volumes.

AMO-ENE: Attention-based Multi-Omics Fusion Model for Outcome Prediction in Extra Nodal Extension and HPV-associated Oropharyngeal Cancer

Extranodal extension (ENE) is an emerging prognostic factor in human papillomavirus (HPV)-associated oropharyngeal cancer (OPC), although it is currently omitted as a clinical staging criteria. Recent works have advocated for the inclusion of iENE as a prognostic marker in HPV-positive OPC staging. However, several practical limitations continue to hinder its clinical integration, including inconsistencies in segmentation, low contrast in the periphery of metastatic lymph nodes on CT imaging, and laborious manual annotations. To address these limitations, we propose a fully automated end-to-end pipeline that uses computed tomography (CT) images with clinical data to assess the status of nodal ENE and predict treatment outcomes. Our approach includes a hierarchical 3D semi-supervised segmentation model designed to detect and delineate relevant iENE from radiotherapy planning CT scans. From these segmentations, a set of radiomics and deep features are extracted to train an imaging-detected ENE grading classifier. The predicted ENE status is then evaluated for its prognostic value and compared with existing staging criteria. Furthermore, we integrate these nodal features with primary tumor characteristics in a multimodal, attention-based outcome prediction model, providing a dynamic framework for outcome prediction. Our method is validated in an internal cohort of 397 HPV-positive OPC patients treated with radiation therapy or chemoradiotherapy between 2009 and 2020. For outcome prediction at the 2-year mark, our pipeline surpassed baseline models with 88.2% (4.8) in AUC for metastatic recurrence, 79.2% (7.4) for overall survival, and 78.1% (8.6) for disease-free survival. We also obtain a concordance index of 83.3% (6.5) for metastatic recurrence, 71.3% (8.9) for overall survival, and 70.0% (8.1) for disease-free survival, making it feasible for clinical decision making.

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.

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.

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.

Exploring the Impact of Skin Color on Skin Lesion Segmentation

Skin cancer, particularly melanoma, remains a major cause of morbidity and mortality, making early detection critical. AI-driven dermatology systems often rely on skin lesion segmentation as a preprocessing step to delineate the lesion from surrounding skin and support downstream analysis. While fairness concerns regarding skin tone have been widely studied for lesion classification, the influence of skin tone on the segmentation stage remains under-quantified and is frequently assessed using coarse, discrete skin tone categories. In this work, we evaluate three strong segmentation architectures (UNet, DeepLabV3 with a ResNet50 backbone, and DINOv2) on two public dermoscopic datasets (HAM10000 and ISIC2017) and introduce a continuous pigment or contrast analysis that treats pixel-wise ITA values as distributions. Using Wasserstein distances between within-image distributions for skin-only, lesion-only, and whole-image regions, we quantify lesion skin contrast and relate it to segmentation performance across multiple metrics. Within the range represented in these datasets, global skin tone metrics (Fitzpatrick grouping or mean ITA) show weak association with segmentation quality. In contrast, low lesion-skin contrast is consistently associated with larger segmentation errors in models, indicating that boundary ambiguity and low contrast are key drivers of failure. These findings suggest that fairness improvements in dermoscopic segmentation should prioritize robust handling of low-contrast lesions, and the distribution-based pigment measures provide a more informative audit signal than discrete skin-tone categories.