Non-Small Cell Lung Cancer

Lung cancer is the leading cause of cancer-related mortality, with approximately 2.5 million new cases and 1.8 million deaths annually, making reliable diagnosis a clinical priority. Although deep learning models have achieved strong performance in lung cancer classification, evaluation has largely focused on predictive accuracy, leaving their decision-making processes insufficiently examined. This study compares three architecturally distinct models: a Convolutional Neural Network (CNN), a pretrained ResNet50, and a Vision Transformer (ViT), trained on the IQ-OTH/NCCD lung cancer CT dataset. Local Interpretable Model-Agnostic Explanations (LIME) were applied to investigate model reasoning. In addition to standard performance metrics, a dual-correlation framework was introduced to measure both prediction agreement and explanation agreement across model pairs. All three models achieved strong classification performance, with ResNet50 attaining 98.61% accuracy, CNN 97.91%, and ViT 93.75%, while all achieved ROC-AUC scores of 0.99. Prediction correlations exceeded 0.99 across all model pairs, indicating highly consistent outputs. However, LIME explanation correlations remained below 0.26, revealing substantial differences in the image regions used to reach those predictions. Analysis of misclassified samples further identified a consistent spatial pattern: incorrect predictions were associated with attention outside the lung parenchyma, whereas correct predictions focused primarily within lung regions. These findings demonstrate that prediction agreement is a poor proxy for reasoning consistency, and that interpretability evaluation must be treated as an independent validation criterion alongside predictive performance in clinical AI systems.

The global elimination of cervical cancer is a key public health goal set by the World Health Organization (WHO), with screening programs reducing mortality by up to 80%. However, access to experts and biopsy services is limited in low- to middle-income countries (LMICs). Deep learning (DL)-based algorithms offer promising support for screening, but most existing approaches have been developed and validated on private datasets from single countries. We present the first DL-based approach to cervical cancer screening validated on data from multiple countries. Technically, we phrase the problem of detecting and classifying lesions in colposcopy images as a multi-task learning problem, in which we simultaneously perform image-level classification and lesion segmentation. Our model was trained on a private data set of acid stain colposcopy images with manually generated lesion segmentation masks and corresponding histopathological results, employing extensive data augmentation to address image variability. In an in-distribution validation with pathology results serving as ground truth, our algorithm outperformed medical experts (Balanced Accuracy: 0.68 vs 0.64) in CIN1- (Cervical intraepithelial neoplasia grade 1 or lower) versus CIN2+ (grade 2 or higher) classification. External validation on four colposcopy data sets from four countries featuring radical differences in prevalence and patient characteristics yielded superior performance of our method compared to baseline methods. Performance variability across countries was high with AUC values ranging from 0.54 - 0.80. Overall, algorithm performance varied with age, transformation zone (cervical area most prone to lesion development), presence of comorbidities and pathognomonic signs, with comorbidities having by far the largest negative effect. Future work should focus on improving model robustness and generalizability.

Glioma grading and survival prediction require the integration of heterogeneous information collected at different spatial and biological scales. Histopathology describes tissue morphology, mRNA expression captures molecular activity, and magnetic resonance imaging provides a non-invasive view of tumor extent and radiological heterogeneity. Existing glioma prognosis models often combine only two of these sources, while their alignment objectives remain mostly pairwise. This paper introduces GLORIA, a novel trimodal framework for GLioma Omics - Radiology - hIstopathology Alignment. GLORIA processes whole-slide image regions, gene-expression profiles, and 3D MRI volumes through modality-specific encoders, projects them into a shared latent space, and aligns them with a Gramian contrastive loss that measures the volume spanned by the three modality embeddings. The aligned representations are fused through a cross-modal gating module and optimized jointly for three-class glioma grading and overall survival prediction. We evaluate GLORIA on a matched TCGA-GBM/LGG and BraTS21 cohort, comprising 132 patients with all three modalities. On the shared trimodal test set, GLORIA improves over the bimodal WSI-mRNA baseline in all the metrics considered.

Accurate prediction of overall survival (OS) from positron emission tomography/computed tomography (PET/CT) can support personalized treatment and follow-up strategies in oncology. However, the impact of temporal modeling on imaging-based survival prediction remains insufficiently explored. We investigate how different temporal formulations influence survival prediction by developing two complementary approaches: Attention-guided Time-Conditioned Survival (ATCS) and Multi-Time Survival (MTS). We retrospectively analyzed pre-treatment PET/CT images from 848 patients with non-small cell lung cancer (NSCLC), including 556 for model development and 292 for held-out testing. A previously proposed Time-Conditioned Survival (TCS) model was used as a baseline. Models were trained using 5-fold cross-validation and evaluated on the test set using time-dependent area under the curve (AUC) at 6-month intervals from 0.5 to 5 years. Both ATCS and MTS outperformed the baseline TCS model, achieving mean AUCs of 0.794 and 0.793, respectively, compared to 0.767. ATCS performed better at earlier time points (0.5-3 years), whereas MTS performed better at later intervals (3.5-5 years). Combining tumor-specific and tissue-wise PET/CT features improved performance over either input alone. Finer temporal discretization improved short-term prediction, while coarser intervals provided more stable long-term estimates. These findings demonstrate that temporal modeling and input design influence PET/CT-based survival prediction. The proposed approaches enable time-specific survival estimation from pre-treatment imaging and may support improved risk stratification and clinical decision-making.

Circulating-tumour DNA (ctDNA) carries evidence of drug resistance months before imaging shows it, but the earliest evidence lives below the assay's limit of detection (LoD): a nascent subclone is detected only intermittently, producing a flickering sequence of faint detects and non-detects. Commercial liquid biopsies treat each draw as an independent snapshot and a non-detect as nothing. We argue a non-detect is a left-censored observation, and the pattern of non-detects and faint detects over time carries actionable evidence of growth before any single value is trustworthy. We introduce Span, a censored-Poisson Bayesian latent-growth change-point detector that models the binary detection process, accumulates a sequential generalised-likelihood-ratio statistic for an upward change-point in the per-variant detection rate, and raises a competing-risks alarm with calibrated false-alarm control. Span has no learned weights, so there is nothing to overfit. On a synthetic cohort of HR+/HER2- metastatic breast cancer on first-line CDK4/6-inhibitor plus endocrine therapy, at a matched 10% false-alarm rate, Span roughly doubles the fraction of impending progressions caught three months ahead (indolent regime: 25% vs 11% for the snapshot), with a falsifiable dose-response: large for indolent emergence, vanishing for fast emergence. A value-trajectory baseline performs identically to the snapshot, isolating the gain to the censored detection model. The survival backbone matches a Cox baseline on real breast-cancer data (GBSG-2, n=686; C-index 0.67 vs 0.68), and on a real longitudinal cohort with clean biomarkers (PBC2, n=312) the same pipeline correctly declines to win, a falsifiable boundary test confirming the mechanism is regime-specific. All ctDNA trajectories are synthetic.

Resistance to first-line osimertinib in EGFR-mutant non-small-cell lung cancer (NSCLC) is the canonical example of predictable clonal evolution under therapeutic pressure, yet no public benchmark exists for training or evaluating computational models on the corresponding longitudinal patient trajectories. We introduce OncoTraj, a public benchmark of 813 EGFR-mutant NSCLC patients receiving first-line osimertinib, harmonized from three real-world clinical-genomic sources: MSK-CHORD (672 patients), AACR Project GENIE BPC NSCLC (34 patients), and the FLAURA molecular-resistance supplement (107 patients). OncoTraj defines three locked tasks: (A) binary classification of progression by a fixed 12-month landmark, (B) regression of time-to-first-progression in days, and (C) six-class classification of the dominant resistance mechanism. We release the harmonized dataset, patient-level train/validation/test splits with an audited no-leakage guarantee, an open-source evaluation harness, and six reference baselines spanning a majority-class predictor, logistic regression, random forest, XGBoost, an LSTM, and a multi-task transformer. With v1's single-timepoint snapshot features, no task clears chance on clean within-source evaluation: the uniformity of this ceiling across every model class localizes the limit to the input modality (single-snapshot tissue NGS rather than serial ctDNA), not the algorithm. The benchmark does recover a reproducible literature-consistent association: TP53 co-mutation raises the 12-month progression rate from 29% to 59% cohort-wide. OncoTraj establishes a reproducible, leakage-audited baseline and converts the modality limit into concrete design requirements for a serial-ctDNA-enriched v2.

Clinicians diagnose brain tumors by synthesizing patient symptoms, medical history, and quantitative imaging data from modalities such as MRI and CT scans into a unified clinical judgement. However, most deep learning models rely on MRI/CT images alone, failing to replicate the clinicians multimodal reasoning. We explore a two-branch multimodal network combining raw MRI scans with 91 extracted radiomic features (intensity, texture, shape, and boundary descriptors) to classify brain tumors into glioma, meningioma, pituitary, and no-tumor. A pre-trained CNN backbone encodes the image stream, whereas a dedicated MLP encodes the radiomic stream. Both streams are fused via concatenation, gated, or bidirectional cross-modal attention strategies. Across nine experimental runs on a balanced 7,200 image dataset, all multimodal configurations outperform unimodal baselines with gated fusion achieving the best accuracy of 96.13%.

Background and purpose: oART enables daily plan adaptation to interfraction anatomical variations, but cumulative dose estimation remains limited by DIR, segmentation, and anatomical uncertainties. We introduce IMPACT-DoseAcc, an uncertainty-aware dose accumulation framework, within IMPACT for semantic feature-driven image analysis. The framework is modality- and disease-agnostic and is applied to CBCT-guided oART for cervical cancer (LACC). Material and Methods: Nine LACC patients were retrospectively analyzed using daily CBCT-derived virtual CTs for dose recalculation. IMPACT-DoseAcc focuses on uncertainty from DIR, without modeling vCT-generation uncertainty. Two DIR uncertainty strategies were tested within IMPACT-Reg: a Bayesian segmentation-guided approach using one probabilistic model to quantify anatomical uncertainty, and an ensemble of segmentation models targeting structures to capture epistemic variability. Voxel-wise uncertainty maps were propagated through dose warping and accumulation to generate probabilistic dose-volume histograms. Ensemble uncertainty was quantified from voxel-wise standard deviation across deformation fields, and geometric error was assessed using surface distance between warped and validated contours. Anatomical-variability weighting refined aggregation. Results: Ensemble DIR uncertainty correlated with geometric error, with Pearson coefficients of 0.63 for CTVt and 0.66 for bladder. For CTVt, pDVHs achieved 96.3 +/- 3.9% coverage, showing calibration of propagated uncertainty. Weighting stabilized estimates across fractions and organs. Conclusions: IMPACT-DoseAcc propagates registration-driven uncertainty to cumulative dose metrics, improving interpretation of accumulated dose under anatomical variations. Its 3DSlicer integration supports reproducible, uncertainty-informed ART workflows.

Routine laboratory panels drawn during cancer treatment constitute longitudinal physiological recordings of organ function, yet their temporal structure is discarded by single-timepoint prognostic tools. A transformer trained on 2,777,595 laboratory measurements from 3,905 patients with multiple myeloma or ovarian cancer predicted the two-year onset of 162 treatment-associated complications, including therapy-related myelodysplastic syndromes, spanning eight clinical categories, achieving 1.5- to 6.1-fold enrichment above prevalence at the group level. It matched or outperformed non-sequential baselines across grouped endpoints (AUROC gains up to +0.11), demonstrating that longitudinal laboratory trajectories capture evolving complication-specific physiology inaccessible from isolated measurements. Predictions generalised across both cancers, divergence concentrating in disease-specific complications, and biomarker masking recovered signatures consistent with established pathophysiology. External validation on MIMIC-IV and MMRF CoMMpass confirmed transferability across independent healthcare systems (AUROC up to 0.85). Routine oncological laboratory data encode organ deterioration weeks to months before clinical onset, enabling complication-specific surveillance without additional testing infrastructure.

Three-dimensional models are widely assumed preferable for volumetric medical imaging, yet their practical value depends on whether performance gains justify added computational cost and complexity. Rather than proposing a new architecture, we study how input dimensionality (2D, 2.5D, 3D) affects model behavior across convolutional neural networks (CNNs) and Vision Transformers (ViTs) under a fixed training protocol. Using a leakage-free NLST cohort (n = 1,977) with supporting LIDC-IDRI data, we find that the 2.5D CNN offers the most favorable discrimination-stability trade-off in our comparison (ROC-AUC 0.682, 95% CI [0.546, 0.799]) with a stable operating point. In contrast, 3D CNNs show threshold instability, and transformers exhibit degenerate predictions, such as all-positive predictions. Confidence intervals are wide and overlapping, so we present these results as a controlled resource-performance frontier and a failure-mode taxonomy rather than as definitive superiority claims. For class-imbalanced lung cancer screening classification, 2D and 2.5D inputs provide a more reliable trade-off between performance, stability, and computational efficiency than full 3D representations.

Modern medicine relies on heterogeneous data sources spanning radiology, pathology, text reports, and structured clinical information. However, real-world patient data are frequently incomplete, with missing or sparsely acquired modalities, limiting the effectiveness of standard multimodal fusion approaches. To this end, we propose the Multimodal Flexible Redundancy-aware decomposed GAted Learning (Multi-FRuGaL) framework, a decomposition-aware, adaptive gated intermediate-fusion framework that performs modality-level representation learning under missing data. Multi-FRuGaL integrates per-modality encoders with a signal decomposition layer, an input-conditioned gating network, and an information-aware fusion objective to separate redundant from modality-specific complementary signals, selectively upweighting informative modalities and suppressing redundant or noisy inputs, and remaining well-defined even when multiple modalities are absent. We evaluate Multi-FRuGaL on two multimodal head and neck cancer cohorts: the HANCOCK challenge dataset (N = 763) comprising five modalities and two prognostic endpoints (5-year survival and 2-year recurrence), and the HECKTOR challenge dataset (N = 588) comprising three modalities for human papillomavirus (HPV) status classification. Multi-FRuGaL consistently achieves higher mean performance than the evaluated baselines across multiple tasks, improving AUC from 0.601 to 0.8496 for survival, from 0.672 to 0.8102 for recurrence, and achieving 0.975 AUC for HPV prediction on HECKTOR. For survival analysis, it further achieves a concordance index of 0.6814 for overall survival, 0.7421 for recurrence-free survival, and 0.7143 for progression-free survival on HANCOCK, and 0.7203 for recurrence-free survival on HECKTOR. Qualitative analyses further show that Multi-FRuGaL learns discriminative and robust multimodal representations, even under severe missing-modality conditions.

Breast cancer remains one of the leading causes of cancer-related mortality among women worldwide, making early detection essential for effective treatment. Mammography is the primary screening modality; however, accurate delineation of suspicious lesions remains challenging and subject to inter-observer variability. Automated segmentation methods can assist radiologists by providing consistent and efficient lesion localization. This study presents DSU-Net, an attention-enhanced Dense Skip U-Net architecture for automated breast lesion segmentation in mammographic images. The proposed framework integrates dense skip connections and attention mechanisms to improve feature propagation, preserve spatial information, and enhance lesion boundary delineation. Experiments were conducted using the Curated Breast Imaging Subset of the Digital Database for Screening Mammography (CBIS-DDSM). To address severe foreground-background imbalance, a composite loss function combining Dice loss, focal loss, and binary cross-entropy loss was employed during training. The proposed model achieved a Dice Similarity Coefficient of 0.9421, an Intersection over Union of 0.8905, an accuracy of 0.9711, and an AUC-ROC of 0.9878 on the validation dataset. Qualitative evaluation demonstrated accurate delineation of lesions with varying sizes and morphologies, while quantitative results confirmed robust discrimination between lesion and background regions. These findings demonstrate that DSU-Net provides accurate and reliable breast lesion segmentation in mammographic images and highlights the potential of attention-guided deep learning for computer-aided breast cancer screening and diagnosis.

Breast cancer remains a leading cause of cancer-related mortality among women. Its clinical management requires multimodal reasoning across a clinical workflow that spans \textit{screening}, \textit{diagnosis} and \textit{treatment planning}, where each stage involves distinct imaging modalities, task objectives, and reasoning patterns. However, constrained by data scarcity and model versatility, existing medical MLLMs are typically evaluated on isolated modalities or narrow task families, limiting their ability to support workflow-level clinical reasoning. In this work, we first introduce \textbf{BreastStage}, a workflow-aligned breast imaging instruction corpus comprising 1.86M instruction-following pairs curated from 17 sub-datasets across 5 imaging modalities and 136 task templates. Its held-out split, \textbf{BreastStage-Bench}, provides a comprehensive benchmark for evaluating multimodal reasoning across the breast cancer care continuum. Building on this corpus, we propose \textbf{BreastGPT}, a unified MLLM equipped with a dual-branch visual encoder and concept-preserving token compression to bridge the scale gap between standard radiology and gigapixel pathology. On BreastStage-Bench, BreastGPT achieves 75.66% closed-ended accuracy and 89.92% open-ended score, outperforming both general-purpose and medical-specific MLLMs across clinical stages and task formats. These results suggest that workflow-aligned data and cross-scale visual modeling are critical for clinically grounded medical MLLMs. All data, code, and model checkpoints are released at https://yangyy-liu.github.io/BreastGPT.io.

Gastric cancer remains a major cause of cancer mortality, yet its histological and molecular heterogeneity complicates diagnosis and risk stratification. General-purpose pathology foundation models (PFMs) often plateau on fine-grained endpoints central to gastric cancer care, and few have undergone rigorous prospective validation or clinical reader studies. We present GRACE, a Gastric-specific foundation model for Real-world Assessment and Clinical dEcision support. GRACE was developed from multicenter gastric pathology datasets totaling 48,364 primarily HE-stained whole-slide images from 37,493 patients. When evaluated on 28 clinically relevant tasks, GRACE consistently outperformed representative pancancer PFMs, achieving a macro-AUC of 0.9188, with strong performance for precancerous lesion diagnosis (macro-AUC 0.9322), tumor histopathological assessment (macro-AUC 0.9119), molecular profiling (macro-AUC 0.8682), and prognostic prediction. Beyond benchmarking, GRACE's translational value was substantiated through a rigorous evidence chain. Under safety-gated criteria requiring 100% NPV for rule-out and 100% PPV for rule-in, GRACE streamlined review for up to 69.6% of malignancy-diagnosis cases and triaged 46.8% of MMR-IHC follow-up requests. This translational feasibility was further strengthened by a randomized crossover reader study of pathologist-AI collaboration. With GRACE assistance, diagnostic accuracy improved from 82.0% to 89.9%, yielding nearly twofold higher adjusted odds of a correct diagnosis (OR 1.987) alongside concurrent gains in sensitivity and specificity. AI assistance also reduced diagnostic time by 14.9%, elevated diagnostic confidence by 9.0%, and markedly improved inter-rater agreement. When calibrated to maintain non-inferior performance to senior pathologists, the AI-assisted workflow could triage 60.7% of atrophy and 82.7% of intestinal metaplasia cases.

Radiomics enables extraction of quantitative imaging biomarkers from medical images and has become an important tool for computer-aided cancer diagnosis. However, radiomics datasets are typically high-dimensional with limited samples, making feature selection a critical step for building reliable predictive models. This study proposes a Gradient-Loss Recursive Feature Elimination (GL-RFE) framework that integrates gradient sensitivity analysis from a deep neural network to identify the most influential radiomic features for lung cancer stage detection. A total of 106 radiomic features were extracted from chest Computed Tomography (CT) scans using the PyRadiomics extension of the 3D Slicer platform. The proposed method evaluates feature importance by computing gradients of the network loss with respect to input features and recursively eliminates features with minimal contribution. The resulting top-15 radiomic features are used to train a deep neural network classifier for distinguishing early-stage and advanced-stage lung cancer. The proposed framework achieves strong classification performance, with accuracy of 90.22%, precision of 90.10%, recall of 90.24%, and F1-score of 90.16% on the test dataset. Visualization analyses, including correlation heat maps and distribution plots, further confirm reduced feature redundancy and improved class separability. Compared to conventional feature selection techniques, GL-RFE effectively captures nonlinear feature interactions and enhances model generalization. The presented protocol provides a reproducible and interpretable methodology for radiomics-based cancer stage detection and is particularly suitable for high-dimensional, small-sample biomedical datasets, with potential applications in other domains such as genomics and multimodal clinical analysis.

Breast cancer recurrence, a leading cause of long-term mortality among survivors, requires timely and accurate risk assessment to guide follow-up care and treatment planning. Traditional predictive models, often limited to either structured or unstructured data alone, struggle to capture the full clinical context. This study examines the impact of integrating multi-modal clinical data, including treatment records, pathology reports, and clinician notes, on recurrence prediction. By integrating a rule-based regular expression extraction mechanism with a rigorous precedence-based conflict reconciliation strategy, our approach effectively recovers definitive tumor characteristics from free-text pathology narratives to augment structured records. We also benchmark performance against commonly used feature sets from prior breast cancer studies to assess the added value of multi-modal integration. Single-source and multi-modal inputs are evaluated across a range of machine learning models. Results show that multi-modal integration consistently improves predictive accuracy compared to single-modal methods.

Modeling patient trajectories from longitudinal electronic health records (EHRs) requires reasoning over sparse, noisy, and long-context multimodal sequences. Existing LLM-based multi-agent systems address context length but process patients in isolation, failing to mirror how clinicians leverage accumulated experience from similar prior cases. We present Traj-Evolve, a self-evolving multi-agent system with two complementary evolving mechanisms. First, an Experience Pool (ExPool) acts as a non-parametric memory, indexing rejection-sampled reasoning traces to retrieve similar patients as few-shot contexts. Second, multi-agent reinforcement learning (MARL) via reward-ranked fine-tuning parametrically optimizes inter-agent and agent-memory collaboration. A leave-one-out cross-retrieval strategy unifies the two, aligning training- and inference-time behavior under retrieval augmentation. On a lung cancer prediction task utilizing up to five years of multimodal EHRs, Traj-Evolve outperforms 9 strong baselines on the overall population and a challenging never-smoker population. Analysis of the evolving dynamics highlights three key findings: (1) expanding the ExPool shifts optimal retrieval from diverse to specific samples; (2) under MARL, the manager agent's prediction loss converges quickly while the worker agents' temporal reasoning continues to benefit from more verified patients; and (3) the two mechanisms are complementary on the predicted risk, where ExPool improves specificity while MARL improves sensitivity.

Anastomotic leak remains one of the most serious complications following colorectal cancer surgery, substantially affecting patient outcomes, recovery trajectories, and healthcare costs. Despite advances in imaging technology, current preoperative assessment relies only on clinical assessment, a process that is subjective, error-prone, and highly dependent on individual expertise. To date, no validated CT-based method exists to predict anastomotic leak risk prior to surgery. This protocol paper outlines a comprehensive framework for developing and validating an AI-driven system for preoperative risk assessment using pre- and post-contrast CT imaging. The study describes the stages of data collection, ethical handling, and preprocessing of patient data in accordance with GDPR, image preprocessing, and the exploration of deep learning architectures designed to generate clinically interpretable outputs. Two integrated tools constitute the main deliverables of this workflow: 1) a risk assessment module, which quantifies the likelihood of leakage by analyzing vascular and tissue features in CT scans, and 2) a Content-Based Medical Image Retrieval (CBMIR) module, which identifies and displays similar historical cases to support evidence-based surgical decision making. The protocol paper requires close collaboration between hospitals and universities; this protocol demonstrates that such a system is technically feasible and clinically implementable within existing healthcare infrastructures. By following the proposed methodological stages and regulatory principles, other institutions can reproduce this workflow to develop analogous decision-support tools. Ultimately, this interdisciplinary framework aims to enhance surgical planning, reduce leak incidence, and contribute to a broader paradigm shift toward explainable, data-driven precision surgery.

Intraoperative ultrasound (ioUS) is a versatile, cost-effective modality in brain tumour surgery, but its interpretation is difficult: acquisition planes are non-standard, artefacts are modality-specific, and its appearance differs markedly from the preoperative MRI on which surgical-planning tools, segmentation models and the surgeon's experience rely. Synthesising MRI-like images from ioUS could let this MRI-based infrastructure be reused intraoperatively without an extra scan. Most prior work evaluates a single architecture in isolation; to our knowledge, no benchmark has spanned architectural paradigms, inference regimes and downstream-task endpoints under a common protocol. We address this gap on the public ReMIND data set (76 patients; 153 paired ioUS/T2w and 104 paired ioUS/FLAIR studies; 60/16 patient-level train/held-out split). Six generators (four GAN baselines: Pix2Pix, SwinPix2Pix, CycleGAN, CUT; the transformer-augmented ResViT; and the few-step diffusion model SynDiff) were each trained under four inference regimes (2D, 2.5D, 2D + 3D-refinement, full-3D) and two targets (T2w only; T2w + FLAIR multi-task), yielding 48 experiments. Image-fidelity metrics (SSIM, PSNR, MAE, LPIPS) were complemented by an nnU-Net v2 downstream segmentation evaluation (tumour and resection cavity) and by subgroup analyses by histological grade and reoperation. No architecture dominated every axis, and, critically, perceptual quality tracked downstream utility most closely (LPIPS, r=-0.66, p<0.001), whereas higher SSIM was associated with worse utility (r=-0.64, p<0.001); SynDiff-2.5D best preserved downstream segmentation (U_Dice=0.55). Perceptual and downstream-task metrics should therefore be reported alongside or in preference to global SSIM, and architecture choice conditioned on surgical phase, patient history and clinical objective.

Breast cancer is a major global health concern, and mammography screening plays a central role in early detection. The large volume of screening examinations creates a substantial workload for radiologists, making accurate and consistent report generation a critical clinical challenge. Existing automated mammography report generation methods primarily focus on direct visual-to-text mapping, while overlooking the structured clinical reasoning process followed by radiologists in real-world practice. To address this limitation, we propose MammoRG, a mammography report generation framework that explicitly simulates the clinical reporting workflow by following the BI-RADS guideline and incorporating prior clinical knowledge to produce diagnostic reports. Specifically, MammoRG adopts a two-stage training framework. In the first stage, the model learns to integrate clinically relevant prior knowledge from a patient's four-view mammograms through classification-based supervision. In the second stage, a terminology-aware supervised fine-tuning strategy is introduced to model mammography-specific clinical terms as atomic semantic units, enabling the generation of high-quality reports with improved clinical consistency. To facilitate clinical efficacy evaluation of generated reports, we further develop MammoRGTool, a dedicated mammography report parsing tool that extracts structured clinical information from free-text reports. Extensive experiments demonstrate that MammoRG consistently outperforms existing methods across multiple clinical efficacy metrics, particularly in diagnosis-related BI-RADS F1, where it surpasses the second-best model by 2.73%, 2.04%, 1.90%, and 3.27% on the internal, external 1, external 2, and VinDr-Mammo datasets, respectively.

Brain cancer's severity necessitates precise brain tumor segmentation, which is crucial for effective brain tumor diagnosis. Manual identification, burdened by high costs, labor, and error risks, highlights the need for automated methods. In this study, we introduce the Global Context-aware Squeeze and Excite Residual UNet (GCSER-UNet), which facilitates a fusion of spatial and channel-wise attention and thus enhances the model's capacity to capture intricate spatial dependencies and contextual information. GCSER-UNet efficiently extracts tumor segments from multimodal MRI slices, delivering exceptional performance. Evaluations on benchmark databases exhibit its superiority, achieving a notable 94 percent dice score on the TCGA LGG dataset, surpassing the state-of-the-art dice score of 91.8 percent. In the BraTS 2020 dataset, the proposed GCSER-UNet ensemble approach yielded dice scores of 95 percent, 92 percent, and 90 percent for the tumor regions - Whole Tumor (W), Tumor Core (T), and Enhancing Tumor (E), respectively. The current state-of-the-art dice scores were 94 percent, 93 percent, and 88 percent. These compelling outcomes highlight the efficacy of GCSER-UNet in precise brain tumor segmentation and thus can aid neurologists in effective brain cancer management and treatment planning.

Earlier detection of pancreatic cancer is key to enabling wider access to curative treatment and reducing cancer deaths; however, screening is presently not viable. Latent indicators of pathology are evident in an individual's disease and blood test trajectories and may predict the development of pancreatic cancer. Longitudinal sequences of coded diagnoses and blood test values accrued by patients throughout their clinical interactions were used to train a custom Transformer-based neural network with a multi-head attention mechanism to predict risk of pancreatic cancer with a multi-year lead time and risk-stratify populations for targeted screening. The cohort comprised 6,017 adults with pancreatic cancer and 177,081 controls (overall median age 75, 45% female) with median 12 years (interquartile range 6.9-16.2) of medical history prior to pancreatic cancer diagnosis. External validation via leave-one-site-out, out-of-sample testing predicting pancreatic cancer 1-, 2-, and 3-years prior to diagnosis demonstrated mean area under the receiver operating characteristic of 0.837 (95% confidence interval 0.827-0.848), 0.797 (95% confidence interval 0.782-0.813), and 0.760 (95% confidence interval 0.745-0.776), respectively. Estimated pancreatic cancer risks were well-calibrated (calibration plot slope 1.08, intercept of -0.077; Brier score 0.025), and a Bayesian population pancreatic cancer prevalence update allows estimated cancer risk outputs to be transportable across settings. At testing, a screening threshold of >3.3% risk of pancreatic cancer in 1-year offered a diagnostic odds ratio of 18.2. Our work therefore lays the foundation for a first population-level digital enrichment tool to widen access to curative-intent management of pancreatic cancer.

Thyroid cancer is said to be the second most common type of cancer in female individuals and the third in males by 2030, according to projections. In general, detecting cancer in its early stages improves the chance of survival of the individual. Thermography is a diagnostic tool that has been increasingly used to detect cancer and abnormalities, including that of thyroid. Various methods to segment and detect hot regions in thermograms and, consequently, to detect suspicious tissues present in these images have been proposed. It is well known that medical diagnosis yields a great deal of information. Thus, physicians have to comprehensively analyse and evaluate this information in a short period of time, which is infeasible in most cases. In this work, we perform a general review of thermography , focusing on the thyroid analysis. We propose protocols for image acquisiton and an autonomous registration for thyroid images. We also perform analyses of the image data, which include feature extraction, image processing, and a possible approach for classification of healthy or unhealthy patients. In summary, this work presents a pilot project for detection of tumors in our university hospital, which is part of an effort to support preventive medical actions in our endocrinology department. Under some future adjustments, this project will be submitted for approval by the ethics and research committee of Hospital Universitário Antonio Pedro at Universidade Federal Fluminense (HUAP-UFF) and to the Brazilian Ministry of Health Ethical committee under the name: Evaluation of the importance of thermography to aid diagnosis of thyroid nodules of patients in HUAP-UFF (in Portuguese: Avaliação da importância da termografia no auxílio à investigação diagnóstica de nódulos tireoidianos em pacientes acompanhados no HUAP-UFF).

AI agents are increasingly useful for biological data analysis, but existing benchmarks mostly test broad biological knowledge, executable workflows, or localized analysis steps rather than end-to-end scientific reasoning over spatial measurements. We introduce SpatialBench-Long, a benchmark for long-horizon spatial biology in which agents must recover biological claims from raw or near-raw data and calibrated experimental context without prescribed methods. SpatialBench-Long contains 24 evaluations across primary pancreatic ductal adenocarcinoma (PDAC), engineered glioblastoma organoids and in vivo tumors, Cas9 lineage-traced lung adenocarcinoma, and mouse optic nerve aging/intervention systems, spanning CosMx, Visium, Xenium, multiplexed error-robust fluorescence in situ hybridization (MERFISH), single-cell RNA sequencing (scRNA-seq), Slide-seq, Slide-tags, histology, and lineage-recording data. Candidate claims are hardened through reproduction, independent scientist review, and trajectory inspection. Final answers are graded deterministically over controlled vocabularies and symbols with companion rubrics capturing progress through key analysis chokepoints. Across the SpatialBench-Long benchmark, three model-harness pairs tie at 8/72 runs (11.1%): Gemini 3.5 Flash / Pi terminal coding harness, GPT-5.5 / Pi, and GPT-5.5 / OpenAI Codex. SpatialBench-Long tests whether agents can move beyond executing procedural analysis to deriving accurate scientific conclusions from complex spatial measurements.

Urgent suspected colorectal cancer (CRC) referrals create operational bottlenecks because semi-structured clinical documents often require manual review and transcription. The original RAPTOR system used Large Language Models for structured extraction but relied on a separate OCR stage, making it vulnerable to handwriting, layout variation, and loss of visual evidence linkage. We present RAPTOR+, a multimodal extension that uses Vision-Language Models (VLMs) for end-to-end referral understanding. We evaluate fine-tuned VLMs, commercial and open-source zero-shot VLMs, and the original OCR-based pipeline on 223 clinically curated CRC urgent referral forms. We also introduce a grounding-aware evaluation framework that measures both extraction accuracy and evidence localisation. Results show a clear grounding gap in zero-shot models. Gemini 2.5 Flash achieved 92.6% Reading Accuracy but only 1.2% Strict Safety. In contrast, fine-tuned Qwen3-VL-8B achieved 96.1% Reading Accuracy and 60.6% Strict Safety, substantially improving verifiable evidence grounding. These findings show that task-specific fine-tuning is essential for reliable, auditable clinical document understanding. RAPTOR+ enables extracted referral decisions to be linked to visual evidence, supporting safer and more efficient cancer referral triage.

Pathological assessment guides lung cancer diagnosis, treatment selection, and prognostic evaluation, yet current CPath approaches rely on task-specific models for isolated objectives. Although pan-cancer foundation models offer versatility, they lack subspecialty-level depth and have not been evaluated across clinical workflows or prospectively validated in real-world settings. We introduce PulmoFoundation, a multi-center, prospectively validated, randomized controlled trial (RCT)-evaluated foundation model for comprehensive lung pathology assessment across pre-operative, intra-operative, and post-operative care. Built upon Virchow2 via subspecialty-specific pretraining using ~40,000 diagnostic H&E-stained whole-slide images (WSIs), PulmoFoundation was systematically evaluated on ~26,000 WSIs across 32 clinically relevant tasks. In addition to accurately predicting molecular markers and patient survival, our model achieves clinical-grade performance in core diagnostic tasks across biopsy, frozen section, and surgical resection slides. In a registered prospective study of 1,357 patients across 11 diagnostic tasks, our model achieved an average AUC of 92.3%. Using pre-specified triage thresholds, PulmoFoundation could reduce additional second-review burden for 68.8% of biopsies and 83.0% of frozen sections, and defer 44.5% of IHC stain orders, with PPVs of 1.0, 0.991, and 0.966. Beyond prospective validation, we conducted a crossover RCT with eight pathologists, in which AI assistance improved diagnostic accuracy across 4,928 case-reader pairs (91.7% w/ AI vs. 83.8% w/o AI). AI assistance also reduced median diagnostic time by 19.6%, increased diagnostic confidence by 8.7%, and improved inter-rater agreement from moderate (kappa = 0.56) to substantial (kappa = 0.76). Together, these evaluations support PulmoFoundation as a clinically validated decision-support system for lung pathology.

Breast ultrasound imaging is an important noninvasive method for early breast cancer diagnosis, but automatic benign/malignant classification remains challenging due to tumor heterogeneity, blurred boundaries, and data imbalance. To improve feature representation and classification accuracy, this paper proposes the Cross-Stage Attention Mixture-of-Experts Network (CSA-MoE-Net). It adopts a Cross-Stage Attention-enhanced ResNet-18 as the backbone, in which the Cross-Stage Attention module adaptively recalibrates multi-level features, thereby enhancing key tumor features and suppressing redundancy. A three-branch Mixture of Experts (MoE) Block learns complementary features from the Whole Tumor Image, Tumor Core, and Boundary, and an Adaptive Gating Network fuses them to capture morphological, textural, and contextual information. The fused features are denoted as Fused Expert Feature (FEF) in the architecture. Experiments on a balanced dataset of 2,129 breast ultrasound images show that, averaged over 20 independent runs, the model achieves an accuracy of 96.33%, precision of 94.09%, recall of 98.53%, F1-score of 96.25%, and AUC of 99.50%. Compared to the baseline ResNet-18, these metrics improve by 3.01, 0.70, 5.37, 2.98, and 5.42 percentage points, respectively. The proposed mechanism requires no invasive modification and can be seamlessly embedded into VGG-16, DenseNet-121, etc., yielding stable performance gains, thus providing reliable support for computer-aided diagnosis.

Integrating multimodal datasets in clinical oncology is frequently hindered by high dimensionality and blockwise missingness, where entire data sources are unavailable for specific patient subsets. Standard survival models often struggle with these gaps, leading to biased results or patient exclusion. We introduce Multimodality Stacking with Blockwise missing values (MSB), a late-fusion framework for survival analysis that independently models modality-specific features before aggregating predictions via a cross-validated stacking meta-learner. MSB was validated on the PIONeeR study (n=443 patients, 378 biomarkers across eight heterogeneous sources) to predict progression-free survival in advanced non-small cell lung cancer patients receiving immunotherapy. MSB yielded higher predictive performance (C-index) than baseline algorithms. Improvements varied by baseline strength: linear models showed a 15.9% increase (p<0.001 for the Wilcoxon signed-rank test), random survival forests gained 5.4% (p=0.002), and gradient boosting methods improved by 2.1% (p=0.030). Beyond discrimination, MSB reduced the generalization gap (train-test difference in 5 folds cross-validation repeated 3 times: 0.055 vs 0.380 for linear models). Permutation importance analysis identified routine laboratory markers, clinical features, and PD-L1 expression as primary predictive drivers. Missing block indicators showed negligible importance, suggesting the model learned from biomarker values rather than data availability patterns. MSB provides a statistically validated framework for multimodal survival prediction with blockwise missingness. By enabling systematic biomarker evaluation without requiring complete data, MSB offers a practical tool for predictive modeling in biomedical research, pending external validation. Implementation is available at https://github.com/MohamedBoussena/MSB under Inria license.

Medical image computing software is essential for identifying imaging biomarkers that can support diagnosis, prognosis, treatment planning, and clinical research. However, the lack of standardized, user-friendly, and reproducible software environments has limited the broader adoption of advanced medical image analysis workflows. We present Radiuma, a freely available modular platform designed to support reliable and reproducible medical image analysis across multiple modalities and file formats. Radiuma integrates image reading, visualization, registration, fusion, processing, segmentation, radiomics feature extraction, and machine learning modules for classification, regression, and clustering. Its modular design allows users to execute each component independently or connect modules through a visual workflow system, where the output of one step can be graphically passed to the next. This enables the creation of custom, executable, and reproducible multi-step pipelines without requiring extensive programming expertise. Results from each module can be inspected directly in the visualization window, providing immediate feedback on processing quality and workflow accuracy. Radiuma also supports saving and sharing customized workflows, promoting transparency, reusability, and consistency across collaborative studies. By combining flexibility, usability, and standardized analysis tools, Radiuma provides a practical environment for radiomics and machine learning research in clinical and translational settings. The platform is designed to be accessible to users with diverse expertise, including radiologists, physicists, clinicians, and data scientists.

Generative augmentation is often proposed as a remedy for small medical-image datasets, but synthetic images are only useful when they improve downstream task performance. "Augmentation" here means synthetic supplementation: GAN-generated samples added to the real training pool, not geometric or photometric transforms of existing images. Twelve class-plane StyleGAN2-ADA generators were trained on constrained BRISC 2025 partitions to test whether their output, with or without InceptionV3 feature-space filtering, improves held-out tumour classification across three classifier families: a random forest (RF) on InceptionV3 features, a compact two-headed convolutional neural network (CNN), and MobileViTV2, a mobile hybrid convolutional-transformer. Each was evaluated at 1:1 and 1:2 real-to-synthetic ratios. An independent GPT-5.5 blind test placed gated real-versus-synthetic discrimination at 57.73% (95% CI: 54.48--60.92%) on the model-legible subset -- modestly above chance. The RF classifier did not benefit from the synthetic MRIs. The CNN showed consistent mean gains that did not survive Holm correction. MobileViTV2 showed the clearest benefit: filtered 1:1 augmentation improved tumour classification accuracy by 1.02% absolute (95% CI: 0.54--1.54%; Holm-corrected p = 0.0104). A secondary efficiency analysis found that every augmented CNN condition selected its checkpoint 42--64% earlier than baseline, while compute-matched MobileViTV2 runs reached selection after 50--67% fewer real-data epochs. Overall, augmentation utility was found to be architecture- and ratio-dependent, not guaranteed by visual fidelity alone.

Decision trees assign identical confidence to instances near and far from each split threshold. We introduce ternary decision trees, which augment each split node with an uncertainty zone of half-width delta. A decision-theoretic framework characterises the optimal zone width delta* as the solution to a node-local cost-minimisation problem; four formal properties are established: accuracy decomposition, a sufficiency condition for decided accuracy improvement, an exact efficiency characterisation (eta = Dec-Acc minus Acc_u, the accuracy gap between decided and boundary-uncertain predictions), and asymptotic consistency of the margin method. Instances within the zone receive predictions by weighted blending of both child subtrees and are flagged as boundary-uncertain. We propose and evaluate five delta-estimation methods: quality-plateau (plateau width of the split criterion curve), class-overlap (empirical class-distribution overlap), gain-ratio (split quality relative to split entropy), node-bootstrap (threshold variance under node-level resampling), and margin (SVM-inspired distance to the nearest cross-class training example). All methods reuse statistics already computed during standard CART split finding, requiring no external noise specification. Evaluated across 71 of the 72 OpenML-CC18 datasets with 5-fold cross-validation, all five methods with probabilistic routing significantly outperform standard CART on decided accuracy (Wilcoxon signed-rank, p < 0.001). The margin method achieves the best efficiency (0.104 accuracy gain per unit flagging rate), wins on 42 of 72 datasets, and requires zero hyperparameters. Analysis on Breiman synthetic benchmarks confirms margin is self-calibrating on clean data. On mammography, node-bootstrap achieves +0.71% decided accuracy by flagging 10.8% of cases as boundary-uncertain.

Accurate classification of breast ultrasound images into benign, malignant, and normal categories is a critical clinical task complicated by speckle noise, acoustic shadowing, and inter-class visual ambiguity. Existing deep learning methods rely on single-stream architectures with generic augmentation that ignores ultrasound acquisition physics, and no prior method dedicates a stream to the lesion boundary features identified as the most diagnostically significant visual cue. We propose HADS-Net, a Hybrid Attention-Augmented Dual-Stream Network exploiting global texture and local boundary cues through two parallel pathways. Stream 1 applies physics-informed augmentation simulating speckle noise, acoustic shadowing, and gain variation before extracting features via pretrained EfficientNet-B3 projected to 512 dimensions. Stream 2 extracts Sobel edge maps processed by a lightweight CNN projected to the same 512-dimensional space. A cross-attention fusion module allows the texture stream to selectively query boundary features, producing a jointly optimised representation classified by an MLP trained with adaptive class-weighted focal loss. Five-fold stratified cross-validation with cosine annealing over 50 epochs is used, with the globally best checkpoint selected by lowest validation loss evaluated on a held-out test set. On the BUSI dataset, HADS-Net achieves 96.58% accuracy, macro ROC-AUC of 0.9978, macro F1 of 0.9654, and per-class F1-scores of 0.970, 0.951, and 0.976 for benign, malignant, and normal. No malignant lesion is misclassified as normal. These results confirm that modality-specific augmentation with cross-modal attention fusion is an effective strategy for ultrasound-based breast cancer diagnosis.

Deep learning methods have demonstrated promising results in predicting BI-RADS scores from mammography images. However, the interpretation of these images can vary, leading to discrepancies even among radiologists. Given the inherent complexity of mammograms, training classification models solely on image labels often yields limited performance. To address this challenge, we curated 2313 mammogram images and their corresponding captions from two mammography atlases. Our proposed approach employs a multi-modal model that uses a pretrained PubMedBERT as the language component. By training this model on image-text pairs with contrastive learning, we enable the vision encoder to absorb the rich information contained in the captions, thereby improving its understanding of mammography findings. We then fine-tune the vision encoder on two datasets for BI-RADS prediction, achieving superior performance compared with models trained without this pretraining, particularly when labeled samples are scarce. The improvement in the 3-class average F1 score ranges from +1% to +14%: a +1% increase with 40K training samples, and a +14% increase with 1K samples. Furthermore, our experiments reveal that 2K image-text pairs from mammography atlases can be more informative than 2K labeled samples for label prediction, with an average margin of +1.1% when more than 10K training samples are available. Overall, our work provides a vision-language model for mammography and highlights the value of textual information from mammography atlases. In addition, we publicly release preprocessed mammography images of the TEKNOFEST dataset. The training code, pre-trained model weights, data extraction scripts, and the released dataset are publicly available at: https://github.com/igulluk/MAM-CLIP

In histopathology, human experts primarily rely on color as a means of enhancing contrast to interpret tissue morphology, whereas machine vision models process color as raw statistical information. This distinction raises a fundamental question: to what extent can pixel intensity alone, independent of structural and morphological cues, support cancer classification? To address this question, we systematically evaluated the standalone discriminative power of global color features while deliberately excluding all morphological information. Specifically, we extracted statistical color moments and discretized RGB and HSV color histograms, and assessed their performance across ten diverse experimental settings using classical machine learning classifiers. Our results demonstrate that color features alone can achieve strong performance in binary diagnostic tasks (e.g., benign versus malignant), with classification accuracies reaching up to 89%. This performance is likely attributable to global chromatic shifts associated with malignancy. Importantly, these simple color-based representations consistently outperformed random baselines by a substantial margin, indicating that raw color distributions encode a non-random and diagnostically relevant signal for cancer detection. Consequently, this study suggests that simple, computationally efficient color features can serve as an effective pre-screening tool. By identifying samples with strong chromatic indicators of malignancy, these lightweight models could function as a first-pass triage system, reducing the computational burden on complex deep learning architectures.

Manual Pap smear analysis for cervical cancer screening is limited by inter-observer variability, time constraints, and restricted expert availability. Although convolutional neural networks (CNNs) have automated cervical cell classification, they remain limited in modeling long-range spatial dependencies and often lack clinical interpretability. In this study, Vision Transformer (ViT) architectures were systematically optimized to enhance automated cervical cancer screening, which resulted in improved interpretability. The Herlev dataset (917 images: 242 normal, 675 abnormal) was utilized to optimize ViT-Tiny, a lightweight Vision Transformer architecture designed for reduced computational complexity, through a comprehensive evaluation of augmentation strategies, class weighting, and hyperparameters. The optimal configuration achieved 94.9%-95.2% cross-validation accuracy, in which random horizontal flipping and class weighting (0.7 x 1.3) were identified as most effective. Gradient-weighted Class Activation Mapping (Grad-CAM) analysis confirmed that model attention corresponded to clinically relevant morphological features, which include nuclear regions, cell boundaries, and chromatin texture, which align with cytopathological criteria. These findings indicate that Vision Transformers can deliver accurate and interpretable decision support for cervical cancer screening, which fulfills both clinical performance and transparency requirements essential for medical AI deployment.

Brain tumors exhibit high heterogeneity in morphology and multimodal contrast, making manual slice-by-slice de lineation time-consuming and experience-dependent, thus necessitating efficient and stable automated segmentation methods. To address the limitations of CNNs in modeling long-range dependencies, and the heavy computational and memory overhead and inter-block contextual in coherence of Transformers in 3D MRI, this paper proposes Multi-Head Mamba (MHMamba). This method combines a U-shaped architecture with a multi-head state-space model (Mamba), splitting the channel dimension into parallel SSM heads and aggregating them with residuals. This enhances long-range representation and improves the stability of multimodal training while maintaining linear complexity. To further align statistics and enhance lesion response, we designed a channel-space calibration module for multi-head outputs and introduced an adaptive fusion mechanism at skip connections to dynamically connect global semantics with local details, thereby improving boundary consistency and the detection of small-volume lesions. We conducted experiments and ablations on BraTS2021 and BraTS2023. The results showed that MHMamba achieved stable and significant improvements in overall accuracy, boundary smoothness, and sensitivity to tumor core and small-volume enhancement areas, while preserving the linear-complexity advantage of Mamba-based modeling, thus verifying the effectiveness and versatility of the method.

Accurate intraoperative and postoperative diagnosis of spread through air spaces (STAS) is essential for guiding surgical decisions and postoperative management in lung cancer. However, histopathological assessment is labor-intensive and is prone to missed or incorrect diagnoses. We propose a Diffusion Attention Expert Model (DAEM) to detect STAS in frozen sections (FSs) and paraffin sections (PSs). Its diffusion attention expert module leverages full attention aggregation to learn multi-scale features from histopathological images, while a dual-branch architecture strengthens multi-scale feature representation. On an internal dataset, DAEM achieves AUCs of 0.8946 for FSs and 0.9112 for PSs. Validation on external multi-center datasets from eight institutions demonstrates strong generalizability and interpretability. Using tumor microenvironment (TME) features in PSs, we further enable semi-automatic measurement of STAS location and its distance from the primary tumor. Several quantitative TME metrics are identified as potential biomarkers for STAS, including micropapillary-type STAS. Overall, DAEM offers a clinically actionable framework for STAS assessment by enabling accurate and interpretable detection on FSs and PSs, supporting postoperative risk stratification through quantitative TME-based analysis.

Gastrointestinal cancers cause approximately 3.4 million deaths annually, and early small-bowel lesions are easily missed at wireless capsule endoscopy (WCE). RGB-trained WCE classifiers conflate hemoglobin contrast with bile staining and illumination falloff, limiting sensitivity to small-vessel vascular findings such as Lymphangiectasia. We introduce a physics-informed framework that injects an analytic, Monte-Carlo-inspired hemoglobin prior into a standard classifier purely at training time -- to our knowledge the first use of an explicit optical light-transport prior in WCE classification. On Kvasir-Capsule (47,238 frames, 43 patients, 11 evaluable classes; patient-disjoint split) we evaluate, across six seeds against an RGB-only EfficientNet-B0 baseline, a five-channel input-fusion variant feeding the prior alongside RGB, a distillation variant that runs on plain three-channel RGB at inference, and a three-stream extension adding a temporal Transformer and an autoencoder-residual stream; we replicate across ResNet-18 and ConvNeXt-Tiny and assess cross-vendor zero-shot transfer on the public Galar cohort. Input fusion lifts cross-seed macro-AUC from 0.760 to 0.783 (5/6 seeds positive); distillation reaches 0.773; the three-stream model reaches 0.804 (+0.044 over baseline, paired DeLong p < 0.0001). Lymphangiectasia AUC rises from 0.238 to 0.337, sign-consistent across all six seeds. A four-variant ablation reveals a parameterization-mechanism boundary: only the spatial-channel form lifts. Cross-vendor zero-shot on Galar retains about 60% of the lift. The distillation variant deploys on plain RGB with a free interpretability heatmap, and we release GalKva-2026, a paired cross-vendor benchmark.

Ovarian cancer is the most lethal gynecologic malignancy: around 60% of patients are diagnosed at an advanced stage, with an associated 5-year survival rate of about 30%. Early identification of non-responders to neoadjuvant chemotherapy remains a key unmet need, as it could prevent ineffective therapy and avoid delays in optimal surgical management. This work proposes a non-invasive deep learning framework to predict neoadjuvant chemotherapy response from pre-treatment contrast-enhanced CT by leveraging automatically derived 3D lesion masks. The approach encodes axial slices with a partially fine-tuned pretrained image encoder and aggregates slice-level representations into a volumetric embedding through an attention-based module. Training combines classification loss with supervised contrastive regularization and hard-negative mining to improve separation between ambiguous responders and non-responders. The method was developed on a retrospective single-center cohort from the European Institute of Oncology (Milan, IT), including 280 eligible patients (147 responder, 133 non-responder). On the test cohort, the model achieved a ROC-AUC of 0.73 (95% CI: 0.58-0.86) and an F1-score of 0.70 (95% CI: 0.56-0.82). Overall, these results suggest that the proposed architecture learns clinically relevant predictive patterns and provides a robust foundation for an imaging-based stratification tool.

A main barrier for the deployment of AI radiomic systems in clinical routine is their drop in performance under heterogeneous multicentre acquisition protocols. This work presents a performance-oriented framework for quantifying scan parameter sensitivity of radiomic AI models, while identifying clinically significant parameter regions associated with improved cross-dataset robustness. We formulate a mixed-effects framework for quantifying the influence that clinically relevant acquisition parameters have on models performance, while accounting for subject-level random effects. We have applied our framework to lung cancer diagnosis in CT scans using two independent multicentre datasets (a public database and own-collected data) and several SoA architectures. To evaluate across-database reproducibility, CT parameters have been adjusted using the data collected and tested on the public set. The optimal configuration selected is the current of the X-ray tube >= 200 mA, spiral pitch <= 1.5, slice thickness <= 1.25 mm, which balances diagnostic quality with low radiation dose. These configuration push metrics from 0.79+-0.04 sensitivity, 0.47+-0.10 specificity in low quality scans to 0.90+-0.10 sensitivity, 0.79 +- 0.13 specificity in high quality ones.

Automated CT triage requires models that are simultaneously accurate across diverse pathologies and reliable under institutional shift. While Vision Transformers provide strong visual representations, many clinically significant findings are defined by quantitative imaging biomarkers rather than appearance alone. We introduce JANUS, a physiology-guided dual-stream architecture that conditions visual embeddings on macro-radiomic priors via Anatomically Guided Gating. On the MERLIN test set (N=5082), JANUS attains macro-AUROC 0.88 and AUPRC 0.74, outperforming all reproduced baselines. It generalizes to an external dataset N=2000; AUROC 0.87), with the largest gains on findings defined by size and attenuation as well as improved calibration on both datasets. We further quantify prediction suppression using the Physiological Veto Rate (PVR), showing that under domain shift JANUS reduces high-confidence false positives substantially more often than true positives. Together, these results are consistent with physically grounded conditioning that improves both discrimination and reliability in CT triage. Code is made publicly available at github repository https://github.com/lavsendahal/janus and model weights are at https://huggingface.co/lavsendahal/janus.

This work studies lung tumor growth prediction from sparse and irregular longitudinal computed tomography (CT) observations with measurement variability. A Bayesian physics-informed neural network is developed by combining Gompertz growth dynamics with low-dimensional Bayesian inference in the log-volume domain. The framework employs a two-stage inference strategy combining maximum a posteriori (MAP) estimation and Hamiltonian Monte Carlo (HMC) sampling to estimate posterior predictive distributions and uncertainty intervals. The method was evaluated on longitudinal data from the National Lung Screening Trial (30 patients). Results show that the model captures heterogeneous tumor growth patterns while maintaining reasonable prediction accuracy under limited observations. Compared with deterministic modeling approaches, the proposed approach additionally provides calibrated uncertainty estimates. The inferred posterior parameter correlations were consistent with expected biological growth behavior. The proposed framework achieved a cohort-level log-space RMSE of approximately 0.20 together with well-calibrated 95% credible interval coverage across 30 patients. These findings suggest that Bayesian physics-informed modeling may be useful for uncertainty-aware tumor growth assessment when only limited longitudinal follow-up scans are available.

Cancer is one of the leading causes of death worldwide, making the development of rapid, minimally invasive, label-free and scalable diagnostic strategies a major challenge in modern oncology. In this context, spectroscopic liquid biopsy has emerged as a promising alternative, as it enables the holistic characterization of biochemical alterations in biological fluids. In this work, we propose a multimodal spectroscopic liquid biopsy framework for multicancer detection based on the combination of Fourier Transform Infrared (FTIR) spectroscopy, Raman spectroscopy, and Excitation-Emission Matrix (EEM) fluorescence spectroscopy together with Machine Learning (ML) methodologies. Serum samples from breast cancer patients, colorectal cancer patients, and healthy controls were analyzed through the three spectroscopic modalities. After modality-specific preprocessing, low-level data fusion (LLDF) was employed to integrate the complementary biochemical information encoded within the different spectroscopic measurements, and classification was performed using XGBoost models. Seven experimental configurations were evaluated, including the three unimodal approaches, all pairwise bimodal configurations, and the full multimodal approach of FTIR, Raman, and EEM fluorescence. The results show that although several individual modalities achieved high discrimination performance, the multimodal fusion provided the most balanced overall results, reaching a ROC-AUC of 0.997 for breast cancer and 0.994 for colorectal cancer, together with highly balanced sensitivity and specificity values.

Clinical trial studies indicate benefit of watch-and-wait (WW) surveillance for patients with rectal cancer showing a complete or near clinical response (CR) directly after treatment (restaging). However, there are no objectively accurate methods to early detect local tumor regrowth (LR) in patients undergoing WW from follow-up exams. Hence, we developed Temporal Rectal Endoscopy Cross-attention (TREX), a longitudinal deep learning approach that combines pairs of images acquired at restaging and follow-up to distinguish CR from LR. TREX uses pretrained Swin Transformers in a siamese setting to extract features from longitudinal images and dual cross-attention to combine the features without spatial co-registration between image pairs. TREX and Swin-based baselines were trained under two settings: (a) detecting LR or CR at the last available follow-up and (b) early detection of LR at 3--6, 6--12, and 12--24 months before clinical confirmation. TREX achieved the highest accuracy in detecting LR with a high sensitivity of 97% $\pm$ 6% and a balanced accuracy of 90% $\pm$ 3%, and outperformed all baselines in early detection at both 3--6 (74% $\pm$ 1%) and 6--12 months (62% $\pm$ 4%) prior to clinical detection. Clinical validation via a surgeon survey showed that TREX matched attending-level overall accuracy (TREX: 86.21% vs.\ Clinicians: 87.84% $\pm$ 1.28%). Finally, we explored TREX's ability to predict treatment response by combining pre-treatment (pre-TNT) and restaging endoscopies, achieving a balanced accuracy of 73% $\pm$ 12%. These results show that longitudinal deep learning analysis of endoscopy may improve surveillance and enable earlier identification of rectal cancer regrowth.

Medical image segmentation models can perform unevenly across subgroups. Most existing fairness methods focus on improving average subgroup performance, implicitly treating each subgroup as internally homogeneous. However, this can hide difficult cases within a subgroup, where high-loss samples are obscured by the subgroup mean. We call this problem \textbf{intra-group hidden failure}. To solve this, we propose \textbf{DuetFair} mechanism, a dual-axis fairness framework that jointly considers inter-subgroup adaptation and intra-subgroup robustness. Based on DuetFair, we introduce \textbf{FairDRO}, which combines distribution-aware mixture-of-experts (dMoE) with subgroup-conditioned distributionally robust optimization (DRO) loss aggregation. This design allows the model to adapt across subgroups while also reducing hidden failures within each subgroup. We evaluate FairDRO on three medical image segmentation benchmarks with varying degrees of within-group heterogeneity. FairDRO achieves the best equity-scaled performance on Harvard-FairSeg and improves worst-case subgroup performance on HAM10000 under both age- and race-based grouping schemes. On the 3D radiotherapy target cohort, FairDRO further improves worst-group Dice by 3.5 points ($\uparrow 6.0\%$) under the tumor-stage grouping and by 4.1 points ($\uparrow 7.4\%$) under the institution grouping over the strongest baseline.

Background: Radiogenomics allows identification of radiological biomarkers for genomic phenotypes. In glioblastoma, these biomarkers could potentially complement patient stratification strategies. We aim to develop and analytically validate radiological biomarkers that capture immune cell signatures within IDH-wildtype glioblastoma microenvironment using radiogenomic analysis. Methods: This was a retrospective multicenter study using curated open-access anonymized imaging and genomic data from TCGA-GBM, CPTAC, IvyGAP, REMBRANDT and CGGA datasets. Imaging data consisted of MRI-based radiomic features extracted from necrotic core, enhancing and edema regions of deep learning-based auto-segmented tumors. Radiomic feature selections were performed using nested cross-validated LASSO. Support vector machine and ensemble models were trained using seventeen immune and cell-specific score labels extracted from deconvoluted transcriptomic data using pan-cancer and glioblastoma immune signature matrices as reference standards. Seventeen classifier models trained in three cross-cohort strategies were validated on three held-out datasets assessing stability and generalizability. Results: One-hundred-and-seventy-six patients were included in the study. The immune-related radiomic signatures obtained after feature selection were shape, first order and higher order radiomic features. Models predicting macrophage subtype immune signature showed stable mean performance on balanced accuracy (0.67) and precision (0.89) metrics for three independent holdout datasets with ensemble model outperforming support vector machine model. Conclusion: Radiogenomic models non-invasively predicted the macrophage subtype M0 immune signature in IDH-wildtype glioblastoma. These biomarkers have the potential to stratify patients for immunotherapy within prospective glioblastoma clinical trials.

Breast density is a key factor that influences mammography interpretation and is a major source of heterogeneity in multicenter datasets. Such heterogeneity poses challenges for collaborative machine learning across institutions, particularly in Federated Learning. This study aims to evaluate the impact of breast density-induced heterogeneity on FL for mammography image classification and to assess the robustness of common FL algorithms in realistic clinical settings. We conducted experiments under two scenarios: (1) a strongly heterogeneous setting where each participating site contributed exclusively low- or high-density cases, based on the BI-RADS density score, and (2) a population-based setting simulating breast density distributions in White and Asian populations. For the strongly heterogeneous setting, we evaluated two configurations: one with 2 clients, where the cases were grouped as BI-RADS A-B and C-D, and one with 4 clients, where each site contained cases of a single BI-RADS density. We compared three FL methods (FedAvg, FedProx, SCAFFOLD) against centralized training, local-only training, and naive aggregation approaches, including ensembling and weight averaging. Across both scenarios, FL achieved performance comparable to centralized training, while local models and naive aggregation approaches underperformed in the presence of strong heterogeneity. Notably, FedAvg achieved accuracy on par with or exceeding centralized training, demonstrating resilience to breast density-induced data imbalance without requiring specialized heterogeneity mitigation algorithms. These findings show that FL can address breast density-related heterogeneity, supporting its feasibility for real-world mammography workflows. The demonstrated robustness of FedAvg underscores the potential for broad clinical deployment of FL, enabling collaborative model development while maintaining data privacy.

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.

Pathological complete response (pCR) is a key prognostic factor in breast cancer patients undergoing neoadjuvant therapy, strongly associated with long-term survival and treatment personalization. However, accurate pre-treatment pCR prediction remains challenging due to severe class imbalance and limited generalizability across diverse clinical settings. In this work, we propose a multimodal stepwise clinically-guided attention learning framework for pCR prediction from breast magnetic resonance imaging (MRI), designed to address these limitations through medically grounded spatial guidance and multimodal integration. The approach follows a stepwise training strategy inspired by physician reasoning: the model first learns global discriminative imaging patterns, then attention mechanisms are introduced to constrain the network toward tumor regions, and finally clinical variables are integrated to refine decision-making. This guidance strategy encourages prioritization of task-relevant features, improving identification of responders despite their limited representation in the dataset. Moreover, grounding attention in anatomically consistent tumor regions reduces reliance on dataset-specific patterns, thereby enhancing cross-institutional generalization. The framework is evaluated through external validation across heterogeneous MRI cohorts. Compared to non-guided single-stage baselines, the proposed approach improves sensitivity while maintaining competitive specificity, and produces anatomically coherent attention maps that support interpretation of the model's predictions. These findings highlight the potential of clinically-guided multimodal attention learning for robust and generalizable pCR prediction in breast cancer.

Precise molecular subtyping of gliomas, including isocitrate dehydrogenase (IDH) mutation and 1p/19q codeletion, directly guides surgical and therapeutic decisions, yet currently relies on invasive tissue sampling. Deep learning on structural MRI has emerged as a non-invasive alternative, but anatomy-only approaches cannot capture the hemodynamic signatures that distinguish molecular subtypes. Radiogenomics based on dynamic susceptibility contrast (DSC) MRI holds immense potential for non-invasively characterizing glioma molecular subtypes, yet clinical deployment has been hindered by inter-site variability and the limitations of voxel-wise analysis. We introduce HiPerfGNN, a framework that first learns discrete hemodynamic representations from raw time-intensity curves using a vector-quantized variational autoencoder (VQ-VAE). These quantized perfusion codes define coarse-level graph nodes representing functional tumor habitats, each of which is hierarchically subdivided into fine-level subregions guided by structural MRI. A hierarchical graph neural network then propagates information across scales for molecular prediction. On an internal cohort (n=475), the model achieved AUCs of 0.96 (IDH), 0.89 (1p/19q), and 0.84 (WHO grade), and maintained robust IDH performance (AUC 0.89) on an independent external cohort (n=397) without recalibration. Gradient-based saliency analysis confirms biologically grounded attention patterns aligned with known glioma pathophysiology. Our results demonstrate the added value of integrating perfusion dynamics into radiogenomic pipelines for glioma molecular subtyping. Code is available at https://github.com/janghana/HiPerfGNN.

Accurate classification of breast cancer subtypes from gene expression data is critical for diagnosis and treatment selection. However, such datasets are characterized by high dimensionality and limited sample size, posing challenges for machine learning models. In this study, we evaluate the impact of model complexity and feature selection on subtype classification performance using TCGA-BRCA gene expression data. Logistic regression, random forest, and support vector machine (SVM) models were trained using varying numbers of highly variable genes (50 to 20,518). Performance was evaluated using stratified 5-fold cross-validation and assessed with accuracy and macro F1 score. While all models achieved high accuracy, macro F1 analysis revealed substantial differences in subtype-level performance. Logistic regression demonstrated the most stable and balanced performance across subtypes, including improved detection of rare classes. Random forest underperformed on minority subtypes despite strong overall accuracy, while SVM showed sensitivity to feature dimensionality. These findings highlight the importance of model simplicity, evaluation metrics, and feature selection in high-dimensional biological classification tasks.

Rheumatoid arthritis (RA) assessment from hand radiographs requires multi-level analysis and modeling of anatomical structures and fine-grained local pathological changes. However, existing public resources do not support such unified multi-level analysis, often lacking full-hand coverage, fine-grained annotations, and consistent integration with clinical scoring systems. In particular, annotations that enable quantitative analysis of bone erosion (BE) remain scarce. RAM-H1200 contains 1,200 hand radiographs collected from six medical centers, with multi-level annotations including (i) whole-hand bone structure instance segmentation, (ii) pixel-level BE masks, (iii) SvdH-defined joint regions of interest, and (iv) joint-level SvdH scores for both BE and joint space narrowing (JSN). It is designed to evaluate whether models can jointly capture anatomical structure, localized erosive pathology, and clinically standardized RA severity from hand radiographs. The proposed BE masks enable, for the first time, quantitative BE analysis beyond coarse categorical grading by providing explicit spatial supervision for lesion extent and morphology. To our knowledge, RAM-H1200 is the first public large-scale benchmark that jointly supports whole-hand bone structure instance segmentation, pixel-level BE delineation, and clinically grounded joint-level SvdH scoring for both BE and JSN. Results across benchmark tasks show that anatomical modeling is substantially more mature than quantitative BE analysis: whole-hand bone segmentation achieves strong performance, whereas BE segmentation remains a major open challenge. By unifying anatomical structure modeling, quantitative lesion analysis, and clinically grounded SvdH scoring, RAM-H1200 provides a single benchmark for comprehensive RA analysis on hand radiographs.

We externally validated three deep learning models (DenseNet121, ViT-B/32, and ResNet50) for predicting mammographic breast density from breast ultrasound exams on an independent cohort. The external validation set comprised 2,000 ultrasound exams, including 500 cancer cases defined by an initial negative exam (BI-RADS 1 or 2) followed by a cancer diagnosis within 6 months to 10 years, and 1,500 negative controls matched by manufacturer and study year. Performance was measured using patient-level AUROC across four density categories: A (fatty), B (scattered), C (heterogeneous), and D (extremely dense). As a downstream assessment, we also evaluated 10-year risk prediction by incorporating age and AI-derived density into the Tyrer-Cuzick model and comparing performance against a reference model using age and mammography-reported density. All three models performed best in extremely dense breasts (AUROC 0.868-0.899), with strong performance in fatty (0.814-0.838) and scattered density (0.764-0.799), and lower performance in heterogeneously dense breasts (0.699-0.729). DenseNet121 achieved the highest overall performance (micro-averaged AUROC 0.885), and performance across categories was comparable between internal and external testing. For risk modeling, age combined with AI-derived density yielded a lower AUROC than age combined with mammography-reported density (0.541 vs. 0.570; p = 0.23), with no statistically significant difference. These findings indicate that deep learning models generalize well to external data with different racial composition for breast density assessment. While performance is strongest in extremely dense breasts, heterogeneously dense remains more challenging, highlighting the need for targeted optimization.

Pathology foundation models have shown strong retrospective performance, but whether such systems can support clinically relevant use remains unclear. This challenge is particularly important in breast cancer, where pathological assessment serves as the gold standard for diagnosis and guides treatment planning, surgical decision-making and risk stratification across pre-, intra- and post-operative stages. Here we present \textbf{BRAVE}, a breast-adaptive pathology foundation model developed and evaluated using a total resource of 101,638 breast whole-slide images from 32 sources across Asia, Europe and North America. We assessed BRAVE across 34 tasks in 82 cohorts spanning pre-operative biopsy, intra-operative frozen section and post-operative resection, using an evidence chain comprising retrospective benchmarking, clinically challenging scenarios, workflow-oriented clinical impact simulations, prospective observational validation with the thresholds locked in the retrospective cohorts and crossover pathologist-AI interaction studies. Across these settings, BRAVE supported practical roles in the clinical workflow, including safe exclusion of low-risk cases from routine review, AI-assisted second-review rescue of initially missed positives and prioritization of cases for further assessment. In prospective validation across three centres, BRAVE excluded 76.9% of negative biopsy cases (NPV 0.953) and 70.1% of negative frozen-section cases (NPV 0.973), and triaged 78.8% of post-operative subtyping cases as high-confidence clear-cut cases (NPV 1.000). In reader studies, AI assistance improved balanced accuracy from 88.5% to 95.1% (OR 3.14, P<0.001), with better efficiency, confidence and inter-rater agreement. BRAVE-derived scores also independently predicted disease-free survival (adjusted HR 4.79, P<0.001) and overall survival (adjusted HR 8.14, P<0.001).

Accurate histological differentiation between adenocarcinoma (ADC) and squamous cell carcinoma (SCC) is critical for personalized treatment in non-small cell lung cancer (NSCLC). While [$^{18}$F]FDG PET/CT is a standard tool for the clinical evaluation of lung cancer, its utility is often limited by high costs and radiation exposure. In this paper, we investigate the feasibility of "virtual scanning" as a feature-enhancement strategy by evaluating whether synthetic PET data can provide complementary feature representations to supplement anatomical CT scans in histological subtype classification. We propose a framework that leverages a 3D Pix2Pix Generative Adversarial Network (GAN), pretrained on the FDG-PET/CT Lesions dataset, to synthesize pseudo-PET volumes from anatomical CT scans. These synthetic volumes are integrated with structural CT data within the MINT framework, a multi-stage intermediate fusion architecture. Our experiments, conducted on a multi-center dataset of 714 subjects, demonstrate that the inclusion of synthetic metabolic features significantly improves classification performance over a CT-only baseline. The multimodal approach achieved a statistically significant increase in the Area Under the Curve (AUC) from 0.489 to 0.591 and improved the Geometric Mean (GMean) from 0.305 to 0.524. These results suggest that synthetic PET scans provide discriminatory metabolic cues that enable deep learning models to exploit complementary cross-modal information, offering a potential feature-enhancement strategy for clinical scenarios where physical PET scans are unavailable.

Predicting microsatellite instability (MSI) status from routine hematoxylin and eosin (H&E) whole slide images (WSIs) offers a practical alternative to molecular testing, but models trained at one institution tend to generalize poorly to slides acquired at a different site. Foundation model representations, despite their generality, still encode site-specific texture alongside the conserved biological morphology underlying MSI. We investigate whether tile-level spatial priors derived from known MSI histology can guide these representations toward more site-invariant features. We introduce a biologically motivated spatial prior based on peripheral distance encoding, reflecting the Crohn's-like peripheral lymphocytic reaction at the tumor invasive margin, and evaluate a secondary local immune neighborhood encoding reflecting the lymphocyte-to-tumor ratio in each tile's immediate spatial neighborhood. Both priors are injected into a TransMIL aggregator before self-attention, allowing the transformer to integrate spatial biological context with UNI2-h or Virchow2 features across all attention layers. We evaluate six foundation model and MIL aggregator combinations as a reference, then assess the effect of each spatial prior. Training on TCGA-COAD (137 slides) and evaluating externally on TCGA-READ (50 slides) without retraining, peripheral distance encoding achieves MSI AUC 0.959 +/- 0.012 on COAD and MSS specificity 1.000 on READ, compared to 0.957 and 0.939 for the strongest reference configuration. Local immune neighborhood encoding achieves comparable internal AUC but lower cross-site specificity, suggesting margin proximity encodes a more site-invariant biological signal than local immune density. Results suggest biologically grounded spatial priors act as regularizers that reduce reliance on site-specific imaging patterns.

Zero-shot vision-language models (VLMs) offer a promptable alternative to task-specific training for gross tumor volume (GTV) delineation in non-small-cell lung cancer (NSCLC), but the prompt dimensions that govern their spatial behavior remain poorly understood. We study this question by probing alignment directions in VoxTell on a held-out internal NSCLC tumor dataset through sub-prompt decomposition into diagnosis, demographic, staging, anatomical, generic, and irrelevant controls; attribute-wise perturbation robustness; specificity ladders; and cross-case prompt swaps, while benchmarking against fine-tuned and zero-shot baselines using the Dice Similarity Coefficient (DSC) with Wilcoxon signed-rank tests and Benjamini-Hochberg correction. Alignment analyses revealed that anatomical location is the dominant driver of VoxTell's spatial attention: 63.4 percent of location perturbations caused catastrophic drops, prompt specificity improved from generic to full descriptions except for diagnosis-only prompts, irrelevant prompts correctly yielded zero segmentation, and cross-case prompt swaps confirmed patient-specific conditioning (matched DSC 0.906 vs. mismatched 0.406). Histology and stage substitutions had minimal effect, indicating that the model prioritizes "where to look" over "what to look for." In this context, VoxTell, operating fully zero-shot, achieved a mean DSC of 0.613, statistically indistinguishable from nnUNet (0.690, adjusted p = 0.156) and Ahmed et al. (0.675, adjusted p = 0.679), while significantly outperforming all other zero-shot models. Together, these findings argue that segmentation VLMs should be evaluated not only by Dice, but also by the prompt dimensions to which they align.

``How long can I live and remain free of cancer?'' is often the first question a patient asks after receiving a cancer diagnosis and treatment. Accurate survival prediction helps alleviate psychological distress and supports risk stratification and personalized treatment planning. Recent survival prediction frameworks have shown strong performance using computed tomography (CT) images. However, variations in imaging acquisition introduce out-of-distribution (OOD) samples caused by covariate shifts that undermine model reliability. Despite this challenge, to our knowledge, no existing benchmark systematically studies OOD detection in cancer survival prediction. To address this gap, we introduce the Cancer sURvival bEnchmark for OOD Detection (CURE-OOD), the first benchmark for systematically evaluating OOD detection in survival prediction under controlled acquisition-induced distribution shifts. CURE-OOD defines scanner-parameter-based training, in-distribution (ID), and OOD test splits across four survival prediction tasks. Our experiments show that covariate shifts notably reduce survival prediction performance. It also shows that mainstream classification-oriented OOD detectors can fail in survival prediction. Finally, we include HazardDev as a simple survival-aware reference baseline for OOD detection. CURE-OOD enables systematic analysis of how distribution shifts affect both downstream survival performance and OOD detectability.

Peritoneal metastases (PM) are staged using the surgically determined Peritoneal Cancer Index (sPCI), which requires invasive laparoscopic assessment. Although CT is routinely used for preoperative evaluation, imaging-based assessment of PM extent remains challenging and is often less structured than surgical PCI scoring. A recent consensus study defined radiological PCI (rPCI) regions for cross-sectional imaging. We present the first deep learning approach to automatically segment 13 rPCI regions on CT. 62 contrast-enhanced CT scans were retrospectively collected across the full PCI range. Each scan was annotated into non-overlapping rPCI regions by one researcher, reviewed by a second, with disagreements resolved by a radiologist. Using five-fold cross-validation, we compared nnU-Net and Swin UNETR with Dice, 95th-percentile Hausdorff distance (HD95) and Average Surface Distance (ASD). We introduce an anatomically constrained pipeline that trains on merged super-regions and splits them during post-processing using TotalSegmentator landmarks at the hips and the ligament of Treitz. On this 62-scan cohort, the baseline nnU-Net reached an overall Dice of 0.81 and outperformed Swin UNETR (0.76). The proposed pipeline improved the overall Dice to 0.84 and reduced boundary error (HD95 13.7 to 11.8 mm; ASD 4.1 to 3.4 mm), with the largest gains in the small-bowel regions, approaching the interobserver Dice of 0.87. Automated rPCI region segmentation on CT is feasible and approaches interobserver agreement. Encoding anatomical boundary constraints substantially improves segmentation quality in the most challenging regions. This provides a reproducible foundation for non-invasive, imaging-based PCI assessment. The main limitations are the single-center cohort and the small interobserver subset.

Surgical resection remains the only potentially curative treatment for pancreatic ductal adenocarcinoma (PDAC), and eligibility depends on accurate assessment of vascular invasion (VI), i.e., tumor extension into adjacent critical vessels. Despite its importance for preoperative staging and surgical planning, computational VI assessment remains underexplored. Two major challenges are the lack of public datasets and the diagnostic ambiguity at the tumor-vessel interface, which leads to substantial inter-rater variability even among expert radiologists. To address these limitations, we introduce the CURVAS-PDACVI Dataset and Challenge, an open benchmark for uncertainty-aware AI in PDAC staging based on a densely annotated dataset with five independent expert annotations per scan. We also propose a multi-metric evaluation framework that extends beyond spatial overlap to include probabilistic calibration and VI assessment. Evaluation of six state-of-the-art methods shows that strong global volumetric overlap does not necessarily translate into reliable performance at clinically critical tumor-vessel interfaces. In particular, methods optimized for binary segmentation perform competitively on average overlap metrics, but often degrade in high-complexity cases with low expert consensus, either collapsing in volume or overextending at uncertain boundaries. In contrast, methods that model inter-rater disagreement produce better calibrated probabilistic maps and show greater robustness in these ambiguous cases. The benchmark highlights the limitations of volumetric accuracy as a proxy for localized surgical utility, motivating uncertainty-aware probabilistic models for preoperative decision-making.