BenchX: Benchmarking AI Models for Cancer Detection and Localization with Demographic and Protocol Biases

Artificial intelligence (AI) has achieved remarkable success in medical imaging, but it is widely recognized that these models often perform inconsistently across real-world clinical settings. Such inconsistencies occur when patient demographics and imaging protocols vary, for example, in detecting small tumors, analyzing scans from different contrast phases, or evaluating patients of different ages or sexes. To quantify these inconsistencies, we develop a large-scale, open benchmark of 85,355 CT scans that systematically evaluates 12 tumor-detection AI models across tumor size, location, patient subgroup, and imaging protocol. We leverage large language models (LLMs) to extract and organize subgroup information from clinical data, which makes the analysis both scalable and reproducible. Our benchmark reveals that current state-of-the-art AI models, optimized for average accuracy, perform poorly in rare or underrepresented subgroups, such as young, female African Americans. However, collecting sufficient annotated data for these rare cases is often impractical. The benchmark provides a foundation for building more reliable and robust AI models for tumor detection and highlighting the need for rigorous, subgroup-level evaluation in medical imaging and computer vision. Datasets, code

Computational Methods and Challenges in Cell-Free DNA Analysis for Multi-Cancer Early Detection

Cell-free DNA (cfDNA) is a promising avenue for non-invasive multicancer early detection (MCED), in that, it can enable multiple cancer detection simultaneously from a single blood draw, with particular sensitivity to cancers that currently lack established screening programs. Here we review the computational methods developed between 2022 and 2025 for cfDNA-based MCED. We focus on how fragmentomics and epigenetic features are extracted and analyzed to detect cancer at early stages. We first briefly outline the biological basis of cfDNA signals, then review classical statistical and machine learning approaches alongside deep learning frameworks including autoencoder-based models. For each method we discuss biological interpretability, validation strategy, and readiness for clinical integration. Furthermore, we categorize the current challenges into technical, computational, and methodological while outlining open problems in the field. This review shows that multimodal ensemble approaches have the strongest promise for clinical integration and the highest readiness. However, for better assessment of future work and side-by-side comparison, standardization of evaluation protocols and reporting results will be crucial.

Fine-UNETR for PSMA PET/CT Lesion Segmentation: Automated Tumor Quantification and Overall Survival Stratification in Prostate Cancer

Introduction: To develop and evaluate Fine-UNETR, a Vision Transformer-based architecture for automated segmentation of PSMA-avid lesions on whole-body PET/CT, and to assess clinical utility of AI-derived tumor burden biomarkers for overall survival stratification in radioligand therapy. Methods: In this retrospective study, 373 PSMA PET/CT scans (mean age, 71+-8 years) from patients with prostate cancer were analyzed. Fine-UNETR, a modified UNETR with 8x8x8 voxel patch embedding and axial sliding window training, was trained on 299 scans and validated on 74 scans. Overall survival stratification was assessed in an independent cohort of 67 pre-radioligand therapy patients using Kaplan-Meier analysis and log-rank testing. External validation was performed on 192 cases from the AutoPET IV PSMA PET/CT dataset. Results: Fine-UNETR achieved a Dice similarity coefficient (DSC) of 66.63%, sensitivity of 70.27%, precision of 67.77%, and a lesion detection rate of 79.53% (96.05% for lesions with SUVmax >= 5). On the external validation dataset, the model achieved a DSC of 44.11% and a lesion detection rate of 87.18%, indicating that lesion detection performance was preserved despite reduced voxel-level overlap. AI-derived biomarkers showed excellent agreement with ground truth (total tumor volume: r=0.984; total lesion uptake: r=0.989; lesion count: r=0.960). In the clinical cohort, total tumor volume (p=0.0019), SUVmax (p=0.014), and SUVmean (p=0.016) significantly stratified overall survival. Conclusion: Fine-UNETR enables accurate automated whole-body PSMA lesion segmentation and tumor burden quantification. Performance on an external dataset demonstrates robustness despite evidence of domain shift. AI-derived biomarkers significantly stratified overall survival in a pre-radioligand therapy cohort, supporting the clinical utility of automated PSMA PET/CT quantification for prognostication.

Intelligent Skin Cancer Detection Using a Multispectral Metasurface and a Hybrid

Skin cancer is among the most prevalent malignancies worldwiAdbe satnradcitts early detection is essential for improving patient survival and reducing treatment costs Conventional dermoscopic and visual imaging techniques are primarily limited to the visible spectrum and often fail to capture subtle spectral signatures associated with early stage malignancies This study proposes an innovative framework that integrates a multispectral metasurface for imaging with a hybrid deep learning architecture based on Convolutional Neural Networks and Vision Transformers The designed metasurface enables noninvasive acquisition of rich spectral information highly sensitive to tissue alterations while the hybrid CNN ViT model simultaneously extracts local and global features to robustly classify skin lesions Simulation-based evaluations demonstrate that the proposed method achieves approximately 98 accuracy 95 percentages sensitivity and 99 perentage specificity surpassing conventional RGB-based and single-architecture approaches Qualitative analyses using attention maps reveal that the model focuses on clinically relevant lesion regions improving interpretability Overall the results indicate that combining metasurface based multispectral imaging with hybrid deep learning can introduce a new generation of diagnostic tools in dermatology and pave the way for portable fast and highly accurate clinical systems

Two-Stage Fine-Tuning of ResNet50 for High-Sensitivity Melanoma Detection on Dermoscopic Images

Melanoma is the most dangerous form of skin cancer with five-year survival rates exceeding 99% when detected early but falling sharply once the disease spreads. This paper proposes and evaluates a two-stage fine-tuning approach for ResNet50 applied to binary melanoma classification on dermoscopic images. The core challenges addressed are class imbalance and suboptimal transfer learning from single-stage fine-tuning. After stratified train/validation/test splitting, random oversampling was applied exclusively to the training set to achieve a 1:1 class balance. Stage 1 trained only the classification head with the ResNet50 base frozen, while Stage 2 fine-tuned all layers jointly at a low learning rate of 1e-5 to prevent catastrophic forgetting of learned visual features. On an independent test set of 3,826 images, the model achieved an AUC-ROC of 0.9559, accuracy of 88.34%, sensitivity of 87.56%, specificity of 89.13%, and F1-score of 88.29%. An ablation study confirms the two-stage protocol significantly outperforms single-stage fine-tuning, with sensitivity gains of over 4%. Grad-CAM visualizations demonstrate correct lesion localization. A fully deployable Streamlit detection application is provided alongside all training code.

Towards Global AI-Driven Cervical Cancer Screening

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.

Seeing Below the Limit of Detection: A Censored-Poisson Bayesian Latent-Growth Change-Point Detector (the Span Detector) for Serial ctDNA in HR+/HER2- Metastatic Breast Cancer

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.

Radiomic Feature Selection Using Gradient Loss of Deep Neural Network for Lung Cancer Stage Detection

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.

Improving PET/CT-Based Whole-Body Lesion Segmentation Using Prediction Uncertainty-Augmented Models

Accurate lesion segmentation from whole-body Positron Emission Tomography (PET)/Computed Tomography (CT) scans is essential for cancer staging and treatment planning. PET provides functional metabolic information with different radiotracers, while CT offers anatomical localization. Lesion delineation from PET/CT imaging is clinically challenging due to subtle imaging features, confounders, and inter-reader variability. Existing deep learning approaches suffer from training-related stochasticity, inconsistent predictions, missed lesions in high tumor-burden cases, and lack uncertainty quantification, limiting their clinical reliability. Using nnU-Net as a baseline, we propose an uncertainty-aware framework for whole-body PET/CT lesion segmentation that integrates (1) Bayesian ensembling to reduce training stochasticity, (2) voxel-wise uncertainty quantification with epistemic and aleatoric decomposition, and (3) epistemic uncertainty-augmented training to improve lesion detection. Two public datasets, AutoPET-III (1,611 scans) and Deep-PSMA (200 scans), comprising FDG and PSMA studies across multiple cancer types, are used for training and evaluation. Bayesian ensembling improves robustness and performance over deterministic nnU-Net models on the unseen AutoPET-III test set. Uncertainty maps highlight regions of model disagreement and correlate with misclassifications, particularly false positives. Uncertainty-augmented training improves lesion recovery at the cost of increased FPVol, reflecting a precision-recall trade-off. A case-adaptive routing strategy further improves Dice by selecting between the base and augmented models. To our knowledge, this is the first study to systematically investigate uncertainty quantification in multi-tracer, pan-cancer PET/CT segmentation and to combine Bayesian ensembling with uncertainty-aware modeling for this task.

Traj-Evolve: A Self-Evolving Multi-Agent System for Patient Trajectory Modeling in Lung Cancer Early Detection

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.