Daily Papers

Breast cancer survival prediction in computational pathology presents a remarkable challenge due to tumor heterogeneity. For instance, different regions of the same tumor in the pathology image can show distinct morphological and molecular characteristics. This makes it difficult to extract representative features from whole slide images (WSIs) that truly reflect the tumor's aggressive potential and likely survival outcomes. In this paper, we present PathoHR, a novel pipeline for accurate breast cancer survival prediction that enhances any size of pathological images to enable more effective feature learning. Our approach entails (1) the incorporation of a plug-and-play high-resolution Vision Transformer (ViT) to enhance patch-wise WSI representation, enabling more detailed and comprehensive feature extraction, (2) the systematic evaluation of multiple advanced similarity metrics for comparing WSI-extracted features, optimizing the representation learning process to better capture tumor characteristics, (3) the demonstration that smaller image patches enhanced follow the proposed pipeline can achieve equivalent or superior prediction accuracy compared to raw larger patches, while significantly reducing computational overhead. Experimental findings valid that PathoHR provides the potential way of integrating enhanced image resolution with optimized feature learning to advance computational pathology, offering a promising direction for more accurate and efficient breast cancer survival prediction. Code will be available at https://github.com/AIGeeksGroup/PathoHR.

Breast cancer remains a leading cause of cancer-related mortality worldwide, making early detection and accurate treatment response monitoring critical priorities. We present BreastDCEDL, a curated, deep learning-ready dataset comprising pre-treatment 3D Dynamic Contrast-Enhanced MRI (DCE-MRI) scans from 2,070 breast cancer patients drawn from the I-SPY1, I-SPY2, and Duke cohorts, all sourced from The Cancer Imaging Archive. The raw DICOM imaging data were rigorously converted into standardized 3D NIfTI volumes with preserved signal integrity, accompanied by unified tumor annotations and harmonized clinical metadata including pathologic complete response (pCR), hormone receptor (HR), and HER2 status. Although DCE-MRI provides essential diagnostic information and deep learning offers tremendous potential for analyzing such complex data, progress has been limited by lack of accessible, public, multicenter datasets. BreastDCEDL addresses this gap by enabling development of advanced models, including state-of-the-art transformer architectures that require substantial training data. To demonstrate its capacity for robust modeling, we developed the first transformer-based model for breast DCE-MRI, leveraging Vision Transformer (ViT) architecture trained on RGB-fused images from three contrast phases (pre-contrast, early post-contrast, and late post-contrast). Our ViT model achieved state-of-the-art pCR prediction performance in HR+/HER2- patients (AUC 0.94, accuracy 0.93). BreastDCEDL includes predefined benchmark splits, offering a framework for reproducible research and enabling clinically meaningful modeling in breast cancer imaging.

Breast-conserving surgery (BCS) aims to completely remove malignant lesions while maximizing healthy tissue preservation. Intraoperative margin assessment is essential to achieve a balance between thorough cancer resection and tissue conservation. A deep ultraviolet fluorescence scanning microscope (DUV-FSM) enables rapid acquisition of whole surface images (WSIs) for excised tissue, providing contrast between malignant and normal tissues. However, breast cancer classification with DUV WSIs is challenged by high resolutions and complex histopathological features. This study introduces a DUV WSI classification framework using a patch-level vision transformer (ViT) model, capturing local and global features. Grad-CAM++ saliency weighting highlights relevant spatial regions, enhances result interpretability, and improves diagnostic accuracy for benign and malignant tissue classification. A comprehensive 5-fold cross-validation demonstrates the proposed approach significantly outperforms conventional deep learning methods, achieving a classification accuracy of 98.33%.

Breast cancer screening plays a pivotal role in early detection and subsequent effective management of the disease, impacting patient outcomes and survival rates. This study aims to assess breast cancer screening rates nationwide in the United States and investigate the impact of social determinants of health on these screening rates. Data on mammography screening at the census tract level for 2018 and 2020 were collected from the Behavioral Risk Factor Surveillance System. We developed a large dataset of social determinants of health, comprising 13 variables for 72337 census tracts. Spatial analysis employing Getis-Ord Gi statistics was used to identify clusters of high and low breast cancer screening rates. To evaluate the influence of these social determinants, we implemented a random forest model, with the aim of comparing its performance to linear regression and support vector machine models. The models were evaluated using R2 and root mean squared error metrics. Shapley Additive Explanations values were subsequently used to assess the significance of variables and direction of their influence. Geospatial analysis revealed elevated screening rates in the eastern and northern United States, while central and midwestern regions exhibited lower rates. The random forest model demonstrated superior performance, with an R2=64.53 and root mean squared error of 2.06 compared to linear regression and support vector machine models. Shapley Additive Explanations values indicated that the percentage of the Black population, the number of mammography facilities within a 10-mile radius, and the percentage of the population with at least a bachelor's degree were the most influential variables, all positively associated with mammography screening rates.

Breast cancer is a significant health concern affecting millions of women worldwide. Accurate survival risk stratification plays a crucial role in guiding personalised treatment decisions and improving patient outcomes. Here we present BioFusionNet, a deep learning framework that fuses image-derived features with genetic and clinical data to achieve a holistic patient profile and perform survival risk stratification of ER+ breast cancer patients. We employ multiple self-supervised feature extractors, namely DINO and MoCoV3, pretrained on histopathology patches to capture detailed histopathological image features. We then utilise a variational autoencoder (VAE) to fuse these features, and harness the latent space of the VAE to feed into a self-attention network, generating patient-level features. Next, we develop a co-dual-cross-attention mechanism to combine the histopathological features with genetic data, enabling the model to capture the interplay between them. Additionally, clinical data is incorporated using a feed-forward network (FFN), further enhancing predictive performance and achieving comprehensive multimodal feature integration. Furthermore, we introduce a weighted Cox loss function, specifically designed to handle imbalanced survival data, which is a common challenge in the field. The proposed model achieves a mean concordance index (C-index) of 0.77 and a time-dependent area under the curve (AUC) of 0.84, outperforming state-of-the-art methods. It predicts risk (high versus low) with prognostic significance for overall survival (OS) in univariate analysis (HR=2.99, 95% CI: 1.88--4.78, p<0.005), and maintains independent significance in multivariate analysis incorporating standard clinicopathological variables (HR=2.91, 95% CI: 1.80--4.68, p<0.005). The proposed method not only improves model performance but also addresses a critical gap in handling imbalanced data.

Breast cancer is a major cause of cancer death among women, emphasising the importance of early detection for improved treatment outcomes and quality of life. Mammography, the primary diagnostic imaging test, poses challenges due to the high variability and patterns in mammograms. Double reading of mammograms is recommended in many screening programs to improve diagnostic accuracy but increases radiologists' workload. Researchers explore Machine Learning models to support expert decision-making. Stand-alone models have shown comparable or superior performance to radiologists, but some studies note decreased sensitivity with multiple datasets, indicating the need for high generalisation and robustness models. This work devises MammoDG, a novel deep-learning framework for generalisable and reliable analysis of cross-domain multi-center mammography data. MammoDG leverages multi-view mammograms and a novel contrastive mechanism to enhance generalisation capabilities. Extensive validation demonstrates MammoDG's superiority, highlighting the critical importance of domain generalisation for trustworthy mammography analysis in imaging protocol variations.

Breast cancer is a prevalent form of cancer among women, with over 1.5 million women being diagnosed each year. Unfortunately, the survival rates for breast cancer patients in certain third-world countries, like South Africa, are alarmingly low, with only 40% of diagnosed patients surviving beyond five years. The inadequate availability of resources, including qualified pathologists, delayed diagnoses, and ineffective therapy planning, contribute to this low survival rate. To address this pressing issue, medical specialists and researchers have turned to domain-specific AI approaches, specifically deep learning models, to develop end-to-end solutions that can be integrated into computer-aided diagnosis (CAD) systems. By improving the workflow of pathologists, these AI models have the potential to enhance the detection and diagnosis of breast cancer. This research focuses on evaluating the performance of various cutting-edge convolutional neural network (CNN) architectures in comparison to a relatively new model called the Vision Trans-former (ViT). The objective is to determine the superiority of these models in terms of their accuracy and effectiveness. The experimental results reveal that the ViT models outperform the other selected state-of-the-art CNN architectures, achieving an impressive accuracy rate of 95.15%. This study signifies a significant advancement in the field, as it explores the utilization of data augmentation and other relevant preprocessing techniques in conjunction with deep learning models for the detection and diagnosis of breast cancer using datasets of Breast Cancer Histopathological Image Classification.

Breast cancer is one of the most threatening diseases in women's life; thus, the early and accurate diagnosis plays a key role in reducing the risk of death in a patient's life. Mammography stands as the reference technique for breast cancer screening; nevertheless, many countries still lack access to mammograms due to economic, social, and cultural issues. Latest advances in computational tools, infrared cameras and devices for bio-impedance quantification, have given a chance to emerge other reference techniques like thermography, infrared thermography, electrical impedance tomography and biomarkers found in blood tests, therefore being faster, reliable and cheaper than other methods. In the last two decades, the techniques mentioned above have been considered as parallel and extended approaches for breast cancer diagnosis, as well many authors concluded that false positives and false negatives rates are significantly reduced. Moreover, when a screening method works together with a computational technique, it generates a "computer-aided diagnosis" system. The present work aims to review the last breakthroughs about the three techniques mentioned earlier, suggested machine learning techniques to breast cancer diagnosis, thus, describing the benefits of some methods in relation with other ones, such as, logistic regression, decision trees, random forest, deep and convolutional neural networks. With this, we studied several hyperparameters optimization approaches with parzen tree optimizers to improve the performance of baseline models. An exploratory data analysis for each database and a benchmark of convolutional neural networks for the database of thermal images are presented. The benchmark process, reviews image classification techniques with convolutional neural networks, like, Resnet50, NasNetmobile, InceptionResnet and Xception.

Breast Cancer is a major public health problem and the most common diagnosed malignancy in woman. There have been significant developments in clinical approaches and theoretical experimental to understand the interactions of cancer cells dynamics with the immune system, also developments on analytical and computational models to help provide insights into clinical observations for a better understanding of cancer cells, but more are needed, especially at the genetic and molecular levels mathematically. Treatments such as immunotherapy, chemotherapy, hormone therapy, radiotherapy, and gene therapy are the main strategies in the fight against breast cancer. The present study aims at investigating the effects of estrogen derived from recent models, but this time combined with immunotherapy as a way to treat or inhibit the cancer growth by a mathematical model of breast cancer in situ, governed by a simplified model of nonlinear-coupled ordinary differential equations, that combines important interactions between natural cells, tumor cells, immune cells, ketogenic diet in the presence of an anticancer drug. Another contribution was to introduce the inhibition effect epsilon for new results and conclusions, A qualitative study was performed and biological interpretations were included to understand the conditions of stability in a realistic way.

Some recent studies have described deep convolutional neural networks to diagnose breast cancer in mammograms with similar or even superior performance to that of human experts. One of the best techniques does two transfer learnings: the first uses a model trained on natural images to create a "patch classifier" that categorizes small subimages; the second uses the patch classifier to scan the whole mammogram and create the "single-view whole-image classifier". We propose to make a third transfer learning to obtain a "two-view classifier" to use the two mammographic views: bilateral craniocaudal and mediolateral oblique. We use EfficientNet as the basis of our model. We "end-to-end" train the entire system using CBIS-DDSM dataset. To ensure statistical robustness, we test our system twice using: (a) 5-fold cross validation; and (b) the original training/test division of the dataset. Our technique reached an AUC of 0.9344 using 5-fold cross validation (accuracy, sensitivity and specificity are 85.13% at the equal error rate point of ROC). Using the original dataset division, our technique achieved an AUC of 0.8483, as far as we know the highest reported AUC for this problem, although the subtle differences in the testing conditions of each work do not allow for an accurate comparison. The inference code and model are available at https://github.com/dpetrini/two-views-classifier

Breast cancer is a common cancer for women. Early detection of breast cancer can considerably increase the survival rate of women. This paper mainly focuses on transfer learning process to detect breast cancer. Modified VGG (MVGG), residual network, mobile network is proposed and implemented in this paper. DDSM dataset is used in this paper. Experimental results show that our proposed hybrid transfers learning model (Fusion of MVGG16 and ImageNet) provides an accuracy of 88.3% where the number of epoch is 15. On the other hand, only modified VGG 16 architecture (MVGG 16) provides an accuracy 80.8% and MobileNet provides an accuracy of 77.2%. So, it is clearly stated that the proposed hybrid pre-trained network outperforms well compared to single architecture. This architecture can be considered as an effective tool for the radiologists in order to reduce the false negative and false positive rate. Therefore, the efficiency of mammography analysis will be improved.

Mammography, an X-ray-based imaging technique, remains central to the early detection of breast cancer. Recent advances in artificial intelligence have enabled increasingly sophisticated computer-aided diagnostic methods, evolving from patch-based classifiers to whole-image approaches and then to multi-view architectures that jointly analyze complementary projections. Despite this progress, several critical questions remain unanswered. In this study, we systematically investigate these issues by addressing five key research questions: (1) the role of patch classifiers in performance, (2) the transferability of natural-image-trained backbones, (3) the advantages of learn-to-resize over conventional downscaling, (4) the contribution of multi-view integration, and (5) the robustness of findings across varying image quality. Beyond benchmarking, our experiments demonstrate clear performance gains over prior work. For the CBIS-DDSM dataset, we improved single-view AUC from 0.8153 to 0.8343, and multiple-view AUC from 0.8483 to 0.8658. Using a new comparative method, we also observed a 0.0217 AUC increase when extending from single to multiple-view analysis. On the complete VinDr-Mammo dataset, the multiple-view approach further improved results, achieving a 0.0492 AUC increase over single view and reaching 0.8511 AUC overall. These results establish new state-of-the-art benchmarks, providing clear evidence of the advantages of multi-view architectures for mammogram interpretation. Beyond performance, our analysis offers principled insights into model design and transfer learning strategies, contributing to the development of more accurate and reliable breast cancer screening tools. The inference code and trained models are publicly available at https://github.com/dpetrini/multiple-view.

This paper presents a comparison of six machine learning (ML) algorithms: GRU-SVM (Agarap, 2017), Linear Regression, Multilayer Perceptron (MLP), Nearest Neighbor (NN) search, Softmax Regression, and Support Vector Machine (SVM) on the Wisconsin Diagnostic Breast Cancer (WDBC) dataset (Wolberg, Street, & Mangasarian, 1992) by measuring their classification test accuracy and their sensitivity and specificity values. The said dataset consists of features which were computed from digitized images of FNA tests on a breast mass (Wolberg, Street, & Mangasarian, 1992). For the implementation of the ML algorithms, the dataset was partitioned in the following fashion: 70% for training phase, and 30% for the testing phase. The hyper-parameters used for all the classifiers were manually assigned. Results show that all the presented ML algorithms performed well (all exceeded 90% test accuracy) on the classification task. The MLP algorithm stands out among the implemented algorithms with a test accuracy of ~99.04%.

Detecting breast cancer early is of the utmost importance to effectively treat the millions of women afflicted by breast cancer worldwide every year. Although mammography is the primary imaging modality for screening breast cancer, there is an increasing interest in adding magnetic resonance imaging (MRI) to screening programmes, particularly for women at high risk. Recent guidelines by the European Society of Breast Imaging (EUSOBI) recommended breast MRI as a supplemental screening tool for women with dense breast tissue. However, acquiring and reading MRI scans requires significantly more time from expert radiologists. This highlights the need to develop new automated methods to detect cancer accurately using MRI and Artificial Intelligence (AI), which have the potential to support radiologists in breast MRI interpretation and classification and help detect cancer earlier. For this reason, the ODELIA consortium has made this multi-centre dataset publicly available to assist in developing AI tools for the detection of breast cancer on MRI.

This study presents a deep learning system for breast cancer detection in mammography, developed using a modified EfficientNetV2 architecture with enhanced attention mechanisms. The model was trained on mammograms from a major Thai medical center and validated on three distinct datasets: an in-domain test set (9,421 cases), a biopsy-confirmed set (883 cases), and an out-of-domain generalizability set (761 cases) collected from two different hospitals. For cancer detection, the model achieved AUROCs of 0.89, 0.96, and 0.94 on the respective datasets. The system's lesion localization capability, evaluated using metrics including Lesion Localization Fraction (LLF) and Non-Lesion Localization Fraction (NLF), demonstrated robust performance in identifying suspicious regions. Clinical validation through concordance tests showed strong agreement with radiologists: 83.5% classification and 84.0% localization concordance for biopsy-confirmed cases, and 78.1% classification and 79.6% localization concordance for out-of-domain cases. Expert radiologists' acceptance rate also averaged 96.7% for biopsy-confirmed cases, and 89.3% for out-of-domain cases. The system achieved a System Usability Scale score of 74.17 for source hospital, and 69.20 for validation hospitals, indicating good clinical acceptance. These results demonstrate the model's effectiveness in assisting mammogram interpretation, with the potential to enhance breast cancer screening workflows in clinical practice.

The rapid identification and accurate diagnosis of breast cancer, known as the killer of women, have become greatly significant for those patients. Numerous breast cancer histopathological image classification methods have been proposed. But they still suffer from two problems. (1) These methods can only hand high-resolution (HR) images. However, the low-resolution (LR) images are often collected by the digital slide scanner with limited hardware conditions. Compared with HR images, LR images often lose some key features like texture, which deeply affects the accuracy of diagnosis. (2) The existing methods have fixed receptive fields, so they can not extract and fuse multi-scale features well for images with different magnification factors. To fill these gaps, we present a Single Histopathological Image Super-Resolution Classification network (SHISRCNet), which consists of two modules: Super-Resolution (SR) and Classification (CF) modules. SR module reconstructs LR images into SR ones. CF module extracts and fuses the multi-scale features of SR images for classification. In the training stage, we introduce HR images into the CF module to enhance SHISRCNet's performance. Finally, through the joint training of these two modules, super-resolution and classified of LR images are integrated into our model. The experimental results demonstrate that the effects of our method are close to the SOTA methods with taking HR images as inputs.

In breast cancer imaging, there has been a trend to directly predict pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) from histological images based on deep learning (DL). However, it has been a commonly known problem that the constructed DL-based models numerically have better performances in internal validation than in external validation. The primary reason for this situation lies in that the distribution of the external data for validation is different from the distribution of the training data for the construction of the predictive model. In this paper, we aim to alleviate this situation with a more intrinsic approach. We propose an experts' cognition-driven ensemble deep learning (ECDEDL) approach for external validation of predicting pCR to NAC from histological images in breast cancer. The proposed ECDEDL, which takes the cognition of both pathology and artificial intelligence experts into consideration to improve the generalization of the predictive model to the external validation, more intrinsically approximates the working paradigm of a human being which will refer to his various working experiences to make decisions. The proposed ECDEDL approach was validated with 695 WSIs collected from the same center as the primary dataset to develop the predictive model and perform the internal validation, and 340 WSIs collected from other three centers as the external dataset to perform the external validation. In external validation, the proposed ECDEDL approach improves the AUCs of pCR prediction from 61.52(59.80-63.26) to 67.75(66.74-68.80) and the Accuracies of pCR prediction from 56.09(49.39-62.79) to 71.01(69.44-72.58). The proposed ECDEDL was quite effective for external validation, numerically more approximating the internal validation.

Cardiotoxicity induced by the breast cancer treatments (i.e., chemotherapy, targeted therapy and radiation therapy) is a significant problem for breast cancer patients. The cardiotoxicity risk for breast cancer patients receiving different treatments remains unclear. We developed and evaluated risk predictive models for cardiotoxicity in breast cancer patients using EHR data. The AUC scores to predict the CHF, CAD, CM and MI are 0.846, 0.857, 0.858 and 0.804 respectively. After adjusting for baseline differences in cardiovascular health, patients who received chemotherapy or targeted therapy appeared to have higher risk of cardiotoxicity than patients who received radiation therapy. Due to differences in baseline cardiac health across the different breast cancer treatment groups, caution is recommended in interpreting the cardiotoxic effect of these treatments.

Recent advances in AI foundation models have significant potential for lightening the clinical workload by mimicking the comprehensive and multi-faceted approaches used by medical professionals. In the field of radiation oncology, the integration of multiple modalities holds great importance, so the opportunity of foundational model is abundant. Inspired by this, here we present RO-LMM, a multi-purpose, comprehensive large multimodal model (LMM) tailored for the field of radiation oncology. This model effectively manages a series of tasks within the clinical workflow, including clinical context summarization, radiation treatment plan suggestion, and plan-guided target volume segmentation by leveraging the capabilities of LMM. In particular, to perform consecutive clinical tasks without error accumulation, we present a novel Consistency Embedding Fine-Tuning (CEFTune) technique, which boosts LMM's robustness to noisy inputs while preserving the consistency of handling clean inputs. We further extend this concept to LMM-driven segmentation framework, leading to a novel Consistency Embedding Segmentation~(CESEG) techniques. Experimental results including multi-centre validation confirm that our RO-LMM with CEFTune and CESEG results in promising performance for multiple clinical tasks with generalization capabilities.

Interpretability is critical in high-stakes domains such as medical imaging, where understanding model decisions is essential for clinical adoption. In this work, we introduce Sparse Autoencoder (SAE)-based interpretability to breast imaging by analyzing {Mammo-CLIP}, a vision--language foundation model pretrained on large-scale mammogram image--report pairs. We train a patch-level Mammo-SAE on Mammo-CLIP to identify and probe latent features associated with clinically relevant breast concepts such as mass and suspicious calcification. Our findings reveal that top activated class level latent neurons in the SAE latent space often tend to align with ground truth regions, and also uncover several confounding factors influencing the model's decision-making process. Additionally, we analyze which latent neurons the model relies on during downstream finetuning for improving the breast concept prediction. This study highlights the promise of interpretable SAE latent representations in providing deeper insight into the internal workings of foundation models at every layer for breast imaging. The code will be released at https://krishnakanthnakka.github.io/MammoSAE/

This work contributes to breast cancer sub-type classification using histopathological images. We utilize masked autoencoders (MAEs) to learn a self-supervised embedding tailored for computer vision tasks in this domain. This embedding captures informative representations of histopathological data, facilitating feature learning without extensive labeled datasets. During pre-training, we investigate employing a random crop technique to generate a large dataset from WSIs automatically. Additionally, we assess the performance of linear probes for multi-class classification tasks of cancer sub-types using the representations learnt by the MAE. Our approach aims to achieve strong performance on downstream tasks by leveraging the complementary strengths of ViTs and autoencoders. We evaluate our model's performance on the BRACS dataset and compare it with existing benchmarks.

Breast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) plays an important role in the screening and prognosis assessment of high-risk breast cancer. The segmentation of cancerous regions is essential useful for the subsequent analysis of breast MRI. To alleviate the annotation effort to train the segmentation networks, we propose a weakly-supervised strategy using extreme points as annotations for breast cancer segmentation. Without using any bells and whistles, our strategy focuses on fully exploiting the learning capability of the routine training procedure, i.e., the train - fine-tune - retrain process. The network first utilizes the pseudo-masks generated using the extreme points to train itself, by minimizing a contrastive loss, which encourages the network to learn more representative features for cancerous voxels. Then the trained network fine-tunes itself by using a similarity-aware propagation learning (SimPLe) strategy, which leverages feature similarity between unlabeled and positive voxels to propagate labels. Finally the network retrains itself by employing the pseudo-masks generated using previous fine-tuned network. The proposed method is evaluated on our collected DCE-MRI dataset containing 206 patients with biopsy-proven breast cancers. Experimental results demonstrate our method effectively fine-tunes the network by using the SimPLe strategy, and achieves a mean Dice value of 81%.

The ODELIA Breast MRI Challenge 2025 addresses a critical issue in breast cancer screening: improving early detection through more efficient and accurate interpretation of breast MRI scans. Even though methods for general-purpose whole-body lesion segmentation as well as multi-time-point analysis exist, breast cancer detection remains highly challenging, largely due to the limited availability of high-quality segmentation labels. Therefore, developing robust classification-based approaches is crucial for the future of early breast cancer detection, particularly in applications such as large-scale screening. In this write-up, we provide a comprehensive overview of our approach to the challenge. We begin by detailing the underlying concept and foundational assumptions that guided our work. We then describe the iterative development process, highlighting the key stages of experimentation, evaluation, and refinement that shaped the evolution of our solution. Finally, we present the reasoning and evidence that informed the design choices behind our final submission, with a focus on performance, robustness, and clinical relevance. We release our full implementation publicly at https://github.com/MIC-DKFZ/MeisenMeister

Gene expression can be used to subtype breast cancer with improved prediction of risk of recurrence and treatment responsiveness over that obtained using routine immunohistochemistry (IHC). However, in the clinic, molecular profiling is primarily used for ER+ breast cancer, which is costly, tissue destructive, requires specialized platforms and takes several weeks to obtain a result. Deep learning algorithms can effectively extract morphological patterns in digital histopathology images to predict molecular phenotypes quickly and cost-effectively. We propose a new, computationally efficient approach called hist2RNA inspired by bulk RNA-sequencing techniques to predict the expression of 138 genes (incorporated from six commercially available molecular profiling tests), including luminal PAM50 subtype, from hematoxylin and eosin (H&E) stained whole slide images (WSIs). The training phase involves the aggregation of extracted features for each patient from a pretrained model to predict gene expression at the patient level using annotated H&E images from The Cancer Genome Atlas (TCGA, n=335). We demonstrate successful gene prediction on a held-out test set (n = 160, corr = 0.82 across patients, corr = 0.29 across genes) and perform exploratory analysis on an external tissue microarray (TMA) dataset (n = 498) with known IHC and survival information. Our model is able to predict gene expression and luminal PAM50 subtype (Luminal A versus Luminal B) on the TMA dataset with prognostic significance for overall survival in univariate analysis (c-index = 0.56, hazard ratio = 2.16 (95% CI 1.12-3.06), p < 5 x 10-3), and independent significance in multivariate analysis incorporating standard clinicopathological variables (c-index = 0.65, hazard ratio = 1.85 (95% CI 1.30-2.68), p < 5 x 10-3).

Deep learning (DL) has proven highly effective for ultrasound-based computer-aided diagnosis (CAD) of breast cancers. In an automaticCAD system, lesion detection is critical for the following diagnosis. However, existing DL-based methods generally require voluminous manually-annotated region of interest (ROI) labels and class labels to train both the lesion detection and diagnosis models. In clinical practice, the ROI labels, i.e. ground truths, may not always be optimal for the classification task due to individual experience of sonologists, resulting in the issue of coarse annotation that limits the diagnosis performance of a CAD model. To address this issue, a novel Two-Stage Detection and Diagnosis Network (TSDDNet) is proposed based on weakly supervised learning to enhance diagnostic accuracy of the ultrasound-based CAD for breast cancers. In particular, all the ROI-level labels are considered as coarse labels in the first training stage, and then a candidate selection mechanism is designed to identify optimallesion areas for both the fully and partially annotated samples. It refines the current ROI-level labels in the fully annotated images and the detected ROIs in the partially annotated samples with a weakly supervised manner under the guidance of class labels. In the second training stage, a self-distillation strategy further is further proposed to integrate the detection network and classification network into a unified framework as the final CAD model for joint optimization, which then further improves the diagnosis performance. The proposed TSDDNet is evaluated on a B-mode ultrasound dataset, and the experimental results show that it achieves the best performance on both lesion detection and diagnosis tasks, suggesting promising application potential.

Explainable AI (XAI) in medical histopathology is essential for enhancing the interpretability and clinical trustworthiness of deep learning models in cancer diagnosis. However, the black-box nature of these models often limits their clinical adoption. We introduce GRAPHITE (Graph-based Interpretable Tissue Examination), a post-hoc explainable framework designed for breast cancer tissue microarray (TMA) analysis. GRAPHITE employs a multiscale approach, extracting patches at various magnification levels, constructing an hierarchical graph, and utilising graph attention networks (GAT) with scalewise attention (SAN) to capture scale-dependent features. We trained the model on 140 tumour TMA cores and four benign whole slide images from which 140 benign samples were created, and tested it on 53 pathologist-annotated TMA samples. GRAPHITE outperformed traditional XAI methods, achieving a mean average precision (mAP) of 0.56, an area under the receiver operating characteristic curve (AUROC) of 0.94, and a threshold robustness (ThR) of 0.70, indicating that the model maintains high performance across a wide range of thresholds. In clinical utility, GRAPHITE achieved the highest area under the decision curve (AUDC) of 4.17e+5, indicating reliable decision support across thresholds. These results highlight GRAPHITE's potential as a clinically valuable tool in computational pathology, providing interpretable visualisations that align with the pathologists' diagnostic reasoning and support precision medicine.

Digital pathology enables automatic analysis of histopathological sections using artificial intelligence (AI). Automatic evaluation could improve diagnostic efficiency and help find associations between morphological features and clinical outcome. For development of such prediction models, identifying invasive epithelial cells, and separating these from benign epithelial cells and in situ lesions would be the first step. In this study, we aimed to develop an AI model for segmentation of epithelial cells in sections from breast cancer. We generated epithelial ground truth masks by restaining hematoxylin and eosin (HE) sections with cytokeratin (CK) AE1/AE3, and by pathologists' annotations. HE/CK image pairs were used to train a convolutional neural network, and data augmentation was used to make the model more robust. Tissue microarrays (TMAs) from 839 patients, and whole slide images from two patients were used for training and evaluation of the models. The sections were derived from four cohorts of breast cancer patients. TMAs from 21 patients from a fifth cohort was used as a second test set. In quantitative evaluation, a mean Dice score of 0.70, 0.79, and 0.75 for invasive epithelial cells, benign epithelial cells, and in situ lesions, respectively, were achieved. In qualitative scoring (0-5) by pathologists, results were best for all epithelium and invasive epithelium, with scores of 4.7 and 4.4. Scores for benign epithelium and in situ lesions were 3.7 and 2.0. The proposed model segmented epithelial cells in HE stained breast cancer slides well, but further work is needed for accurate division between the classes. Immunohistochemistry, together with pathologists' annotations, enabled the creation of accurate ground truths. The model is made freely available in FastPathology and the code is available at https://github.com/AICAN-Research/breast-epithelium-segmentation

Large annotated datasets are essential for training robust Computer-Aided Diagnosis (CAD) models for breast cancer detection or risk prediction. However, acquiring such datasets with fine-detailed annotation is both costly and time-consuming. Vision-Language Models (VLMs), such as CLIP, which are pre-trained on large image-text pairs, offer a promising solution by enhancing robustness and data efficiency in medical imaging tasks. This paper introduces a novel Multi-View Mammography and Language Model for breast cancer classification and risk prediction, trained on a dataset of paired mammogram images and synthetic radiology reports. Our MV-MLM leverages multi-view supervision to learn rich representations from extensive radiology data by employing cross-modal self-supervision across image-text pairs. This includes multiple views and the corresponding pseudo-radiology reports. We propose a novel joint visual-textual learning strategy to enhance generalization and accuracy performance over different data types and tasks to distinguish breast tissues or cancer characteristics(calcification, mass) and utilize these patterns to understand mammography images and predict cancer risk. We evaluated our method on both private and publicly available datasets, demonstrating that the proposed model achieves state-of-the-art performance in three classification tasks: (1) malignancy classification, (2) subtype classification, and (3) image-based cancer risk prediction. Furthermore, the model exhibits strong data efficiency, outperforming existing fully supervised or VLM baselines while trained on synthetic text reports and without the need for actual radiology reports.

Most papers caution against using predictive models for disease stratification based on unselected radiomic features, as these features are affected by contouring variability. Instead, they advocate for the use of the Intraclass Correlation Coefficient (ICC) as a measure of stability for feature selection. However, the direct effect of segmentation variability on the predictive models is rarely studied. This study investigates the impact of segmentation variability on feature stability and predictive performance in radiomics-based prediction of Triple-Negative Breast Cancer (TNBC) subtype using Magnetic Resonance Imaging. A total of 244 images from the Duke dataset were used, with segmentation variability introduced through modifications of manual segmentations. For each mask, explainable radiomic features were selected using the Shapley Additive exPlanations method and used to train logistic regression models. Feature stability across segmentations was assessed via ICC, Pearson's correlation, and reliability scores quantifying the relationship between feature stability and segmentation variability. Results indicate that segmentation accuracy does not significantly impact predictive performance. While incorporating peritumoral information may reduce feature reproducibility, it does not diminish feature predictive capability. Moreover, feature selection in predictive models is not inherently tied to feature stability with respect to segmentation, suggesting that an overreliance on ICC or reliability scores for feature selection might exclude valuable predictive features.

Survival risk stratification is an important step in clinical decision making for breast cancer management. We propose a novel deep learning approach for this purpose by integrating histopathological imaging, genetic and clinical data. It employs vision transformers, specifically the MaxViT model, for image feature extraction, and self-attention to capture intricate image relationships at the patient level. A dual cross-attention mechanism fuses these features with genetic data, while clinical data is incorporated at the final layer to enhance predictive accuracy. Experiments on the public TCGA-BRCA dataset show that our model, trained using the negative log likelihood loss function, can achieve superior performance with a mean C-index of 0.64, surpassing existing methods. This advancement facilitates tailored treatment strategies, potentially leading to improved patient outcomes.

This research paper investigates the effectiveness of simple linear models versus complex machine learning techniques in breast cancer diagnosis, emphasizing the importance of interpretability and computational efficiency in the medical domain. We focus on Logistic Regression (LR), Decision Trees (DT), and Support Vector Machines (SVM) and optimize their performance using the UCI Machine Learning Repository dataset. Our findings demonstrate that the simpler linear model, LR, outperforms the more complex DT and SVM techniques, with a test score mean of 97.28%, a standard deviation of 1.62%, and a computation time of 35.56 ms. In comparison, DT achieved a test score mean of 93.73%, and SVM had a test score mean of 96.44%. The superior performance of LR can be attributed to its simplicity and interpretability, which provide a clear understanding of the relationship between input features and the outcome. This is particularly valuable in the medical domain, where interpretability is crucial for decision-making. Moreover, the computational efficiency of LR offers advantages in terms of scalability and real-world applicability. The results of this study highlight the power of simplicity in the context of breast cancer diagnosis and suggest that simpler linear models like LR can be more effective, interpretable, and computationally efficient than their complex counterparts, making them a more suitable choice for medical applications.

Breast cancer is one of the leading causes of death among women worldwide. We introduce Mammo-FM, the first foundation model specifically for mammography, pretrained on the largest and most diverse dataset to date - 140,677 patients (821,326 mammograms) across four U.S. institutions. Mammo-FM provides a unified foundation for core clinical tasks in breast imaging, including cancer diagnosis, pathology localization, structured report generation, and cancer risk prognosis within a single framework. Its alignment between images and text enables both visual and textual interpretability, improving transparency and clinical auditability, which are essential for real-world adoption. We rigorously evaluate Mammo-FM across diagnosis, prognosis, and report-generation tasks in in- and out-of-distribution datasets. Despite operating on native-resolution mammograms and using only one-third of the parameters of state-of-the-art generalist FMs, Mammo-FM consistently outperforms them across multiple public and private benchmarks. These results highlight the efficiency and value of domain-specific foundation models designed around the full spectrum of tasks within a clinical domain and emphasize the importance of rigorous, domain-aligned evaluation.

Breast cancer is one of the most common causes of death among women worldwide. Early detection helps in reducing the number of deaths. Automated 3D Breast Ultrasound (ABUS) is a newer approach for breast screening, which has many advantages over handheld mammography such as safety, speed, and higher detection rate of breast cancer. Tumor detection, segmentation, and classification are key components in the analysis of medical images, especially challenging in the context of 3D ABUS due to the significant variability in tumor size and shape, unclear tumor boundaries, and a low signal-to-noise ratio. The lack of publicly accessible, well-labeled ABUS datasets further hinders the advancement of systems for breast tumor analysis. Addressing this gap, we have organized the inaugural Tumor Detection, Segmentation, and Classification Challenge on Automated 3D Breast Ultrasound 2023 (TDSC-ABUS2023). This initiative aims to spearhead research in this field and create a definitive benchmark for tasks associated with 3D ABUS image analysis. In this paper, we summarize the top-performing algorithms from the challenge and provide critical analysis for ABUS image examination. We offer the TDSC-ABUS challenge as an open-access platform at https://tdsc-abus2023.grand-challenge.org/ to benchmark and inspire future developments in algorithmic research.

Precise breast cancer classification on histopathological images has the potential to greatly improve the diagnosis and patient outcome in oncology. The data imbalance problem largely stems from the inherent imbalance within medical image datasets, where certain tumor subtypes may appear much less frequently. This constitutes a considerable limitation in biased model predictions that can overlook critical but rare classes. In this work, we adopted EfficientNet, a state-of-the-art convolutional neural network (CNN) model that balances high accuracy with computational cost efficiency. To address data imbalance, we introduce an intensive data augmentation pipeline and cost-sensitive learning, improving representation and ensuring that the model does not overly favor majority classes. This approach provides the ability to learn effectively from rare tumor types, improving its robustness. Additionally, we fine-tuned the model using transfer learning, where weights in the beginning trained on a binary classification task were adopted to multi-class classification, improving the capability to detect complex patterns within the BreakHis dataset. Our results underscore significant improvements in the binary classification performance, achieving an exceptional recall increase for benign cases from 0.92 to 0.95, alongside an accuracy enhancement from 97.35 % to 98.23%. Our approach improved the performance of multi-class tasks from 91.27% with regular augmentation to 94.54% with intensive augmentation, reaching 95.04% with transfer learning. This framework demonstrated substantial gains in precision in the minority classes, such as Mucinous carcinoma and Papillary carcinoma, while maintaining high recall consistently across these critical subtypes, as further confirmed by confusion matrix analysis.

Background Precise prediction of cancer types is vital for cancer diagnosis and therapy. Important cancer marker genes can be inferred through predictive model. Several studies have attempted to build machine learning models for this task however none has taken into consideration the effects of tissue of origin that can potentially bias the identification of cancer markers. Results In this paper, we introduced several Convolutional Neural Network (CNN) models that take unstructured gene expression inputs to classify tumor and non-tumor samples into their designated cancer types or as normal. Based on different designs of gene embeddings and convolution schemes, we implemented three CNN models: 1D-CNN, 2D-Vanilla-CNN, and 2D-Hybrid-CNN. The models were trained and tested on combined 10,340 samples of 33 cancer types and 731 matched normal tissues of The Cancer Genome Atlas (TCGA). Our models achieved excellent prediction accuracies (93.9-95.0%) among 34 classes (33 cancers and normal). Furthermore, we interpreted one of the models, known as 1D-CNN model, with a guided saliency technique and identified a total of 2,090 cancer markers (108 per class). The concordance of differential expression of these markers between the cancer type they represent and others is confirmed. In breast cancer, for instance, our model identified well-known markers, such as GATA3 and ESR1. Finally, we extended the 1D-CNN model for prediction of breast cancer subtypes and achieved an average accuracy of 88.42% among 5 subtypes. The codes can be found at https://github.com/chenlabgccri/CancerTypePrediction.

Interval and large invasive breast cancers, which are associated with worse prognosis than other cancers, are usually detected at a late stage due to false negative assessments of screening mammograms. The missed screening-time detection is commonly caused by the tumor being obscured by its surrounding breast tissues, a phenomenon called masking. To study and benchmark mammographic masking of cancer, in this work we introduce CSAW-M, the largest public mammographic dataset, collected from over 10,000 individuals and annotated with potential masking. In contrast to the previous approaches which measure breast image density as a proxy, our dataset directly provides annotations of masking potential assessments from five specialists. We also trained deep learning models on CSAW-M to estimate the masking level and showed that the estimated masking is significantly more predictive of screening participants diagnosed with interval and large invasive cancers -- without being explicitly trained for these tasks -- than its breast density counterparts.

Breast density estimation is one of the key tasks in recognizing individuals predisposed to breast cancer. It is often challenging because of low contrast and fluctuations in mammograms' fatty tissue background. Most of the time, the breast density is estimated manually where a radiologist assigns one of the four density categories decided by the Breast Imaging and Reporting Data Systems (BI-RADS). There have been efforts in the direction of automating a breast density classification pipeline. Breast density estimation is one of the key tasks performed during a screening exam. Dense breasts are more susceptible to breast cancer. The density estimation is challenging because of low contrast and fluctuations in mammograms' fatty tissue background. Traditional mammograms are being replaced by tomosynthesis and its other low radiation dose variants (for example Hologic' Intelligent 2D and C-View). Because of the low-dose requirement, increasingly more screening centers are favoring the Intelligent 2D view and C-View. Deep-learning studies for breast density estimation use only a single modality for training a neural network. However, doing so restricts the number of images in the dataset. In this paper, we show that a neural network trained on all the modalities at once performs better than a neural network trained on any single modality. We discuss these results using the area under the receiver operator characteristics curves.

Deep neural networks (DNNs) offer significant promise for improving breast cancer diagnosis in medical imaging. However, these models are highly susceptible to adversarial attacks--small, imperceptible changes that can mislead classifiers--raising critical concerns about their reliability and security. Traditional attacks rely on fixed-norm perturbations, misaligning with human perception. In contrast, diffusion-based attacks require pre-trained models, demanding substantial data when these models are unavailable, limiting practical use in data-scarce scenarios. In medical imaging, however, this is often unfeasible due to the limited availability of datasets. Building on recent advancements in learnable prompts, we propose Prompt2Perturb (P2P), a novel language-guided attack method capable of generating meaningful attack examples driven by text instructions. During the prompt learning phase, our approach leverages learnable prompts within the text encoder to create subtle, yet impactful, perturbations that remain imperceptible while guiding the model towards targeted outcomes. In contrast to current prompt learning-based approaches, our P2P stands out by directly updating text embeddings, avoiding the need for retraining diffusion models. Further, we leverage the finding that optimizing only the early reverse diffusion steps boosts efficiency while ensuring that the generated adversarial examples incorporate subtle noise, thus preserving ultrasound image quality without introducing noticeable artifacts. We show that our method outperforms state-of-the-art attack techniques across three breast ultrasound datasets in FID and LPIPS. Moreover, the generated images are both more natural in appearance and more effective compared to existing adversarial attacks. Our code will be publicly available https://github.com/yasamin-med/P2P.

Dynamic contrast-enhanced (DCE) MRI is essential for breast cancer diagnosis and treatment. However, its reliance on contrast agents introduces safety concerns, contraindications, increased cost, and workflow complexity. To this end, we present pre-contrast conditioned denoising diffusion probabilistic models to synthesize DCE-MRI, introducing, evaluating, and comparing a total of 22 generative model variants in both single-breast and full breast settings. Towards enhancing lesion fidelity, we introduce both tumor-aware loss functions and explicit tumor segmentation mask conditioning. Using a public multicenter dataset and comparing to respective pre-contrast baselines, we observe that subtraction image-based models consistently outperform post-contrast-based models across five complementary evaluation metrics. Apart from assessing the entire image, we also separately evaluate the region of interest, where both tumor-aware losses and segmentation mask inputs improve evaluation metrics. The latter notably enhance qualitative results capturing contrast uptake, albeit assuming access to tumor localization inputs that are not guaranteed to be available in screening settings. A reader study involving 2 radiologists and 4 MRI technologists confirms the high realism of the synthetic images, indicating an emerging clinical potential of generative contrast-enhancement. We share our codebase at https://github.com/sebastibar/conditional-diffusion-breast-MRI.

Cancer is the uncontrollable cell division of abnormal cells inside the human body, which can spread to other body organs. It is one of the non-communicable diseases (NCDs) and NCDs accounts for 71% of total deaths worldwide whereas lung cancer is the second most diagnosed cancer after female breast cancer. Cancer survival rate of lung cancer is only 19%. There are various methods for the diagnosis of lung cancer, such as X-ray, CT scan, PET-CT scan, bronchoscopy and biopsy. However, to know the subtype of lung cancer based on the tissue type H and E staining is widely used, where the staining is done on the tissue aspirated from a biopsy. Studies have reported that the type of histology is associated with prognosis and treatment in lung cancer. Therefore, early and accurate detection of lung cancer histology is an urgent need and as its treatment is dependent on the type of histology, molecular profile and stage of the disease, it is most essential to analyse the histopathology images of lung cancer. Hence, to speed up the vital process of diagnosis of lung cancer and reduce the burden on pathologists, Deep learning techniques are used. These techniques have shown improved efficacy in the analysis of histopathology slides of cancer. Several studies reported the importance of convolution neural networks (CNN) in the classification of histopathological pictures of various cancer types such as brain, skin, breast, lung, colorectal cancer. In this study tri-category classification of lung cancer images (normal, adenocarcinoma and squamous cell carcinoma) are carried out by using ResNet 50, VGG-19, Inception_ResNet_V2 and DenseNet for the feature extraction and triplet loss to guide the CNN such that it increases inter-cluster distance and reduces intra-cluster distance.

Efficient, reliable and reproducible target volume delineation is a key step in the effective planning of breast radiotherapy. However, post-operative breast target delineation is challenging as the contrast between the tumor bed volume (TBV) and normal breast tissue is relatively low in CT images. In this study, we propose to mimic the marker-guidance procedure in manual target delineation. We developed a saliency-based deep learning segmentation (SDL-Seg) algorithm for accurate TBV segmentation in post-operative breast irradiation. The SDL-Seg algorithm incorporates saliency information in the form of markers' location cues into a U-Net model. The design forces the model to encode the location-related features, which underscores regions with high saliency levels and suppresses low saliency regions. The saliency maps were generated by identifying markers on CT images. Markers' locations were then converted to probability maps using a distance-transformation coupled with a Gaussian filter. Subsequently, the CT images and the corresponding saliency maps formed a multi-channel input for the SDL-Seg network. Our in-house dataset was comprised of 145 prone CT images from 29 post-operative breast cancer patients, who received 5-fraction partial breast irradiation (PBI) regimen on GammaPod. The performance of the proposed method was compared against basic U-Net. Our model achieved mean (standard deviation) of 76.4 %, 6.76 mm, and 1.9 mm for DSC, HD95, and ASD respectively on the test set with computation time of below 11 seconds per one CT volume. SDL-Seg showed superior performance relative to basic U-Net for all the evaluation metrics while preserving low computation cost. The findings demonstrate that SDL-Seg is a promising approach for improving the efficiency and accuracy of the on-line treatment planning procedure of PBI, such as GammaPod based PBI.

Breast cancer is one of the leading causes of death across the world in women. Early diagnosis of this type of cancer is critical for treatment and patient care. Computer-aided detection (CAD) systems using convolutional neural networks (CNN) could assist in the classification of abnormalities. In this study, we proposed an ensemble deep learning-based approach for automatic binary classification of breast histology images. The proposed ensemble model adapts three pre-trained CNNs, namely VGG19, MobileNet, and DenseNet. The ensemble model is used for the feature representation and extraction steps. The extracted features are then fed into a multi-layer perceptron classifier to carry out the classification task. Various pre-processing and CNN tuning techniques such as stain-normalization, data augmentation, hyperparameter tuning, and fine-tuning are used to train the model. The proposed method is validated on four publicly available benchmark datasets, i.e., ICIAR, BreakHis, PatchCamelyon, and Bioimaging. The proposed multi-model ensemble method obtains better predictions than single classifiers and machine learning algorithms with accuracies of 98.13%, 95.00%, 94.64% and 83.10% for BreakHis, ICIAR, PatchCamelyon and Bioimaging datasets, respectively.

In recent years, the integration of advanced imaging techniques and deep learning methods has significantly advanced computer-aided diagnosis (CAD) systems for breast cancer detection and classification. Transformers, which have shown great promise in computer vision, are now being applied to medical image analysis. However, their application to histopathological images presents challenges due to the need for extensive manual annotations of whole-slide images (WSIs), as these models require large amounts of data to work effectively, which is costly and time-consuming. Furthermore, the quadratic computational cost of Vision Transformers (ViTs) is particularly prohibitive for large, high-resolution histopathological images, especially on edge devices with limited computational resources. In this study, we introduce a novel lightweight breast cancer classification approach using transformers that operates effectively without large datasets. By incorporating parallel processing pathways for Discrete Cosine Transform (DCT) Attention and MobileConv, we convert image data from the spatial domain to the frequency domain to utilize the benefits such as filtering out high frequencies in the image, which reduces computational cost. This demonstrates the potential of our approach to improve breast cancer classification in histopathological images, offering a more efficient solution with reduced reliance on extensive annotated datasets. Our proposed model achieves an accuracy of 96.00% pm 0.48% for binary classification and 87.85% pm 0.93% for multiclass classification, which is comparable to state-of-the-art models while significantly reducing computational costs. This demonstrates the potential of our approach to improve breast cancer classification in histopathological images, offering a more efficient solution with reduced reliance on extensive annotated datasets.

Deep learning models have shown promise in histopathology image analysis, but their opaque decision-making process poses challenges in high-risk medical scenarios. Here we introduce HIPPO, an explainable AI method that interrogates attention-based multiple instance learning (ABMIL) models in computational pathology by generating counterfactual examples through tissue patch modifications in whole slide images. Applying HIPPO to ABMIL models trained to detect breast cancer metastasis reveals that they may overlook small tumors and can be misled by non-tumor tissue, while attention mapsx2014widely used for interpretationx2014often highlight regions that do not directly influence predictions. By interpreting ABMIL models trained on a prognostic prediction task, HIPPO identified tissue areas with stronger prognostic effects than high-attention regions, which sometimes showed counterintuitive influences on risk scores. These findings demonstrate HIPPO's capacity for comprehensive model evaluation, bias detection, and quantitative hypothesis testing. HIPPO greatly expands the capabilities of explainable AI tools to assess the trustworthy and reliable development, deployment, and regulation of weakly-supervised models in computational pathology.

The lack of large and diverse training data on Computer-Aided Diagnosis (CAD) in breast cancer detection has been one of the concerns that impedes the adoption of the system. Recently, pre-training with large-scale image text datasets via Vision-Language models (VLM) (\eg CLIP) partially addresses the issue of robustness and data efficiency in computer vision (CV). This paper proposes Mammo-CLIP, the first VLM pre-trained on a substantial amount of screening mammogram-report pairs, addressing the challenges of dataset diversity and size. Our experiments on two public datasets demonstrate strong performance in classifying and localizing various mammographic attributes crucial for breast cancer detection, showcasing data efficiency and robustness similar to CLIP in CV. We also propose Mammo-FActOR, a novel feature attribution method, to provide spatial interpretation of representation with sentence-level granularity within mammography reports. Code is available publicly: https://github.com/batmanlab/Mammo-CLIP.

We present WeakSTIL, an interpretable two-stage weak label deep learning pipeline for scoring the percentage of stromal tumor infiltrating lymphocytes (sTIL%) in H&E-stained whole-slide images (WSIs) of breast cancer tissue. The sTIL% score is a prognostic and predictive biomarker for many solid tumor types. However, due to the high labeling efforts and high intra- and interobserver variability within and between expert annotators, this biomarker is currently not used in routine clinical decision making. WeakSTIL compresses tiles of a WSI using a feature extractor pre-trained with self-supervised learning on unlabeled histopathology data and learns to predict precise sTIL% scores for each tile in the tumor bed by using a multiple instance learning regressor that only requires a weak WSI-level label. By requiring only a weak label, we overcome the large annotation efforts required to train currently existing TIL detection methods. We show that WeakSTIL is at least as good as other TIL detection methods when predicting the WSI-level sTIL% score, reaching a coefficient of determination of 0.45pm0.15 when compared to scores generated by an expert pathologist, and an AUC of 0.89pm0.05 when treating it as the clinically interesting sTIL-high vs sTIL-low classification task. Additionally, we show that the intermediate tile-level predictions of WeakSTIL are highly interpretable, which suggests that WeakSTIL pays attention to latent features related to the number of TILs and the tissue type. In the future, WeakSTIL may be used to provide consistent and interpretable sTIL% predictions to stratify breast cancer patients into targeted therapy arms.

Recent breakthroughs in self-supervised learning have enabled the use of large unlabeled datasets to train visual foundation models that can generalize to a variety of downstream tasks. While this training paradigm is well suited for the medical domain where annotations are scarce, large-scale pre-training in the medical domain, and in particular pathology, has not been extensively studied. Previous work in self-supervised learning in pathology has leveraged smaller datasets for both pre-training and evaluating downstream performance. The aim of this project is to train the largest academic foundation model and benchmark the most prominent self-supervised learning algorithms by pre-training and evaluating downstream performance on large clinical pathology datasets. We collected the largest pathology dataset to date, consisting of over 3 billion images from over 423 thousand microscopy slides. We compared pre-training of visual transformer models using the masked autoencoder (MAE) and DINO algorithms. We evaluated performance on six clinically relevant tasks from three anatomic sites and two institutions: breast cancer detection, inflammatory bowel disease detection, breast cancer estrogen receptor prediction, lung adenocarcinoma EGFR mutation prediction, and lung cancer immunotherapy response prediction. Our results demonstrate that pre-training on pathology data is beneficial for downstream performance compared to pre-training on natural images. Additionally, the DINO algorithm achieved better generalization performance across all tasks tested. The presented results signify a phase change in computational pathology research, paving the way into a new era of more performant models based on large-scale, parallel pre-training at the billion-image scale.

Cytology is essential for cancer diagnostics and screening due to its minimally invasive nature. However, the development of robust deep learning models for digital cytology is challenging due to the heterogeneity in staining and preparation methods of samples, differences across organs, and the limited availability of large, diverse, annotated datasets. Developing a task-specific model for every cytology application is impractical and non-cytology-specific foundation models struggle to generalize to tasks in this domain where the emphasis is on cell morphology. To address these challenges, we introduce CytoFM, the first cytology self-supervised foundation model. Using iBOT, a self-supervised Vision Transformer (ViT) training framework incorporating masked image modeling and self-distillation, we pretrain CytoFM on a diverse collection of cytology datasets to learn robust, transferable representations. We evaluate CytoFM on multiple downstream cytology tasks, including breast cancer classification and cell type identification, using an attention-based multiple instance learning framework. Our results demonstrate that CytoFM performs better on two out of three downstream tasks than existing foundation models pretrained on histopathology (UNI) or natural images (iBOT-Imagenet). Visualizations of learned representations demonstrate our model is able to attend to cytologically relevant features. Despite a small pre-training dataset, CytoFM's promising results highlight the ability of task-agnostic pre-training approaches to learn robust and generalizable features from cytology data.

Developing self-supervised learning (SSL) models that can learn universal and transferable representations of H&E gigapixel whole-slide images (WSIs) is becoming increasingly valuable in computational pathology. These models hold the potential to advance critical tasks such as few-shot classification, slide retrieval, and patient stratification. Existing approaches for slide representation learning extend the principles of SSL from small images (e.g., 224 x 224 patches) to entire slides, usually by aligning two different augmentations (or views) of the slide. Yet the resulting representation remains constrained by the limited clinical and biological diversity of the views. Instead, we postulate that slides stained with multiple markers, such as immunohistochemistry, can be used as different views to form a rich task-agnostic training signal. To this end, we introduce Madeleine, a multimodal pretraining strategy for slide representation learning. Madeleine is trained with a dual global-local cross-stain alignment objective on large cohorts of breast cancer samples (N=4,211 WSIs across five stains) and kidney transplant samples (N=12,070 WSIs across four stains). We demonstrate the quality of slide representations learned by Madeleine on various downstream evaluations, ranging from morphological and molecular classification to prognostic prediction, comprising 21 tasks using 7,299 WSIs from multiple medical centers. Code is available at https://github.com/mahmoodlab/MADELEINE.

Pathology text mining is a challenging task given the reporting variability and constant new findings in cancer sub-type definitions. However, successful text mining of a large pathology database can play a critical role to advance 'big data' cancer research like similarity-based treatment selection, case identification, prognostication, surveillance, clinical trial screening, risk stratification, and many others. While there is a growing interest in developing language models for more specific clinical domains, no pathology-specific language space exist to support the rapid data-mining development in pathology space. In literature, a few approaches fine-tuned general transformer models on specialized corpora while maintaining the original tokenizer, but in fields requiring specialized terminology, these models often fail to perform adequately. We propose PathologyBERT - a pre-trained masked language model which was trained on 347,173 histopathology specimen reports and publicly released in the Huggingface repository. Our comprehensive experiments demonstrate that pre-training of transformer model on pathology corpora yields performance improvements on Natural Language Understanding (NLU) and Breast Cancer Diagnose Classification when compared to nonspecific language models.

Large language models (LLMs) have shown remarkable progress in encoding clinical knowledge and responding to complex medical queries with appropriate clinical reasoning. However, their applicability in subspecialist or complex medical settings remains underexplored. In this work, we probe the performance of AMIE, a research conversational diagnostic AI system, in the subspecialist domain of breast oncology care without specific fine-tuning to this challenging domain. To perform this evaluation, we curated a set of 50 synthetic breast cancer vignettes representing a range of treatment-naive and treatment-refractory cases and mirroring the key information available to a multidisciplinary tumor board for decision-making (openly released with this work). We developed a detailed clinical rubric for evaluating management plans, including axes such as the quality of case summarization, safety of the proposed care plan, and recommendations for chemotherapy, radiotherapy, surgery and hormonal therapy. To improve performance, we enhanced AMIE with the inference-time ability to perform web search retrieval to gather relevant and up-to-date clinical knowledge and refine its responses with a multi-stage self-critique pipeline. We compare response quality of AMIE with internal medicine trainees, oncology fellows, and general oncology attendings under both automated and specialist clinician evaluations. In our evaluations, AMIE outperformed trainees and fellows demonstrating the potential of the system in this challenging and important domain. We further demonstrate through qualitative examples, how systems such as AMIE might facilitate conversational interactions to assist clinicians in their decision making. However, AMIE's performance was overall inferior to attending oncologists suggesting that further research is needed prior to consideration of prospective uses.

Histopathological cancer diagnostics has become more complex, and the increasing number of biopsies is a challenge for most pathology laboratories. Thus, development of automatic methods for evaluation of histopathological cancer sections would be of value. In this study, we used 624 whole slide images (WSIs) of breast cancer from a Norwegian cohort. We propose a cascaded convolutional neural network design, called H2G-Net, for semantic segmentation of gigapixel histopathological images. The design involves a detection stage using a patch-wise method, and a refinement stage using a convolutional autoencoder. To validate the design, we conducted an ablation study to assess the impact of selected components in the pipeline on tumour segmentation. Guiding segmentation, using hierarchical sampling and deep heatmap refinement, proved to be beneficial when segmenting the histopathological images. We found a significant improvement when using a refinement network for postprocessing the generated tumour segmentation heatmaps. The overall best design achieved a Dice score of 0.933 on an independent test set of 90 WSIs. The design outperformed single-resolution approaches, such as cluster-guided, patch-wise high-resolution classification using MobileNetV2 (0.872) and a low-resolution U-Net (0.874). In addition, segmentation on a representative x400 WSI took ~58 seconds, using only the CPU. The findings demonstrate the potential of utilizing a refinement network to improve patch-wise predictions. The solution is efficient and does not require overlapping patch inference or ensembling. Furthermore, we showed that deep neural networks can be trained using a random sampling scheme that balances on multiple different labels simultaneously, without the need of storing patches on disk. Future work should involve more efficient patch generation and sampling, as well as improved clustering.

In democratic societies, electoral systems play a crucial role in translating public preferences into political representation. Among these, the D'Hondt method is widely used to ensure proportional representation, balancing fair representation with governmental stability. Recently, there has been a growing interest in applying similar principles of proportional representation to enhance interpretability in machine learning, specifically in Explainable AI (XAI). This study investigates the integration of D'Hondt-based voting principles in the DhondtXAI method, which leverages resource allocation concepts to interpret feature importance within AI models. Through a comparison of SHAP (Shapley Additive Explanations) and DhondtXAI, we evaluate their effectiveness in feature attribution within CatBoost and XGBoost models for breast cancer and diabetes prediction, respectively. The DhondtXAI approach allows for alliance formation and thresholding to enhance interpretability, representing feature importance as seats in a parliamentary view. Statistical correlation analyses between SHAP values and DhondtXAI allocations support the consistency of interpretations, demonstrating DhondtXAI's potential as a complementary tool for understanding feature importance in AI models. The results highlight that integrating electoral principles, such as proportional representation and alliances, into AI explainability can improve user understanding, especially in high-stakes fields like healthcare.

In this paper, we introduce the gated perceptron, an enhancement of the conventional perceptron, which incorporates an additional input computed as the product of the existing inputs. This allows the perceptron to capture non-linear interactions between features, significantly improving its ability to classify and regress on complex datasets. We explore its application in both linear and non-linear regression tasks using the Iris dataset, as well as binary and multi-class classification problems, including the PIMA Indian dataset and Breast Cancer Wisconsin dataset. Our results demonstrate that the gated perceptron can generate more distinct decision regions compared to traditional perceptrons, enhancing its classification capabilities, particularly in handling non-linear data. Performance comparisons show that the gated perceptron competes with state-of-the-art classifiers while maintaining a simple architecture.

Driven by the recent advances in deep learning methods and, in particular, by the development of modern self-supervised learning algorithms, increased interest and efforts have been devoted to build foundation models (FMs) for medical images. In this work, we present our scalable training pipeline for large pathology imaging data, and a comprehensive analysis of various hyperparameter choices and training techniques for building pathology FMs. We release and make publicly available the first batch of our pathology FMs (https://github.com/kaiko-ai/towards_large_pathology_fms) trained on open-access TCGA whole slide images, a commonly used collection of pathology images. The experimental evaluation shows that our models reach state-of-the-art performance on various patch-level downstream tasks, ranging from breast cancer subtyping to colorectal nuclear segmentation. Finally, to unify the evaluation approaches used in the field and to simplify future comparisons of different FMs, we present an open-source framework (https://github.com/kaiko-ai/eva) designed for the consistent evaluation of pathology FMs across various downstream tasks.

Early identification of sensitive cancer cell lines is essential for accelerating biomarker discovery and elucidating drug mechanism of action. Given the efficiency and low cost of small-scale drug screens relative to extensive omics profiling, we compared drug-response panel (DRP) descriptors against omics features for predictive capacity using gradient boosting tree models across the GDSC and CCLE drug response datasets. DRP descriptors consistently outperformed omics data across key performance metrics, with variable performance across different drugs. Using complementary explainability approaches, we confirmed known MAPK-inhibitor sensitivity signatures, and identified novel potential biomarker candidates for MEK1/2 and BTK/MNK inhibitors. Lastly, to demonstrate the utility of this approach in distinguishing phenotypes, we applied our models to the breast cancer line MCF7 versus the non-tumorigenic MCF10A, and successfully identified compounds that selectively inhibit MCF7 while sparing the non-tumorigenic MCF10A. This methodology, developed using focused drug and cell line panels, supports early-stage drug development by facilitating rational cell line selection and compound prioritisation, enabling more efficient biomarker identification and candidate assessment.

Medical image segmentation plays a crucial role in assisting healthcare professionals with accurate diagnoses and enabling automated diagnostic processes. Traditional convolutional neural networks (CNNs) often struggle with capturing long-range dependencies, while transformer-based architectures, despite their effectiveness, come with increased computational complexity. Recent efforts have focused on combining CNNs and transformers to balance performance and efficiency, but existing approaches still face challenges in achieving high segmentation accuracy while maintaining low computational costs. Furthermore, many methods underutilize the CNN encoder's capability to capture local spatial information, concentrating primarily on mitigating long-range dependency issues. To address these limitations, we propose QTSeg, a novel architecture for medical image segmentation that effectively integrates local and global information. QTSeg features a dual-mix attention decoder designed to enhance segmentation performance through: (1) a cross-attention mechanism for improved feature alignment, (2) a spatial attention module to capture long-range dependencies, and (3) a channel attention block to learn inter-channel relationships. Additionally, we introduce a multi-level feature distribution module, which adaptively balances feature propagation between the encoder and decoder, further boosting performance. Extensive experiments on five publicly available datasets covering diverse segmentation tasks, including lesion, polyp, breast cancer, cell, and retinal vessel segmentation, demonstrate that QTSeg outperforms state-of-the-art methods across multiple evaluation metrics while maintaining lower computational costs. Our implementation can be found at: https://github.com/tpnam0901/QTSeg (v1.0.0)

Immunohistochemical (IHC) staining highlights the molecular information critical to diagnostics in tissue samples. However, compared to H&E staining, IHC staining can be much more expensive in terms of both labor and the laboratory equipment required. This motivates recent research that demonstrates that the correlations between the morphological information present in the H&E-stained slides and the molecular information in the IHC-stained slides can be used for H&E-to-IHC stain translation. However, due to a lack of pixel-perfect H&E-IHC groundtruth pairs, most existing methods have resorted to relying on expert annotations. To remedy this situation, we present a new loss function, Adaptive Supervised PatchNCE (ASP), to directly deal with the input to target inconsistencies in a proposed H&E-to-IHC image-to-image translation framework. The ASP loss is built upon a patch-based contrastive learning criterion, named Supervised PatchNCE (SP), and augments it further with weight scheduling to mitigate the negative impact of noisy supervision. Lastly, we introduce the Multi-IHC Stain Translation (MIST) dataset, which contains aligned H&E-IHC patches for 4 different IHC stains critical to breast cancer diagnosis. In our experiment, we demonstrate that our proposed method outperforms existing image-to-image translation methods for stain translation to multiple IHC stains. All of our code and datasets are available at https://github.com/lifangda01/AdaptiveSupervisedPatchNCE.

Machine learning techniques are effective for building predictive models because they identify patterns in large datasets. Development of a model for complex real-life problems often stop at the point of publication, proof of concept or when made accessible through some mode of deployment. However, a model in the medical domain risks becoming obsolete as patient demographics, systems and clinical practices change. The maintenance and monitoring of predictive model performance post-publication is crucial to enable their safe and effective long-term use. We will assess the infrastructure required to monitor the outputs of a machine learning algorithm, and present two scenarios with examples of monitoring and updates of models, firstly on a breast cancer prognosis model trained on public longitudinal data, and secondly on a neurodegenerative stratification algorithm that is currently being developed and tested in clinic.

Around half of all cancer patients, world-wide, will receive some form of radiotherapy (RT) as part of their treatment. And yet, despite the rapid advance of high-throughput screening to identify successful chemotherapy drug candidates, there is no current analogue for RT protocol screening or discovery at any scale. Here we introduce and demonstrate the application of a high-throughput/high-fidelity coupled tumour-irradiation simulation approach, we call "GPU-GA", and apply it to human breast cancer analogue - EMT6/Ro spheroids. By analysing over 9.5 million candidate protocols, GPU-GA yields significant gains in tumour suppression versus prior state-of-the-art high-fidelity/-low-throughput computational search under two clinically relevant benchmarks. By extending the search space to hypofractionated areas (> 2 Gy/day) yet within total dose limits, further tumour suppression of up to 33.7% compared to state-of-the-art is obtained. GPU-GA could be applied to any cell line with sufficient empirical data, and to many clinically relevant RT considerations.

We provide an optimization-based framework to perform counterfactual analysis in a dynamic model with hidden states. Our framework is grounded in the ``abduction, action, and prediction'' approach to answer counterfactual queries and handles two key challenges where (1) the states are hidden and (2) the model is dynamic. Recognizing the lack of knowledge on the underlying causal mechanism and the possibility of infinitely many such mechanisms, we optimize over this space and compute upper and lower bounds on the counterfactual quantity of interest. Our work brings together ideas from causality, state-space models, simulation, and optimization, and we apply it on a breast cancer case study. To the best of our knowledge, we are the first to compute lower and upper bounds on a counterfactual query in a dynamic latent-state model.

Deep AUC Maximization (DAM) is a new paradigm for learning a deep neural network by maximizing the AUC score of the model on a dataset. Most previous works of AUC maximization focus on the perspective of optimization by designing efficient stochastic algorithms, and studies on generalization performance of large-scale DAM on difficult tasks are missing. In this work, we aim to make DAM more practical for interesting real-world applications (e.g., medical image classification). First, we propose a new margin-based min-max surrogate loss function for the AUC score (named as AUC min-max-margin loss or simply AUC margin loss for short). It is more robust than the commonly used AUC square loss, while enjoying the same advantage in terms of large-scale stochastic optimization. Second, we conduct extensive empirical studies of our DAM method on four difficult medical image classification tasks, namely (i) classification of chest x-ray images for identifying many threatening diseases, (ii) classification of images of skin lesions for identifying melanoma, (iii) classification of mammogram for breast cancer screening, and (iv) classification of microscopic images for identifying tumor tissue. Our studies demonstrate that the proposed DAM method improves the performance of optimizing cross-entropy loss by a large margin, and also achieves better performance than optimizing the existing AUC square loss on these medical image classification tasks. Specifically, our DAM method has achieved the 1st place on Stanford CheXpert competition on Aug. 31, 2020. To the best of our knowledge, this is the first work that makes DAM succeed on large-scale medical image datasets. We also conduct extensive ablation studies to demonstrate the advantages of the new AUC margin loss over the AUC square loss on benchmark datasets. The proposed method is implemented in our open-sourced library LibAUC (www.libauc.org).

Tumor protein P53 is believed to be involved in over half of human cancers cases, the prediction of malignancies plays essential roles not only in advance detection for cancer, but also in discovering effective prevention and treatment of cancer, till now there isn't approach be able in prediction the mutated in tumor protein P53 which is caused high ratio of human cancers like breast, Blood, skin, liver, lung, bladder etc. This research proposed a new approach for prediction pre-cancer via detection malignant mutations in tumor protein P53 using bioinformatics tools like FASTA, BLAST, CLUSTALW and TP53 databases worldwide. Implement and apply this new approach of prediction pre-cancer through mutations at tumor protein P53 shows an effective result when used more specific parameters/features to extract the prediction result that means when the user increase the number of filters of the results which obtained from the database gives more specific diagnosis and classify, addition that the detecting pre-cancer via prediction mutated tumor protein P53 will reduces a person's cancers in the future by avoiding exposure to toxins, radiation or monitoring themselves at older ages by change their food, environment, even the pace of living. Also that new approach of prediction pre-cancer will help if there is any treatment can give for that person to therapy the mutated tumor protein P53. Index Terms (Normal Homology TP53 gene, Tumor Protein P53, Oncogene Labs, GC and AT content, FASTA, BLAST, ClustalW)

Deep neural networks have introduced significant advancements in the field of machine learning-based analysis of digital pathology images including prostate tissue images. With the help of transfer learning, classification and segmentation performance of neural network models have been further increased. However, due to the absence of large, extensively annotated, publicly available prostate histopathology datasets, several previous studies employ datasets from well-studied computer vision tasks such as ImageNet dataset. In this work, we propose a transfer learning scheme from breast histopathology images to improve prostate cancer detection performance. We validate our approach on annotated prostate whole slide images by using a publicly available breast histopathology dataset as pre-training. We show that the proposed cross-cancer approach outperforms transfer learning from ImageNet dataset.

There is a widening recognition that cancer cells are products of complex developmental processes. Carcinogenesis and metastasis formation are increasingly described as systems-level, network phenomena. Here we propose that malignant transformation is a two-phase process, where an initial increase of system plasticity is followed by a decrease of plasticity at late stages of carcinogenesis as a model of cellular learning. We describe the hallmarks of increased system plasticity of early, tumor initiating cells, such as increased noise, entropy, conformational and phenotypic plasticity, physical deformability, cell heterogeneity and network rearrangements. Finally, we argue that the large structural changes of molecular networks during cancer development necessitate a rather different targeting strategy in early and late phase of carcinogenesis. Plastic networks of early phase cancer development need a central hit, while rigid networks of late stage primary tumors or established metastases should be attacked by the network influence strategy, such as by edgetic, multi-target, or allo-network drugs. Cancer stem cells need special diagnosis and targeting, since their dormant and rapidly proliferating forms may have more rigid, or more plastic networks, respectively. The extremely high ability to change their rigidity/plasticity may be a key differentiating hallmark of cancer stem cells. The application of early stage-optimized anti-cancer drugs to late-stage patients may be a reason of many failures in anti-cancer therapies. Our hypotheses presented here underlie the need for patient-specific multi-target therapies applying the correct ratio of central hits and network influences -- in an optimized sequence.

While machine learning is currently transforming the field of histopathology, the domain lacks a comprehensive evaluation of state-of-the-art models based on essential but complementary quality requirements beyond a mere classification accuracy. In order to fill this gap, we developed a new methodology to extensively evaluate a wide range of classification models, including recent vision transformers, and convolutional neural networks such as: ConvNeXt, ResNet (BiT), Inception, ViT and Swin transformer, with and without supervised or self-supervised pretraining. We thoroughly tested the models on five widely used histopathology datasets containing whole slide images of breast, gastric, and colorectal cancer and developed a novel approach using an image-to-image translation model to assess the robustness of a cancer classification model against stain variations. Further, we extended existing interpretability methods to previously unstudied models and systematically reveal insights of the models' classifications strategies that can be transferred to future model architectures.

Vision-Language Models (VLMs) have shown impressive performance in vision tasks, but adapting them to new domains often requires expensive fine-tuning. Prompt tuning techniques, including textual, visual, and multimodal prompting, offer efficient alternatives by leveraging learnable prompts. However, their application to Vision-Language Segmentation Models (VLSMs) and evaluation under significant domain shifts remain unexplored. This work presents an open-source benchmarking framework, TuneVLSeg, to integrate various unimodal and multimodal prompt tuning techniques into VLSMs, making prompt tuning usable for downstream segmentation datasets with any number of classes. TuneVLSeg includes 6 prompt tuning strategies on various prompt depths used in 2 VLSMs totaling of 8 different combinations. We test various prompt tuning on 8 diverse medical datasets, including 3 radiology datasets (breast tumor, echocardiograph, chest X-ray pathologies) and 5 non-radiology datasets (polyp, ulcer, skin cancer), and two natural domain segmentation datasets. Our study found that textual prompt tuning struggles under significant domain shifts, from natural-domain images to medical data. Furthermore, visual prompt tuning, with fewer hyperparameters than multimodal prompt tuning, often achieves performance competitive to multimodal approaches, making it a valuable first attempt. Our work advances the understanding and applicability of different prompt-tuning techniques for robust domain-specific segmentation. The source code is available at https://github.com/naamiinepal/tunevlseg.

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

Radiology reports are one of the main forms of communication between radiologists and other clinicians and contain important information for patient care. In order to use this information for research and automated patient care programs, it is necessary to convert the raw text into structured data suitable for analysis. State-of-the-art natural language processing (NLP) domain-specific contextual word embeddings have been shown to achieve impressive accuracy for these tasks in medicine, but have yet to be utilized for section structure segmentation. In this work, we pre-trained a contextual embedding BERT model using breast radiology reports and developed a classifier that incorporated the embedding with auxiliary global textual features in order to perform section segmentation. This model achieved a 98% accuracy at segregating free text reports sentence by sentence into sections of information outlined in the Breast Imaging Reporting and Data System (BI-RADS) lexicon, a significant improvement over the Classic BERT model without auxiliary information. We then evaluated whether using section segmentation improved the downstream extraction of clinically relevant information such as modality/procedure, previous cancer, menopausal status, the purpose of the exam, breast density, and breast MRI background parenchymal enhancement. Using the BERT model pre-trained on breast radiology reports combined with section segmentation resulted in an overall accuracy of 95.9% in the field extraction tasks. This is a 17% improvement compared to an overall accuracy of 78.9% for field extraction with models using Classic BERT embeddings and not using section segmentation. Our work shows the strength of using BERT in radiology report analysis and the advantages of section segmentation in identifying key features of patient factors recorded in breast radiology reports.

Accurate breast lesion risk estimation can significantly reduce unnecessary biopsies and help doctors decide optimal treatment plans. Most existing computer-aided systems rely solely on mammogram features to classify breast lesions. While this approach is convenient, it does not fully exploit useful information in clinical reports to achieve the optimal performance. Would clinical features significantly improve breast lesion classification compared to using mammograms alone? How to handle missing clinical information caused by variation in medical practice? What is the best way to combine mammograms and clinical features? There is a compelling need for a systematic study to address these fundamental questions. This paper investigates several multimodal deep networks based on feature concatenation, cross-attention, and co-attention to combine mammograms and categorical clinical variables. We show that the proposed architectures significantly increase the lesion classification performance (average area under ROC curves from 0.89 to 0.94). We also evaluate the model when clinical variables are missing.

Cancer is a complex disease, the understanding and treatment of which are being aided through increases in the volume of collected data and in the scale of deployed computing power. Consequently, there is a growing need for the development of data-driven and, in particular, deep learning methods for various tasks such as cancer diagnosis, detection, prognosis, and prediction. Despite recent successes, however, designing high-performing deep learning models for nonimage and nontext cancer data is a time-consuming, trial-and-error, manual task that requires both cancer domain and deep learning expertise. To that end, we develop a reinforcement-learning-based neural architecture search to automate deep-learning-based predictive model development for a class of representative cancer data. We develop custom building blocks that allow domain experts to incorporate the cancer-data-specific characteristics. We show that our approach discovers deep neural network architectures that have significantly fewer trainable parameters, shorter training time, and accuracy similar to or higher than those of manually designed architectures. We study and demonstrate the scalability of our approach on up to 1,024 Intel Knights Landing nodes of the Theta supercomputer at the Argonne Leadership Computing Facility.

We present a general computational theory of cancer and its developmental dynamics. The theory is based on a theory of the architecture and function of developmental control networks which guide the formation of multicellular organisms. Cancer networks are special cases of developmental control networks. Cancer results from transformations of normal developmental networks. Our theory generates a natural classification of all possible cancers based on their network architecture. Each cancer network has a unique topology and semantics and developmental dynamics that result in distinct clinical tumor phenotypes. We apply this new theory with a series of proof of concept cases for all the basic cancer types. These cases have been computationally modeled, their behavior simulated and mathematically described using a multicellular systems biology approach. There are fascinating correspondences between the dynamic developmental phenotype of computationally modeled {\em in silico} cancers and natural {\em in vivo} cancers. The theory lays the foundation for a new research paradigm for understanding and investigating cancer. The theory of cancer networks implies that new diagnostic methods and new treatments to cure cancer will become possible.

We introduce the first publicly available breast MRI dataset with explicit left and right breast segmentation labels, encompassing more than 13,000 annotated cases. Alongside this dataset, we provide a robust deep-learning model trained for left-right breast segmentation. This work addresses a critical gap in breast MRI analysis and offers a valuable resource for the development of advanced tools in women's health. The dataset and trained model are publicly available at: www.github.com/MIC-DKFZ/BreastDivider

Cancer is known as a disease mainly caused by gene alterations. Discovery of mutated driver pathways or gene sets is becoming an important step to understand molecular mechanisms of carcinogenesis. However, systematically investigating commonalities and specificities of driver gene sets among multiple cancer types is still a great challenge, but this investigation will undoubtedly benefit deciphering cancers and will be helpful for personalized therapy and precision medicine in cancer treatment. In this study, we propose two optimization models to de novo discover common driver gene sets among multiple cancer types (ComMDP) and specific driver gene sets of one certain or multiple cancer types to other cancers (SpeMDP), respectively. We first apply ComMDP and SpeMDP to simulated data to validate their efficiency. Then, we further apply these methods to 12 cancer types from The Cancer Genome Atlas (TCGA) and obtain several biologically meaningful driver pathways. As examples, we construct a common cancer pathway model for BRCA and OV, infer a complex driver pathway model for BRCA carcinogenesis based on common driver gene sets of BRCA with eight cancer types, and investigate specific driver pathways of the liquid cancer lymphoblastic acute myeloid leukemia (LAML) versus other solid cancer types. In these processes more candidate cancer genes are also found.

Developing and validating artificial intelligence models in medical imaging requires datasets that are large, granular, and diverse. To date, the majority of publicly available breast imaging datasets lack in one or more of these areas. Models trained on these data may therefore underperform on patient populations or pathologies that have not previously been encountered. The EMory BrEast imaging Dataset (EMBED) addresses these gaps by providing 3650,000 2D and DBT screening and diagnostic mammograms for 116,000 women divided equally between White and African American patients. The dataset also contains 40,000 annotated lesions linked to structured imaging descriptors and 61 ground truth pathologic outcomes grouped into six severity classes. Our goal is to share this dataset with research partners to aid in development and validation of breast AI models that will serve all patients fairly and help decrease bias in medical AI.

Purpose. Patients with advanced cancer may undergo multiple lines of treatment, switching therapies as their disease progresses. Motivated by a study of metastatic prostate cancer, we develop a microsimulation framework to study therapy sequence. Methods. We propose a discrete-time state transition model to study two lines of anti-cancer therapy. Based on digitized published progression-free survival (PFS) and overall survival (OS) curves, we infer event types (progression or death), and estimate transition probabilities using cumulative incidence functions with competing risks. Our model incorporates within-patient dependence over time, such that response to first-line therapy informs subsequent event probabilities. Parameters governing the degree of within-patient dependence can be used to calibrate the model-based results to those of a target trial. We demonstrate these methods in a study of two therapy sequences for metastatic prostate cancer, where Docetaxel (DCT) and Abiraterone Acetate (AA) are both appropriate for use in either first or second line treatment. We assess costs, Quality-Adjusted Life Years (QALYs) and Incremental Cost Effectiveness Ratio (ICER) for two treatment strategies: DCT then AA vs AA then DCT. Results. Using digitized survival curves from relevant clinical trials, we identified 8.6-13.9% of PFS times that should be categorized as deaths, allowing for estimation of cumulative incidence functions. Models assuming within-patient independence overestimated OS time, corrected with our calibration approach. Correction resulted in meaningful changes in the difference in QALYs between treatment strategies (0.07 vs 0.15) and the ICER (-\76,836/QALY vs -21,030/QALY). Conclusions. Microsimulation models can be successfully used to study cost-effectiveness of therapy sequences, taking care to account correctly for within-patient dependence.

In recent years, cancer genome sequencing and other high-throughput studies of cancer genomes have generated many notable discoveries. In this review, Novel genomic alteration mechanisms, such as chromothripsis (chromosomal crisis) and kataegis (mutation storms), and their implications for cancer are discussed. Genomic alterations spur cancer genome evolution. Thus, the relationship between cancer clonal evolution and cancer stems cells is commented. The key question in cancer biology concerns how these genomic alterations support cancer development and metastasis in the context of biological functioning. Thus far, efforts such as pathway analysis have improved the understanding of the functional contributions of genetic mutations and DNA copy number variations to cancer development, progression and metastasis. However, the known pathways correspond to a small fraction, plausibly 5-10%, of somatic mutations and genes with an altered copy number. To develop a comprehensive understanding of the function of these genomic alterations in cancer, an integrative network framework is proposed and discussed. Finally, the challenges and the directions of studying cancer omic data using an integrative network approach are commented.

Background: Cancer remains one of the leading causes of morbidity and mortality worldwide. Comprehensive datasets that combine histopathological images with genetic and survival data across various tumour sites are essential for advancing computational pathology and personalised medicine. Results: We present SurGen, a dataset comprising 1,020 H&E-stained whole slide images (WSIs) from 843 colorectal cancer cases. The dataset includes detailed annotations for key genetic mutations (KRAS, NRAS, BRAF) and mismatch repair status, as well as survival data for 426 cases. To demonstrate SurGen's practical utility, we conducted a proof-of-concept machine learning experiment predicting mismatch repair status from the WSIs, achieving a test AUROC of 0.8316. These preliminary results underscore the dataset's potential to facilitate research in biomarker discovery, prognostic modelling, and advanced machine learning applications in colorectal cancer. Conclusions: SurGen offers a valuable resource for the scientific community, enabling studies that require high-quality WSIs linked with comprehensive clinical and genetic information on colorectal cancer. Our initial findings affirm the dataset's capacity to advance diagnostic precision and foster the development of personalised treatment strategies in colorectal oncology. Data available online at https://doi.org/10.6019/S-BIAD1285.

Deep learning has enabled the development of highly robust foundation models for various pathological tasks across diverse diseases and patient cohorts. Among these models, vision-language pre-training, which leverages large-scale paired data to align pathology image and text embedding spaces, and provides a novel zero-shot paradigm for downstream tasks. However, existing models have been primarily data-driven and lack the incorporation of domain-specific knowledge, which limits their performance in cancer diagnosis, especially for rare tumor subtypes. To address this limitation, we establish a Knowledge-enhanced Pathology (KEEP) foundation model that harnesses disease knowledge to facilitate vision-language pre-training. Specifically, we first construct a disease knowledge graph (KG) that covers 11,454 human diseases with 139,143 disease attributes, including synonyms, definitions, and hypernym relations. We then systematically reorganize the millions of publicly available noisy pathology image-text pairs, into 143K well-structured semantic groups linked through the hierarchical relations of the disease KG. To derive more nuanced image and text representations, we propose a novel knowledge-enhanced vision-language pre-training approach that integrates disease knowledge into the alignment within hierarchical semantic groups instead of unstructured image-text pairs. Validated on 18 diverse benchmarks with more than 14,000 whole slide images (WSIs), KEEP achieves state-of-the-art performance in zero-shot cancer diagnostic tasks. Notably, for cancer detection, KEEP demonstrates an average sensitivity of 89.8% at a specificity of 95.0% across 7 cancer types. For cancer subtyping, KEEP achieves a median balanced accuracy of 0.456 in subtyping 30 rare brain cancers, indicating strong generalizability for diagnosing rare tumors.

Cancer has relational information residing at varying scales, modalities, and resolutions of the acquired data, such as radiology, pathology, genomics, proteomics, and clinical records. Integrating diverse data types can improve the accuracy and reliability of cancer diagnosis and treatment. There can be disease-related information that is too subtle for humans or existing technological tools to discern visually. Traditional methods typically focus on partial or unimodal information about biological systems at individual scales and fail to encapsulate the complete spectrum of the heterogeneous nature of data. Deep neural networks have facilitated the development of sophisticated multimodal data fusion approaches that can extract and integrate relevant information from multiple sources. Recent deep learning frameworks such as Graph Neural Networks (GNNs) and Transformers have shown remarkable success in multimodal learning. This review article provides an in-depth analysis of the state-of-the-art in GNNs and Transformers for multimodal data fusion in oncology settings, highlighting notable research studies and their findings. We also discuss the foundations of multimodal learning, inherent challenges, and opportunities for integrative learning in oncology. By examining the current state and potential future developments of multimodal data integration in oncology, we aim to demonstrate the promising role that multimodal neural networks can play in cancer prevention, early detection, and treatment through informed oncology practices in personalized settings.

With an estimated 160,000 deaths in 2018, lung cancer is the most common cause of cancer death in the United States. Lung cancer CT screening has been shown to reduce mortality by up to 40% and is now included in US screening guidelines. Reducing the high error rates in lung cancer screening is imperative because of the high clinical and financial costs caused by diagnosis mistakes. Despite the use of standards for radiological diagnosis, persistent inter-grader variability and incomplete characterization of comprehensive imaging findings remain as limitations of current methods. These limitations suggest opportunities for more sophisticated systems to improve performance and inter-reader consistency. In this report, we reproduce a state-of-the-art deep learning algorithm for lung cancer risk prediction. Our model predicts malignancy probability and risk bucket classification from lung CT studies. This allows for risk categorization of patients being screened and suggests the most appropriate surveillance and management. Combining our solution high accuracy, consistency and fully automated nature, our approach may enable highly efficient screening procedures and accelerate the adoption of lung cancer screening.

Cancer is the second leading cause of death, with chemotherapy as one of the primary forms of treatment. As a result, researchers are turning to drug combination therapy to decrease drug resistance and increase efficacy. Current methods of drug combination screening, such as in vivo and in vitro, are inefficient due to stark time and monetary costs. In silico methods have become increasingly important for screening drugs, but current methods are inaccurate and generalize poorly to unseen anticancer drugs. In this paper, I employ a geometric deep-learning model utilizing a graph attention network that is equivariant to 3D rotations, translations, and reflections with structural motifs. Additionally, the gene expression of cancer cell lines is utilized to classify synergistic drug combinations specific to each cell line. I compared the proposed geometric deep learning framework to current state-of-the-art (SOTA) methods, and the proposed model architecture achieved greater performance on all 12 benchmark tasks performed on the DrugComb dataset. Specifically, the proposed framework outperformed other SOTA methods by an accuracy difference greater than 28%. Based on these results, I believe that the equivariant graph attention network's capability of learning geometric data accounts for the large performance improvements. The model's ability to generalize to foreign drugs is thought to be due to the structural motifs providing a better representation of the molecule. Overall, I believe that the proposed equivariant geometric deep learning framework serves as an effective tool for virtually screening anticancer drug combinations for further validation in a wet lab environment. The code for this work is made available online at: https://github.com/WeToTheMoon/EGAT_DrugSynergy.

We investigate a new dynamical system that describes tumor-host interaction. The equation that describes the untreated tumor growth is based on non-extensive statistical mechanics. Recently, this model has been shown to fit successfully exponential, Gompertz, logistic, and power-law tumor growths. We have been able to include as many hallmarks of cancer as possible. We study also the dynamic response of cancer under therapy. Using our model, we can make predictions about the different outcomes when we change the parameters, and/or the initial conditions. We can determine the importance of different factors to influence tumor growth. We discover synergistic therapeutic effects of different treatments and drugs. Cancer is generally untreatable using conventional monotherapy. We consider conventional therapies, oncogene-targeted therapies, tumor-suppressors gene-targeted therapies, immunotherapies, anti-angiogenesis therapies, virotherapy, among others. We need therapies with the potential to target both tumor cells and the tumors' microenvironment. Drugs that target oncogenes and tumor-suppressor genes can be effective in the treatment of some cancers. However, most tumors do reoccur. We have found that the success of the new therapeutic agents can be seen when used in combination with other cancer-cell-killing therapies. Our results have allowed us to design a combinational therapy that can lead to the complete eradication of cancer.

In recent years, a standard computational pathology workflow has emerged where whole slide images are cropped into tiles, these tiles are processed using a foundation model, and task-specific models are built using the resulting representations. At least 15 different foundation models have been proposed, and the vast majority are trained exclusively with tiles using the 20times magnification. However, it is well known that certain histologic features can only be discerned with larger context windows and requires a pathologist to zoom in and out when analyzing a whole slide image. Furthermore, creating 224times224 pixel crops at 20times leads to a large number of tiles per slide, which can be gigapixel in size. To more accurately capture multi-resolution features and investigate the possibility of reducing the number of representations per slide, we propose a region-level mixing encoder. Our approach jointly fuses image tile representations of a mixed magnification foundation model using a masked embedding modeling pretraining step. We explore a design space for pretraining the proposed mixed-magnification region aggregators and evaluate our models on transfer to biomarker prediction tasks representing various cancer types. Results demonstrate cancer dependent improvements in predictive performance, highlighting the importance of spatial context and understanding.

Genomic alterations lead to cancer complexity and form a major hurdle for a comprehensive understanding of the molecular mechanisms underlying oncogenesis. In this review, we describe the recent advances in studying cancer-associated genes from a systems biological point of view. The integration of known cancer genes onto protein and signaling networks reveals the characteristics of cancer genes within networks. This approach shows that cancer genes often function as network hub proteins which are involved in many cellular processes and form focal nodes in the information exchange between many signaling pathways. Literature mining allows constructing gene-gene networks, in which new cancer genes can be identified. The gene expression profiles of cancer cells are used for reconstructing gene regulatory networks. By doing so, the genes, which are involved in the regulation of cancer progression, can be picked up from these networks after which their functions can be further confirmed in the laboratory.

In oncology, treating cancer with a beam of photons is a well established therapeutic technique, developed over 100 years, and today over 50% of cancer patients will undergo traditional X-ray radiotherapy. However, ionizing radiation therapy is not the only option, as the high-energy photons delivering their cell-killing radiation energy into cancerous tumor can lead to significant damage to healthy tissues surrounding the tumor, located throughout the beam's path. Therefore, in nowadays, advances in ionizing radiation therapy are competitive to non-ionizing ones, as for example the laser light based therapy, resulting in a synergism that has revolutionized medicine. The use of non-invasive or minimally invasive (e.g. through flexible endoscopes) therapeutic procedures in the management of patients represents a very interesting treatment option. Moreover, as the major breakthrough in cancer management is the individualized patient treatment, new biophotonic techniques, e.g. photo-activated drug carriers, help the improvement of treatment efficacy and/or normal tissue toxicity. Additionally, recent studies support that laser technology progresses could revolutionize cancer proton therapy, by reducing the cost of the needed installations. The aim of this review is to present some laser-based future objectives for cancer radiation therapy, aiming to address the relevant advances in the ionizing and non-ionizing radiation therapy, i.e. protons and heavy ions therapy, as well as photodynamic targeted and molecular therapies.

Complex prediction models such as deep learning are the output from fitting machine learning, neural networks, or AI models to a set of training data. These are now standard tools in science. A key challenge with the current generation of models is that they are highly parameterized, which makes describing and interpreting the prediction strategies difficult. We use topological data analysis to transform these complex prediction models into pictures representing a topological view. The result is a map of the predictions that enables inspection. The methods scale up to large datasets across different domains and enable us to detect labeling errors in training data, understand generalization in image classification, and inspect predictions of likely pathogenic mutations in the BRCA1 gene.

A principal component analysis of the TCGA data for 15 cancer localizations unveils the following qualitative facts about tumors: 1) The state of a tissue in gene expression space may be described by a few variables. In particular, there is a single variable describing the progression from a normal tissue to a tumor. 2) Each cancer localization is characterized by a gene expression profile, in which genes have specific weights in the definition of the cancer state. There are no less than 2500 differentially-expressed genes, which lead to power-like tails in the expression distribution functions. 3) Tumors in different localizations share hundreds or even thousands of differentially expressed genes. There are 6 genes common to the 15 studied tumor localizations. 4) The tumor region is a kind of attractor. Tumors in advanced stages converge to this region independently of patient age or genetic variability. 5) There is a landscape of cancer in gene expression space with an approximate border separating normal tissues from tumors.

Environmental and genetic mutations can transform the cells in a co-operating healthy tissue into an ecosystem of individualistic tumour cells that compete for space and resources. Various selection forces are responsible for driving the evolution of cells in a tumour towards more malignant and aggressive phenotypes that tend to have a fitness advantage over the older populations. Although the evolutionary nature of cancer has been recognised for more than three decades (ever since the seminal work of Nowell) it has been only recently that tools traditionally used by ecological and evolutionary researchers have been adopted to study the evolution of cancer phenotypes in populations of individuals capable of co-operation and competition. In this chapter we will describe game theory as an important tool to study the emergence of cell phenotypes in a tumour and will critically review some of its applications in cancer research. These applications demonstrate that game theory can be used to understand the dynamics of somatic cancer evolution and suggest new therapies in which this knowledge could be applied to gain some control over the evolution of the tumour.

Multi-omics research has enhanced our understanding of cancer heterogeneity and progression. Investigating molecular data through multi-omics approaches is crucial for unraveling the complex biological mechanisms underlying cancer, thereby enabling effective diagnosis, treatment, and prevention strategies. However, predicting patient outcomes through integration of all available multi-omics data is an under-study research direction. Here, we present SeNMo (Self-normalizing Network for Multi-omics), a deep neural network trained on multi-omics data across 33 cancer types. SeNMo is efficient in handling multi-omics data characterized by high-width (many features) and low-length (fewer samples) attributes. We trained SeNMo for the task of overall survival using pan-cancer data involving 33 cancer sites from Genomics Data Commons (GDC). The training data includes gene expression, DNA methylation, miRNA expression, DNA mutations, protein expression modalities, and clinical data. We evaluated the model's performance in predicting overall survival using concordance index (C-Index). SeNMo performed consistently well in training regime, with the validation C-Index of 0.76 on GDC's public data. In the testing regime, SeNMo performed with a C-Index of 0.758 on a held-out test set. The model showed an average accuracy of 99.8% on the task of classifying the primary cancer type on the pan-cancer test cohort. SeNMo proved to be a mini-foundation model for multi-omics oncology data because it demonstrated robust performance, and adaptability not only across molecular data types but also on the classification task of predicting the primary cancer type of patients. SeNMo can be further scaled to any cancer site and molecular data type. We believe SeNMo and similar models are poised to transform the oncology landscape, offering hope for more effective, efficient, and patient-centric cancer care.

During their formative years, radiology trainees are required to interpret hundreds of mammograms per month, with the objective of becoming apt at discerning the subtle patterns differentiating benign from malignant lesions. Unfortunately, medico-legal and technical hurdles make it difficult to access and query medical images for training. In this paper we train a generative adversarial network (GAN) to synthesize 512 x 512 high-resolution mammograms. The resulting model leads to the unsupervised separation of high-level features (e.g. the standard mammography views and the nature of the breast lesions), with stochastic variation in the generated images (e.g. breast adipose tissue, calcification), enabling user-controlled global and local attribute-editing of the synthesized images. We demonstrate the model's ability to generate anatomically and medically relevant mammograms by achieving an average AUC of 0.54 in a double-blind study on four expert mammography radiologists to distinguish between generated and real images, ascribing to the high visual quality of the synthesized and edited mammograms, and to their potential use in advancing and facilitating medical education.

Purpose: To evaluate the performance of an automated deep learning method in detecting ascites and subsequently quantifying its volume in patients with liver cirrhosis and ovarian cancer. Materials and Methods: This retrospective study included contrast-enhanced and non-contrast abdominal-pelvic CT scans of patients with cirrhotic ascites and patients with ovarian cancer from two institutions, National Institutes of Health (NIH) and University of Wisconsin (UofW). The model, trained on The Cancer Genome Atlas Ovarian Cancer dataset (mean age, 60 years +/- 11 [s.d.]; 143 female), was tested on two internal (NIH-LC and NIH-OV) and one external dataset (UofW-LC). Its performance was measured by the Dice coefficient, standard deviations, and 95% confidence intervals, focusing on ascites volume in the peritoneal cavity. Results: On NIH-LC (25 patients; mean age, 59 years +/- 14 [s.d.]; 14 male) and NIH-OV (166 patients; mean age, 65 years +/- 9 [s.d.]; all female), the model achieved Dice scores of 0.855 +/- 0.061 (CI: 0.831-0.878) and 0.826 +/- 0.153 (CI: 0.764-0.887), with median volume estimation errors of 19.6% (IQR: 13.2-29.0) and 5.3% (IQR: 2.4-9.7) respectively. On UofW-LC (124 patients; mean age, 46 years +/- 12 [s.d.]; 73 female), the model had a Dice score of 0.830 +/- 0.107 (CI: 0.798-0.863) and median volume estimation error of 9.7% (IQR: 4.5-15.1). The model showed strong agreement with expert assessments, with r^2 values of 0.79, 0.98, and 0.97 across the test sets. Conclusion: The proposed deep learning method performed well in segmenting and quantifying the volume of ascites in concordance with expert radiologist assessments.

Breast ultrasound (BUS) is a critical diagnostic tool in the field of breast imaging, aiding in the early detection and characterization of breast abnormalities. Interpreting breast ultrasound images commonly involves creating comprehensive medical reports, containing vital information to promptly assess the patient's condition. However, the ultrasound imaging system necessitates capturing multiple images of various parts to compile a single report, presenting a time-consuming challenge. To address this problem, we propose the integration of multiple image analysis tools through a LangChain using Large Language Models (LLM), into the breast reporting process. Through a combination of designated tools and text generation through LangChain, our method can accurately extract relevant features from ultrasound images, interpret them in a clinical context, and produce comprehensive and standardized reports. This approach not only reduces the burden on radiologists and healthcare professionals but also enhances the consistency and quality of reports. The extensive experiments shows that each tools involved in the proposed method can offer qualitatively and quantitatively significant results. Furthermore, clinical evaluation on the generated reports demonstrates that the proposed method can make report in clinically meaningful way.

We introduce a general, flexible, parametric survival modelling framework which encompasses key shapes of hazard function (constant, increasing, decreasing, up-then-down, down-then-up), various common survival distributions (log-logistic, Burr type XII, Weibull, Gompertz), and includes defective distributions (i.e., cure models). This generality is achieved using four basic distributional parameters: two scale-type parameters and two shape parameters. Generalising to covariate dependence, the scale-type regression components correspond to accelerated failure time (AFT) and proportional hazards (PH) models. Therefore, this general formulation unifies the most popular survival models which allows us to consider the practical value of possible modelling choices for survival data. Furthermore, in line with our proposed flexible baseline distribution, we advocate the use of multi-parameter regression in which more than one distributional parameter depends on covariates - rather than the usual convention of having a single covariate-dependent (scale) parameter. While many choices are available, we suggest introducing covariates through just one or other of the two scale parameters, which covers AFT and PH models, in combination with a `power' shape parameter, which allows for more complex non-AFT/non-PH effects, while the other shape parameter remains covariate-independent, and handles automatic selection of the baseline distribution. We explore inferential issues in simulations, both with and without a covariate, with particular focus on evidence concerning the need, or otherwise, to include both AFT and PH parameters. We illustrate the efficacy of our modelling framework by investigating differences between treatment groups using data from a lung cancer study and a melanoma study. Censoring is accommodated throughout.

To investigate whether the pleurae, airways and vessels surrounding a nodule on non-contrast computed tomography (CT) can discriminate benign and malignant pulmonary nodules. The LIDC-IDRI dataset, one of the largest publicly available CT database, was exploited for study. A total of 1556 nodules from 694 patients were involved in statistical analysis, where nodules with average scorings <3 and >3 were respectively denoted as benign and malignant. Besides, 339 nodules from 113 patients with diagnosis ground-truth were independently evaluated. Computer algorithms were developed to segment pulmonary structures and quantify the distances to pleural surface, airways and vessels, as well as the counting number and normalized volume of airways and vessels near a nodule. Odds ratio (OR) and Chi-square (\chi^2) testing were performed to demonstrate the correlation between features of surrounding structures and nodule malignancy. A non-parametric receiver operating characteristic (ROC) analysis was conducted in logistic regression to evaluate discrimination ability of each structure. For benign and malignant groups, the average distances from nodules to pleural surface, airways and vessels are respectively (6.56, 5.19), (37.08, 26.43) and (1.42, 1.07) mm. The correlation between nodules and the counting number of airways and vessels that contact or project towards nodules are respectively (OR=22.96, \chi^2=105.04) and (OR=7.06, \chi^2=290.11). The correlation between nodules and the volume of airways and vessels are (OR=9.19, \chi^2=159.02) and (OR=2.29, \chi^2=55.89). The areas-under-curves (AUCs) for pleurae, airways and vessels are respectively 0.5202, 0.6943 and 0.6529. Our results show that malignant nodules are often surrounded by more pulmonary structures compared with benign ones, suggesting that features of these structures could be viewed as lung cancer biomarkers.

Clinical trials drive improvements in cancer treatments and outcomes. However, most adults with cancer do not participate in trials, and trials often fail to enroll enough patients to answer their scientific questions. Artificial intelligence could accelerate matching of patients to appropriate clinical trials. Here, we describe the development and evaluation of the MatchMiner-AI pipeline for clinical trial searching and ranking. MatchMiner-AI focuses on matching patients to potential trials based on core criteria describing clinical "spaces," or disease contexts, targeted by a trial. It aims to accelerate the human work of identifying potential matches, not to fully automate trial screening. The pipeline includes modules for extraction of key information from a patient's longitudinal electronic health record; rapid ranking of candidate trial-patient matches based on embeddings in vector space; and classification of whether a candidate match represents a reasonable clinical consideration. Code and synthetic data are available at https://huggingface.co/ksg-dfci/MatchMiner-AI . Model weights based on synthetic data are available at https://huggingface.co/ksg-dfci/TrialSpace and https://huggingface.co/ksg-dfci/TrialChecker . A simple cancer clinical trial search engine to demonstrate pipeline components is available at https://huggingface.co/spaces/ksg-dfci/trial_search_alpha .

While the use of combination therapy is increasing in prevalence for cancer treatment, it is often difficult to predict the exact interactions between different treatment forms, and their synergistic/antagonistic effects on patient health and therapy outcome. In this research, a system of ordinary differential equations is constructed to model nonlinear dynamics between tumor cells, immune cells, and three forms of therapy: chemotherapy, immunotherapy, and radiotherapy. This model is then used to generate optimized combination therapy plans using optimal control theory. In-silico experiments are conducted to simulate the response of the patient model to various treatment plans. This is the first mathematical model in current literature to introduce radiotherapy as an option alongside immuno- and chemotherapy, permitting more flexible and effective treatment plans that reflect modern therapeutic approaches.

Lung cancer stands as the preeminent cause of cancer-related mortality globally. Prompt and precise diagnosis, coupled with effective treatment, is imperative to reduce the fatality rates associated with this formidable disease. This study introduces a cutting-edge deep learning framework for the classification of lung cancer from CT scan imagery. The research encompasses a suite of image pre-processing strategies, notably Canny edge detection, and wavelet transformations, which precede the extraction of salient features and subsequent classification via a Multi-Layer Perceptron (MLP). The optimization process is further refined using the Dragonfly Algorithm (DA). The methodology put forth has attained an impressive training and testing accuracy of 99.82\%, underscoring its efficacy and reliability in the accurate diagnosis of lung cancer.

Whole-Slide Image (WSI) is an important tool for evaluating the prognosis of cancer patients. Present WSI-based prognosis studies generally follow a conventional paradigm -- cancer-specific model development -- where one cancer disease corresponds to one model and this model cannot make use of the prognostic knowledge from others. Despite its notable success in recent years, this paradigm has inherent limitations and has always been struggling with practical requirements: (i) scaling to the rare tumor diseases with very limited samples and (ii) benefiting from the generalizable prognostic knowledge in other cancers. To this end, this paper presents the first systematic study on Prognostic Knowledge Transfer in Pathology, called Path-PKT. It comprises three main parts. (1) We curate a large dataset (UNI2-h-DSS) with 13 cancers and use it to evaluate the transferability of prognostic knowledge between different cancers computationally. (2) We design experiments to understand what factors affect knowledge transfer and what causes positive transfers. (3) Motivated by empirical findings, we propose a new baseline approach (MoE-PKT) with a routing mechanism to utilize the generalizable prognostic knowledge in other cancers. Finally, we show the transferability of source models to rare tumor diseases. This study could lay solid foundations for the study of knowledge transfer in WSI-based cancer prognosis. Source code is available at https://github.com/liupei101/Path-PKT.

Lung cancer patients frequently experience breakthrough pain episodes, with up to 91% requiring timely intervention. To enable proactive pain management, we propose a hybrid machine learning and large language model pipeline that predicts pain episodes within 48 and 72 hours of hospitalization using both structured and unstructured electronic health record data. A retrospective cohort of 266 inpatients was analyzed, with features including demographics, tumor stage, vital signs, and WHO-tiered analgesic use. The machine learning module captured temporal medication trends, while the large language model interpreted ambiguous dosing records and free-text clinical notes. Integrating these modalities improved sensitivity and interpretability. Our framework achieved an accuracy of 0.874 (48h) and 0.917 (72h), with an improvement in sensitivity of 8.6% and 10.4% due to the augmentation of large language model. This hybrid approach offers a clinically interpretable and scalable tool for early pain episode forecasting, with potential to enhance treatment precision and optimize resource allocation in oncology care.

A key component of deep learning (DL) for natural language processing (NLP) is word embeddings. Word embeddings that effectively capture the meaning and context of the word that they represent can significantly improve the performance of downstream DL models for various NLP tasks. Many existing word embeddings techniques capture the context of words based on word co-occurrence in documents and text; however, they often cannot capture broader domain-specific relationships between concepts that may be crucial for the NLP task at hand. In this paper, we propose a method to integrate external knowledge from medical terminology ontologies into the context captured by word embeddings. Specifically, we use a medical knowledge graph, such as the unified medical language system (UMLS), to find connections between clinical terms in cancer pathology reports. This approach aims to minimize the distance between connected clinical concepts. We evaluate the proposed approach using a Multitask Convolutional Neural Network (MT-CNN) to extract six cancer characteristics -- site, subsite, laterality, behavior, histology, and grade -- from a dataset of ~900K cancer pathology reports. The results show that the MT-CNN model which uses our domain informed embeddings outperforms the same MT-CNN using standard word2vec embeddings across all tasks, with an improvement in the overall micro- and macro-F1 scores by 4.97\%and 22.5\%, respectively.

This paper presents a Patherea, a framework for point-based cell detection and classification that provides a complete solution for developing and evaluating state-of-the-art approaches. We introduce a large-scale dataset collected to directly replicate a clinical workflow for Ki-67 proliferation index estimation and use it to develop an efficient point-based approach that directly predicts point-based predictions, without the need for intermediate representations. The proposed approach effectively utilizes point proposal candidates with the hybrid Hungarian matching strategy and a flexible architecture that enables the usage of various backbones and (pre)training strategies. We report state-of-the-art results on existing public datasets - Lizard, BRCA-M2C, BCData, and the newly proposed Patherea dataset. We show that the performance on existing public datasets is saturated and that the newly proposed Patherea dataset represents a significantly harder challenge for the recently proposed approaches. We also demonstrate the effectiveness of recently proposed pathology foundational models that our proposed approach can natively utilize and benefit from. We also revisit the evaluation protocol that is used in the broader field of cell detection and classification and identify the erroneous calculation of performance metrics. Patherea provides a benchmarking utility that addresses the identified issues and enables a fair comparison of different approaches. The dataset and the code will be publicly released upon acceptance.

Foundation models (FMs) are transforming computational pathology by offering new ways to analyze histopathology images. However, FMs typically require weeks of training on large databases, making their creation a resource-intensive process. In this paper, we present a training for foundation models from whole slide images using supervised, end-to-end, multitask learning on slide-level labels. Notably, it is the first model to incorporate cancer subtyping, risk estimation, and genetic mutation prediction into one model. The presented model outperforms self-supervised models on seven benchmark tasks while the training only required 5% of the computational resources. The results not only show that supervised training can outperform self-supervision with less data, but also offer a solution to annotation problems, as patient-based labels are widely available through routine clinical processes. Furthermore, an attention module provides a layer of explainability across different tasks and serves as a tumor detector for unseen cancer types. To address the issue of closed-source datasets, the model was fully trained on openly available data. The code and model weights are made available under https://github.com/FraunhoferMEVIS/MedicalMultitaskModeling.

Pathology Foundation Models (FMs) hold great promise for healthcare. Before they can be used in clinical practice, it is essential to ensure they are robust to variations between medical centers. We measure whether pathology FMs focus on biological features like tissue and cancer type, or on the well known confounding medical center signatures introduced by staining procedure and other differences. We introduce the Robustness Index. This novel robustness metric reflects to what degree biological features dominate confounding features. Ten current publicly available pathology FMs are evaluated. We find that all current pathology foundation models evaluated represent the medical center to a strong degree. Significant differences in the robustness index are observed. Only one model so far has a robustness index greater than one, meaning biological features dominate confounding features, but only slightly. A quantitative approach to measure the influence of medical center differences on FM-based prediction performance is described. We analyze the impact of unrobustness on classification performance of downstream models, and find that cancer-type classification errors are not random, but specifically attributable to same-center confounders: images of other classes from the same medical center. We visualize FM embedding spaces, and find these are more strongly organized by medical centers than by biological factors. As a consequence, the medical center of origin is predicted more accurately than the tissue source and cancer type. The robustness index introduced here is provided with the aim of advancing progress towards clinical adoption of robust and reliable pathology FMs.

In here presented in silico study we suggest a way how to implement the evolutionary principles into anti-cancer therapy design. We hypothesize that instead of its ongoing supervised adaptation, the therapy may be constructed as a self-sustaining evolutionary process in a dynamic fitness landscape established implicitly by evolving cancer cells, microenvironment and the therapy itself. For these purposes, we replace a unified therapy with the `therapy species', which is a population of heterogeneous elementary therapies, and propose a way how to turn the toxicity of the elementary therapy into its fitness in a way conforming to evolutionary causation. As a result, not only the therapies govern the evolution of different cell phenotypes, but the cells' resistances govern the evolution of the therapies as well. We illustrate the approach by the minimalistic ad hoc evolutionary model. Its results indicate that the resistant cells could bias the evolution towards more toxic elementary therapies by inhibiting the less toxic ones. As the evolutionary causation of cancer drug resistance has been intensively studied for a few decades, we refer to cancer as a special case to illustrate purely theoretical analysis.

Clinical monitoring of metastatic disease to the brain can be a laborious and time-consuming process, especially in cases involving multiple metastases when the assessment is performed manually. The Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) guideline, which utilizes the unidimensional longest diameter, is commonly used in clinical and research settings to evaluate response to therapy in patients with brain metastases. However, accurate volumetric assessment of the lesion and surrounding peri-lesional edema holds significant importance in clinical decision-making and can greatly enhance outcome prediction. The unique challenge in performing segmentations of brain metastases lies in their common occurrence as small lesions. Detection and segmentation of lesions that are smaller than 10 mm in size has not demonstrated high accuracy in prior publications. The brain metastases challenge sets itself apart from previously conducted MICCAI challenges on glioma segmentation due to the significant variability in lesion size. Unlike gliomas, which tend to be larger on presentation scans, brain metastases exhibit a wide range of sizes and tend to include small lesions. We hope that the BraTS-METS dataset and challenge will advance the field of automated brain metastasis detection and segmentation.

The remarkable success of deep learning in recent years has prompted applications in medical image classification and diagnosis tasks. While classification models have demonstrated robustness in classifying simpler datasets like MNIST or natural images such as ImageNet, this resilience is not consistently observed in complex medical image datasets where data is more scarce and lacks diversity. Moreover, previous findings on natural image datasets have indicated a potential trade-off between data likelihood and classification accuracy. In this study, we explore the use of score-based generative models as classifiers for medical images, specifically mammographic images. Our findings suggest that our proposed generative classifier model not only achieves superior classification results on CBIS-DDSM, INbreast and Vin-Dr Mammo datasets, but also introduces a novel approach to image classification in a broader context. Our code is publicly available at https://github.com/sushmitasarker/sgc_for_medical_image_classification

While pathology foundation models have transformed cancer image analysis, they often lack integration with molecular data at single-cell resolution, limiting their utility for precision oncology. Here, we present PAST, a pan-cancer single-cell foundation model trained on 20 million paired histopathology images and single-cell transcriptomes spanning multiple tumor types and tissue contexts. By jointly encoding cellular morphology and gene expression, PAST learns unified cross-modal representations that capture both spatial and molecular heterogeneity at the cellular level. This approach enables accurate prediction of single-cell gene expression, virtual molecular staining, and multimodal survival analysis directly from routine pathology slides. Across diverse cancers and downstream tasks, PAST consistently exceeds the performance of existing approaches, demonstrating robust generalizability and scalability. Our work establishes a new paradigm for pathology foundation models, providing a versatile tool for high-resolution spatial omics, mechanistic discovery, and precision cancer research.

To generate evidence regarding the safety and efficacy of artificial intelligence (AI) enabled medical devices, AI models need to be evaluated on a diverse population of patient cases, some of which may not be readily available. We propose an evaluation approach for testing medical imaging AI models that relies on in silico imaging pipelines in which stochastic digital models of human anatomy (in object space) with and without pathology are imaged using a digital replica imaging acquisition system to generate realistic synthetic image datasets. Here, we release M-SYNTH, a dataset of cohorts with four breast fibroglandular density distributions imaged at different exposure levels using Monte Carlo x-ray simulations with the publicly available Virtual Imaging Clinical Trial for Regulatory Evaluation (VICTRE) toolkit. We utilize the synthetic dataset to analyze AI model performance and find that model performance decreases with increasing breast density and increases with higher mass density, as expected. As exposure levels decrease, AI model performance drops with the highest performance achieved at exposure levels lower than the nominal recommended dose for the breast type.

Early tumor detection save lives. Each year, more than 300 million computed tomography (CT) scans are performed worldwide, offering a vast opportunity for effective cancer screening. However, detecting small or early-stage tumors on these CT scans remains challenging, even for experts. Artificial intelligence (AI) models can assist by highlighting suspicious regions, but training such models typically requires extensive tumor masks--detailed, voxel-wise outlines of tumors manually drawn by radiologists. Drawing these masks is costly, requiring years of effort and millions of dollars. In contrast, nearly every CT scan in clinical practice is already accompanied by medical reports describing the tumor's size, number, appearance, and sometimes, pathology results--information that is rich, abundant, and often underutilized for AI training. We introduce R-Super, which trains AI to segment tumors that match their descriptions in medical reports. This approach scales AI training with large collections of readily available medical reports, substantially reducing the need for manually drawn tumor masks. When trained on 101,654 reports, AI models achieved performance comparable to those trained on 723 masks. Combining reports and masks further improved sensitivity by +13% and specificity by +8%, surpassing radiologists in detecting five of the seven tumor types. Notably, R-Super enabled segmentation of tumors in the spleen, gallbladder, prostate, bladder, uterus, and esophagus, for which no public masks or AI models previously existed. This study challenges the long-held belief that large-scale, labor-intensive tumor mask creation is indispensable, establishing a scalable and accessible path toward early detection across diverse tumor types. We plan to release our trained models, code, and dataset at https://github.com/MrGiovanni/R-Super

Histopathological images contain rich phenotypic information that can be used to monitor underlying mechanisms contributing to diseases progression and patient survival outcomes. Recently, deep learning has become the mainstream methodological choice for analyzing and interpreting cancer histology images. In this paper, we present a comprehensive review of state-of-the-art deep learning approaches that have been used in the context of histopathological image analysis. From the survey of over 130 papers, we review the fields progress based on the methodological aspect of different machine learning strategies such as supervised, weakly supervised, unsupervised, transfer learning and various other sub-variants of these methods. We also provide an overview of deep learning based survival models that are applicable for disease-specific prognosis tasks. Finally, we summarize several existing open datasets and highlight critical challenges and limitations with current deep learning approaches, along with possible avenues for future research.

Cancer is a genetic disorder whose clonal evolution can be monitored by tracking noisy genome-wide copy number variants. We introduce the Copy Number Stochastic Block Model (CN-SBM), a probabilistic framework that jointly clusters samples and genomic regions based on discrete copy number states using a bipartite categorical block model. Unlike models relying on Gaussian or Poisson assumptions, CN-SBM respects the discrete nature of CNV calls and captures subpopulation-specific patterns through block-wise structure. Using a two-stage approach, CN-SBM decomposes CNV data into primary and residual components, enabling detection of both large-scale chromosomal alterations and finer aberrations. We derive a scalable variational inference algorithm for application to large cohorts and high-resolution data. Benchmarks on simulated and real datasets show improved model fit over existing methods. Applied to TCGA low-grade glioma data, CN-SBM reveals clinically relevant subtypes and structured residual variation, aiding patient stratification in survival analysis. These results establish CN-SBM as an interpretable, scalable framework for CNV analysis with direct relevance for tumor heterogeneity and prognosis.

Complex gene interactions play a significant role in cancer progression, driving cellular behaviors that contribute to tumor growth, invasion, and metastasis. Gene co-expression networks model the functional connectivity between genes under various biological conditions. Understanding the system-level evolution of these networks in cancer is critical for elucidating disease mechanisms and informing the development of targeted therapies. While previous studies have primarily focused on structural differences between cancer and normal cell co-expression networks, this study applies graph frequency analysis to cancer transcriptomic signals defined on gene co-expression networks, highlighting the graph spectral characteristics of cancer systems. Using a range of graph frequency filters, we showed that cancer cells display distinctive patterns in the graph frequency content of their gene transcriptomic signals, effectively distinguishing between cancer types and stages. The transformation of the original gene feature space into the graph spectral space captured more intricate cancer properties, as validated by significantly higher F-statistic scores for graph frequency-filtered gene features compared to those in the original space.

Remarkable strides in computational pathology have been made in the task-agnostic foundation model that advances the performance of a wide array of downstream clinical tasks. Despite the promising performance, there are still several challenges. First, prior works have resorted to either vision-only or image-caption data, disregarding pathology reports with more clinically authentic information from pathologists and gene expression profiles which respectively offer distinct knowledge for versatile clinical applications. Second, the current progress in pathology FMs predominantly concentrates on the patch level, where the restricted context of patch-level pretraining fails to capture whole-slide patterns. Even recent slide-level FMs still struggle to provide whole-slide context for patch representation. In this study, for the first time, we develop a pathology foundation model incorporating three levels of modalities: pathology slides, pathology reports, and gene expression data, which resulted in 26,169 slide-level modality pairs from 10,275 patients across 32 cancer types, amounting to over 116 million pathological patch images. To leverage these data for CPath, we propose a novel whole-slide pretraining paradigm that injects the multimodal whole-slide context into the patch representation, called Multimodal Self-TAught PRetraining (mSTAR). The proposed paradigm revolutionizes the pretraining workflow for CPath, enabling the pathology FM to acquire the whole-slide context. To the best of our knowledge, this is the first attempt to incorporate three modalities at the whole-slide context for enhancing pathology FMs. To systematically evaluate the capabilities of mSTAR, we built the largest spectrum of oncological benchmark, spanning 7 categories of oncological applications in 15 types of 97 practical oncological tasks.

Rare cancers comprise 20-25% of all malignancies but face major diagnostic challenges due to limited expert availability-especially in pediatric oncology, where they represent over 70% of cases. While pathology vision-language (VL) foundation models show promising zero-shot capabilities for common cancer subtyping, their clinical performance for rare cancers remains limited. Existing multi-instance learning (MIL) methods rely only on visual features, overlooking cross-modal knowledge and compromising interpretability critical for rare cancer diagnosis. To address this limitation, we propose PathPT, a novel framework that fully exploits the potential of vision-language pathology foundation models through spatially-aware visual aggregation and task-specific prompt tuning. Unlike conventional MIL, PathPT converts WSI-level supervision into fine-grained tile-level guidance by leveraging the zero-shot capabilities of VL models, thereby preserving localization on cancerous regions and enabling cross-modal reasoning through prompts aligned with histopathological semantics. We benchmark PathPT on eight rare cancer datasets(four adult and four pediatric) spanning 56 subtypes and 2,910 WSIs, as well as three common cancer datasets, evaluating four state-of-the-art VL models and four MIL frameworks under three few-shot settings. Results show that PathPT consistently delivers superior performance, achieving substantial gains in subtyping accuracy and cancerous region grounding ability. This work advances AI-assisted diagnosis for rare cancers, offering a scalable solution for improving subtyping accuracy in settings with limited access to specialized expertise.