hepatocellular carcinoma
Adversarial Multi-Task Learning for Liver Tumor Segmentation, Dynamic Enhancement Regression, and Classification
Xiao, Xiaojiao, Hu, Qinmin Vivian, Kim, Tae Hyun, Wang, Guanghui
Liver tumor segmentation, dynamic enhancement regression, and classification are critical for clinical assessment and diagnosis. However, no prior work has attempted to achieve these tasks simultaneously in an end-to-end framework, primarily due to the lack of an effective framework that captures inter-task relevance for mutual improvement and the absence of a mechanism to extract dynamic MRI information effectively. To address these challenges, we propose the Multi-Task Interaction adversarial learning Network (MTI-Net), a novel integrated framework designed to tackle these tasks simultaneously. MTI-Net incorporates Multi-domain Information Entropy Fusion (MdIEF), which utilizes entropy-aware, high-frequency spectral information to effectively integrate features from both frequency and spectral domains, enhancing the extraction and utilization of dynamic MRI data. The network also introduces a task interaction module that establishes higher-order consistency between segmentation and regression, thus fostering inter-task synergy and improving overall performance. Additionally, we designed a novel task-driven discriminator (TDD) to capture internal high-order relationships between tasks. For dynamic MRI information extraction, we employ a shallow Transformer network to perform positional encoding, which captures the relationships within dynamic MRI sequences. In experiments on a dataset of 238 subjects, MTI-Net demonstrates high performance across multiple tasks, indicating its strong potential for assisting in the clinical assessment of liver tumors.
Learning ON Large Datasets Using Bit-String Trees
This thesis develops computational methods in similarity-preserving hashing, classification, and cancer genomics. Standard space partitioning-based hashing relies on Binary Search Trees (BSTs), but their exponential growth and sparsity hinder efficiency. To overcome this, we introduce Compressed BST of Inverted hash tables (ComBI), which enables fast approximate nearest-neighbor search with reduced memory. On datasets of up to one billion samples, ComBI achieves 0.90 precision with 4X-296X speed-ups over Multi-Index Hashing, and also outperforms Cellfishing.jl on single-cell RNA-seq searches with 2X-13X gains. Building on hashing structures, we propose Guided Random Forest (GRAF), a tree-based ensemble classifier that integrates global and local partitioning, bridging decision trees and boosting while reducing generalization error. Across 115 datasets, GRAF delivers competitive or superior accuracy, and its unsupervised variant (uGRAF) supports guided hashing and importance sampling. We show that GRAF and ComBI can be used to estimate per-sample classifiability, which enables scalable prediction of cancer patient survival. To address challenges in interpreting mutations, we introduce Continuous Representation of Codon Switches (CRCS), a deep learning framework that embeds genetic changes into numerical vectors. CRCS allows identification of somatic mutations without matched normals, discovery of driver genes, and scoring of tumor mutations, with survival prediction validated in bladder, liver, and brain cancers. Together, these methods provide efficient, scalable, and interpretable tools for large-scale data analysis and biomedical applications.
Enhancing Hepatopathy Clinical Trial Efficiency: A Secure, Large Language Model-Powered Pre-Screening Pipeline
Gui, Xiongbin, Lv, Hanlin, Wang, Xiao, Lv, Longting, Xiao, Yi, Wang, Lei
Background: Recruitment for cohorts involving complex liver diseases, such as hepatocellular carcinoma and liver cirrhosis, often requires interpreting semantically complex criteria. Traditional manual screening methods are time-consuming and prone to errors. While AI-powered pre-screening offers potential solutions, challenges remain regarding accuracy, efficiency, and data privacy. Methods: We developed a novel patient pre-screening pipeline that leverages clinical expertise to guide the precise, safe, and efficient application of large language models. The pipeline breaks down complex criteria into a series of composite questions and then employs two strategies to perform semantic question-answering through electronic health records - (1) Pathway A, Anthropomorphized Experts' Chain of Thought strategy, and (2) Pathway B, Preset Stances within an Agent Collaboration strategy, particularly in managing complex clinical reasoning scenarios. The pipeline is evaluated on three key metrics-precision, time consumption, and counterfactual inference - at both the question and criterion levels. Results: Our pipeline achieved high precision (0.921, in criteria level) and efficiency (0.44s per task). Pathway B excelled in complex reasoning, while Pathway A was effective in precise data extraction with faster processing times. Both pathways achieved comparable precision. The pipeline showed promising results in hepatocellular carcinoma (0.878) and cirrhosis trials (0.843). Conclusions: This data-secure and time-efficient pipeline shows high precision in hepatopathy trials, providing promising solutions for streamlining clinical trial workflows. Its efficiency and adaptability make it suitable for improving patient recruitment. And its capability to function in resource-constrained environments further enhances its utility in clinical settings.
Prediction of Lung Metastasis from Hepatocellular Carcinoma using the SEER Database
Kim, Jeff J. H., Nahass, George R., Dai, Yang, Tulabandhula, Theja
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality, with lung metastases being the most common site of distant spread and significantly worsening prognosis. Despite the growing availability of clinical and demographic data, predictive models for lung metastasis in HCC remain limited in scope and clinical applicability. In this study, we develop and validate an end-to-end machine learning pipeline using data from the Surveillance, Epidemiology, and End Results (SEER) database. We evaluated three machine learning models (Random Forest, XGBoost, and Logistic Regression) alongside a multilayer perceptron (MLP) neural network. Our models achieved high AUROC values and recall, with the Random Forest and MLP models demonstrating the best overall performance (AUROC = 0.82). However, the low precision across models highlights the challenges of accurately predicting positive cases. To address these limitations, we developed a custom loss function incorporating recall optimization, enabling the MLP model to achieve the highest sensitivity. An ensemble approach further improved overall recall by leveraging the strengths of individual models. Feature importance analysis revealed key predictors such as surgery status, tumor staging, and follow up duration, emphasizing the relevance of clinical interventions and disease progression in metastasis prediction. While this study demonstrates the potential of machine learning for identifying high-risk patients, limitations include reliance on imbalanced datasets, incomplete feature annotations, and the low precision of predictions. Future work should leverage the expanding SEER dataset, improve data imputation techniques, and explore advanced pre-trained models to enhance predictive accuracy and clinical utility.
Guiding the classification of hepatocellular carcinoma on 3D CT-scans using deep and handcrafted radiological features
Sarfati, E., Bône, A., Rohé, M-M., Aubé, C., Ronot, M., Gori, P., Bloch, I.
Hepatocellular carcinoma is the most spread primary liver cancer across the world ($\sim$80\% of the liver tumors). The gold standard for HCC diagnosis is liver biopsy. However, in the clinical routine, expert radiologists provide a visual diagnosis by interpreting hepatic CT-scans according to a standardized protocol, the LI-RADS, which uses five radiological criteria with an associated decision tree. In this paper, we propose an automatic approach to predict histology-proven HCC from CT images in order to reduce radiologists' inter-variability. We first show that standard deep learning methods fail to accurately predict HCC from CT-scans on a challenging database, and propose a two-step approach inspired by the LI-RADS system to improve the performance. We achieve improvements from 6 to 18 points of AUC with respect to deep learning baselines trained with different architectures. We also provide clinical validation of our method, achieving results that outperform non-expert radiologists and are on par with expert ones.
ReflecTool: Towards Reflection-Aware Tool-Augmented Clinical Agents
Liao, Yusheng, Jiang, Shuyang, Wang, Yanfeng, Wang, Yu
Large Language Models (LLMs) have shown promising potential in the medical domain, assisting with tasks like clinical note generation and patient communication. However, current LLMs are limited to text-based communication, hindering their ability to interact with diverse forms of information in clinical environments. Despite clinical agents succeeding in diverse signal interaction, they are oriented to a single clinical scenario and hence fail for broader applications. To evaluate clinical agents holistically, we propose ClinicalAgent Bench~(CAB), a comprehensive medical agent benchmark consisting of 18 tasks across five key realistic clinical dimensions. Building on this, we introduce ReflecTool, a novel framework that excels at utilizing domain-specific tools within two stages. The first optimization stage progressively enlarges a long-term memory by saving successful solving processes and tool-wise experience of agents in a tiny pre-defined training set. In the following inference stage, ReflecTool can search for supportive successful demonstrations from already built long-term memory to guide the tool selection strategy, and a verifier improves the tool usage according to the tool-wise experience with two verification methods--iterative refinement and candidate selection. Extensive experiments on ClinicalAgent Benchmark demonstrate that ReflecTool surpasses the pure LLMs with more than 10 points and the well-established agent-based methods with 3 points, highlighting its adaptability and effectiveness in solving complex clinical tasks.
Primary liver cancer classification from routine tumour biopsy using weakly supervised deep learning
Beaufrère, Aurélie, Ouzir, Nora, Zafar, Paul Emile, Laurent-Bellue, Astrid, Albuquerque, Miguel, Lubuela, Gwladys, Grégory, Jules, Guettier, Catherine, Mondet, Kévin, Pesquet, Jean-Christophe, Paradis, Valérie
The diagnosis of primary liver cancers (PLCs) can be challenging, especially on biopsies and for combined hepatocellular-cholangiocarcinoma (cHCC-CCA). We automatically classified PLCs on routine-stained biopsies using a weakly supervised learning method. Weak tumour/non-tumour annotations served as labels for training a Resnet18 neural network, and the network's last convolutional layer was used to extract new tumour tile features. Without knowledge of the precise labels of the malignancies, we then applied an unsupervised clustering algorithm. Our model identified specific features of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). Despite no specific features of cHCC-CCA being recognized, the identification of HCC and iCCA tiles within a slide could facilitate the diagnosis of primary liver cancers, particularly cHCC-CCA. Method and results: 166 PLC biopsies were divided into training, internal and external validation sets: 90, 29 and 47 samples. Two liver pathologists reviewed each whole-slide hematein eosin saffron (HES)-stained image (WSI). After annotating the tumour/non-tumour areas, 256x256 pixel tiles were extracted from the WSIs and used to train a ResNet18. The network was used to extract new tile features. An unsupervised clustering algorithm was then applied to the new tile features. In a two-cluster model, Clusters 0 and 1 contained mainly HCC and iCCA histological features. The diagnostic agreement between the pathological diagnosis and the model predictions in the internal and external validation sets was 100% (11/11) and 96% (25/26) for HCC and 78% (7/9) and 87% (13/15) for iCCA, respectively. For cHCC-CCA, we observed a highly variable proportion of tiles from each cluster (Cluster 0: 5-97%; Cluster 1: 2-94%).
Deep Learning Approaches for Improving Question Answering Systems in Hepatocellular Carcinoma Research
Huo, Shuning, Xiang, Yafei, Yu, Hanyi, Zhu, Mengran, Gong, Yulu
In recent years, advancements in natural language processing (NLP) have been fueled by deep learning techniques, particularly through the utilization of powerful computing resources like GPUs and TPUs. Models such as BERT and GPT-3, trained on vast amounts of data, have revolutionized language understanding and generation. These pre-trained models serve as robust bases for various tasks including semantic understanding, intelligent writing, and reasoning, paving the way for a more generalized form of artificial intelligence. NLP, as a vital application of AI, aims to bridge the gap between humans and computers through natural language interaction. This paper delves into the current landscape and future prospects of large-scale model-based NLP, focusing on the question-answering systems within this domain. Practical cases and developments in artificial intelligence-driven question-answering systems are analyzed to foster further exploration and research in the realm of large-scale NLP.
Anisotropic Hybrid Networks for liver tumor segmentation with uncertainty quantification
Lambert, Benjamin, Roca, Pauline, Forbes, Florence, Doyle, Senan, Dojat, Michel
The burden of liver tumors is important, ranking as the fourth leading cause of cancer mortality. In case of hepatocellular carcinoma (HCC), the delineation of liver and tumor on contrast-enhanced magnetic resonance imaging (CE-MRI) is performed to guide the treatment strategy. As this task is time-consuming, needs high expertise and could be subject to inter-observer variability there is a strong need for automatic tools. However, challenges arise from the lack of available training data, as well as the high variability in terms of image resolution and MRI sequence. In this work we propose to compare two different pipelines based on anisotropic models to obtain the segmentation of the liver and tumors. The first pipeline corresponds to a baseline multi-class model that performs the simultaneous segmentation of the liver and tumor classes. In the second approach, we train two distinct binary models, one segmenting the liver only and the other the tumors. Our results show that both pipelines exhibit different strengths and weaknesses. Moreover we propose an uncertainty quantification strategy allowing the identification of potential false positive tumor lesions. Both solutions were submitted to the MICCAI 2023 Atlas challenge regarding liver and tumor segmentation.
AI develops cancer drug in 30 days - and predicts survival rates
Artificial intelligence has developed a treatment for an aggressive form of cancer in just 30 days and demonstrated it can predict a patient's survival rate using doctors' notes. The breakthroughs were performed by separate systems, but show how the powerful technology's uses go far beyond the generation of images and text. University of Toronto researchers worked with Insilico Medicine to develop potential treatment for hepatocellular carcinoma (HCC) using an AI drug discovery platform called Pharma. HCC is a form of liver cancer, but the AI discovered a previously unknown treatment pathway and designed a'novel hit molecule' that could bind to that target. The system, which can also predict survival rate, is the invention of scientists from the University of British Columbia and B.C. Cancer, who found the model is 80 percent accurate.