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Peng M, Gong J, An T, Cheng H, Chen L, Cai M, Lan J, Tang Y. Application of liquid biopsy in differentiating lung cancer from benign pulmonary nodules (Review). Int J Mol Med 2025; 56:106. [PMID: 40341969 PMCID: PMC12101102 DOI: 10.3892/ijmm.2025.5547] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2024] [Accepted: 04/08/2025] [Indexed: 05/11/2025] Open
Abstract
The diagnosis of malignant and benign pulmonary nodules has always been a prominent research topic. Accurately distinguishing between these types of lesions, particularly small or ground glass nodules, is crucial for the early detection and proactive treatment of lung cancer, ultimately leading to improved patient survival. Although various imaging methods and tissue biopsies have advanced the diagnostic efficacy of pulmonary nodules, each approach possesses inherent limitations. In recent years, there has been a growing interest in liquid biopsy as a non‑invasive and easily obtainable alternative. Furthermore, in‑depth investigations into the mechanisms underlying tumor initiation and progression have contributed to the development of circulating biomarkers for monitoring treatment response and efficacy in lung cancer. This review provides a comprehensive overview of the current landscape of pulmonary nodule diagnosis while highlighting the latest advancements in liquid biopsy techniques, such as extracellular vesicles, tumor‑educated platelets, non‑coding RNA, circulating tumor DNA and circulating antibodies.
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Affiliation(s)
- Mingcheng Peng
- Department of Clinical Laboratory, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China
| | - Jun Gong
- Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China
| | - Taixue An
- Department of Laboratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
| | - Hongbing Cheng
- Department of Thoracic Surgery, Xiantao First People's Hospital, Xiantao, Hubei 433099, P.R. China
| | - Liangji Chen
- Department of Clinical Laboratory, Xiantao First People's Hospital, Xiantao, Hubei 433099, P.R. China
| | - Mengyang Cai
- Department of Clinical Laboratory, Xiantao First People's Hospital, Xiantao, Hubei 433099, P.R. China
| | - Jinhua Lan
- Department of Clinical Laboratory, Xiantao First People's Hospital, Xiantao, Hubei 433099, P.R. China
| | - Yueting Tang
- Department of Clinical Laboratory, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China
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2
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Al-Rubaian A, Gunesli GN, Althakfi WA, Azam A, Snead D, Rajpoot NM, Raza SEA. CellOMaps: A compact representation for robust classification of lung adenocarcinoma growth patterns. Comput Biol Med 2025; 192:110127. [PMID: 40311463 DOI: 10.1016/j.compbiomed.2025.110127] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2024] [Revised: 01/24/2025] [Accepted: 04/01/2025] [Indexed: 05/03/2025]
Abstract
Lung adenocarcinoma (LUAD) is a morphologically heterogeneous disease, characterized by five primary histological growth patterns. The classification of such patterns is crucial due to their direct relation to prognosis but the high subjectivity and observer variability pose a major challenge. Related studies in the literature focus on machine learning methods for growth pattern classification, often formulating the problem as a slide-level predominant pattern classification problem. We propose a generalizable machine learning pipeline capable of classifying lung tissue into one of the five patterns or as non-tumor. The proposed pipeline's strength lies in a novel compact Cell Organization Maps (cellOMaps) representation that captures the cellular spatial patterns from Hematoxylin and Eosin (H&E) whole slide images (WSIs). The proposed pipeline provides state-of-the-art performance on LUAD growth pattern classification when evaluated on both internal unseen slides and external datasets, comparing favorably with the current approaches. In addition, our preliminary results show that the model's outputs can be used to predict patients Tumor Mutational Burden (TMB) levels.
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Affiliation(s)
- Arwa Al-Rubaian
- Tissue Image Analytics Centre, Department of Computer Science, University of Warwick, UK.
| | - Gozde N Gunesli
- Tissue Image Analytics Centre, Department of Computer Science, University of Warwick, UK
| | - Wajd A Althakfi
- Histopathology Unit, Department of Pathology, King Saud University, Riyadh, Kingdom of Saudi Arabia
| | - Ayesha Azam
- Department of Histopathology, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK
| | - David Snead
- Tissue Image Analytics Centre, Department of Computer Science, University of Warwick, UK; Department of Histopathology, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK; Histofy Ltd, Coventry, UK
| | - Nasir M Rajpoot
- Tissue Image Analytics Centre, Department of Computer Science, University of Warwick, UK; Histofy Ltd, Coventry, UK
| | - Shan E Ahmed Raza
- Tissue Image Analytics Centre, Department of Computer Science, University of Warwick, UK.
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3
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Hu XY, Dai YC, Zhu LY, Yang JJ, Sun J, Ji MH. Association between intraoperative electroencephalograph complexity index and postoperative delirium in elderly patients undergoing orthopedic surgery: a prospective cohort study. J Anesth 2025; 39:355-365. [PMID: 40035837 DOI: 10.1007/s00540-025-03471-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2024] [Accepted: 02/15/2025] [Indexed: 03/06/2025]
Abstract
PURPOSE The primary method for predicting POD (postoperative confusion) relies on the analysis of clinical features. Brain activity complexity is a promising factor associated with the state of consciousness. The aim of this study was to investigate the role of EEG (electroencephalography) complexity changes in predicting POD in elderly patients undergoing orthopedic surgery. METHODS From January 2024 to August 2024, 289 elderly patients undergoing orthopedic surgery were recruited at the Second Affiliated Hospital of Nanjing Medical University. Intraoperative EEG data from patients were collected and then EEG nonlinear features were extracted by MATLAB custom scripts. The logistic regression and CNN (convolutional neural networks) were used to explore the predictive effect of nonlinear features on POD from both static and dynamic perspectives. RESULTS Low permutation Lempel-Ziv complexity (PLZC) among the EEG nonlinear features emerged as an independent risk factor for POD [OR = 0.210; 95% CI (0.050-0.850); p = 0.029]. Receiver operating characteristic curve (ROC) analysis revealed a poor area under the curve of 0.615 (95% CI 0.517-0.711) for PLZC in predicting POD. After the inclusion of temporal factors, the ROC analysis indicated that the EEG nonlinear indices had a moderate predictive effect on POD [AUC = 0.701; (95% CI 0.541-0.862)]. CONCLUSIONS EEG nonlinear feature indices may be effective biomarkers for POD and could help predict POD in elderly patients undergoing orthopedic surgery.
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Affiliation(s)
- Xiao-Yi Hu
- Department of Anesthesiology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yu-Chen Dai
- Department of Anesthesiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Lan-Yue Zhu
- Department of Anesthesiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Jian-Jun Yang
- Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Jie Sun
- Department of Anesthesiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
| | - Mu-Huo Ji
- Department of Anesthesiology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
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Qin C, Dai LP, Zhang YL, Wu RC, Du KL, Zhang CQ, Liu WG. The value of MRI radiomics in distinguishing different types of spinal infections. COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE 2025; 264:108719. [PMID: 40088507 DOI: 10.1016/j.cmpb.2025.108719] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/23/2024] [Revised: 02/19/2025] [Accepted: 03/09/2025] [Indexed: 03/17/2025]
Abstract
BACKGROUND In clinical practice, the three most prevalent forms of infectious spondylitis are tuberculous spondylitis (TS), brucellosis spondylitis (BS), and pyogenic spondylitis (PS). It is possible to successfully lessen neurological and spinal damage by detecting them early. In the medical field, radiomics has been applied extensively. It is crucial to find out if MRI imaging can be used to diagnose spinal infections early. PURPOSE To explore the diagnostic value of establishing models based on MRI radiomics for different spinal infections. METHODS This retrospective study collected clinical and magnetic resonance imaging information on a total of 136 patients diagnosed with spondylitis in April 2019 and August 2023, who were classified into specific spinal infections (TS or BS) and non-specific spinal infections (PS) based on treatment. 3D Slicer software was used to outline the region of interest (ROI) and extracted ROI features. All patients were randomly divided into a training set and a test set (7:3), and after standardized, the t-test and LASSO were sequentially performed in the training set to extract the optimal radiomic features. These features were used to calculate the Radscore and construct the features classifier model and evaluated by test set. Univariate and multivariate logistic regression of Radscore and clinical features to identify predictors contributing to the diagnosis were used to plot nomograms, the area under the receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis (DCA) to assess the nomogram. The same approach described above was used to diagnose both subgroups of BS and TS in SSI. RESULTS 321 radiological features were extracted from the three different sequences. The remaining 7 optimal radiomics features were used to calculate the Radscore and establish three feature classifier models, with RF having the best performance (AUC=1 and 0.86). And after univariate and multivariate logistic regression, the final nomogram constructed by Radscore and had good discriminatory performance in the training set and the test set (AUC =0.924 and 0.868), and the calibration curve and DCA showed good clinical efficacy. In the subgroup, the AUC of the training and test sets was 0.929and0.863. CONCLUSION The diagnostic model based on MR radiomics can gradually differentiate tuberculous spondylitis, brucellosis spondylitis, and pyogenic spondylitis.
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Affiliation(s)
- Chao Qin
- Department of orthopedics, Fujian Medical University Union Hospital, Fuzhou, PR China
| | - Li-Ping Dai
- Department of orthopedics, First Affiliated Hospital of Kunming Medical University, Kunming, PR China
| | - Ye-Lei Zhang
- Department of orthopedics, Fujian Medical University Union Hospital, Fuzhou, PR China
| | - Rong-Can Wu
- Department of orthopedics, Fujian Medical University Union Hospital, Fuzhou, PR China
| | - Kai-Li Du
- Department of orthopedics, First Affiliated Hospital of Kunming Medical University, Kunming, PR China
| | - Chun-Qiang Zhang
- Department of orthopedics, First Affiliated Hospital of Kunming Medical University, Kunming, PR China
| | - Wen-Ge Liu
- Department of orthopedics, Fujian Medical University Union Hospital, Fuzhou, PR China.
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Isaac A, Klontzas ME, Dalili D, Akdogan AI, Fawzi M, Gugliemi G, Filippiadis D. Revolutionising osseous biopsy: the impact of artificial intelligence in the era of personalized medicine. Br J Radiol 2025; 98:795-809. [PMID: 39878877 PMCID: PMC12089761 DOI: 10.1093/bjr/tqaf018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Revised: 01/13/2025] [Accepted: 01/16/2025] [Indexed: 01/31/2025] Open
Abstract
In a rapidly evolving healthcare environment, artificial intelligence (AI) is transforming diagnostic techniques and personalized medicine. This is also seen in osseous biopsies. AI applications in radiomics, histopathology, predictive modelling, biopsy navigation, and interdisciplinary communication are reshaping how bone biopsies are conducted and interpreted. We provide a brief review of AI in image- guided biopsy of bone tumours (primary and secondary) and specimen handling, in the era of personalized medicine. This article explores AI's role in enhancing diagnostic accuracy, improving safety in biopsies, and enabling more precise targeting in bone lesion biopsies, ultimately contributing to better patient outcomes in personalized medicine. We dive into various AI technologies applied to osseous biopsies, such as traditional machine learning, deep learning, radiomics, simulation, and generative models. We explore their roles in tumour-board meetings, communication between clinicians, radiologists, and pathologists. Additionally, we inspect ethical considerations associated with the integration of AI in bone biopsy procedures, technical limitations, and we delve into health equity, generalizability, deployment issues, and reimbursement challenges in AI-powered healthcare. Finally, we explore potential future developments and offer a list of open-source AI tools and algorithms relevant to bone biopsies, which we include to encourage further discussion and research.
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Affiliation(s)
- Amanda Isaac
- School of Biomedical Engineering and Imaging Sciences, King’s College London, 100 Lambeth Palace Rd, London SE1 7AR, United Kingdom
| | - Michail E Klontzas
- Department of Radiology, School of Medicine, University of Crete, Heraklion, Crete, P.C. 71003, Greece
| | - Danoob Dalili
- Southwest London Elective Orthopaedic Centre, Epsom and St Helier Hospitals, Surrey, London SM5 1AA, United Kingdom
| | - Asli Irmak Akdogan
- Ataturk Training and Research Hospital, Izmir Katip Çelebi University, Izmir, Turkey
| | - Mohamed Fawzi
- Department of Radiology, National Hepatology and Tropical Research Institute, Cairo, Egypt
| | | | - Dimitrios Filippiadis
- 2nd Department of Radiology, University General Hospital “ATTIKON”, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece
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Tran M, Schmidle P, Guo RR, Wagner SJ, Koch V, Lupperger V, Novotny B, Murphree DH, Hardway HD, D'Amato M, Lefkes J, Geijs DJ, Feuchtinger A, Böhner A, Kaczmarczyk R, Biedermann T, Amir AL, Mooyaart AL, Ciompi F, Litjens G, Wang C, Comfere NI, Eyerich K, Braun SA, Marr C, Peng T. Generating dermatopathology reports from gigapixel whole slide images with HistoGPT. Nat Commun 2025; 16:4886. [PMID: 40419470 DOI: 10.1038/s41467-025-60014-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2024] [Accepted: 05/12/2025] [Indexed: 05/28/2025] Open
Abstract
Histopathology is the reference standard for diagnosing the presence and nature of many diseases, including cancer. However, analyzing tissue samples under a microscope and summarizing the findings in a comprehensive pathology report is time-consuming, labor-intensive, and non-standardized. To address this problem, we present HistoGPT, a vision language model that generates pathology reports from a patient's multiple full-resolution histology images. It is trained on 15,129 whole slide images from 6705 dermatology patients with corresponding pathology reports. The generated reports match the quality of human-written reports for common and homogeneous malignancies, as confirmed by natural language processing metrics and domain expert analysis. We evaluate HistoGPT in an international, multi-center clinical study and show that it can accurately predict tumor subtypes, tumor thickness, and tumor margins in a zero-shot fashion. Our model demonstrates the potential of artificial intelligence to assist pathologists in evaluating, reporting, and understanding routine dermatopathology cases.
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Affiliation(s)
- Manuel Tran
- Helmholtz AI, Helmholtz Munich, Neuherberg, Germany
- School of Computation, Information and Technology, Technical University of Munich, Munich, Germany
| | - Paul Schmidle
- Department of Dermatology, Medical Center, University of Freiburg, Freiburg, Germany
| | - Ruifeng Ray Guo
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Jacksonville, FL, USA
| | - Sophia J Wagner
- Helmholtz AI, Helmholtz Munich, Neuherberg, Germany
- School of Computation, Information and Technology, Technical University of Munich, Munich, Germany
| | - Valentin Koch
- School of Computation, Information and Technology, Technical University of Munich, Munich, Germany
- Institute of AI for Health, Helmholtz Munich, Neuherberg, Germany
| | | | - Brenna Novotny
- Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA
| | - Dennis H Murphree
- Digital Health, Artificial Intelligence and Innovations Program, Mayo Clinic, Rochester, MN, USA
| | - Heather D Hardway
- Digital Health, Artificial Intelligence and Innovations Program, Mayo Clinic, Rochester, MN, USA
| | - Marina D'Amato
- Computational Pathology Group, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Judith Lefkes
- Computational Pathology Group, Radboud University Medical Center, Nijmegen, The Netherlands
- Oncode Institute, Utrecht, The Netherlands
| | - Daan J Geijs
- Computational Pathology Group, Radboud University Medical Center, Nijmegen, The Netherlands
- Oncode Institute, Utrecht, The Netherlands
| | - Annette Feuchtinger
- Core Facility Pathology and Tissue Analytics, Helmholtz Munich, Neuherberg, Germany
| | - Alexander Böhner
- Department of Dermatology and Allergy, Technical University of Munich, Munich, Germany
| | - Robert Kaczmarczyk
- Department of Dermatology and Allergy, Technical University of Munich, Munich, Germany
| | - Tilo Biedermann
- Department of Dermatology and Allergy, Technical University of Munich, Munich, Germany
| | - Avital L Amir
- Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Antien L Mooyaart
- Department of Pathology, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Francesco Ciompi
- Computational Pathology Group, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Geert Litjens
- Computational Pathology Group, Radboud University Medical Center, Nijmegen, The Netherlands
- Oncode Institute, Utrecht, The Netherlands
| | - Chen Wang
- Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA
| | - Nneka I Comfere
- Digital Health, Artificial Intelligence and Innovations Program, Mayo Clinic, Rochester, MN, USA
- Department of Dermatology and Laboratory Medicine & Pathology, Mayo Clinic, Rochester, MN, USA
| | - Kilian Eyerich
- Department of Dermatology, Medical Center, University of Freiburg, Freiburg, Germany.
| | - Stephan A Braun
- Dermatology Department, University Hospital Münster, Münster, Germany.
- Department of Dermatology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany.
| | - Carsten Marr
- Helmholtz AI, Helmholtz Munich, Neuherberg, Germany.
- Institute of AI for Health, Helmholtz Munich, Neuherberg, Germany.
| | - Tingying Peng
- Helmholtz AI, Helmholtz Munich, Neuherberg, Germany.
- School of Computation, Information and Technology, Technical University of Munich, Munich, Germany.
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Schuurmans M, Saha A, Alves N, Vendittelli P, Yakar D, Sabroso-Lasa S, Xue N, Malats N, Huisman H, Hermans J, Litjens G. End-to-end prognostication in pancreatic cancer by multimodal deep learning: a retrospective, multicenter study. Eur Radiol 2025:10.1007/s00330-025-11694-y. [PMID: 40410330 DOI: 10.1007/s00330-025-11694-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2024] [Revised: 03/26/2025] [Accepted: 04/21/2025] [Indexed: 05/25/2025]
Abstract
OBJECTIVES Pancreatic cancer treatment plans involving surgery and/or chemotherapy are highly dependent on disease stage. However, current staging systems are ineffective and poorly correlated with survival outcomes. We investigate how artificial intelligence (AI) can enhance prognostic accuracy in pancreatic cancer by integrating multiple data sources. MATERIALS AND METHODS Patients with histopathology and/or radiology/follow-up confirmed pancreatic ductal adenocarcinoma (PDAC) from a Dutch center (2004-2023) were included in the development cohort. Two additional PDAC cohorts from a Dutch and Spanish center were used for external validation. Prognostic models including clinical variables, contrast-enhanced CT images, and a combination of both were developed to predict high-risk short-term survival. All models were trained using five-fold cross-validation and assessed by the area under the time-dependent receiver operating characteristic curve (AUC). RESULTS The models were developed on 401 patients (203 females, 198 males, median survival (OS) = 347 days, IQR: 171-585), with 98 (24.4%) short-term survivors (OS < 230 days) and 303 (75.6%) long-term survivors. The external validation cohorts included 361 patients (165 females, 138 males, median OS = 404 days, IQR: 173-736), with 110 (30.5%) short-term survivors and 251 (69.5%) longer survivors. The best AUC for predicting short vs. long-term survival was achieved with the multi-modal model (AUC = 0.637 (95% CI: 0.500-0.774)) in the internal validation set. External validation showed AUCs of 0.571 (95% CI: 0.453-0.689) and 0.675 (95% CI: 0.593-0.757). CONCLUSION Multimodal AI can predict long vs. short-term survival in PDAC patients, showing potential as a prognostic tool in clinical decision-making. KEY POINTS Question Prognostic tools for pancreatic ductal adenocarcinoma (PDAC) remain limited, with TNM staging offering suboptimal accuracy in predicting patient survival outcomes. Findings The multimodal AI model demonstrated improved prognostic performance over TNM and unimodal models for predicting short- and long-term survival in PDAC patients. Clinical relevance Multimodal AI provides enhanced prognostic accuracy compared to current staging systems, potentially improving clinical decision-making and personalized management strategies for PDAC patients.
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Affiliation(s)
- Megan Schuurmans
- Diagnostic Image Analysis Group, Radboud University Medical Center, Nijmegen, The Netherlands.
- Department of Medical Imaging, University Medical Center Groningen, Groningen, The Netherlands.
| | - Anindo Saha
- Diagnostic Image Analysis Group, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Natália Alves
- Diagnostic Image Analysis Group, Radboud University Medical Center, Nijmegen, The Netherlands
- Department of Medical Imaging, University Medical Center Groningen, Groningen, The Netherlands
| | - Pierpaolo Vendittelli
- Diagnostic Image Analysis Group, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Derya Yakar
- Department of Medical Imaging, University Medical Center Groningen, Groningen, The Netherlands
| | - Sergio Sabroso-Lasa
- Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center, Madrid, Spain
| | - Nannan Xue
- Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center, Madrid, Spain
| | - Núria Malats
- Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center, Madrid, Spain
| | - Henkjan Huisman
- Diagnostic Image Analysis Group, Radboud University Medical Center, Nijmegen, The Netherlands
| | - John Hermans
- Department of Medical Imaging, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Geert Litjens
- Diagnostic Image Analysis Group, Radboud University Medical Center, Nijmegen, The Netherlands
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Chen J, Huang J, Shen L. Construction of lung adenocarcinoma subtype and prognosis model based on fatty acid metabolism-related genes. Discov Oncol 2025; 16:866. [PMID: 40405049 PMCID: PMC12098254 DOI: 10.1007/s12672-025-02613-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2025] [Accepted: 05/07/2025] [Indexed: 05/24/2025] Open
Abstract
OBJECTIVE To explore the role of genes related to fatty acid metabolism in lung adenocarcinoma classification and prognosis. METHODS Transcriptome and clinical data from the TCGA database and GEO database were collected, the expression of prognostic fatty acid metabolism-related genes in LUAD patients was analyzed, and key genes related to both fatty acid metabolism and subtype were identified. These key genes were further filtered via the LASSO regression method, and the retained genes were used to construct a risk-scoring model. The biological function of RPS4Y1 was verified by cell viability, colony formation, migration, and flow cytometry assays. Finally, immune infiltration and drug sensitivity were analyzed in the high- and low-risk groups. RESULTS 31 key FAMGs associated with prognosis were identified in LUAD patients. LUAD cases were divided into 3 subtypes on the basis of the expression of these genes. The DEGs between the different subtypes were associated mainly with amino acid metabolic pathways. In addition, among the 46 DEGs between subtypes, 5 key FAMGs (SCGB3 A2, PGC, ADH7, RPS4Y1, and KRT6 A) were identified as the best prognostic markers via LASSO regression to establish a risk scoring model. Patients with low risk scores had a better prognosis and a greater degree of immune cell infiltration than those with high risk scores. RPS4Y1 is highly expressed in LUAD, and its knockdown significantly inhibits the growth of tumor cells. Moreover, we also analyzed drugs likely to be effective for the high- and low-risk groups. CONCLUSION FAMGs play important roles in LUAD, and the key genes identified may be new targets for LUAD treatment.
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Affiliation(s)
- Jing Chen
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Jinyu Huang
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Liangfang Shen
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
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Nambiar R, Bhat R, Achar H V B. Advancements in Hematologic Malignancy Detection: A Comprehensive Survey of Methodologies and Emerging Trends. ScientificWorldJournal 2025; 2025:1671766. [PMID: 40421320 PMCID: PMC12103971 DOI: 10.1155/tswj/1671766] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2024] [Accepted: 04/24/2025] [Indexed: 05/28/2025] Open
Abstract
The investigation and diagnosis of hematologic malignancy using blood cell image analysis are major and emerging subjects that lie at the intersection of artificial intelligence and medical research. This survey systematically examines the state-of-the-art in blood cancer detection through image-based analysis, aimed at identifying the most effective computational strategies and highlighting emerging trends. This review focuses on three principal objectives, namely, to categorize and compare traditional machine learning (ML), deep learning (DL), and hybrid learning approaches; to evaluate performance metrics such as accuracy, precision, recall, and area under the ROC curve; and to identify methodological gaps and propose directions for future research. Methodologically, we organize the literature by categorizing the malignancy types-leukemia, lymphoma, and multiple myeloma-and particularizing the preprocessing steps, feature extraction techniques, network architectures, and ensemble strategies employed. For ML methods, we discuss classical classifiers including support vector machines and random forests; for DL, we analyze convolutional neural networks (e.g., AlexNet, VGG, and ResNet) and transformer-based models; and for hybrid systems, we examine combinations of CNNs with attention mechanisms or traditional classifiers. Our synthesis reveals that DL models consistently outperform ML baselines, achieving classification accuracies above 95% in benchmark datasets, with hybrid models pushing peak accuracy to 99.7%. However, challenges remain in data scarcity, class imbalance, and generalizability to clinical settings. We conclude by recommending the integration of multimodal data, semisupervised learning, and rigorous external validation to advance toward deployable diagnostic tools. This survey also provides a comprehensive roadmap for researchers and clinicians striving to harness AI for reliable hematologic cancer detection.
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Affiliation(s)
- Rajashree Nambiar
- Department of Robotics and AI Engineering, NMAM Institute of Technology, NITTE (Deemed to be University), Nitte, India
| | - Ranjith Bhat
- Department of Robotics and AI Engineering, NMAM Institute of Technology, NITTE (Deemed to be University), Nitte, India
| | - Balachandra Achar H V
- Department of Electronics and Communication Engineering, Manipal Institute of Technology Bengaluru, Manipal Academy of Higher Education, Manipal, India
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Boz PB, Özden C. Decision support system based on ensemble models in distinguishing epilepsy types. Epilepsy Behav 2025; 170:110470. [PMID: 40382997 DOI: 10.1016/j.yebeh.2025.110470] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2025] [Revised: 03/16/2025] [Accepted: 05/02/2025] [Indexed: 05/20/2025]
Abstract
This study aimed to classify patients' focal (frontal, temporal, parietal, occipital), multifocal, and generalized epileptiform activities based on EEG findings using artificial intelligence models. The study included 575 patients followed in the Neurology Epilepsy Polyclinics of Adana City Training and Research Hospital between June 2021 and July 2024. Patient history, examination findings, seizure characteristics and EEG results were retrospectively reviewed to create a comprehensive database. Initially, machine learning architectures were applied to differentiate generalized and focal epilepsy. Subsequently, EEG findings were categorized into eight subgroups, and machine learning methods were utilized for classification. Three AI models-Multilayer Perceptron (MLP), Random Forest, and Support Vector Machine (SVM)-were employed. The dataset was further improved through data augmentation with SMOTE. The initial deep learning model achieved 89 % accuracy, recall, and F1 scores. Then, Optuna framework was incorporated into model to optimize hyperparameters, thus the accuracy reached 96 %. In comparison, the proposed ensemble model combining MLP, SVM and XGBoost achieved the highest accuracy of 98 %. The study demonstrates that data augmentation and ensemble AI models can provide robust decision support for physicians in classifying epilepsy types.
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Affiliation(s)
- Pınar Bengi Boz
- Department of Neurology, Adana City Training and Research Hospital, Adana Faculty of Medicine, Health Sciences University, Adana, Türkiye.
| | - Cevher Özden
- Department of Computer Technology, Vocational School of Karaisali, Çukurova University, Adana 01330, Türkiye.
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11
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Yanping H, Haixia Z, Minmin Y, Nan W, Miaomiao K, Mingming Z. Application of the joint clustering algorithm based on Gaussian kernels and differential privacy in lung cancer identification. Sci Rep 2025; 15:17094. [PMID: 40379735 PMCID: PMC12084312 DOI: 10.1038/s41598-025-01873-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2024] [Accepted: 05/08/2025] [Indexed: 05/19/2025] Open
Abstract
In the age of big data, privacy, particularly medical data privacy, is becoming increasingly important. Differential privacy (DP) has emerged as a key method for safeguarding privacy during data analysis and publishing. Cancer identification and classification play a vital role in early detection and treatment. This paper introduces a novel algorithm, DPFCM_GK, which combines differential privacy with fuzzy c-means (FCM) clustering using a Gaussian kernel function. The algorithm enhances cancer detection while ensuring data privacy. Three publicly available lung cancer datasets, along with a dataset from our hospital, are used to test and demonstrate the effectiveness of DPFCM_GK. The experimental results show that DPFCM_GK achieves high clustering accuracy and enhanced privacy as the privacy budget (ε) increases. For the UCIML, NLST, and NSCLC datasets, it reaches optimal results at lower ε (1.52, 1.24, and 2.32) compared to DPFCM. In the lung cancer dataset, DPFCM_GK outperforms DPFCM within, 0.05 ≤ ε ≤ 2.5, with significant differences (χ2 = 4.54 ∼ 29.12; P < 0.05), and both methods converge to an accuracy of 94.5% as ε increases. Although differential privacy initially increases iteration counts, DPFCM_GK demonstrates faster convergence and fewer iterations compared to DPFCM, with significant reductions (T= 23.08, 43.47, and 48.93; P<0.05). For the UCIML dataset, DPFCM_GK significantly reduces runtime compared to other models (DPFCM, LDP-SGD, LDP-Fed, LDP-FedSGD, MGM-DPL, LDP-FL) under the same privacy budget. The runtime reduction is statistically significant with T-values of (T = 21.08, 316.24, 102.35, 222.37, 162.23, 159.25; P < 0.05). DPFCM_GK still maintains excellent time efficiency when applied to the NLST and NSCLC datasets(P < 0.05). For the LLCS dataset, For the LLCS dataset, the DPFCM_GK demonstrates significant improvement as the privacy budget increases, especially in low-budget scenarios, where the performance gap is most pronounced (T=4.20, 8.44, 10.92, 3.95, 7.16, 8.51, P < 0.05). These results confirm DPFCM_GK as a practical solution for medical data analysis, balancing accuracy, privacy, and efficiency.
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Affiliation(s)
- Hang Yanping
- Department of Respiratory and Critical Care Medicine, Affiliated Nanjing Gaochun People's Hospital, Jiangsu University, Nanjing, 210000, Jiangsu, China
| | - Zheng Haixia
- Department of Respiratory and Critical Care Medicine, Affiliated Nanjing Gaochun People's Hospital, Jiangsu University, Nanjing, 210000, Jiangsu, China
| | - Yang Minmin
- Department of Respiratory and Critical Care Medicine, Affiliated Nanjing Gaochun People's Hospital, Jiangsu University, Nanjing, 210000, Jiangsu, China
| | - Wang Nan
- Department of Respiratory and Critical Care Medicine, Affiliated Nanjing Gaochun People's Hospital, Jiangsu University, Nanjing, 210000, Jiangsu, China
| | - Kong Miaomiao
- Department of Respiratory and Critical Care Medicine, Affiliated Nanjing Gaochun People's Hospital, Jiangsu University, Nanjing, 210000, Jiangsu, China
| | - Zhao Mingming
- Department of Respiratory and Critical Care Medicine, Affiliated Nanjing Gaochun People's Hospital, Jiangsu University, Nanjing, 210000, Jiangsu, China.
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12
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Giarnieri E, Carico E, Scarpino S, Ricci A, Bruno P, Scardapane S, Giansanti D. Bringing AI to Clinicians: Simplifying Pleural Effusion Cytology Diagnosis with User-Friendly Models. Diagnostics (Basel) 2025; 15:1240. [PMID: 40428233 DOI: 10.3390/diagnostics15101240] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2025] [Revised: 04/25/2025] [Accepted: 04/27/2025] [Indexed: 05/29/2025] Open
Abstract
Background: Malignant pleural effusions (MPEs) are common in advanced lung cancer patients. Cytological examination of pleural fluid is essential for identifying cell types but presents diagnostic challenges, particularly when reactive mesothelial cells mimic neoplastic cells. AI-powered diagnostic systems have emerged as valuable tools in digital cytopathology. This study explores the applicability of machine-learning (ML) models and highlights the importance of accessible tools for clinicians, enabling them to develop AI solutions and make advanced diagnostic tools available even in resource-limited settings. The focus is on differentiating normal/reactive cells from neoplastic cells in pleural effusions linked to lung adenocarcinoma. Methods: A dataset from the Cytopathology Unit at the Sant'Andrea University Hospital comprising 969 raw images, annotated with 3130 single mesothelial cells and 3260 adenocarcinoma cells, was categorized into two classes based on morphological features. Object-detection models were developed using YOLOv8 and the latest YOLOv11 instance segmentation models. Results: The models achieved an Intersection over Union (IoU) score of 0.72, demonstrating robust performance in class prediction for both categories, with YOLOv11 showing performance improvements over YOLOv8 in different metrics. Conclusions: The application of machine learning in cytopathology offers clinicians valuable support in differential diagnosis while also expanding their ability to engage with AI tools and methodologies. The diagnosis of MPEs is marked by substantial morphological and technical variability, underscoring the need for high-quality datasets and advanced deep-learning models. These technologies have the potential to enhance data interpretation and support more effective clinical treatment strategies in the era of precision medicine.
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Affiliation(s)
- Enrico Giarnieri
- Cytopathology Unit, Department of Clinical and Molecular Medicine, Sant'Andrea University Hospital, Sapienza University of Rome, Via di Grottarossa 1035, 00189 Rome, Italy
| | - Elisabetta Carico
- Cytopathology Unit, Department of Clinical and Molecular Medicine, Sant'Andrea University Hospital, Sapienza University of Rome, Via di Grottarossa 1035, 00189 Rome, Italy
| | - Stefania Scarpino
- Morphologic and Molecular Pathology Unit, Department of Clinical and Molecular Medicine, Sant' Andrea University Hospital, Sapienza University of Rome, Via di Grottarossa 1035, 00189 Rome, Italy
| | - Alberto Ricci
- Respiratory Disease Unit, Sant'Andrea University Hospital, Sapienza University of Rome, Via di Grottarossa 1035, 00189 Rome, Italy
| | - Pierdonato Bruno
- Respiratory Disease Unit, Sant'Andrea University Hospital, Sapienza University of Rome, Via di Grottarossa 1035, 00189 Rome, Italy
| | - Simone Scardapane
- Department of Information Engineering, Electronics and Telecommunications, Sapienza University of Rome, Via Eudossiana 18, 00196 Rome, Italy
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13
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Trandafir TE, Heijboer FWJ, Akram F, Derks JL, Li Y, Hillen LM, Speel EJM, Megyesfalvi Z, Dome B, Stubbs AP, Dingemans AMC, von der Thüsen JH. Deep Learning-Based Retinoblastoma Protein Subtyping of Pulmonary Large-Cell Neuroendocrine Carcinoma on Small Hematoxylin and Eosin-Stained Specimens. J Transl Med 2025; 105:104192. [PMID: 40345665 DOI: 10.1016/j.labinv.2025.104192] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2024] [Revised: 04/15/2025] [Accepted: 04/30/2025] [Indexed: 05/11/2025] Open
Abstract
Molecular subtyping of pulmonary large-cell neuroendocrine carcinoma (LCNEC) based on retinoblastoma protein (pRb) expression may influence systemic treatment decisions. Current histomorphologic assessments of hematoxylin and eosin-stained tissue samples cannot reliably differentiate LCNEC molecular subtypes. This study explores the potential of deep learning (DL) to identify histologic patterns that distinguish these subtypes, by developing a custom convolutional neural network to predict the binary expression of pRb in small LCNEC tissue samples. Our model was trained, cross-validated, and tested on tissue microarray cores from 143 resection specimens and biopsies from 21 additional patients, with corresponding immunohistochemical pRb status. The best-performing DL model achieved a patient-wise balanced accuracy value of 0.75 and an area under the receiver operating characteristic curve value of 0.77 when tested on biopsies, significantly outperforming the hematoxylin and eosin-based subtype classification by lung pathologists. Explainable artificial intelligence techniques further highlighted coarse chromatin patterns and distinct nucleoli as distinguishing features for pRb retained status. Meanwhile, pRb lost cases were characterized by limited cytoplasm and morphologic similarities with small cell lung cancer. These findings suggest that DL analysis of small histopathology samples could ultimately replace immunohistochemical pRb testing. Such a development may assist in guiding chemotherapy decisions, particularly in metastatic cases.
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Affiliation(s)
- Teodora E Trandafir
- Department of Pathology and Clinical Bioinformatics, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Frank W J Heijboer
- Department of Respiratory Medicine, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Farhan Akram
- Department of Pathology and Clinical Bioinformatics, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Jules L Derks
- Department of Respiratory Medicine, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Pulmonary Diseases, GROW School for Oncology and Reproduction, Maastricht University Medical Centre, Maastricht, The Netherlands
| | - Yunlei Li
- Department of Pathology and Clinical Bioinformatics, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Lisa M Hillen
- Department of Pathology, GROW School for Oncology and Reproduction, Maastricht University Medical Centre, Maastricht, The Netherlands
| | - Ernst-Jan M Speel
- Department of Pathology and Clinical Bioinformatics, Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Pathology, GROW School for Oncology and Reproduction, Maastricht University Medical Centre, Maastricht, The Netherlands
| | - Zsolt Megyesfalvi
- Department of Thoracic Surgery, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Thoracic Surgery, Semmelweis University and National Institute of Oncology, Budapest, Hungary; National Koranyi Institute of Pulmonology, Budapest, Hungary
| | - Balazs Dome
- Department of Thoracic Surgery, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Thoracic Surgery, Semmelweis University and National Institute of Oncology, Budapest, Hungary; National Koranyi Institute of Pulmonology, Budapest, Hungary; Department of Translational Medicine, Lund University, Lund, Sweden
| | - Andrew P Stubbs
- Department of Pathology and Clinical Bioinformatics, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Anne-Marie C Dingemans
- Department of Respiratory Medicine, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Jan H von der Thüsen
- Department of Pathology and Clinical Bioinformatics, Erasmus University Medical Center, Rotterdam, The Netherlands.
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14
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Nguyen MH, Le MHN, Bui AT, Le NQK. Artificial intelligence in predicting EGFR mutations from whole slide images in lung Cancer: A systematic review and Meta-Analysis. Lung Cancer 2025; 204:108577. [PMID: 40339270 DOI: 10.1016/j.lungcan.2025.108577] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Revised: 04/11/2025] [Accepted: 05/02/2025] [Indexed: 05/10/2025]
Abstract
BACKGROUND Epidermal growth factor receptor (EGFR) mutations play a pivotal role in guiding targeted therapy for lung cancer, making their accurate detection essential for personalized treatment. Recently, artificial intelligence (AI) has emerged as a promising tool for identifying EGFR mutation status from digital pathology images. This systematic review and meta-analysis evaluate the diagnostic accuracy of AI models in predicting EGFR mutations from whole slide images (WSIs) in lung cancer patients. METHODS A comprehensive search was conducted across four databases (EMBASE, PubMed, Web of Science, and Scopus) for studies published up to June 20th, 2024. Studies employing AI algorithms, including machine learning and deep learning techniques, to predict EGFR mutations from digital pathology images were included. The risk of bias and applicability concerns were assessed using the QUADAS-AI tool. Diagnostic accuracy metrics such as sensitivity, specificity, and the Area Under the Curve (AUC) were extracted. Random-effects models were applied to synthesize the AI model performance. This study is registered with PROSPERO (CRD42024570496). RESULTS Out of 1,828 identified studies, 16 met the inclusion criteria, with 4 eligible for meta-analysis. The pooled results demonstrated that AI algorithms achieved an AUC of 0.756 (95% CI: 0.669-0.824), a sensitivity of 66.3% (95% CI: X-Y), and a specificity of 68.1% (95% CI: X-Y). Subgroup analyses revealed that AI models using in-house datasets, surgical resection samples, the ResNet architecture, and tumor-focused regions exhibited improved predictive performance. CONCLUSION AI models exhibit potential for non-invasive prediction of EGFR mutations in lung cancer patients using WSIs, although current accuracy and precision warrant further refinement. Future research should aim to enhance AI algorithms, validate findings on larger datasets, and integrate these tools into clinical workflows to optimize lung cancer management.
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Affiliation(s)
- Mai Hanh Nguyen
- International Ph.D. Program in Cell Therapy and Regenerative Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan; Pathology and Forensic Medicine Department, 103 Military Hospital, Hanoi, Vietnam; AIBioMed Research Group, Taipei Medical University, Taipei 110, Taiwan
| | - Minh Huu Nhat Le
- International Ph.D. Program in Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan; AIBioMed Research Group, Taipei Medical University, Taipei 110, Taiwan
| | - Anh Tuan Bui
- Department of Spine Surgery, 103 Military Hospital, Hanoi, Vietnam
| | - Nguyen Quoc Khanh Le
- In-Service Master Program in Artificial Intelligence in Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan; AIBioMed Research Group, Taipei Medical University, Taipei 110, Taiwan; Translational Imaging Research Center, Taipei Medical University Hospital, Taipei 110, Taiwan.
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15
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Wang X, Liu H, Zhang Y, Zhao B, Duan H, Hu W, Mou Y, Price S, Li C. Joint modeling histology and molecular markers for cancer classification. Med Image Anal 2025; 102:103505. [PMID: 39999764 DOI: 10.1016/j.media.2025.103505] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2024] [Revised: 12/15/2024] [Accepted: 02/11/2025] [Indexed: 02/27/2025]
Abstract
Cancers are characterized by remarkable heterogeneity and diverse prognosis. Accurate cancer classification is essential for patient stratification and clinical decision-making. Although digital pathology has been advancing cancer diagnosis and prognosis, the paradigm in cancer pathology has shifted from purely relying on histology features to incorporating molecular markers. There is an urgent need for digital pathology methods to meet the needs of the new paradigm. We introduce a novel digital pathology approach to jointly predict molecular markers and histology features and model their interactions for cancer classification. Firstly, to mitigate the challenge of cross-magnification information propagation, we propose a multi-scale disentangling module, enabling the extraction of multi-scale features from high-magnification (cellular-level) to low-magnification (tissue-level) whole slide images. Further, based on the multi-scale features, we propose an attention-based hierarchical multi-task multi-instance learning framework to simultaneously predict histology and molecular markers. Moreover, we propose a co-occurrence probability-based label correlation graph network to model the co-occurrence of molecular markers. Lastly, we design a cross-modal interaction module with the dynamic confidence constrain loss and a cross-modal gradient modulation strategy, to model the interactions of histology and molecular markers. Our experiments demonstrate that our method outperforms other state-of-the-art methods in classifying glioma, histology features and molecular markers. Our method promises to promote precise oncology with the potential to advance biomedical research and clinical applications. The code is available at github.
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Affiliation(s)
- Xiaofei Wang
- Department of Clinical Neurosciences, University of Cambridge, UK
| | - Hanyu Liu
- School of Science and Engineering, University of Dundee, UK
| | - Yupei Zhang
- Department of Clinical Neurosciences, University of Cambridge, UK
| | - Boyang Zhao
- School of Science and Engineering, University of Dundee, UK
| | - Hao Duan
- Department of Neurosurgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, China
| | - Wanming Hu
- Department of Pathology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, China
| | - Yonggao Mou
- Department of Neurosurgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, China
| | - Stephen Price
- Department of Clinical Neurosciences, University of Cambridge, UK
| | - Chao Li
- Department of Clinical Neurosciences, University of Cambridge, UK; School of Science and Engineering, University of Dundee, UK; Department of Applied Mathematics and Theoretical Physics, University of Cambridge, UK; School of Medicine, University of Dundee, UK.
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16
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Li B, He Q, Chang J, Yang B, Tang X, He Y, Guan T, Zhou G. Toward efficient slide-level grading of liver biopsy via explainable deep learning framework. Med Biol Eng Comput 2025; 63:1435-1449. [PMID: 39806118 DOI: 10.1007/s11517-024-03266-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2024] [Accepted: 12/05/2024] [Indexed: 01/16/2025]
Abstract
In the context of chronic liver diseases, where variability in progression necessitates early and precise diagnosis, this study addresses the limitations of traditional histological analysis and the shortcomings of existing deep learning approaches. A novel patch-level classification model employing multi-scale feature extraction and fusion was developed to enhance the grading accuracy and interpretability of liver biopsies, analyzing 1322 cases across various staining methods. The study also introduces a slide-level aggregation framework, comparing different diagnostic models, to efficiently integrate local histological information. Results from extensive validation show that the slide-level model consistently achieved high F1 scores, notably 0.9 for inflammatory activity and steatosis, and demonstrated rapid diagnostic capabilities with less than one minute per slide on average. The patch-level model also performed well, with an F1 score of 0.64 for ballooning and 0.99 for other indicators, and proved transferable to public datasets. The conclusion drawn is that the proposed analytical framework offers a reliable basis for the diagnosis and treatment of chronic liver diseases, with the added benefit of robust interpretability, suggesting its practical utility in clinical settings.
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Affiliation(s)
- Bingchen Li
- Shenzhen International Graduate School, Tsinghua University, Shenzhen, Guangdong, 518000, China
| | - Qiming He
- Shenzhen International Graduate School, Tsinghua University, Shenzhen, Guangdong, 518000, China
| | - Jing Chang
- Pathology Department, Beijing Youan Hospital, Capital Medical University, Beijing, 100000, China
| | - Bo Yang
- Shenzhen International Graduate School, Tsinghua University, Shenzhen, Guangdong, 518000, China
| | - Xi Tang
- Shenzhen International Graduate School, Tsinghua University, Shenzhen, Guangdong, 518000, China
| | - Yonghong He
- Shenzhen International Graduate School, Tsinghua University, Shenzhen, Guangdong, 518000, China
| | - Tian Guan
- Shenzhen International Graduate School, Tsinghua University, Shenzhen, Guangdong, 518000, China.
| | - Guangde Zhou
- Pathology Department, Beijing Youan Hospital, Capital Medical University, Beijing, 100000, China.
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17
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Tran M, Wagner S, Weichert W, Matek C, Boxberg M, Peng T. Navigating Through Whole Slide Images With Hierarchy, Multi-Object, and Multi-Scale Data. IEEE TRANSACTIONS ON MEDICAL IMAGING 2025; 44:2002-2015. [PMID: 40031287 DOI: 10.1109/tmi.2025.3532728] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/05/2025]
Abstract
Building deep learning models that can rapidly segment whole slide images (WSIs) using only a handful of training samples remains an open challenge in computational pathology. The difficulty lies in the histological images themselves: many morphological structures within a slide are closely related and very similar in appearance, making it difficult to distinguish between them. However, a skilled pathologist can quickly identify the relevant phenotypes. Through years of training, they have learned to organize visual features into a hierarchical taxonomy (e.g., identifying carcinoma versus healthy tissue, or distinguishing regions within a tumor as cancer cells, the microenvironment, …). Thus, each region is associated with multiple labels representing different tissue types. Pathologists typically deal with this by analyzing the specimen at multiple scales and comparing visual features between different magnifications. Inspired by this multi-scale diagnostic workflow, we introduce the Navigator, a vision model that navigates through WSIs like a domain expert: it searches for the region of interest at a low scale, zooms in gradually, and localizes ever finer microanatomical classes. As a result, the Navigator can detect coarse-grained patterns at lower resolution and fine-grained features at higher resolution. In addition, to deal with sparsely annotated samples, we train the Navigator with a novel semi-supervised framework called S5CL v2. The proposed model improves the F1 score by up to 8% on various datasets including our challenging new TCGA-COAD-30CLS and Erlangen cohorts.
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18
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Klauschen F, Dippel J, Müller KR. [Foundation models in pathology]. PATHOLOGIE (HEIDELBERG, GERMANY) 2025; 46:152-155. [PMID: 40272536 DOI: 10.1007/s00292-025-01429-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 03/10/2025] [Indexed: 04/25/2025]
Abstract
Foundation models prepare neural networks for applications in specific domains, such as speech applications or image analysis, through self-supervised pretraining. These models can be adapted for specific applications, such as histopathological diagnostics. While adaptation still requires supervised training, AI applications based on foundation models achieve significantly better prediction accuracy with fewer training data compared to conventional approaches. This article introduces the topic and provides an overview of foundation models in pathology.
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Affiliation(s)
- Frederick Klauschen
- Pathologisches Institut, Ludwig-Maximilians-Universität München, Thalkirchner Str. 36, 80337, München, Deutschland.
- Berlin Institute for the Foundations of Learning and Data (BIFOLD), Berlin, Deutschland.
- Bayerisches Zentrum für Krebsforschung (BZKF), München, Deutschland.
| | - Jonas Dippel
- Machine Learning Group, Technische Universität Berlin, Berlin, Deutschland
- Aignostics GmbH, Berlin, Deutschland
| | - Klaus-Robert Müller
- Berlin Institute for the Foundations of Learning and Data (BIFOLD), Berlin, Deutschland
- Machine Learning Group, Technische Universität Berlin, Berlin, Deutschland
- Department of Artificial Intelligence, Korea University, Seoul, Südkorea
- Max-Planck-Institut für Informatik, Saarbrücken, Deutschland
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19
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Yang T, Wang X, Jin Y, Yao X, Sun Z, Chen P, Zhou S, Zhu W, Chen W. Deep learning radiopathomics predicts targeted therapy sensitivity in EGFR-mutant lung adenocarcinoma. J Transl Med 2025; 23:482. [PMID: 40301933 PMCID: PMC12039126 DOI: 10.1186/s12967-025-06480-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2024] [Accepted: 04/11/2025] [Indexed: 05/01/2025] Open
Abstract
BACKGROUND Ttyrosine kinase inhibitors (TKIs) represent the standard first-line treatment for patients with epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma. However, not all patients with EGFR mutations respond to TKIs. This study aims to develop a deep learning radiological-pathological-clinical (DLRPC) model that integrates computed tomography (CT) images, hematoxylin and eosin (H&E)-stained aspiration biopsy samples, and clinical data to predict the response in EGFR-mutant lung adenocarcinoma patients undergoing TKIs treatment. METHODS We retrospectively analyzed data from 214 lung adenocarcinoma patients who received TKIs treatment from two medical centers between September 2013 and June 2023. The DLRPC model leverages paired CT, pathological images and clinical data, incorporating a clinical-based attention mask to further explore the cross-modality associations. To evaluate its diagnostic performance, we compared the DLRPC model against single-modality models and a decision level fusion model based on Dempster-Shafer theory. Model performances metrics, including area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), were used for evaluation. The Delong test assessed statistically significantly differences in AUC among models. RESULTS The DLRPC model demonstrated strong performance, achieving an AUC value of 0.8424. It outperformed the single-modality models (AUC = 0.6894, 0.7753, 0.8052 for CT model, pathology model and clinical model, respectively. P < 0.05). Additionally, the DLRPC model surpassed the decision level fusion model (AUC = 0.8132, P < 0.05). CONCLUSION The DLRPC model effectively predicts the response of EGFR-mutant lung adenocarcinoma patients to TKIs, providing a promising tool for personalized treatment decisions in lung cancer management.
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Affiliation(s)
- Taotao Yang
- Department of Radiology, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, 400038, China
- Yu-Yue Pathology Scientific Research Center, Chongqing, 400039, China
| | - Xianqi Wang
- Department of Radiology, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, 400038, China
- Yu-Yue Pathology Scientific Research Center, Chongqing, 400039, China
| | - Yuan Jin
- Zhejiang Lab, Hangzhou, 311121, China
| | - Xiaohong Yao
- Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Army Medical University, (Third Military Medical University), Chongqing, 400038, China
| | - Zhiyuan Sun
- Department of Radiology, Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, China
| | - Pinzhen Chen
- Department of Radiology, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, 400038, China
| | - Suyi Zhou
- Department of Radiology, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, 400038, China
| | | | - Wei Chen
- Department of Radiology, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, 400038, China.
- Yu-Yue Pathology Scientific Research Center, Chongqing, 400039, China.
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20
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Marra A, Morganti S, Pareja F, Campanella G, Bibeau F, Fuchs T, Loda M, Parwani A, Scarpa A, Reis-Filho JS, Curigliano G, Marchiò C, Kather JN. Artificial intelligence entering the pathology arena in oncology: current applications and future perspectives. Ann Oncol 2025:S0923-7534(25)00112-7. [PMID: 40307127 DOI: 10.1016/j.annonc.2025.03.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2024] [Revised: 02/19/2025] [Accepted: 03/07/2025] [Indexed: 05/02/2025] Open
Abstract
BACKGROUND Artificial intelligence (AI) is rapidly transforming the fields of pathology and oncology, offering novel opportunities for advancing diagnosis, prognosis, and treatment of cancer. METHODS Through a systematic review-based approach, the representatives from the European Society for Medical Oncology (ESMO) Precision Oncology Working Group (POWG) and international experts identified studies in pathology and oncology that applied AI-based algorithms for tumour diagnosis, molecular biomarker detection, and cancer prognosis assessment. These findings were synthesised to provide a comprehensive overview of current AI applications and future directions in cancer pathology. RESULTS The integration of AI tools in digital pathology is markedly improving the accuracy and efficiency of image analysis, allowing for automated tumour detection and classification, identification of prognostic molecular biomarkers, and prediction of treatment response and patient outcomes. Several barriers for the adoption of AI in clinical workflows, such as data availability, explainability, and regulatory considerations, still persist. There are currently no prognostic or predictive AI-based biomarkers supported by level IA or IB evidence. The ongoing advancements in AI algorithms, particularly foundation models, generalist models and transformer-based deep learning, offer immense promise for the future of cancer research and care. AI is also facilitating the integration of multi-omics data, leading to more precise patient stratification and personalised treatment strategies. CONCLUSIONS The application of AI in pathology is poised to not only enhance the accuracy and efficiency of cancer diagnosis and prognosis but also facilitate the development of personalised treatment strategies. Although barriers to implementation remain, ongoing research and development in this field coupled with addressing ethical and regulatory considerations will likely lead to a future where AI plays an integral role in cancer management and precision medicine. The continued evolution and adoption of AI in pathology and oncology are anticipated to reshape the landscape of cancer care, heralding a new era of precision medicine and improved patient outcomes.
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Affiliation(s)
- A Marra
- Division of Early Drug Development for Innovative Therapies, European Institute of Oncology IRCCS, Milan, Italy
| | - S Morganti
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, USA; Department of Medicine, Harvard Medical School, Boston, USA; Gerstner Center for Cancer Diagnostics, Broad Institute of MIT and Harvard, Boston, USA
| | - F Pareja
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, USA
| | - G Campanella
- Hasso Plattner Institute for Digital Health, Mount Sinai Medical School, New York, USA; Department of AI and Human Health, Icahn School of Medicine at Mount Sinai, New York, USA
| | - F Bibeau
- Department of Pathology, University Hospital of Besançon, Besancon, France
| | - T Fuchs
- Hasso Plattner Institute for Digital Health, Mount Sinai Medical School, New York, USA; Department of AI and Human Health, Icahn School of Medicine at Mount Sinai, New York, USA
| | - M Loda
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, USA; Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK; Department of Oncologic Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, USA
| | - A Parwani
- Department of Pathology, Wexner Medical Center, Ohio State University, Columbus, USA
| | - A Scarpa
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona, Italy; ARC-Net Research Center, University of Verona, Verona, Italy
| | - J S Reis-Filho
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, USA
| | - G Curigliano
- Division of Early Drug Development for Innovative Therapies, European Institute of Oncology IRCCS, Milan, Italy; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
| | - C Marchiò
- Candiolo Cancer Institute, FPO IRCCS, Candiolo, Italy; Department of Medical Sciences, University of Turin, Turin, Italy
| | - J N Kather
- Else Kroener Fresenius Center for Digital Health, Medical Faculty Carl Gustav Carus, Technical University Dresden, Dresden, Germany; Department of Medicine I, University Hospital and Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Medical Oncology, National Center for Tumor Diseases (NCT), University Hospital Heidelberg, Heidelberg, Germany.
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21
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Campanella G, Chen S, Singh M, Verma R, Muehlstedt S, Zeng J, Stock A, Croken M, Veremis B, Elmas A, Shujski I, Neittaanmäki N, Huang KL, Kwan R, Houldsworth J, Schoenfeld AJ, Vanderbilt C. A clinical benchmark of public self-supervised pathology foundation models. Nat Commun 2025; 16:3640. [PMID: 40240324 PMCID: PMC12003829 DOI: 10.1038/s41467-025-58796-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Accepted: 04/02/2025] [Indexed: 04/18/2025] Open
Abstract
The use of self-supervised learning to train pathology foundation models has increased substantially in the past few years. Notably, several models trained on large quantities of clinical data have been made publicly available in recent months. This will significantly enhance scientific research in computational pathology and help bridge the gap between research and clinical deployment. With the increase in availability of public foundation models of different sizes, trained using different algorithms on different datasets, it becomes important to establish a benchmark to compare the performance of such models on a variety of clinically relevant tasks spanning multiple organs and diseases. In this work, we present a collection of pathology datasets comprising clinical slides associated with clinically relevant endpoints including cancer diagnoses and a variety of biomarkers generated during standard hospital operation from three medical centers. We leverage these datasets to systematically assess the performance of public pathology foundation models and provide insights into best practices for training foundation models and selecting appropriate pretrained models. To enable the community to evaluate their models on our clinical datasets, we make available an automated benchmarking pipeline for external use.
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Affiliation(s)
- Gabriele Campanella
- Windreich Department of AI and Human Health, Icahn School of Medicine at Mount Sinai, New York, 10029, NY, USA.
- Hasso Plattner Institute at Mount Sinai, Icahn School of Medicine at Mount Sinai, New York, 10029, NY, USA.
| | - Shengjia Chen
- Windreich Department of AI and Human Health, Icahn School of Medicine at Mount Sinai, New York, 10029, NY, USA
- Hasso Plattner Institute at Mount Sinai, Icahn School of Medicine at Mount Sinai, New York, 10029, NY, USA
| | - Manbir Singh
- Windreich Department of AI and Human Health, Icahn School of Medicine at Mount Sinai, New York, 10029, NY, USA
- Hasso Plattner Institute at Mount Sinai, Icahn School of Medicine at Mount Sinai, New York, 10029, NY, USA
| | - Ruchika Verma
- Windreich Department of AI and Human Health, Icahn School of Medicine at Mount Sinai, New York, 10029, NY, USA
- Hasso Plattner Institute at Mount Sinai, Icahn School of Medicine at Mount Sinai, New York, 10029, NY, USA
| | - Silke Muehlstedt
- Windreich Department of AI and Human Health, Icahn School of Medicine at Mount Sinai, New York, 10029, NY, USA
- Hasso Plattner Institute at Mount Sinai, Icahn School of Medicine at Mount Sinai, New York, 10029, NY, USA
| | - Jennifer Zeng
- Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, 10029, NY, USA
| | - Aryeh Stock
- Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, 10029, NY, USA
| | - Matt Croken
- Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, 10029, NY, USA
| | - Brandon Veremis
- Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, 10029, NY, USA
| | - Abdulkadir Elmas
- Department of Genetics and Genomics, Icahn School of Medicine at Mount Sinai, New York, 10029, NY, USA
| | - Ivan Shujski
- Department of Clinical Pathology, Sahlgrenska University Hospital, Gothenburg, Sweden
- Department of Laboratory Medicine, University of Gothenburg, Gothenburg, Sweden
| | - Noora Neittaanmäki
- Department of Clinical Pathology, Sahlgrenska University Hospital, Gothenburg, Sweden
- Department of Laboratory Medicine, University of Gothenburg, Gothenburg, Sweden
| | - Kuan-Lin Huang
- Department of Genetics and Genomics, Icahn School of Medicine at Mount Sinai, New York, 10029, NY, USA
| | - Ricky Kwan
- Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, 10029, NY, USA
| | - Jane Houldsworth
- Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, 10029, NY, USA
| | - Adam J Schoenfeld
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, 10065, NY, USA
| | - Chad Vanderbilt
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, 10065, NY, USA.
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22
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Cao H, Wu X, Shi H, Chu B, He Y, Wang H, Dong F. AI-assisted SERS imaging method for label-free and rapid discrimination of clinical lymphoma. J Nanobiotechnology 2025; 23:295. [PMID: 40241186 PMCID: PMC12001690 DOI: 10.1186/s12951-025-03339-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2024] [Accepted: 03/18/2025] [Indexed: 04/18/2025] Open
Abstract
BACKGROUND Lymphoma is a malignant tumor of the immune system and its incidence is increasing year after year, causing a major threat to people's health. Conventional diagnosis of lymphoma basically depends on histological images consuming long-time and tedious manipulations (e.g., 7-15 days) and large-field view (e.g., > 1000 × 1000 μm2). Artificial intelligence has recently revolutionized cancer diagnosis by training pathological image databases via deep learning. Current approaches, however, remain dependent on analyzing wide-field pathological images to detect distinct nuclear, cytologic, and histomorphologic traits for diagnostic categorization, limiting their applicability to minimally invasive lesion. RESULTS Herein, we develop a molecular imaging strategy for minimally invasive lymphoma diagnosis. By spreading lymphoma tissue sections tightly on a surface-enhanced Raman scattering (SERS) chip, label-free images of DNA double strand breaks (DSBs) in 30 × 30 μm2 tissue sections could be achieved in ~ 15 min. To establish a proof of concept, the Raman image datasets collected from clinical samples of normal lymphatic tissues and non-Hodgkin's lymphoma (NHL) tissues were well organized and trained in a deep convolutional neural network model, finally achieving a recognition rate of ~ 91.7 ± 2.1%. CONCLUSIONS The molecular imaging strategy for minimally invasive lymphoma diagnosis that can achieve a recognition rate of ~ 91.7 ± 2.1%. We anticipate that these results will catalyze the development of a series of histological SERS-AI technologies for diagnosing various diseases, including other types of cancer. In this work, we present a reliable tool to facilitate clinicians in the diagnosis of lymphoma.
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Affiliation(s)
- Haiting Cao
- Suzhou Key Laboratory of Nanotechnology and Biomedicine, Institute of Functional Nano & Soft Materials (FUNSOM), and Collaborative Innovation Center of Suzhou Nano Science and Technology (NANO-CIC), Soochow University, Suzhou, 215123, Jiangsu, China
| | - Xiaofeng Wu
- Department of Ultrasound, The First Affiliated Hospital of Soochow University, Suzhou, 215031, Jiangsu, China
| | - Huayi Shi
- Suzhou Key Laboratory of Nanotechnology and Biomedicine, Institute of Functional Nano & Soft Materials (FUNSOM), and Collaborative Innovation Center of Suzhou Nano Science and Technology (NANO-CIC), Soochow University, Suzhou, 215123, Jiangsu, China
| | - Binbin Chu
- Suzhou Key Laboratory of Nanotechnology and Biomedicine, Institute of Functional Nano & Soft Materials (FUNSOM), and Collaborative Innovation Center of Suzhou Nano Science and Technology (NANO-CIC), Soochow University, Suzhou, 215123, Jiangsu, China.
| | - Yao He
- Suzhou Key Laboratory of Nanotechnology and Biomedicine, Institute of Functional Nano & Soft Materials (FUNSOM), and Collaborative Innovation Center of Suzhou Nano Science and Technology (NANO-CIC), Soochow University, Suzhou, 215123, Jiangsu, China.
- Macao Translational Medicine Center, Macau University of Science and Technology, Taipa, 999078, Macau SAR, China.
- Macao Institute of Materials Science and Engineering, Macau University of Science and Technology, Taipa, 999078, Macau SAR, China.
| | - Houyu Wang
- Suzhou Key Laboratory of Nanotechnology and Biomedicine, Institute of Functional Nano & Soft Materials (FUNSOM), and Collaborative Innovation Center of Suzhou Nano Science and Technology (NANO-CIC), Soochow University, Suzhou, 215123, Jiangsu, China.
| | - Fenglin Dong
- Department of Ultrasound, The First Affiliated Hospital of Soochow University, Suzhou, 215031, Jiangsu, China.
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23
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Shin Y, Lee M, Lee Y, Kim K, Kim T. Artificial Intelligence-Powered Quality Assurance: Transforming Diagnostics, Surgery, and Patient Care-Innovations, Limitations, and Future Directions. Life (Basel) 2025; 15:654. [PMID: 40283208 PMCID: PMC12028931 DOI: 10.3390/life15040654] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2025] [Revised: 04/09/2025] [Accepted: 04/14/2025] [Indexed: 04/29/2025] Open
Abstract
Artificial intelligence is rapidly transforming quality assurance in healthcare, driving advancements in diagnostics, surgery, and patient care. This review presents a comprehensive analysis of artificial intelligence integration-particularly convolutional and recurrent neural networks-across key clinical domains, significantly enhancing diagnostic accuracy, surgical performance, and pathology evaluation. Artificial intelligence-based approaches have demonstrated clear superiority over conventional methods: convolutional neural networks achieved 91.56% accuracy in scanner fault detection, surpassing manual inspections; endoscopic lesion detection sensitivity rose from 2.3% to 6.1% with artificial intelligence assistance; and gastric cancer invasion depth classification reached 89.16% accuracy, outperforming human endoscopists by 17.25%. In pathology, artificial intelligence achieved 93.2% accuracy in identifying out-of-focus regions and an F1 score of 0.94 in lymphocyte quantification, promoting faster and more reliable diagnostics. Similarly, artificial intelligence improved surgical workflow recognition with over 81% accuracy and exceeded 95% accuracy in skill assessment classification. Beyond traditional diagnostics and surgical support, AI-powered wearable sensors, drug delivery systems, and biointegrated devices are advancing personalized treatment by optimizing physiological monitoring, automating care protocols, and enhancing therapeutic precision. Despite these achievements, challenges remain in areas such as data standardization, ethical governance, and model generalizability. Overall, the findings underscore artificial intelligence's potential to outperform traditional techniques across multiple parameters, emphasizing the need for continued development, rigorous clinical validation, and interdisciplinary collaboration to fully realize its role in precision medicine and patient safety.
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Affiliation(s)
- Yoojin Shin
- College of Medicine, The Catholic University of Korea, 222 Banpo-Daero, Seocho-gu, Seoul 06591, Republic of Korea; (Y.S.); (M.L.); (Y.L.)
| | - Mingyu Lee
- College of Medicine, The Catholic University of Korea, 222 Banpo-Daero, Seocho-gu, Seoul 06591, Republic of Korea; (Y.S.); (M.L.); (Y.L.)
| | - Yoonji Lee
- College of Medicine, The Catholic University of Korea, 222 Banpo-Daero, Seocho-gu, Seoul 06591, Republic of Korea; (Y.S.); (M.L.); (Y.L.)
| | - Kyuri Kim
- College of Medicine, Ewha Womans University, 25 Magokdong-ro 2-gil, Gangseo-gu, Seoul 07804, Republic of Korea;
| | - Taejung Kim
- Department of Hospital Pathology, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 10, 63-ro, Yeongdeungpo-gu, Seoul 07345, Republic of Korea
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24
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Liang X, Wang G, Zhu Z, Zhang W, Li Y, Luo J, Wang H, Wu S, Chen R, Deng M, Wu H, Shen C, Hu G, Zhang K, Sun Q, Wang Z. Using pathology images and artificial intelligence to identify bacterial infections and their types. J Microbiol Methods 2025; 232-234:107131. [PMID: 40233851 DOI: 10.1016/j.mimet.2025.107131] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2025] [Revised: 04/07/2025] [Accepted: 04/11/2025] [Indexed: 04/17/2025]
Abstract
Bacterial infections pose a significant biosafety concern, making early and accurate diagnosis essential for effective treatment and prognosis. Traditional diagnostic methods, while reliable, are often slow and fail to meet urgent clinical demands. In contrast, emerging technologies offer greater efficiency but are often costly and inaccessible. In this study, we utilized easily accessible pathology images to diagnose bacterial infections. Our initial findings indicate that, in the absence of postmortem phenomena, microscopic examination of pathological images can confirm the presence of a bacterial infection. However, distinguishing between different types of bacterial infections remains challenging due to similarities in pathological changes. To address this limitation, we applied a computational pathology approach by integrating pathology images with artificial intelligence (AI) algorithms. Our model classified bacterial infections at both the patch-level and whole slide image (WSI)-level. The results demonstrated strong performance, with an overall AUC consistently above 0.950 across training, testing, and external validation datasets, indicating high accuracy, robustness, and generalizability. This study highlights AI's potential in identifying bacterial infection types and provides valuable technical support for clinical diagnostics, paving the way for faster and more precise infection management.
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Affiliation(s)
- Xinggong Liang
- Department of Forensic Pathology, College of Forensic Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China
| | - Gongji Wang
- College of Forensic Medicine, NHC Key Laboratory of Drug Addition Medicine, Kunming Medical University, Kunming, Yunnan 650500, China
| | - Zhengyang Zhu
- Department of Forensic Pathology, College of Forensic Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China
| | - Wanqing Zhang
- Department of Forensic Pathology, College of Forensic Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China
| | - Yuqian Li
- Department of Forensic Pathology, College of Forensic Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China
| | - Jianliang Luo
- Department of Forensic Pathology, College of Forensic Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China
| | - Han Wang
- Department of Forensic Pathology, College of Forensic Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China
| | - Shuo Wu
- Department of Forensic Pathology, College of Forensic Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China
| | - Run Chen
- Department of Forensic Pathology, College of Forensic Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China
| | - Mingyan Deng
- Department of Forensic Pathology, College of Forensic Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China
| | - Hao Wu
- Department of Forensic Pathology, College of Forensic Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China
| | - Chen Shen
- Department of Forensic Pathology, College of Forensic Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China
| | - Gengwang Hu
- Department of Forensic Pathology, College of Forensic Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China
| | - Kai Zhang
- Department of Forensic Pathology, College of Forensic Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
| | - Qinru Sun
- Department of Forensic Pathology, College of Forensic Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
| | - Zhenyuan Wang
- Department of Forensic Pathology, College of Forensic Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
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25
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Yang X, Yang R, Liu X, Chen Z, Zheng Q. Recent Advances in Artificial Intelligence for Precision Diagnosis and Treatment of Bladder Cancer: A Review. Ann Surg Oncol 2025:10.1245/s10434-025-17228-6. [PMID: 40221553 DOI: 10.1245/s10434-025-17228-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2024] [Accepted: 03/09/2025] [Indexed: 04/14/2025]
Abstract
BACKGROUND Bladder cancer is one of the top ten cancers globally, with its incidence steadily rising in China. Early detection and prognosis risk assessment play a crucial role in guiding subsequent treatment decisions for bladder cancer. However, traditional diagnostic methods such as bladder endoscopy, imaging, or pathology examinations heavily rely on the clinical expertise and experience of clinicians, exhibiting subjectivity and poor reproducibility. MATERIALS AND METHODS With the rise of artificial intelligence, novel approaches, particularly those employing deep learning technology, have shown significant advancements in clinical tasks related to bladder cancer, including tumor detection, molecular subtyping identification, tumor staging and grading, prognosis prediction, and recurrence assessment. RESULTS Artificial intelligence, with its robust data mining capabilities, enhances diagnostic efficiency and reproducibility when assisting clinicians in decision-making, thereby reducing the risks of misdiagnosis and underdiagnosis. This not only helps alleviate the current challenges of talent shortages and uneven distribution of medical resources but also fosters the development of precision medicine. CONCLUSIONS This study provides a comprehensive review of the latest research advances and prospects of artificial intelligence technology in the precise diagnosis and treatment of bladder cancer.
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Affiliation(s)
- Xiangxiang Yang
- Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China
- Institute of Urologic Disease, Renmin Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China
| | - Rui Yang
- Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China
- Institute of Urologic Disease, Renmin Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China
| | - Xiuheng Liu
- Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China
- Institute of Urologic Disease, Renmin Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China
| | - Zhiyuan Chen
- Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China.
- Institute of Urologic Disease, Renmin Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China.
| | - Qingyuan Zheng
- Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China.
- Institute of Urologic Disease, Renmin Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China.
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26
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Boubnovski Martell M, Linton-Reid K, Chen M, Aboagye EO. Radiomics for lung cancer diagnosis, management, and future prospects. Clin Radiol 2025; 86:106926. [PMID: 40344812 DOI: 10.1016/j.crad.2025.106926] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2024] [Revised: 03/29/2025] [Accepted: 04/04/2025] [Indexed: 05/11/2025]
Abstract
Lung cancer remains the leading cause of cancer-related mortality worldwide, with its early detection and effective treatment posing significant clinical challenges. Radiomics, the extraction of quantitative features from medical imaging, has emerged as a promising approach for enhancing diagnostic accuracy, predicting treatment responses, and personalising patient care. This review explores the role of radiomics in lung cancer diagnosis and management, with methods ranging from handcrafted radiomics to deep learning techniques that can capture biological intricacies. The key applications are highlighted across various stages of lung cancer care, including nodule detection, histology prediction, and disease staging, where artificial intelligence (AI) models demonstrate superior specificity and sensitivity. The article also examines future directions, emphasising the integration of large language models, explainable AI (XAI), and super-resolution imaging techniques as transformative developments. By merging diverse data sources and incorporating interpretability into AI models, radiomics stands poised to redefine clinical workflows, offering more robust and reliable tools for lung cancer diagnosis, treatment planning, and outcome prediction. These advancements underscore radiomics' potential in supporting precision oncology and improving patient outcomes through data-driven insights.
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Affiliation(s)
| | - K Linton-Reid
- Imperial College London Hammersmith Campus, London, W12 0NN, United Kingdom.
| | - M Chen
- Imperial College London Hammersmith Campus, London, W12 0NN, United Kingdom.
| | - E O Aboagye
- Imperial College London Hammersmith Campus, London, W12 0NN, United Kingdom.
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27
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Nguyen T, Panwar V, Jamale V, Perny A, Dusek C, Cai Q, Kapur P, Danuser G, Rajaram S. Autonomous learning of pathologists' cancer grading rules. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2025:2025.03.18.643999. [PMID: 40166226 PMCID: PMC11956981 DOI: 10.1101/2025.03.18.643999] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/02/2025]
Abstract
Deep learning (DL) algorithms have demonstrated remarkable proficiency in histopathology classification tasks, presenting an opportunity to discover disease-related features escaping visual inspection. However, the "black box" nature of DL obfuscates the basis of the classification. Here, we develop an algorithm for interpretable Deep Learning (IDL) that sheds light on the links between tissue morphology and cancer biology. We make use of a generative model trained to represent images via a combination of a semantic latent space and a noise vector to capture low level image details. We traversed the latent space so as to induce prototypical image changes associated with the disease state, which we identified via a second DL model. Applied to a dataset of clear cell renal cell carcinoma (ccRCC) tissue images the AI system pinpoints nuclear size and nucleolus density in tumor cells (but not other cell types) as the decisive features of tumor progression from grade 1 to grade 4 - mirroring the rules that have been used for decades in the clinic and are taught in textbooks. Moreover, the AI system posits a decrease in vasculature with increasing grade. While the association has been illustrated by some previous reports, the correlation is not part of currently implemented grading systems. These results indicate the potential of IDL to autonomously formalize the connection between the histopathological presentation of a disease and the underlying tissue architectural drivers.
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Affiliation(s)
- Thuong Nguyen
- Lyda Hill Department of Bioinformatics, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Vandana Panwar
- Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Vipul Jamale
- Lyda Hill Department of Bioinformatics, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Averi Perny
- Lyda Hill Department of Bioinformatics, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Cecilia Dusek
- Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Qi Cai
- Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Payal Kapur
- Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA
- Kidney Cancer Program, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA
- Department of Urology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA
| | - Gaudenz Danuser
- Lyda Hill Department of Bioinformatics, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Satwik Rajaram
- Lyda Hill Department of Bioinformatics, University of Texas Southwestern Medical Center, Dallas, TX, USA
- Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA
- Kidney Cancer Program, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA
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28
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Ke X, Yang M, Chen J, Hong R, Wang Z, Wang S, Zhang H, Lu J, Pan B, Gao Y, Liu X, Li X, Zhang Y, Su S, Wu H, Liang Z. Labor-Efficient Pathological Auxiliary Diagnostic Model for Primary and Metastatic Tumor Tissue Detection in Pancreatic Ductal Adenocarcinoma. Mod Pathol 2025; 38:100764. [PMID: 40199428 DOI: 10.1016/j.modpat.2025.100764] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2024] [Revised: 03/09/2025] [Accepted: 03/20/2025] [Indexed: 04/10/2025]
Abstract
Accurate histopathological evaluation of pancreatic ductal adenocarcinoma (PDAC), including primary tumor lesions and lymph node metastases, is critical for prognostic evaluation and personalized therapeutic strategies. Distinct from other solid tumors, PDAC presents unique diagnostic challenges owing to its extensive desmoplasia, unclear tumor boundary, and difficulty in differentiating from chronic pancreatitis. These characteristics not only complicate pathological diagnosis but also hinder the acquisition of pixel-level annotations required for training computational pathology models. In this study, we present PANseg, a multiscale weakly supervised deep learning framework for PDAC segmentation, trained and tested on 368 whole-slide images (WSIs) from 208 patients across 2 independent centers. Using only image-level labels (2048 × 2048 pixels), PANseg achieved comparable performance with fully supervised baseline (FSB) across the internal test set 1 (17 patients/58 WSIs; PANseg area under the receiver operating characteristic curve [AUROC]: 0.969 vs FSB AUROC: 0.968), internal test set 2 (40 patients/44 WSIs; PANseg AUROC: 0.991 vs FSB AUROC: 0.980), and external test set (20 patients/20 WSIs; PANseg AUROC: 0.950 vs FSB AUROC: 0.958). Moreover, the model demonstrated considerable generalizability with previously unseen sample types, attaining AUROCs of 0.878 on fresh-frozen specimens (20 patients/20 WSIs) and 0.821 on biopsy sections (20 patients/20 WSIs). In lymph node metastasis detection, PANseg augmented the diagnostic accuracy of 6 pathologists from 0.888 to 0.961, while reducing the average diagnostic time by 32.6% (72.0 vs 48.5 minutes). This study demonstrates that our weakly supervised model can achieve expert-level segmentation performance and substantially reduce annotation burden. The clinical implementation of PANseg holds great potential in enhancing diagnostic precision and workflow efficiency in the routine histopathological assessment of PDAC.
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Affiliation(s)
- Xinyi Ke
- Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Moxuan Yang
- Thorough Lab, Thorough Future, Beijing, China; Department of Physics, Capital Normal University, Beijing, China
| | - Jingci Chen
- Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ruping Hong
- Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zheng Wang
- Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Shuhao Wang
- Thorough Lab, Thorough Future, Beijing, China
| | - Hui Zhang
- Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Junliang Lu
- Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Boju Pan
- Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yike Gao
- Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xiaoding Liu
- Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xiaoyu Li
- Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yang Zhang
- Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Si Su
- Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Huanwen Wu
- Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
| | - Zhiyong Liang
- Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
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Lewis C, Groarke J, Graham-Wisener L, James J. Public Awareness of and Attitudes Toward the Use of AI in Pathology Research and Practice: Mixed Methods Study. J Med Internet Res 2025; 27:e59591. [PMID: 40173441 PMCID: PMC12004022 DOI: 10.2196/59591] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2024] [Revised: 11/07/2024] [Accepted: 02/04/2025] [Indexed: 04/04/2025] Open
Abstract
BACKGROUND The last decade has witnessed major advances in the development of artificial intelligence (AI) technologies for use in health care. One of the most promising areas of research that has potential clinical utility is the use of AI in pathology to aid cancer diagnosis and management. While the value of using AI to improve the efficiency and accuracy of diagnosis cannot be underestimated, there are challenges in the development and implementation of such technologies. Notably, questions remain about public support for the use of AI to assist in pathological diagnosis and for the use of health care data, including data obtained from tissue samples, to train algorithms. OBJECTIVE This study aimed to investigate public awareness of and attitudes toward AI in pathology research and practice. METHODS A nationally representative, cross-sectional, web-based mixed methods survey (N=1518) was conducted to assess the UK public's awareness of and views on the use of AI in pathology research and practice. Respondents were recruited via Prolific, an online research platform. To be eligible for the study, participants had to be aged >18 years, be UK residents, and have the capacity to express their own opinion. Respondents answered 30 closed-ended questions and 2 open-ended questions. Sociodemographic information and previous experience with cancer were collected. Descriptive and inferential statistics were used to analyze quantitative data; qualitative data were analyzed thematically. RESULTS Awareness was low, with only 23.19% (352/1518) of the respondents somewhat or moderately aware of AI being developed for use in pathology. Most did not support a diagnosis of cancer (908/1518, 59.82%) or a diagnosis based on biomarkers (694/1518, 45.72%) being made using AI only. However, most (1478/1518, 97.36%) supported diagnoses made by pathologists with AI assistance. The adjusted odds ratio (aOR) for supporting AI in cancer diagnosis and management was higher for men (aOR 1.34, 95% CI 1.02-1.75). Greater awareness (aOR 1.25, 95% CI 1.10-1.42), greater trust in data security and privacy protocols (aOR 1.04, 95% CI 1.01-1.07), and more positive beliefs (aOR 1.27, 95% CI 1.20-1.36) also increased support, whereas identifying more risks reduced the likelihood of support (aOR 0.80, 95% CI 0.73-0.89). In total, 3 main themes emerged from the qualitative data: bringing the public along, the human in the loop, and more hard evidence needed, indicating conditional support for AI in pathology with human decision-making oversight, robust measures for data handling and protection, and evidence for AI benefit and effectiveness. CONCLUSIONS Awareness of AI's potential use in pathology was low, but attitudes were positive, with high but conditional support. Challenges remain, particularly among women, regarding AI use in cancer diagnosis and management. Apprehension persists about the access to and use of health care data by private organizations.
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Affiliation(s)
- Claire Lewis
- School of Medicine Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, United Kingdom
| | - Jenny Groarke
- School of Psychology, University of Galway, Galway, Ireland
| | | | - Jacqueline James
- School of Medicine Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, United Kingdom
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30
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Vigdorovits A, Olteanu GE, Tica O, Pascalau A, Boros M, Pop O. Predicting the Evolution of Lung Squamous Cell Carcinoma In Situ Using Computational Pathology. Bioengineering (Basel) 2025; 12:377. [PMID: 40281737 PMCID: PMC12024523 DOI: 10.3390/bioengineering12040377] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2025] [Revised: 03/19/2025] [Accepted: 03/31/2025] [Indexed: 04/29/2025] Open
Abstract
Lung squamous cell carcinoma in situ (SCIS) is the preinvasive precursor lesion of lung squamous cell carcinoma (SCC). Only around two-thirds of these lesions progress to invasive cancer, while one-third undergo spontaneous regression, which presents a significant clinical challenge due to the risk of overtreatment. The ability to predict the evolution of SCIS lesions can significantly impact patient management. Our study explores the use of computational pathology in predicting the evolution of SCIS. We used a dataset consisting of 112 H&E-stained whole slide images (WSIs) that were obtained from the Image Data Resource public repository. The dataset corresponded to tumors of patients who underwent biopsies of SCIS lesions and were subsequently followed up by bronchoscopy and CT scans to monitor for progression to SCC. We used this dataset to train two models: a pathomics-based ridge classifier trained on 80 principal components derived from almost 2000 extracted features and a deep convolutional neural network with a modified ResNet18 architecture. The performance of both approaches in predicting progression was assessed. The pathomics-based ridge classifier model obtained an F1-score of 0.77, precision of 0.80, and recall of 0.77. The deep learning model performance was similar, with a WSI-level F1-score of 0.80, precision of 0.71, and recall of 0.90. These findings highlight the potential of computational pathology approaches in providing insights into the evolution of SCIS. Larger datasets will be required in order to train highly accurate models. In the future, computational pathology could be used in predicting outcomes in other preinvasive lesions.
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Affiliation(s)
- Alon Vigdorovits
- Department of Pathology, Bihor County Clinical Emergency Hospital, 410169 Oradea, Romania; (A.V.); (O.T.); (A.P.); (M.B.); (O.P.)
- Department of Morphological Sciences, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania
| | | | - Ovidiu Tica
- Department of Pathology, Bihor County Clinical Emergency Hospital, 410169 Oradea, Romania; (A.V.); (O.T.); (A.P.); (M.B.); (O.P.)
| | - Andrei Pascalau
- Department of Pathology, Bihor County Clinical Emergency Hospital, 410169 Oradea, Romania; (A.V.); (O.T.); (A.P.); (M.B.); (O.P.)
- Department of Morphological Sciences, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania
| | - Monica Boros
- Department of Pathology, Bihor County Clinical Emergency Hospital, 410169 Oradea, Romania; (A.V.); (O.T.); (A.P.); (M.B.); (O.P.)
- Department of Morphological Sciences, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania
| | - Ovidiu Pop
- Department of Pathology, Bihor County Clinical Emergency Hospital, 410169 Oradea, Romania; (A.V.); (O.T.); (A.P.); (M.B.); (O.P.)
- Department of Morphological Sciences, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania
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31
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Aggarwal A, Bharadwaj S, Corredor G, Pathak T, Badve S, Madabhushi A. Artificial intelligence in digital pathology - time for a reality check. Nat Rev Clin Oncol 2025; 22:283-291. [PMID: 39934323 DOI: 10.1038/s41571-025-00991-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/24/2025] [Indexed: 02/13/2025]
Abstract
The past decade has seen the introduction of artificial intelligence (AI)-based approaches aimed at optimizing several workflows across many medical specialties. In clinical oncology, the most promising applications include those involving image analysis, such as digital pathology. In this Perspective, we provide a comprehensive examination of the developments in AI in digital pathology between 2019 and 2024. We evaluate the current landscape from the lens of technological innovations, regulatory trends, deployment and implementation, reimbursement and commercial implications. We assess the technological advances that have driven improvements in AI, enabling more robust and scalable solutions for digital pathology. We also examine regulatory developments, in particular those affecting in-house devices and laboratory-developed tests, which are shaping the landscape of AI-based tools in digital pathology. Finally, we discuss the role of reimbursement frameworks and commercial investment in the clinical adoption of AI-based technologies. In this Perspective, we highlight both the progress and challenges in AI-driven digital pathology over the past 5 years, outlining the path forward for its adoption into routine practice in clinical oncology.
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Affiliation(s)
- Arpit Aggarwal
- Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA, USA
| | - Satvika Bharadwaj
- Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA, USA
| | - Germán Corredor
- Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA, USA
- Atlanta Veterans Affairs Medical Center, Atlanta, GA, USA
| | - Tilak Pathak
- Department of Biomedical Engineering, Emory University, Atlanta, GA, USA
| | - Sunil Badve
- Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA
| | - Anant Madabhushi
- Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA, USA.
- Atlanta Veterans Affairs Medical Center, Atlanta, GA, USA.
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32
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Holowatyj AN, Overman MJ, Votanopoulos KI, Lowy AM, Wagner P, Washington MK, Eng C, Foo WC, Goldberg RM, Hosseini M, Idrees K, Johnson DB, Shergill A, Ward E, Zachos NC, Shelton D. Defining a 'cells to society' research framework for appendiceal tumours. Nat Rev Cancer 2025; 25:293-315. [PMID: 39979656 DOI: 10.1038/s41568-024-00788-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/12/2024] [Indexed: 02/22/2025]
Abstract
Tumours of the appendix - a vestigial digestive organ attached to the colon - are rare. Although we estimate that around 3,000 new appendiceal cancer cases are diagnosed annually in the USA, the challenges of accurately diagnosing and identifying this tumour type suggest that this number may underestimate true population incidence. In the current absence of disease-specific screening and diagnostic imaging modalities, or well-established risk factors, the incidental discovery of appendix tumours is often prompted by acute presentations mimicking appendicitis or when the tumour has already spread into the abdominal cavity - wherein the potential misclassification of appendiceal tumours as malignancies of the colon and ovaries also increases. Notwithstanding these diagnostic difficulties, our understanding of appendix carcinogenesis has advanced in recent years. However, there persist considerable challenges to accelerating the pace of research discoveries towards the path to improved treatments and cures for patients with this group of orphan malignancies. The premise of this Expert Recommendation article is to discuss the current state of the field, to delineate unique challenges for the study of appendiceal tumours, and to propose key priority research areas that will deliver a more complete picture of appendix carcinogenesis and metastasis. The Appendix Cancer Pseudomyxoma Peritonei (ACPMP) Research Foundation Scientific Think Tank delivered a consensus of core research priorities for appendiceal tumours that are poised to be ground-breaking and transformative for scientific discovery and innovation. On the basis of these six research areas, here, we define the first 'cells to society' research framework for appendix tumours.
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Affiliation(s)
- Andreana N Holowatyj
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
- Vanderbilt-Ingram Cancer Center, Nashville, TN, USA.
- Vanderbilt University School of Medicine, Nashville, TN, USA.
| | - Michael J Overman
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | | | - Andrew M Lowy
- Department of Surgery, Division of Surgical Oncology, Moores Cancer Center, University of California San Diego, La Jolla, CA, USA
| | - Patrick Wagner
- Division of Surgical Oncology, Allegheny Health Network Cancer Institute, Allegheny Health Network, Pittsburgh, PA, USA
| | - Mary K Washington
- Vanderbilt-Ingram Cancer Center, Nashville, TN, USA
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Cathy Eng
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
- Vanderbilt-Ingram Cancer Center, Nashville, TN, USA
| | - Wai Chin Foo
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | | | - Mojgan Hosseini
- Department of Pathology, University of California, San Diego, San Diego, CA, USA
| | - Kamran Idrees
- Vanderbilt-Ingram Cancer Center, Nashville, TN, USA
- Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Douglas B Johnson
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
- Vanderbilt-Ingram Cancer Center, Nashville, TN, USA
| | - Ardaman Shergill
- Department of Medicine, University of Chicago Medical Center, Chicago, IL, USA
| | - Erin Ward
- Section of Surgical Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA
| | - Nicholas C Zachos
- Vanderbilt-Ingram Cancer Center, Nashville, TN, USA
- Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Deborah Shelton
- Appendix Cancer Pseudomyxoma Peritonei (ACPMP) Research Foundation, Springfield, PA, USA
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O'Connor O, McVeigh TP. Increasing use of artificial intelligence in genomic medicine for cancer care- the promise and potential pitfalls. BJC REPORTS 2025; 3:20. [PMID: 40169715 PMCID: PMC11962076 DOI: 10.1038/s44276-025-00135-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/15/2024] [Revised: 03/05/2025] [Accepted: 03/19/2025] [Indexed: 04/03/2025]
Abstract
The field of genomic medicine produces large datasets, which need to be rapidly analysed to produce clinically actionable insights in cancer care. Artificial intelligence thrives on data, processing and learning from datasets with a degree of accuracy and efficiency that traditional computing algorithms can not achieve. Based on a patient's genome sequence, AI could allow earlier detection of cancer, inform personalised treatment plans and provide insights into prognostication. However, this valuable tool is met with skepticism, with stakeholders concerned over data security, liability for AI's mistakes due to hallucination and the threat to clinical jobs. This review highlights both the benefits and potential problems of using AI in genomic medicine for cancer care, with the aim to lessen the knowledge gap between clinicians and data scientists and facilitate the future deployment of AI in cancer care.
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Affiliation(s)
| | - Terri P McVeigh
- Cancer Genetics Unit, The Royal Marsden NHS Foundation Trust, England, UK
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34
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Kong X, Shi J, Sun D, Cheng L, Wu C, Jiang Z, Zheng Y, Wang W, Wu H. A deep-learning model for predicting tyrosine kinase inhibitor response from histology in gastrointestinal stromal tumor. J Pathol 2025; 265:462-471. [PMID: 39950223 DOI: 10.1002/path.6399] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Revised: 09/01/2024] [Accepted: 01/06/2025] [Indexed: 03/06/2025]
Abstract
Over 90% of gastrointestinal stromal tumors (GISTs) harbor mutations in KIT or PDGFRA that can predict response to tyrosine kinase inhibitor (TKI) therapies, as recommended by NCCN (National Comprehensive Cancer Network) guidelines. However, gene sequencing for mutation testing is expensive and time-consuming and is susceptible to a variety of preanalytical factors. To overcome the challenges associated with genetic screening by sequencing, in the current study we developed an artificial intelligence-based deep-learning (DL) model that uses convolutional neural networks (CNN) to analyze digitized hematoxylin and eosin staining in tumor histological sections to predict potential response to imatinib or avapritinib treatment in GIST patients. Assessment with an independent testing set showed that our DL model could predict imatinib sensitivity with an area under the curve (AUC) of 0.902 in case-wise analysis and 0.807 in slide-wise analysis. Case-level AUCs for predicting imatinib-dose-adjustment cases, avapritinib-sensitive cases, and wildtype GISTs were 0.920, 0.958, and 0.776, respectively, while slide-level AUCs for these respective groups were 0.714, 0.922, and 0.886, respectively. Our model showed comparable or better prediction of actual response to TKI than sequencing-based screening (accuracy 0.9286 versus 0.8929; DL model versus sequencing), while predictions of nonresponse to imatinib/avapritinib showed markedly higher accuracy than sequencing (0.7143 versus 0.4286). These results demonstrate the potential of a DL model to improve predictions of treatment response to TKI therapy from histology in GIST patients. © 2025 The Pathological Society of Great Britain and Ireland.
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Affiliation(s)
- Xue Kong
- Department of Pathology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of PR China, Hefei, PR China
- Intelligent Pathology Institute, Division of Life Sciences and Medicine, University of Science and Technology of PR China, Hefei, PR China
| | - Jun Shi
- School of Software, Hefei University of Technology, Hefei, PR China
| | - Dongdong Sun
- School of Computer Science and Information Engineering, Hefei University of Technology, Hefei, PR China
| | - Lanqing Cheng
- Department of Pathology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of PR China, Hefei, PR China
- Intelligent Pathology Institute, Division of Life Sciences and Medicine, University of Science and Technology of PR China, Hefei, PR China
| | - Can Wu
- Department of Pathology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of PR China, Hefei, PR China
- Intelligent Pathology Institute, Division of Life Sciences and Medicine, University of Science and Technology of PR China, Hefei, PR China
| | - Zhiguo Jiang
- Image Processing Center, School of Astronautics, Beihang University, Beijing, PR China
| | - Yushan Zheng
- School of Engineering Medicine, Beijing Advanced Innovation Center on Biomedical Engineering, Beihang University, Beijing, PR China
| | - Wei Wang
- Department of Pathology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of PR China, Hefei, PR China
- Intelligent Pathology Institute, Division of Life Sciences and Medicine, University of Science and Technology of PR China, Hefei, PR China
| | - Haibo Wu
- Department of Pathology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of PR China, Hefei, PR China
- Intelligent Pathology Institute, Division of Life Sciences and Medicine, University of Science and Technology of PR China, Hefei, PR China
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35
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Hölscher DL, Bülow RD. Decoding pathology: the role of computational pathology in research and diagnostics. Pflugers Arch 2025; 477:555-570. [PMID: 39095655 PMCID: PMC11958429 DOI: 10.1007/s00424-024-03002-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2024] [Revised: 07/25/2024] [Accepted: 07/25/2024] [Indexed: 08/04/2024]
Abstract
Traditional histopathology, characterized by manual quantifications and assessments, faces challenges such as low-throughput and inter-observer variability that hinder the introduction of precision medicine in pathology diagnostics and research. The advent of digital pathology allowed the introduction of computational pathology, a discipline that leverages computational methods, especially based on deep learning (DL) techniques, to analyze histopathology specimens. A growing body of research shows impressive performances of DL-based models in pathology for a multitude of tasks, such as mutation prediction, large-scale pathomics analyses, or prognosis prediction. New approaches integrate multimodal data sources and increasingly rely on multi-purpose foundation models. This review provides an introductory overview of advancements in computational pathology and discusses their implications for the future of histopathology in research and diagnostics.
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Affiliation(s)
- David L Hölscher
- Department for Nephrology and Clinical Immunology, RWTH Aachen University Hospital, Pauwelsstraße 30, 52074, Aachen, Germany
- Institute for Pathology, RWTH Aachen University Hospital, Pauwelsstraße 30, 52074, Aachen, Germany
| | - Roman D Bülow
- Institute for Pathology, RWTH Aachen University Hospital, Pauwelsstraße 30, 52074, Aachen, Germany.
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36
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Hu Y, Sirinukunwattana K, Li B, Gaitskell K, Domingo E, Bonnaffé W, Wojciechowska M, Wood R, Alham NK, Malacrino S, Woodcock DJ, Verrill C, Ahmed A, Rittscher J. Self-interactive learning: Fusion and evolution of multi-scale histomorphology features for molecular traits prediction in computational pathology. Med Image Anal 2025; 101:103437. [PMID: 39798526 DOI: 10.1016/j.media.2024.103437] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2024] [Revised: 10/06/2024] [Accepted: 12/09/2024] [Indexed: 01/15/2025]
Abstract
Predicting disease-related molecular traits from histomorphology brings great opportunities for precision medicine. Despite the rich information present in histopathological images, extracting fine-grained molecular features from standard whole slide images (WSI) is non-trivial. The task is further complicated by the lack of annotations for subtyping and contextual histomorphological features that might span multiple scales. This work proposes a novel multiple-instance learning (MIL) framework capable of WSI-based cancer morpho-molecular subtyping by fusion of different-scale features. Our method, debuting as Inter-MIL, follows a weakly-supervised scheme. It enables the training of the patch-level encoder for WSI in a task-aware optimisation procedure, a step normally not modelled in most existing MIL-based WSI analysis frameworks. We demonstrate that optimising the patch-level encoder is crucial to achieving high-quality fine-grained and tissue-level subtyping results and offers a significant improvement over task-agnostic encoders. Our approach deploys a pseudo-label propagation strategy to update the patch encoder iteratively, allowing discriminative subtype features to be learned. This mechanism also empowers extracting fine-grained attention within image tiles (the small patches), a task largely ignored in most existing weakly supervised-based frameworks. With Inter-MIL, we carried out four challenging cancer molecular subtyping tasks in the context of ovarian, colorectal, lung, and breast cancer. Extensive evaluation results show that Inter-MIL is a robust framework for cancer morpho-molecular subtyping with superior performance compared to several recently proposed methods, in small dataset scenarios where the number of available training slides is less than 100. The iterative optimisation mechanism of Inter-MIL significantly improves the quality of the image features learned by the patch embedded and generally directs the attention map to areas that better align with experts' interpretation, leading to the identification of more reliable histopathology biomarkers. Moreover, an external validation cohort is used to verify the robustness of Inter-MIL on molecular trait prediction.
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Affiliation(s)
- Yang Hu
- Nuffield Department of Medicine, University of Oxford, Oxford, UK; Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK.
| | - Korsuk Sirinukunwattana
- Department of Engineering Science, University of Oxford, Oxford, UK; Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK
| | - Bin Li
- Department of Engineering Science, University of Oxford, Oxford, UK; Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK
| | - Kezia Gaitskell
- Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, Oxford, UK; Department of Cellular Pathology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - Enric Domingo
- Department of Oncology, University of Oxford, Oxford, UK
| | - Willem Bonnaffé
- Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK; Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK
| | - Marta Wojciechowska
- Nuffield Department of Medicine, University of Oxford, Oxford, UK; Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK
| | - Ruby Wood
- Department of Engineering Science, University of Oxford, Oxford, UK; Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK
| | - Nasullah Khalid Alham
- Department of Engineering Science, University of Oxford, Oxford, UK; Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK
| | - Stefano Malacrino
- Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK
| | - Dan J Woodcock
- Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK; Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK
| | - Clare Verrill
- Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK; Department of Cellular Pathology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Oxford National Institute for Health Research (NIHR) Biomedical Research Centre, Oxford, UK
| | - Ahmed Ahmed
- MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK; Nuffield Department of Womenś and Reproductive Health, University of Oxford, Oxford, UK; Oxford National Institute for Health Research (NIHR) Biomedical Research Centre, Oxford, UK
| | - Jens Rittscher
- Nuffield Department of Medicine, University of Oxford, Oxford, UK; Department of Engineering Science, University of Oxford, Oxford, UK; Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK; Ludwig Institute for Cancer Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; Oxford National Institute for Health Research (NIHR) Biomedical Research Centre, Oxford, UK.
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37
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Le H, Tsirigos A. AI accurately identifies targetable alterations in lung cancer histological images. Nat Rev Clin Oncol 2025; 22:239-240. [PMID: 39930263 DOI: 10.1038/s41571-025-00999-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/27/2025]
Affiliation(s)
- Hortense Le
- Department of Pathology, NYU Grossman School of Medicine, New York, NY, USA.
- Division of Precision Medicine, Department of Medicine, NYU Grossman School of Medicine, New York, NY, USA.
| | - Aristotelis Tsirigos
- Department of Pathology, NYU Grossman School of Medicine, New York, NY, USA.
- Division of Precision Medicine, Department of Medicine, NYU Grossman School of Medicine, New York, NY, USA.
- Applied Bioinformatics Laboratories, NYU Grossman School of Medicine, New York, NY, USA.
- Laura and Isaac Perlmutter Cancer Center, New York University Langone Health, New York, NY, USA.
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38
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Furtado LV, Ikemura K, Benkli CY, Moncur JT, Huang RSP, Zehir A, Stellato K, Vasalos P, Sadri N, Suarez CJ. General Applicability of Existing College of American Pathologists Accreditation Requirements to Clinical Implementation of Machine Learning-Based Methods in Molecular Oncology Testing. Arch Pathol Lab Med 2025; 149:319-327. [PMID: 38871357 DOI: 10.5858/arpa.2024-0037-cp] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/07/2024] [Indexed: 06/15/2024]
Abstract
CONTEXT.— The College of American Pathologists (CAP) accreditation requirements for clinical laboratory testing help ensure laboratories implement and maintain systems and processes that are associated with quality. Machine learning (ML)-based models share some features of conventional laboratory testing methods. Accreditation requirements that specifically address clinical laboratories' use of ML remain in the early stages of development. OBJECTIVE.— To identify relevant CAP accreditation requirements that may be applied to the clinical adoption of ML-based molecular oncology assays, and to provide examples of current and emerging ML applications in molecular oncology testing. DESIGN.— CAP accreditation checklists related to molecular pathology and general laboratory practices (Molecular Pathology, All Common and Laboratory General) were reviewed. Examples of checklist requirements that are generally applicable to validation, revalidation, quality management, infrastructure, and analytical procedures of ML-based molecular oncology assays were summarized. Instances of ML use in molecular oncology testing were assessed from literature review. RESULTS.— Components of the general CAP accreditation framework that exist for traditional molecular oncology assay validation and maintenance are also relevant for implementing ML-based tests in a clinical laboratory. Current and emerging applications of ML in molecular oncology testing include DNA methylation profiling for central nervous system tumor classification, variant calling, microsatellite instability testing, mutational signature analysis, and variant prediction from histopathology images. CONCLUSIONS.— Currently, much of the ML activity in molecular oncology is within early clinical implementation. Despite specific considerations that apply to the adoption of ML-based methods, existing CAP requirements can serve as general guidelines for the clinical implementation of ML-based assays in molecular oncology testing.
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Affiliation(s)
- Larissa V Furtado
- From the Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee (Furtado)
| | - Kenji Ikemura
- the Department of Pathology, Mass General Brigham, Boston, Massachusetts (Ikemura)
| | - Cagla Y Benkli
- the Department of Pathology, Baylor College of Medicine, Houston, Texas (Benkli)
| | - Joel T Moncur
- Office of the Director, The Joint Pathology Center, Silver Spring, Maryland (Moncur)
| | - Richard S P Huang
- Clinical Development, Foundation Medicine Inc, Cambridge, Massachusetts (Huang)
| | - Ahmet Zehir
- Precision Medicine & Biosamples, AstraZeneca, New York, New York (Zehir)
| | - Katherine Stellato
- Proficiency Testing, College of American Pathologists, Northfield, Illinois (Stellato, Vasalos)
| | - Patricia Vasalos
- Proficiency Testing, College of American Pathologists, Northfield, Illinois (Stellato, Vasalos)
| | - Navid Sadri
- the Department of Pathology, University Hospitals Cleveland Medical Center, Cleveland, Ohio (Sadri)
| | - Carlos J Suarez
- the Department of Pathology, Stanford University School of Medicine, Palo Alto, California (Suarez)
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39
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Tang Z, Yang L, Chen Z, Liu L, Li C, Chen R, Zhang X, Zheng Q. CTUSurv: A Cell-Aware Transformer-Based Network With Uncertainty for Survival Prediction Using Whole Slide Images. IEEE TRANSACTIONS ON MEDICAL IMAGING 2025; 44:1750-1764. [PMID: 40031069 DOI: 10.1109/tmi.2025.3526848] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/05/2025]
Abstract
Image-based survival prediction through deep learning techniques represents a burgeoning frontier aimed at augmenting the diagnostic capabilities of pathologists. However, directly applying existing deep learning models to survival prediction may not be a panacea due to the inherent complexity and sophistication of whole slide images (WSIs). The intricate nature of high-resolution WSIs, characterized by sophisticated patterns and inherent noise, presents significant challenges in terms of effectiveness and trustworthiness. In this paper, we propose CTUSurv, a novel survival prediction model designed to simultaneously capture cell-to-cell and cell-to-microenvironment interactions, complemented by a region-based uncertainty estimation framework to assess the reliability of survival predictions. Our approach incorporates an innovative region sampling strategy to extract task-relevant, informative regions from high-resolution WSIs. To address the challenges posed by sophisticated biological patterns, a cell-aware encoding module is integrated to model the interactions among biological entities. Furthermore, CTUSurv includes a novel aleatoric uncertainty estimation module to provide fine-grained uncertainty scores at the region level. Extensive evaluations across four datasets demonstrate the superiority of our proposed approach in terms of both predictive accuracy and reliability.
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40
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Zhang X, Wang T, Yan C, Najdawi F, Zhou K, Ma Y, Cheung YM, Malin BA. Implementing Trust in Non-Small Cell Lung Cancer Diagnosis with a Conformalized Uncertainty-Aware AI Framework in Whole-Slide Images. RESEARCH SQUARE 2025:rs.3.rs-5723270. [PMID: 40195980 PMCID: PMC11975025 DOI: 10.21203/rs.3.rs-5723270/v1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/09/2025]
Abstract
Ensuring trustworthiness is fundamental to the development of artificial intelligence (AI) that is considered societally responsible, particularly in cancer diagnostics, where a misdiagnosis can have dire consequences. Current digital pathology AI models lack systematic solutions to address trustworthiness concerns arising from model limitations and data discrepancies between model deployment and development environments. To address this issue, we developed TRUECAM, a framework designed to ensure both data and model trustworthiness in non-small cell lung cancer subtyping with whole-slide images. TRUECAM integrates 1) a spectral-normalized neural Gaussian process for identifying out-of-scope inputs and 2) an ambiguity-guided elimination of tiles to filter out highly ambiguous regions, addressing data trustworthiness, as well as 3) conformal prediction to ensure controlled error rates. We systematically evaluated the framework across multiple large-scale cancer datasets, leveraging both task-specific and foundation models, illustrate that an AI model wrapped with TRUECAM significantly outperforms models that lack such guidance, in terms of classification accuracy, robustness, interpretability, and data efficiency, while also achieving improvements in fairness. These findings highlight TRUECAM as a versatile wrapper framework for digital pathology AI models with diverse architectural designs, promoting their responsible and effective applications in real-world settings.
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Affiliation(s)
- Xiaoge Zhang
- Department of Industrial and Systems Engineering, The Hong Kong Polytechnic University, Kowloon, Hong Kong
| | - Tao Wang
- Department of Industrial and Systems Engineering, The Hong Kong Polytechnic University, Kowloon, Hong Kong
| | - Chao Yan
- Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Fedaa Najdawi
- Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Kai Zhou
- Department of Computing, The Hong Kong Polytechnic University, Kowloon, Hong Kong
| | - Yuan Ma
- Department of Mechanical Engineering and Research Institute for Intelligent Wearable Systems, The Hong Kong Polytechnic University, Kowloon, Hong Kong
| | - Yiu-Ming Cheung
- Department of Computer Science, Hong Kong Baptist University, Kowloon Tong, Kowloon, Hong Kong
| | - Bradley A Malin
- Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, USA
- Department of Computer Science, Vanderbilt University, Nashville, TN, USA
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA
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41
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Theodorou SDP, Ntostoglou K, Nikas IP, Goutas D, Georgoulias V, Kittas C, Pateras IS. Double-Multiplex Immunostainings for Immune Profiling of Invasive Breast Carcinoma: Emerging Novel Immune-Based Biomarkers. Int J Mol Sci 2025; 26:2838. [PMID: 40243442 PMCID: PMC11988469 DOI: 10.3390/ijms26072838] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2025] [Revised: 03/17/2025] [Accepted: 03/18/2025] [Indexed: 04/18/2025] Open
Abstract
The role of tumor microenvironment in invasive breast cancer prognosis and treatment is highly appreciated. With the advent of immunotherapy, immunophenotypic characterization in primary tumors is gaining attention as it can improve patient stratification. Here, we discuss the benefits of spatial analysis employing double and multiplex immunostaining, allowing the simultaneous detection of more than one protein on the same tissue section, which in turn helps us provide functional insight into infiltrating immune cells within tumors. We focus on studies demonstrating the prognostic and predictive impact of distinct tumor-infiltrating lymphocyte subpopulations including different CD8(+) T subsets as well as CD4(+) T cells and tumor-associated macrophages in invasive breast carcinoma. The clinical value of immune cell topography is also appreciated. We further refer to how the integration of digital pathology and artificial intelligence in routine practice could enhance the accuracy of multiplex immunostainings evaluation within the tumor microenvironment, maximizing our perception of host immune response, improving in turn decision-making towards more precise immune-associated therapies.
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Affiliation(s)
- Sofia D. P. Theodorou
- Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece; (S.D.P.T.); (K.N.); (C.K.)
| | - Konstantinos Ntostoglou
- Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece; (S.D.P.T.); (K.N.); (C.K.)
| | - Ilias P. Nikas
- Medical School, University of Cyprus, 2029 Nicosia, Cyprus;
| | - Dimitrios Goutas
- 2nd Department of Pathology, “Attikon” University Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece;
| | | | - Christos Kittas
- Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece; (S.D.P.T.); (K.N.); (C.K.)
| | - Ioannis S. Pateras
- 2nd Department of Pathology, “Attikon” University Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece;
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42
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Mao Y, Xu N, Wu Y, Wang L, Wang H, He Q, Zhao T, Ma S, Zhou M, Jin H, Pei D, Zhang L, Song J. Assessments of lung nodules by an artificial intelligence chatbot using longitudinal CT images. Cell Rep Med 2025; 6:101988. [PMID: 40043704 PMCID: PMC11970393 DOI: 10.1016/j.xcrm.2025.101988] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2024] [Revised: 11/21/2024] [Accepted: 02/04/2025] [Indexed: 03/21/2025]
Abstract
Large language models have shown efficacy across multiple medical tasks. However, their value in the assessment of longitudinal follow-up computed tomography (CT) images of patients with lung nodules is unclear. In this study, we evaluate the ability of the latest generative pre-trained transformer (GPT)-4o model to assess changes in malignancy probability, size, and features of lung nodules on longitudinal CT scans from 647 patients (547 from two local centers and 100 from a public dataset). GPT-4o achieves an average accuracy of 0.88 in predicting lung nodule malignancy compared to pathological results and an average intraclass correlation coefficient of 0.91 in measuring nodule size compared with manual measurements by radiologists. Six radiologists' evaluations demonstrate GPT-4o's ability to capture changes in nodule features with a median Likert score of 4.17 (out of 5.00). In summary, GPT-4o could capture dynamic changes in lung nodules across longitudinal follow-up CT images, thus providing high-quality radiological evidence to assist in clinical management.
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Affiliation(s)
- Yuqiang Mao
- Department of Thoracic Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, China
| | - Nan Xu
- School of Health Management, China Medical University, Shenyang, Liaoning 110122, China
| | - Yanan Wu
- School of Health Management, China Medical University, Shenyang, Liaoning 110122, China
| | - Lu Wang
- School of Health Management, China Medical University, Shenyang, Liaoning 110122, China; Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, China
| | - Hongtao Wang
- Department of Hematology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, China
| | - Qianqian He
- School of Health Management, China Medical University, Shenyang, Liaoning 110122, China
| | - Tianqi Zhao
- Department of Radiology, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning 110032, China
| | - Shuangchun Ma
- Department of Radiology, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning 110032, China
| | - Meihong Zhou
- Department of Radiology, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning 110032, China
| | - Hongjie Jin
- Department of Thoracic Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, China
| | - Dongmei Pei
- Department of Health Management, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, China.
| | - Lina Zhang
- Department of Radiology, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning 110032, China.
| | - Jiangdian Song
- School of Health Management, China Medical University, Shenyang, Liaoning 110122, China.
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Stojchevski R, Sutanto EA, Sutanto R, Hadzi-Petrushev N, Mladenov M, Singh SR, Sinha JK, Ghosh S, Yarlagadda B, Singh KK, Verma P, Sengupta S, Bhaskar R, Avtanski D. Translational Advances in Oncogene and Tumor-Suppressor Gene Research. Cancers (Basel) 2025; 17:1008. [PMID: 40149342 PMCID: PMC11940485 DOI: 10.3390/cancers17061008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2025] [Revised: 03/10/2025] [Accepted: 03/15/2025] [Indexed: 03/29/2025] Open
Abstract
Cancer, characterized by the uncontrolled proliferation of cells, is one of the leading causes of death globally, with approximately one in five people developing the disease in their lifetime. While many driver genes were identified decades ago, and most cancers can be classified based on morphology and progression, there is still a significant gap in knowledge about genetic aberrations and nuclear DNA damage. The study of two critical groups of genes-tumor suppressors, which inhibit proliferation and promote apoptosis, and oncogenes, which regulate proliferation and survival-can help to understand the genomic causes behind tumorigenesis, leading to more personalized approaches to diagnosis and treatment. Aberration of tumor suppressors, which undergo two-hit and loss-of-function mutations, and oncogenes, activated forms of proto-oncogenes that experience one-hit and gain-of-function mutations, are responsible for the dysregulation of key signaling pathways that regulate cell division, such as p53, Rb, Ras/Raf/ERK/MAPK, PI3K/AKT, and Wnt/β-catenin. Modern breakthroughs in genomics research, like next-generation sequencing, have provided efficient strategies for mapping unique genomic changes that contribute to tumor heterogeneity. Novel therapeutic approaches have enabled personalized medicine, helping address genetic variability in tumor suppressors and oncogenes. This comprehensive review examines the molecular mechanisms behind tumor-suppressor genes and oncogenes, the key signaling pathways they regulate, epigenetic modifications, tumor heterogeneity, and the drug resistance mechanisms that drive carcinogenesis. Moreover, the review explores the clinical application of sequencing techniques, multiomics, diagnostic procedures, pharmacogenomics, and personalized treatment and prevention options, discussing future directions for emerging technologies.
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Affiliation(s)
- Radoslav Stojchevski
- Friedman Diabetes Institute, Lenox Hill Hospital, Northwell Health, New York, NY 10022, USA;
- Feinstein Institutes for Medical Research, Manhasset, NY 11030, USA
- Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY 11549, USA
| | - Edward Agus Sutanto
- CUNY School of Medicine, The City College of New York, 160 Convent Avenue, New York, NY 10031, USA;
| | - Rinni Sutanto
- New York Institute of Technology College of Osteopathic Medicine, Glen Head, NY 11545, USA;
| | - Nikola Hadzi-Petrushev
- Faculty of Natural Sciences and Mathematics, Institute of Biology, Ss. Cyril and Methodius University, 1000 Skopje, North Macedonia; (N.H.-P.)
| | - Mitko Mladenov
- Faculty of Natural Sciences and Mathematics, Institute of Biology, Ss. Cyril and Methodius University, 1000 Skopje, North Macedonia; (N.H.-P.)
| | - Sajal Raj Singh
- GloNeuro, Sector 107, Vishwakarma Road, Noida 201301, Uttar Pradesh, India (J.K.S.)
| | - Jitendra Kumar Sinha
- GloNeuro, Sector 107, Vishwakarma Road, Noida 201301, Uttar Pradesh, India (J.K.S.)
| | - Shampa Ghosh
- GloNeuro, Sector 107, Vishwakarma Road, Noida 201301, Uttar Pradesh, India (J.K.S.)
| | | | - Krishna Kumar Singh
- Symbiosis Centre for Information Technology (SCIT), Rajiv Gandhi InfoTech Park, Hinjawadi, Pune 411057, Maharashtra, India;
| | - Prashant Verma
- School of Management, BML Munjal University, NH8, Sidhrawali, Gurugram 122413, Haryana, India
| | - Sonali Sengupta
- Department of Gastroenterology, All India Institute of Medical Sciences (AIIMS), New Delhi 110029, India
| | - Rakesh Bhaskar
- School of Chemical Engineering, Yeungnam University, Gyeongsan 38541, Republic of Korea
- Research Institute of Cell Culture, Yeungnam University, Gyeongsan 38541, Republic of Korea
| | - Dimiter Avtanski
- Friedman Diabetes Institute, Lenox Hill Hospital, Northwell Health, New York, NY 10022, USA;
- Feinstein Institutes for Medical Research, Manhasset, NY 11030, USA
- Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY 11549, USA
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Aftab J, Khan MA, Arshad S, Rehman SU, AlHammadi DA, Nam Y. Artificial intelligence based classification and prediction of medical imaging using a novel framework of inverted and self-attention deep neural network architecture. Sci Rep 2025; 15:8724. [PMID: 40082642 PMCID: PMC11906919 DOI: 10.1038/s41598-025-93718-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2024] [Accepted: 03/10/2025] [Indexed: 03/16/2025] Open
Abstract
Classifying medical images is essential in computer-aided diagnosis (CAD). Although the recent success of deep learning in the classification tasks has proven advantages over the traditional feature extraction techniques, it remains challenging due to the inter and intra-class similarity caused by the diversity of imaging modalities (i.e., dermoscopy, mammography, wireless capsule endoscopy, and CT). In this work, we proposed a novel deep-learning framework for classifying several medical imaging modalities. In the training phase of the deep learning models, data augmentation is performed at the first stage on all selected datasets. After that, two novel custom deep learning architectures were introduced, called the Inverted Residual Convolutional Neural Network (IRCNN) and Self Attention CNN (SACNN). Both models are trained on the augmented datasets with manual hyperparameter selection. Each dataset's testing images are used to extract features during the testing stage. The extracted features are fused using a modified serial fusion with a strong correlation approach. An optimization algorithm- slap swarm controlled standard Error mean (SScSEM) has been employed, and the best features that passed to the shallow wide neural network (SWNN) classifier for the final classification have been selected. GradCAM, an explainable artificial intelligence (XAI) approach, analyzes custom models. The proposed architecture was tested on five publically available datasets of different imaging modalities and obtained improved accuracy of 98.6 (INBreast), 95.3 (KVASIR), 94.3 (ISIC2018), 95.0 (Lung Cancer), and 98.8% (Oral Cancer), respectively. A detailed comparison is conducted based on precision and accuracy, showing that the proposed architecture performs better. The implemented models are available on GitHub ( https://github.com/ComputerVisionLabPMU/ScientificImagingPaper.git ).
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Affiliation(s)
- Junaid Aftab
- Department of Computer Engineering, HITEC University, Taxila, 47080, Pakistan
| | - Muhammad Attique Khan
- Department of Artificial Intelligence, College of Computer Engineering and Science, Prince Mohammad bin Fahd University, Al Khobar, Saudi Arabia.
| | - Sobia Arshad
- Department of Computer Engineering, HITEC University, Taxila, 47080, Pakistan
| | - Shams Ur Rehman
- Department of Computer Engineering, HITEC University, Taxila, 47080, Pakistan
| | - Dina Abdulaziz AlHammadi
- Department of Information Systems, College of Computer and Information Sciences, Princess Nourah Bint Abdulrahman University, P.O.Box 84428, 11671, Riyadh, Saudi Arabia
| | - Yunyoung Nam
- Department of ICT Convergence, Soonchunhyang University, Asan, South Korea.
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45
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Lee K, Jeon J, Park JW, Yu S, Won JK, Kim K, Park CK, Park SH. SNUH methylation classifier for CNS tumors. Clin Epigenetics 2025; 17:47. [PMID: 40075518 PMCID: PMC11905536 DOI: 10.1186/s13148-025-01824-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Accepted: 01/23/2025] [Indexed: 03/14/2025] Open
Abstract
BACKGROUND Methylation profiling of central nervous system (CNS) tumors, pioneered by the German Cancer Research Center, has significantly improved diagnostic accuracy. This study aimed to further enhance the performance of methylation classifiers by leveraging publicly available data and innovative machine-learning techniques. RESULTS Seoul National University Hospital Methylation Classifier (SNUH-MC) addressed data imbalance using the Synthetic Minority Over-sampling Technique (SMOTE) algorithm and incorporated OpenMax within a Multi-Layer Perceptron to prevent labeling errors in low-confidence diagnoses. Compared to two published CNS tumor methylation classification models (DKFZ-MC: Deutsches Krebsforschungszentrum Methylation Classifier v11b4: RandomForest, 767-MC: Multi-Layer Perceptron), our SNUH-MC showed improved performance in F1-score. For 'Filtered Test Data Set 1,' the SNUH-MC achieved higher F1-micro (0.932) and F1-macro (0.919) scores compared to DKFZ-MC v11b4 (F1-micro: 0.907, F1-macro: 0.627). We evaluated the performance of three classifiers; SNUH-MC, DKFZ-MC v11b4, and DKFZ-MC v12.5, using specific criteria. We set established 'Decisions' categories based on histopathology, clinical information, and next-generation sequencing to assess the classification results. When applied to 193 unknown SNUH methylation data samples, SNUH-MC notably improved diagnosis compared to DKFZ-MC v11b4. Specifically, 17 cases were reclassified as 'Match' and 34 cases as 'Likely Match' when transitioning from DKFZ-MC v11b4 to SNUH-MC. Additionally, SNUH-MC demonstrated similar results to DKFZ-MC v12.5 for 23 cases that were unclassified by v11b4. CONCLUSIONS This study presents SNUH-MC, an innovative methylation-based classification tool that significantly advances the field of neuropathology and bioinformatics. Our classifier incorporates cutting-edge techniques such as the SMOTE and OpenMax resulting in improved diagnostic accuracy and robustness, particularly when dealing with unknown or noisy data.
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Affiliation(s)
- Kwanghoon Lee
- Department of Pathology, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, Republic of Korea
| | - Jaemin Jeon
- Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul, Republic of Korea
| | - Jin Woo Park
- Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Suwan Yu
- Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul, Republic of Korea
| | - Jae-Kyung Won
- Department of Pathology, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, Republic of Korea
| | - Kwangsoo Kim
- Department of Transdisciplinary Medicine, Seoul National University Hospital, Seoul, Republic of Korea
- Department of Medicine, Seoul National University, Seoul, Republic of Korea
| | - Chul-Kee Park
- Department of Neurosurgery, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Sung-Hye Park
- Department of Pathology, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, Republic of Korea.
- Neuroscience Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
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46
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Yang Z, Wei T, Liang Y, Yuan X, Gao R, Xia Y, Zhou J, Zhang Y, Yu Z. A foundation model for generalizable cancer diagnosis and survival prediction from histopathological images. Nat Commun 2025; 16:2366. [PMID: 40064883 PMCID: PMC11894166 DOI: 10.1038/s41467-025-57587-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2024] [Accepted: 02/21/2025] [Indexed: 03/14/2025] Open
Abstract
Computational pathology, utilizing whole slide images (WSIs) for pathological diagnosis, has advanced the development of intelligent healthcare. However, the scarcity of annotated data and histological differences hinder the general application of existing methods. Extensive histopathological data and the robustness of self-supervised models in small-scale data demonstrate promising prospects for developing foundation pathology models. Here we show BEPH (BEiT-based model Pre-training on Histopathological image), a foundation model that leverages self-supervised learning to learn meaningful representations from 11 million unlabeled histopathological images. These representations are then efficiently adapted to various tasks, including patch-level cancer diagnosis, WSI-level cancer classification, and survival prediction for multiple cancer subtypes. By leveraging the masked image modeling (MIM) pre-training approach, BEPH offers an efficient solution to enhance model performance, reduce the reliance on expert annotations, and facilitate the broader application of artificial intelligence in clinical settings. The pre-trained model is available at https://github.com/Zhcyoung/BEPH .
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Affiliation(s)
- Zhaochang Yang
- Department of Bioinformatics and Biostatistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China
| | - Ting Wei
- Department of Bioinformatics and Biostatistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China
| | - Ying Liang
- Department of Bioinformatics and Biostatistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China
- Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China
| | - Xin Yuan
- Department of Bioinformatics and Biostatistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China
- SJTU-Yale Joint Center for Biostatistics and Data Science Organization, Shanghai Jiao Tong University, Shanghai, China
- Center for Biomedical Data Science, Translational Science Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - RuiTian Gao
- Department of Bioinformatics and Biostatistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China
| | - Yujia Xia
- Department of Bioinformatics and Biostatistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China
| | - Jie Zhou
- School of Mathematical sciences, Shanghai Jiao Tong University, Shanghai, China
| | - Yue Zhang
- Department of Bioinformatics and Biostatistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
- SJTU-Yale Joint Center for Biostatistics and Data Science Organization, Shanghai Jiao Tong University, Shanghai, China.
| | - Zhangsheng Yu
- Department of Bioinformatics and Biostatistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
- SJTU-Yale Joint Center for Biostatistics and Data Science Organization, Shanghai Jiao Tong University, Shanghai, China.
- Center for Biomedical Data Science, Translational Science Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
- School of Mathematical sciences, Shanghai Jiao Tong University, Shanghai, China.
- Clinical Research Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
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47
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Penault-Llorca F, Socinski MA. Emerging molecular testing paradigms in non-small cell lung cancer management-current perspectives and recommendations. Oncologist 2025; 30:oyae357. [PMID: 40126879 PMCID: PMC11966107 DOI: 10.1093/oncolo/oyae357] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2024] [Accepted: 11/20/2024] [Indexed: 03/26/2025] Open
Abstract
Advances in molecular testing and precision oncology have transformed the clinical management of lung cancer, especially non-small cell lung cancer, enhancing diagnosis, treatment, and outcomes. Practical guidelines offer insights into selecting appropriate biomarkers and assays, emphasizing the importance of comprehensive testing. However, real-world data reveal the underutilization of biomarker testing and consequently targeted therapies. Molecular testing often occurs late in diagnosis or not at all in clinical practice, leading to delayed or inadequate treatment. Enhancing precision requires adherence to best practices by all health care professionals involved, which can ultimately improve lung cancer patient outcomes. The future of precision oncology for lung cancer will likely involve a more personalized approach, starting increasingly from earlier disease settings, with novel and more complex targeted therapies, immunotherapies, and combination regimens, and relying on liquid biopsies, muti-detection advanced genomic technologies and data integration, with artificial intelligence as a central orchestrator. This review presents the currently known actionable mutations in lung cancer and new upcoming ones that are likely to enter clinical practice soon and provides an overview of established and emerging concepts in testing methodologies. Challenges are discussed and best practice recommendations are made that are relevant today, will continue to be relevant in the future, and are likely to be relevant for other cancer types too.
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Affiliation(s)
- Frédérique Penault-Llorca
- Department of Pathology, Centre Jean Perrin, Université Clermont Auvergne, INSERM, U1240 Imagerie Moléculaire et Stratégies Théranostiques, Clermont Ferrand F-63000, France
| | - Mark A Socinski
- Oncology and Hematology, AdventHealth Cancer Institute, Orlando, FL 32804, United States
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48
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Liu B, Polack M, Coudray N, Claudio Quiros A, Sakellaropoulos T, Le H, Karimkhan A, Crobach ASLP, van Krieken JHJM, Yuan K, Tollenaar RAEM, Mesker WE, Tsirigos A. Self-supervised learning reveals clinically relevant histomorphological patterns for therapeutic strategies in colon cancer. Nat Commun 2025; 16:2328. [PMID: 40057490 PMCID: PMC11890774 DOI: 10.1038/s41467-025-57541-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Accepted: 02/26/2025] [Indexed: 05/13/2025] Open
Abstract
Self-supervised learning (SSL) automates the extraction and interpretation of histopathology features on unannotated hematoxylin-eosin-stained whole slide images (WSIs). We train an SSL Barlow Twins encoder on 435 colon adenocarcinoma WSIs from The Cancer Genome Atlas to extract features from small image patches (tiles). Leiden community detection groups tiles into histomorphological phenotype clusters (HPCs). HPC reproducibility and predictive ability for overall survival are confirmed in an independent clinical trial (N = 1213 WSIs). This unbiased atlas results in 47 HPCs displaying unique and shared clinically significant histomorphological traits, highlighting tissue type, quantity, and architecture, especially in the context of tumor stroma. Through in-depth analyses of these HPCs, including immune landscape and gene set enrichment analyses, and associations to clinical outcomes, we shine light on the factors influencing survival and responses to treatments of standard adjuvant chemotherapy and experimental therapies. Further exploration of HPCs may unveil additional insights and aid decision-making and personalized treatments for colon cancer patients.
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Affiliation(s)
- Bojing Liu
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Karolinska, Sweden
- Applied Bioinformatics Laboratories, New York University Grossman School of Medicine, New York, NY, USA
| | - Meaghan Polack
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - Nicolas Coudray
- Applied Bioinformatics Laboratories, New York University Grossman School of Medicine, New York, NY, USA
- Department of Cell Biology, New York University Grossman School of Medicine, New York, NY, USA
| | | | - Theodore Sakellaropoulos
- Applied Bioinformatics Laboratories, New York University Grossman School of Medicine, New York, NY, USA
| | - Hortense Le
- Applied Bioinformatics Laboratories, New York University Grossman School of Medicine, New York, NY, USA
| | - Afreen Karimkhan
- Department of Pathology, New York University Grossman School of Medicine, New York, NY, USA
| | | | - J Han J M van Krieken
- Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Ke Yuan
- Department of Computing Science, University of Glasgow, Glasgow, United Kingdom
- School of Cancer Sciences, University of Glasgow, Glasgow, Scotland, UK
| | - Rob A E M Tollenaar
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - Wilma E Mesker
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - Aristotelis Tsirigos
- Applied Bioinformatics Laboratories, New York University Grossman School of Medicine, New York, NY, USA.
- Department of Pathology, New York University Grossman School of Medicine, New York, NY, USA.
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49
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Matias-Guiu X, Temprana-Salvador J, Garcia Lopez P, Kammerer-Jacquet SF, Rioux-Leclercq N, Clark D, Schürch CM, Fend F, Mattern S, Snead D, Fusco N, Guerini-Rocco E, Rojo F, Brevet M, Salto Tellez M, Dei Tos A, di Maio T, Ramírez-Peinado S, Sheppard E, Bannister H, Gkiokas A, Arpaia M, Ben Dhia O, Martino N. Implementing digital pathology: qualitative and financial insights from eight leading European laboratories. Virchows Arch 2025:10.1007/s00428-025-04064-y. [PMID: 40056197 DOI: 10.1007/s00428-025-04064-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2025] [Revised: 02/13/2025] [Accepted: 02/21/2025] [Indexed: 03/10/2025]
Abstract
Digital Pathology (DP) revolutionizes the diagnostic workflow. Digitized scanned slides enhance operational efficiency by facilitating remote access, slide storage, reporting and automated AI image analysis, and enabling collaboration and research. However, substantial upfront and maintenance costs remain significant barriers to adoption. This study evaluates DP's financial and qualitative value, exploring whether the long-term financial benefits justify investments and addressing implementation challenges in large public and private European laboratory settings. A targeted literature review, semi-structured interviews, surveys, and a net present value (NPV) model were employed to assess DP's impact on clinical practice and laboratory financials. Qualitative findings validate the key benefits of DP, including optimized workflow, enhanced logistics, and improved laboratory organization. Pathologists reported a smooth integration, improved training, teaching, and research capabilities, and increased flexibility through remote work. Collaboration within multidisciplinary teams was strengthened, while case examination efficiency and access to archival slides were notably improved. Quantitative results indicate that DP demonstrates strong financial potential, achieving cost recovery within 6 years. DP investment results in a 7-year NPV of + €0.21 million (m) driven by increased productivity and diagnosis volumes. Although the high upfront costs for scanners, training, and system integration pose a significant barrier to the adoption of DP, larger institutions are better positioned to leverage economies of scale. This study underscores the importance of sustained financial support to cope with the initial investment and regional collaboration in driving widespread adoption of DP. Expanding reimbursement policies for pathology procedures could significantly reduce financial barriers.
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Affiliation(s)
- Xavier Matias-Guiu
- Hospital Universitari de Bellvitge and Hospital Universitari Arnau de Vilanova IDIBELL, IRBLLEIDA, University of Lleida, CIBERONC, Lleida, Spain.
| | | | | | | | | | - David Clark
- Nottingham University Hospitals NHS Trust, HMDN, Dept of Histopathology, City Hospital, Hucknall Road, Nottingham, NG5 1PB, UK
| | - Christian M Schürch
- Department of Pathology and Neuropathology, University Hospital and Comprehensive Cancer Center Tübingen, Tübingen, Germany
- Cluster of Excellence Ifit (EXC 2180) "Image-Guided and Functionally Instructed Tumor Therapies", University of Tübingen, Tübingen, Germany
| | - Falko Fend
- Department of Pathology and Neuropathology, University Hospital and Comprehensive Cancer Center Tübingen, Tübingen, Germany
| | - Sven Mattern
- Institute of Pathology and Neuropathology, Tübingen University Hospital, Tübingen, Germany
| | - David Snead
- UHCW NHS Trust, Coventry, CV2 2DX, UK
- Department of Computer Science, University of Warwick, Coventry, UK
| | - Nicola Fusco
- European Institute of Oncology IRCCS, Milan, Italy
| | | | | | - Marie Brevet
- Technipath, Dommartin, France & Biwako, Lyon, France
| | - Manuel Salto Tellez
- Precision Medicine Centre, Queen'S University Belfast, Belfast, UK
- Integrated Patholog Unit, Institute for Cancer Research, London, UK
| | - Angelo Dei Tos
- Department of Integrated Diagnostics, University of Padua, Padua, Italy
| | - Thomas di Maio
- Regional Diagnostics AstraZeneca, 6340, Basel, Zug/CH, Switzerland
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50
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Goel I, Bhaskar Y, Kumar N, Singh S, Amanullah M, Dhar R, Karmakar S. Role of AI in empowering and redefining the oncology care landscape: perspective from a developing nation. Front Digit Health 2025; 7:1550407. [PMID: 40103737 PMCID: PMC11913822 DOI: 10.3389/fdgth.2025.1550407] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2024] [Accepted: 02/17/2025] [Indexed: 03/20/2025] Open
Abstract
Early diagnosis and accurate prognosis play a pivotal role in the clinical management of cancer and in preventing cancer-related mortalities. The burgeoning population of Asia in general and South Asian countries like India in particular pose significant challenges to the healthcare system. Regrettably, the demand for healthcare services in India far exceeds the available resources, resulting in overcrowded hospitals, prolonged wait times, and inadequate facilities. The scarcity of trained manpower in rural settings, lack of awareness and low penetrance of screening programs further compounded the problem. Artificial Intelligence (AI), driven by advancements in machine learning, deep learning, and natural language processing, can profoundly transform the underlying shortcomings in the healthcare industry, more for populous nations like India. With about 1.4 million cancer cases reported annually and 0.9 million deaths, India has a significant cancer burden that surpassed several nations. Further, India's diverse and large ethnic population is a data goldmine for healthcare research. Under these circumstances, AI-assisted technology, coupled with digital health solutions, could support effective oncology care and reduce the economic burden of GDP loss in terms of years of potential productive life lost (YPPLL) due to India's stupendous cancer burden. This review explores different aspects of cancer management, such as prevention, diagnosis, precision treatment, prognosis, and drug discovery, where AI has demonstrated promising clinical results. By harnessing the capabilities of AI in oncology research, healthcare professionals can enhance their ability to diagnose cancers at earlier stages, leading to more effective treatments and improved patient outcomes. With continued research and development, AI and digital health can play a transformative role in mitigating the challenges posed by the growing population and advancing the fight against cancer in India. Moreover, AI-driven technologies can assist in tailoring personalized treatment plans, optimizing therapeutic strategies, and supporting oncologists in making well-informed decisions. However, it is essential to ensure responsible implementation and address potential ethical and privacy concerns associated with using AI in healthcare.
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Affiliation(s)
- Isha Goel
- Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), New Delhi, India
- Department of Psychiatry, All India Institute of Medical Sciences (AIIMS), New Delhi, India
| | - Yogendra Bhaskar
- ICMR Computational Genomics Centre, Indian Council of Medical Research (ICMR), New Delhi, India
| | - Nand Kumar
- Department of Psychiatry, All India Institute of Medical Sciences (AIIMS), New Delhi, India
| | - Sunil Singh
- Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), New Delhi, India
| | - Mohammed Amanullah
- Department of Clinical Biochemistry, College of Medicine, King Khalid University, Abha, Saudi Arabia
| | - Ruby Dhar
- Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), New Delhi, India
| | - Subhradip Karmakar
- Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), New Delhi, India
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