1
|
Lobanova OA, Kolesnikova AO, Ponomareva VA, Vekhova KA, Shaginyan AL, Semenova AB, Nekhoroshkov DP, Kochetkova SE, Kretova NV, Zanozin AS, Peshkova MA, Serezhnikova NB, Zharkov NV, Kogan EA, Biryukov AA, Rudenko EE, Demura TA. Artificial intelligence (AI) for tumor microenvironment (TME) and tumor budding (TB) identification in colorectal cancer (CRC) patients: A systematic review. J Pathol Inform 2024; 15:100353. [PMID: 39712977 PMCID: PMC11662261 DOI: 10.1016/j.jpi.2023.100353] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Revised: 09/19/2023] [Accepted: 11/16/2023] [Indexed: 12/24/2024] Open
Abstract
Evaluation of the parameters such as tumor microenvironment (TME) and tumor budding (TB) is one of the most important steps in colorectal cancer (CRC) diagnosis and cancer development prognosis. In recent years, artificial intelligence (AI) has been successfully used to solve such problems. In this paper, we summarize the latest data on the use of artificial intelligence to predict tumor microenvironment and tumor budding in histological scans of patients with colorectal cancer. We performed a systematic literature search using 2 databases (Medline and Scopus) with the following search terms: ("tumor microenvironment" OR "tumor budding") AND ("colorectal cancer" OR CRC) AND ("artificial intelligence" OR "machine learning " OR "deep learning"). During the analysis, we gathered from the articles performance scores such as sensitivity, specificity, and accuracy of identifying TME and TB using artificial intelligence. The systematic review showed that machine learning and deep learning successfully cope with the prediction of these parameters. The highest accuracy values in TB and TME prediction were 97.7% and 97.3%, respectively. This review led us to the conclusion that AI platforms can already be used as diagnostic aids, which will greatly facilitate the work of pathologists in detection and estimation of TB and TME as instruments and second-opinion services. A key limitation in writing this systematic review was the heterogeneous use of performance metrics for machine learning models by different authors, as well as relatively small datasets used in some studies.
Collapse
Affiliation(s)
- Olga Andreevna Lobanova
- I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Trubetskaya street, 8, p. 2, 119991 Moscow, Russia
| | - Anastasia Olegovna Kolesnikova
- I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Trubetskaya street, 8, p. 2, 119991 Moscow, Russia
| | | | - Ksenia Andreevna Vekhova
- I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Trubetskaya street, 8, p. 2, 119991 Moscow, Russia
| | - Anaida Lusparonovna Shaginyan
- I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Trubetskaya street, 8, p. 2, 119991 Moscow, Russia
| | - Alisa Borisovna Semenova
- I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Trubetskaya street, 8, p. 2, 119991 Moscow, Russia
| | | | - Svetlana Evgenievna Kochetkova
- I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Trubetskaya street, 8, p. 2, 119991 Moscow, Russia
| | - Natalia Valeryevna Kretova
- I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Trubetskaya street, 8, p. 2, 119991 Moscow, Russia
| | - Alexander Sergeevich Zanozin
- I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Trubetskaya street, 8, p. 2, 119991 Moscow, Russia
| | - Maria Alekseevna Peshkova
- I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Trubetskaya street, 8, p. 2, 119991 Moscow, Russia
| | - Natalia Borisovna Serezhnikova
- I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Trubetskaya street, 8, p. 2, 119991 Moscow, Russia
| | - Nikolay Vladimirovich Zharkov
- I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Trubetskaya street, 8, p. 2, 119991 Moscow, Russia
| | - Evgeniya Altarovna Kogan
- I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Trubetskaya street, 8, p. 2, 119991 Moscow, Russia
| | - Alexander Alekseevich Biryukov
- I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Trubetskaya street, 8, p. 2, 119991 Moscow, Russia
| | - Ekaterina Evgenievna Rudenko
- I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Trubetskaya street, 8, p. 2, 119991 Moscow, Russia
| | - Tatiana Alexandrovna Demura
- I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Trubetskaya street, 8, p. 2, 119991 Moscow, Russia
| |
Collapse
|
2
|
Bokhorst JM, Nagtegaal ID, Zlobec I, Dawson H, Sheahan K, Simmer F, Kirsch R, Vieth M, Lugli A, van der Laak J, Ciompi F. Semi-Supervised Learning to Automate Tumor Bud Detection in Cytokeratin-Stained Whole-Slide Images of Colorectal Cancer. Cancers (Basel) 2023; 15:cancers15072079. [PMID: 37046742 PMCID: PMC10093661 DOI: 10.3390/cancers15072079] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Revised: 03/24/2023] [Accepted: 03/29/2023] [Indexed: 04/03/2023] Open
Abstract
Tumor budding is a histopathological biomarker associated with metastases and adverse survival outcomes in colorectal carcinoma (CRC) patients. It is characterized by the presence of single tumor cells or small clusters of cells within the tumor or at the tumor-invasion front. In order to obtain a tumor budding score for a patient, the region with the highest tumor bud density must first be visually identified by a pathologist, after which buds will be counted in the chosen hotspot field. The automation of this process will expectedly increase efficiency and reproducibility. Here, we present a deep learning convolutional neural network model that automates the above procedure. For model training, we used a semi-supervised learning method, to maximize the detection performance despite the limited amount of labeled training data. The model was tested on an independent dataset in which human- and machine-selected hotspots were mapped in relation to each other and manual and machine detected tumor bud numbers in the manually selected fields were compared. We report the results of the proposed method in comparison with visual assessment by pathologists. We show that the automated tumor bud count achieves a prognostic value comparable with visual estimation, while based on an objective and reproducible quantification. We also explore novel metrics to quantify buds such as density and dispersion and report their prognostic value. We have made the model available for research use on the grand-challenge platform.
Collapse
|
3
|
Liang F, Wang S, Zhang K, Liu TJ, Li JN. Development of artificial intelligence technology in diagnosis, treatment, and prognosis of colorectal cancer. World J Gastrointest Oncol 2022; 14:124-152. [PMID: 35116107 PMCID: PMC8790413 DOI: 10.4251/wjgo.v14.i1.124] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Revised: 08/19/2021] [Accepted: 11/15/2021] [Indexed: 02/06/2023] Open
Abstract
Artificial intelligence (AI) technology has made leaps and bounds since its invention. AI technology can be subdivided into many technologies such as machine learning and deep learning. The application scope and prospect of different technologies are also totally different. Currently, AI technologies play a pivotal role in the highly complex and wide-ranging medical field, such as medical image recognition, biotechnology, auxiliary diagnosis, drug research and development, and nutrition. Colorectal cancer (CRC) is a common gastrointestinal cancer that has a high mortality, posing a serious threat to human health. Many CRCs are caused by the malignant transformation of colorectal polyps. Therefore, early diagnosis and treatment are crucial to CRC prognosis. The methods of diagnosing CRC are divided into imaging diagnosis, endoscopy, and pathology diagnosis. Treatment methods are divided into endoscopic treatment, surgical treatment, and drug treatment. AI technology is in the weak era and does not have communication capabilities. Therefore, the current AI technology is mainly used for image recognition and auxiliary analysis without in-depth communication with patients. This article reviews the application of AI in the diagnosis, treatment, and prognosis of CRC and provides the prospects for the broader application of AI in CRC.
Collapse
Affiliation(s)
- Feng Liang
- Department of General Surgery, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, China
| | - Shu Wang
- Department of Radiotherapy, Jilin University Second Hospital, Changchun 130041, Jilin Province, China
| | - Kai Zhang
- Department of General Surgery, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, China
| | - Tong-Jun Liu
- Department of General Surgery, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, China
| | - Jian-Nan Li
- Department of General Surgery, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, China
| |
Collapse
|
4
|
Pai RK, Hartman D, Schaeffer DF, Rosty C, Shivji S, Kirsch R, Pai RK. Development and initial validation of a deep learning algorithm to quantify histological features in colorectal carcinoma including tumour budding/poorly differentiated clusters. Histopathology 2021; 79:391-405. [PMID: 33590485 DOI: 10.1111/his.14353] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2020] [Revised: 02/03/2021] [Accepted: 02/14/2021] [Indexed: 12/14/2022]
Abstract
AIMS To develop and validate a deep learning algorithm to quantify a broad spectrum of histological features in colorectal carcinoma. METHODS AND RESULTS A deep learning algorithm was trained on haematoxylin and eosin-stained slides from tissue microarrays of colorectal carcinomas (N = 230) to segment colorectal carcinoma digitised images into 13 regions and one object. The segmentation algorithm demonstrated moderate to almost perfect agreement with interpretations by gastrointestinal pathologists, and was applied to an independent test cohort of digitised whole slides of colorectal carcinoma (N = 136). The algorithm correctly classified mucinous and high-grade tumours, and identified significant differences between mismatch repair-proficient and mismatch repair-deficient (MMRD) tumours with regard to mucin, inflammatory stroma, and tumour-infiltrating lymphocytes (TILs). A cutoff of >44.4 TILs per mm2 carcinoma gave a sensitivity of 88% and a specificity of 73% in classifying MMRD carcinomas. Algorithm measures of tumour budding (TB) and poorly differentiated clusters (PDCs) outperformed TB grade derived from routine sign-out, and compared favourably with manual counts of TB/PDCs with regard to lymphatic, venous and perineural invasion. Comparable associations were seen between algorithm measures of TB/PDCs and manual counts of TB/PDCs for lymph node metastasis (all P < 0.001); however, stronger correlations were seen between the proportion of positive lymph nodes and algorithm measures of TB/PDCs. Stronger associations were also seen between distant metastasis and algorithm measures of TB/PDCs (P = 0.004) than between distant metastasis and TB (P = 0.04) and TB/PDC counts (P = 0.06). CONCLUSIONS Our results highlight the potential of deep learning to identify and quantify a broad spectrum of histological features in colorectal carcinoma.
Collapse
Affiliation(s)
- Reetesh K Pai
- Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Douglas Hartman
- Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - David F Schaeffer
- Department of Pathology, University of British Columbia, Vancouver, British Columbia, Canada
| | - Christophe Rosty
- Colorectal Oncogenomics Group, Department of Clinical Pathology, University of Melbourne, Parkville, Victoria, Australia.,Envoi Specialist Pathologists, University of Queensland, Brisbane, Queensland, Australia.,Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia
| | - Sameer Shivji
- Department of Pathology, Mount Sinai Hospital, Toronto, Ontario, Canada
| | - Richard Kirsch
- Department of Pathology, Mount Sinai Hospital, Toronto, Ontario, Canada
| | - Rish K Pai
- Department of Pathology and Laboratory Medicine, Mayo Clinic Arizona, Scottsdale, AZ, USA
| |
Collapse
|
5
|
Studer L, Blank A, Bokhorst JM, Nagtegaal ID, Zlobec I, Lugli A, Fischer A, Dawson H. Taking tumour budding to the next frontier - a post International Tumour Budding Consensus Conference (ITBCC) 2016 review. Histopathology 2020; 78:476-484. [PMID: 33001500 DOI: 10.1111/his.14267] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Revised: 09/03/2020] [Accepted: 09/25/2020] [Indexed: 12/19/2022]
Abstract
Tumour budding in colorectal cancer, defined as single tumour cells or small clusters containing four or fewer tumour cells, is a robust and independent biomarker of aggressive tumour biology. On the basis of published data in the literature, the evidence is certainly in favour of reporting tumour budding in routine practice. One important aspect of implementing tumour budding has been to establish a standardised and evidence-based scoring method, as was recommended by the International Tumour Budding Consensus Conference (ITBCC) in 2016. Further developments have aimed at establishing methods for automated tumour budding assessment. A digital approach to scoring tumour buds has great potential to assist in performing an objective budding count but, like the manual consensus method, must be validated and standardised. The aim of the present review is to present general considerations behind the ITBCC scoring method, and a broad overview of the current situation and challenges regarding automated tumour budding detection methods.
Collapse
Affiliation(s)
- Linda Studer
- Institute of Pathology, University of Bern, Bern, Switzerland.,iCoSys Institute, University of Applied Sciences and Arts Western Switzerland, HES-SO/Fribourg, Fribourg, Switzerland.,DIVA Research Group, University of Fribourg, Fribourg, Switzerland
| | - Annika Blank
- Institute of Pathology, University of Bern, Bern, Switzerland
| | - John-Melle Bokhorst
- Department of Pathology, RIMLS/RIHS Radboud University Medical Centre, Nijmegen, The Netherlands
| | - Iris D Nagtegaal
- Department of Pathology, RIMLS/RIHS Radboud University Medical Centre, Nijmegen, The Netherlands
| | - Inti Zlobec
- Institute of Pathology, University of Bern, Bern, Switzerland
| | | | - Andreas Fischer
- iCoSys Institute, University of Applied Sciences and Arts Western Switzerland, HES-SO/Fribourg, Fribourg, Switzerland.,DIVA Research Group, University of Fribourg, Fribourg, Switzerland
| | - Heather Dawson
- Institute of Pathology, University of Bern, Bern, Switzerland
| |
Collapse
|
6
|
Bokhorst JM, Blank A, Lugli A, Zlobec I, Dawson H, Vieth M, Rijstenberg LL, Brockmoeller S, Urbanowicz M, Flejou JF, Kirsch R, Ciompi F, van der Laak JAWM, Nagtegaal ID. Assessment of individual tumor buds using keratin immunohistochemistry: moderate interobserver agreement suggests a role for machine learning. Mod Pathol 2020; 33:825-833. [PMID: 31844269 PMCID: PMC7190566 DOI: 10.1038/s41379-019-0434-2] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2019] [Revised: 11/07/2019] [Accepted: 11/23/2019] [Indexed: 02/07/2023]
Abstract
Tumor budding is a promising and cost-effective biomarker with strong prognostic value in colorectal cancer. However, challenges related to interobserver variability persist. Such variability may be reduced by immunohistochemistry and computer-aided tumor bud selection. Development of computer algorithms for this purpose requires unequivocal examples of individual tumor buds. As such, we undertook a large-scale, international, and digital observer study on individual tumor bud assessment. From a pool of 46 colorectal cancer cases with tumor budding, 3000 tumor bud candidates were selected, largely based on digital image analysis algorithms. For each candidate bud, an image patch (size 256 × 256 µm) was extracted from a pan cytokeratin-stained whole-slide image. Members of an International Tumor Budding Consortium (n = 7) were asked to categorize each candidate as either (1) tumor bud, (2) poorly differentiated cluster, or (3) neither, based on current definitions. Agreement was assessed with Cohen's and Fleiss Kappa statistics. Fleiss Kappa showed moderate overall agreement between observers (0.42 and 0.51), while Cohen's Kappas ranged from 0.25 to 0.63. Complete agreement by all seven observers was present for only 34% of the 3000 tumor bud candidates, while 59% of the candidates were agreed on by at least five of the seven observers. Despite reports of moderate-to-substantial agreement with respect to tumor budding grade, agreement with respect to individual pan cytokeratin-stained tumor buds is moderate at most. A machine learning approach may prove especially useful for a more robust assessment of individual tumor buds.
Collapse
Affiliation(s)
- J. M. Bokhorst
- grid.10417.330000 0004 0444 9382Radboud University Medical Center, Nijmegen, Netherlands
| | - A. Blank
- grid.5734.50000 0001 0726 5157University of Bern, Bern, Switzerland
| | - A. Lugli
- grid.5734.50000 0001 0726 5157University of Bern, Bern, Switzerland
| | - I. Zlobec
- grid.5734.50000 0001 0726 5157University of Bern, Bern, Switzerland
| | - H. Dawson
- grid.5734.50000 0001 0726 5157University of Bern, Bern, Switzerland
| | - M. Vieth
- grid.7384.80000 0004 0467 6972University of Bayreuth, Bayreuth, Germany
| | - L. L. Rijstenberg
- grid.10417.330000 0004 0444 9382Radboud University Medical Center, Nijmegen, Netherlands
| | - S. Brockmoeller
- grid.9909.90000 0004 1936 8403University of Leeds, Leeds, UK
| | - M. Urbanowicz
- grid.418936.10000 0004 0610 0854EORTC Translational Research Unit, Brussels, Belgium
| | - J. F. Flejou
- grid.412370.30000 0004 1937 1100Saint-Antoine Hospital, Paris, France
| | - R. Kirsch
- grid.17063.330000 0001 2157 2938University of Toronto, Toronto, Canada
| | - F. Ciompi
- grid.10417.330000 0004 0444 9382Radboud University Medical Center, Nijmegen, Netherlands
| | - J. A. W. M. van der Laak
- grid.10417.330000 0004 0444 9382Radboud University Medical Center, Nijmegen, Netherlands ,grid.5640.70000 0001 2162 9922Center for Medical Image Science and Visualization, Linköping University, Linköping, Sweden
| | - I. D. Nagtegaal
- grid.10417.330000 0004 0444 9382Radboud University Medical Center, Nijmegen, Netherlands
| |
Collapse
|