CONFIDENT-trial protocol: A pragmatic template for clinical implementation of artificial intelligence assistance in pathology

Introduction Artificial intelligence (AI) has been on the rise in the field of pathology. Despite promising results in retrospective studies, and several CE-IVD certified algorithms on the market, prospective clinical implementation studies of AI have yet to be performed, to the best of our knowledge. In this trial, we will explore the benefits of an AI-assisted pathology workflow, while maintaining diagnostic safety standards. Methods and analysis This is a Standard Protocol Items: Recommendations for Interventional Trials-Artificial Intelligence compliant single-centre, controlled clinical trial, in a fully digital academic pathology laboratory. We will prospectively include prostate cancer patients who undergo prostate needle biopsies (CONFIDENT-P) and breast cancer patients who undergo a sentinel node procedure (CONFIDENT-B) in the University Medical Centre Utrecht. For both the CONFIDENT-B and CONFIDENT-P trials, the specific pathology specimens will be pseudo-randomised to be assessed by a pathologist with or without AI assistance in a pragmatic (bi-)weekly sequential design. In the intervention group, pathologists will assess whole slide images (WSI) of the standard hematoxylin and eosin (H&E)-stained sections assisted by the output of the algorithm. In the control group, pathologists will assess H&E WSI according to the current clinical workflow. If no tumour cells are identified or when the pathologist is in doubt, immunohistochemistry (IHC) staining will be performed. At least 80 patients in the CONFIDENT-P and 180 patients in the CONFIDENT-B trial will need to be enrolled to detect superiority, allocated as 1:1. Primary endpoint for both trials is the number of saved resources of IHC staining procedures for detecting tumour cells, since this will clarify tangible cost savings that will support the business case for AI. Ethics and dissemination The ethics committee (MREC NedMec) waived the need of official ethical approval, since participants are not subjected to procedures nor are they required to follow rules. Results of both trials (CONFIDENT-B and CONFIDENT-P) will be published in scientific peer-reviewed journals

Компьютеризированная диагностика рака простаты на основе полнослайдовых гистологических изображений и методов глубокого обучения

This paper presents the results of an experimental study and the development of tools for automatic analysis and recognition of histological images in order to obtain quantitative estimates of the presence and degree of aggressiveness of prostate cancer in the commonly used Gleason and ISUP scales. The input data consisted of 10 616 whole-slide histological images with the size of the largest side up to 100 000 pixels and22 089 of their image tiles of 256×256 pixels in size. Two solutions were chosen as the final ones. The first solution is based on sequential analysis of image fragments and includes feature extraction using the ResNet50 network and the subsequent generalization of particular recognition results using a small convolutional network. The second solution is based on the simultaneous analysis of the selected informative sections, presented in the form of an intermediate pseudo-image, and its subsequent recognition using an ensemble of four variants of convolutional networks with the EfficientNetB0 architecture. Being independently tested on an unknown image dataset that was not available for authors, these approaches achieved the prediction accuracy of 0,9277 according to the ISUP scale.Представлены результаты экспериментальных исследований и разработки средств автоматического анализа и распознавания гистологических изображений с целью получения количественных оценок наличия и степени агрессивности рака простаты в общепринятых шкалах Глисона  и ISUP. В качестве исходных данных использовались 10 616 полнослайдовых гистологических изображений с размером большей стороны до 100 000 пикселов и 22 089 их фрагментов размером 256×256 пикселов. Проведена оценка эффективности решения задачи с применением как традиционных методов, так и методов глубокого обучения. В качестве финальных выбраны два решения. Первое решение основано на последовательном анализе фрагментов изображений и включает выделение признаков с использованием сети ResNet50 и последующим обобщением частных результатов распознавания с помощью небольшой сверточной сети. Второе решение базируется на одновременном анализе отобранных информативных участков, представленных в виде промежуточного псевдоизображения, и последующем его распознавании с использованием ансамбля из четырех вариантов сверточных сетей с архитектурой EfficientNetB0. В результате независимого тестирования на закрытом наборе изображений, недоступных авторам, достигнута точность предсказания финальной оценки по шкале ISUP, равная 0,9277

Artificial intelligence for diagnosis and Gleason grading of prostate cancer: The PANDA challenge

Through a community-driven competition, the PANDA challenge provides a curated diverse dataset and a catalog of models for prostate cancer pathology, and represents a blueprint for evaluating AI algorithms in digital pathology. Artificial intelligence (AI) has shown promise for diagnosing prostate cancer in biopsies. However, results have been limited to individual studies, lacking validation in multinational settings. Competitions have been shown to be accelerators for medical imaging innovations, but their impact is hindered by lack of reproducibility and independent validation. With this in mind, we organized the PANDA challenge-the largest histopathology competition to date, joined by 1,290 developers-to catalyze development of reproducible AI algorithms for Gleason grading using 10,616 digitized prostate biopsies. We validated that a diverse set of submitted algorithms reached pathologist-level performance on independent cross-continental cohorts, fully blinded to the algorithm developers. On United States and European external validation sets, the algorithms achieved agreements of 0.862 (quadratically weighted kappa, 95% confidence interval (CI), 0.840-0.884) and 0.868 (95% CI, 0.835-0.900) with expert uropathologists. Successful generalization across different patient populations, laboratories and reference standards, achieved by a variety of algorithmic approaches, warrants evaluating AI-based Gleason grading in prospective clinical trials.KWF Kankerbestrijding ; Netherlands Organization for Scientific Research (NWO) ; Swedish Research Council European Commission ; Swedish Cancer Society ; Swedish eScience Research Center ; Ake Wiberg Foundation ; Prostatacancerforbundet ; Academy of Finland ; Cancer Foundation Finland ; Google Incorporated ; MICCAI board challenge working group ; Verily Life Sciences ; EIT Health ; Karolinska Institutet ; MICCAI 2020 satellite event team ; ERAPerMe

Artificial Intelligence and Machine Learning in Prostate Cancer Patient Management-Current Trends and Future Perspectives

Artificial intelligence (AI) is the field of computer science that aims to build smart devices performing tasks that currently require human intelligence. Through machine learning (ML), the deep learning (DL) model is teaching computers to learn by example, something that human beings are doing naturally. AI is revolutionizing healthcare. Digital pathology is becoming highly assisted by AI to help researchers in analyzing larger data sets and providing faster and more accurate diagnoses of prostate cancer lesions. When applied to diagnostic imaging, AI has shown excellent accuracy in the detection of prostate lesions as well as in the prediction of patient outcomes in terms of survival and treatment response. The enormous quantity of data coming from the prostate tumor genome requires fast, reliable and accurate computing power provided by machine learning algorithms. Radiotherapy is an essential part of the treatment of prostate cancer and it is often difficult to predict its toxicity for the patients. Artificial intelligence could have a future potential role in predicting how a patient will react to the therapy side effects. These technologies could provide doctors with better insights on how to plan radiotherapy treatment. The extension of the capabilities of surgical robots for more autonomous tasks will allow them to use information from the surgical field, recognize issues and implement the proper actions without the need for human intervention

Artificial intelligence for diagnosis and Gleason grading of prostate cancer: the PANDA challenge

Through a community-driven competition, the PANDA challenge provides a curated diverse dataset and a catalog of models for prostate cancer pathology, and represents a blueprint for evaluating AI algorithms in digital pathology.Artificial intelligence (AI) has shown promise for diagnosing prostate cancer in biopsies. However, results have been limited to individual studies, lacking validation in multinational settings. Competitions have been shown to be accelerators for medical imaging innovations, but their impact is hindered by lack of reproducibility and independent validation. With this in mind, we organized the PANDA challenge-the largest histopathology competition to date, joined by 1,290 developers-to catalyze development of reproducible AI algorithms for Gleason grading using 10,616 digitized prostate biopsies. We validated that a diverse set of submitted algorithms reached pathologist-level performance on independent cross-continental cohorts, fully blinded to the algorithm developers. On United States and European external validation sets, the algorithms achieved agreements of 0.862 (quadratically weighted kappa, 95% confidence interval (CI), 0.840-0.884) and 0.868 (95% CI, 0.835-0.900) with expert uropathologists. Successful generalization across different patient populations, laboratories and reference standards, achieved by a variety of algorithmic approaches, warrants evaluating AI-based Gleason grading in prospective clinical trials

Artificial intelligence assistance significantly improves Gleason grading of prostate biopsies by pathologists

The Gleason score is the most important prognostic marker for prostate cancer patients, but it suffers from significant observer variability. Artificial intelligence (AI) systems based on deep learning can achieve pathologist-level performance at Gleason grading. However, the performance of such systems can degrade in the presence of artifacts, foreign tissue, or other anomalies. Pathologists integrating their expertise with feedback from an AI system could result in a synergy that outperforms both the individual pathologist and the system. Despite the hype around AI assistance, existing literature on this topic within the pathology domain is limited. We investigated the value of AI assistance for grading prostate biopsies. A panel of 14 observers graded 160 biopsies with and without AI assistance. Using AI, the agreement of the panel with an expert reference standard increased significantly (quadratically weighted Cohen’s kappa, 0.799 vs. 0.872; p = 0.019). On an external validation set of 87 cases, the panel showed a significant increase in agreement with a panel of international experts in prostate pathology (quadratically weighted Cohen’s kappa, 0.733 vs. 0.786; p = 0.003). In both experiments, on a group-level, AI-assisted pathologists outperformed the unassisted pathologists and the standalone AI system. Our results show the potential of AI systems for Gleason grading, but more importantly, show the benefits of pathologist-AI synergy

AI in medical diagnosis : AI prediction & human judgment

AI has long been regarded as a panacea for decision-making and many other aspects of knowledge work; as something that will help humans get rid of their shortcomings. We believe that AI can be a useful asset to support decision-makers, but not that it should replace decision-makers. Decision-making uses algorithmic analysis, but it is not solely algorithmic analysis; it also involves other factors, many of which are very human, such as creativity, intuition, emotions, feelings, and value judgments. We have conducted semi-structured open-ended research interviews with 17 dermatologists to understand what they expect from an AI application to deliver to medical diagnosis. We have found four aggregate dimensions along which the thinking of dermatologists can be described: the ways in which our participants chose to interact with AI, responsibility, 'explainability', and the new way of thinking (mindset) needed for working with AI. We believe that our findings will help physicians who might consider using AI in their diagnosis to understand how to use AI beneficially. It will also be useful for AI vendors in improving their understanding of how medics want to use AI in diagnosis. Further research will be needed to examine if our findings have relevance in the wider medical field and beyond

A review of artificial intelligence in prostate cancer detection on imaging

A multitude of studies have explored the role of artificial intelligence (AI) in providing diagnostic support to radiologists, pathologists, and urologists in prostate cancer detection, risk-stratification, and management. This review provides a comprehensive overview of relevant literature regarding the use of AI models in (1) detecting prostate cancer on radiology images (magnetic resonance and ultrasound imaging), (2) detecting prostate cancer on histopathology images of prostate biopsy tissue, and (3) assisting in supporting tasks for prostate cancer detection (prostate gland segmentation, MRI-histopathology registration, MRI-ultrasound registration). We discuss both the potential of these AI models to assist in the clinical workflow of prostate cancer diagnosis, as well as the current limitations including variability in training data sets, algorithms, and evaluation criteria. We also discuss ongoing challenges and what is needed to bridge the gap between academic research on AI for prostate cancer and commercial solutions that improve routine clinical care