Real-world data (RWD) from sources like administrative claims, electronic health records, and cancer registries offer insights into patient populations beyond the tightly regulated environment of randomized controlled trials. To leverage this and to advance cancer research, 6 university hospitals in Bavaria have established a joint research IT infrastructure.

This study aimed to outline the design, implementation, and deployment of a modular data transformation pipeline that transforms oncological RWD into a Health Level 7 (HL7) Fast Healthcare Interoperability Resources (FHIR) format and then into a tabular format in preparation for a federated analysis (FA) across the 6 Bavarian Cancer Research Center university hospitals.

To harness RWD effectively, we designed a pipeline to convert the oncological basic dataset (oBDS) into HL7 FHIR format and prepare it for FA. The pipeline handles diverse IT infrastructures and systems while maintaining privacy by keeping data decentralized for analysis. To assess the functionality and validity of our implementation, we defined a cohort to address two specific medical research questions. We evaluated our findings by comparing the results of the FA with reports from the Bavarian Cancer Registry and the original data from local tumor documentation systems.

We conducted an FA of 17,885 cancer cases from 2021/2022. Breast cancer was the most common diagnosis at 3 sites, prostate cancer ranked in the top 2 at 4 sites, and malignant melanoma was notably prevalent. Gender-specific trends showed larynx and esophagus cancers were more common in males, while breast and thyroid cancers were more frequent in females. Discrepancies between the Bavarian Cancer Registry and our data, such as higher rates of malignant melanoma (3400/63,771, 5.3% vs 1921/17,885, 10.7%) and lower representation of colorectal cancers (8100/63,771, 12.7% vs 1187/17,885, 6.6%) likely result from differences in the time periods analyzed (2019 vs 2021/2022) and the scope of data sources used. The Bavarian Cancer Registry reports approximately 3 times more cancer cases than the 6 university hospitals alone.

The modular pipeline successfully transformed oncological RWD across 6 hospitals, and the federated approach preserved privacy while enabling comprehensive analysis. Future work will add support for recent oBDS versions, automate data quality checks, and integrate additional clinical data. Our findings highlight the potential of federated health data networks and lay the groundwork for future research that can leverage high-quality RWD, aiming to contribute valuable knowledge to the field of cancer research.

Aggregation of cohort data increases precision for studying neurodegenerative disease pathways, but efforts to combine data and expertise are often hampered by infrastructural, ethical and legal considerations. We aimed to unite various cohort studies in the Netherlands to enhance research infrastructure and facilitate research on dementia etiology and its public health implications.

The Netherlands Consortium of Dementia Cohorts (NCDC) includes participants with initially no established cognitive impairment from 9 Dutch cohorts: the Amsterdam Dementia Cohort (ADC), Doetinchem Cohort Study (DCS), European Medical Information Framework for Alzheimer's Disease (EMIF-AD), Longitudinal Aging Study Amsterdam (LASA), the Leiden Longevity Study (LLS), The Maastricht Study, the Memolife substudy of the Lifelines cohort, Rotterdam Study and Second Manifestations of ARTerial disease-Magnetic Resonance (SMART-MR) study. The objectives of NCDC are to improve data infrastructure and access to cohorts related to aging and dementia, investigate the role of Alzheimer's disease and vascular pathology in the development of dementia and estimate the public health impact of established dementia risk factors by assessing their relative contribution to the population burden of dementia.

We increased the findability, accessibility, interoperability and reusability (FAIR) status of the cohorts through harmonization of data across cohorts, implementation of medical imaging repositories for scan management, implementation of the Personal Health Train infrastructure and provision of meta-data in existing cohort catalogues. We established the ethical and legal frameworks required for federated and pooled analyses and performed the first remote federated data analyses using the Personal Health Train infrastructure. To determine biomarkers of Alzheimer's disease, endothelial dysfunction and inflammation, 2554 plasma samples were analyzed centrally. Federated, pooled, and coordinated meta-analyses have led to multiple publications in the context of NCDC.

The combination of population-based and clinical cohorts, the coordinated assessment of plasma markers in previously collected samples and implementation and use of the Personal Health Train infrastructure for federated analysis are both feasible and promising for future collaborative efforts.

The rapid advancement of deep learning in health care presents significant opportunities for automating complex medical tasks and improving clinical workflows. However, widespread adoption is impeded by data privacy concerns and the necessity for large, diverse datasets across multiple institutions. Federated learning (FL) has emerged as a viable solution, enabling collaborative artificial intelligence model development without sharing individual patient data. To effectively implement FL in health care, robust and secure infrastructures are essential. Developing such federated deep learning frameworks is crucial to harnessing the full potential of artificial intelligence while ensuring patient data privacy and regulatory compliance.

The objective is to introduce an innovative FL infrastructure called the Personal Health Train (PHT) that includes the procedural, technical, and governance components needed to implement FL on real-world health care data, including training deep learning neural networks. The study aims to apply this federated deep learning infrastructure to the use case of gross tumor volume segmentation on chest computed tomography images of patients with lung cancer and present the results from a proof-of-concept experiment.

The PHT framework addresses the challenges of data privacy when sharing data, by keeping data close to the source and instead bringing the analysis to the data. Technologically, PHT requires 3 interdependent components: "tracks" (protected communication channels), "trains" (containerized software apps), and "stations" (institutional data repositories), which are supported by the open source "Vantage6" software. The study applies this federated deep learning infrastructure to the use case of gross tumor volume segmentation on chest computed tomography images of patients with lung cancer, with the introduction of an additional component called the secure aggregation server, where the model averaging is done in a trusted and inaccessible environment.

We demonstrated the feasibility of executing deep learning algorithms in a federated manner using PHT and presented the results from a proof-of-concept study. The infrastructure linked 12 hospitals across 8 nations, covering 4 continents, demonstrating the scalability and global reach of the proposed approach. During the execution and training of the deep learning algorithm, no data were shared outside the hospital.

The findings of the proof-of-concept study, as well as the implications and limitations of the infrastructure and the results, are discussed. The application of federated deep learning to unstructured medical imaging data, facilitated by the PHT framework and Vantage6 platform, represents a significant advancement in the field. The proposed infrastructure addresses the challenges of data privacy and enables collaborative model development, paving the way for the widespread adoption of deep learning-based tools in the medical domain and beyond. The introduction of the secure aggregation server implied that data leakage problems in FL can be prevented by careful design decisions of the infrastructure.

ClinicalTrials.gov NCT05775068; https://clinicaltrials.gov/study/NCT05775068.

In oncology, medical imaging is crucial for diagnosis, treatment planning and therapy execution. Treatment responses can be complex and varied and are known to involve factors of treatment, patient characteristics and tumor microenvironment. Longitudinal image analysis is able to track temporal changes, aiding in disease monitoring, treatment evaluation, and outcome prediction. This allows for the enhancement of personalized medicine. However, analyzing longitudinal 2D and 3D images presents unique challenges, including image registration, reliable segmentation, dealing with variable imaging intervals, and sparse data. This review presents an overview of techniques and methodologies in longitudinal image analysis, with a primary focus on outcome modeling in radiation oncology.

There is increasing interest in the opportunities offered by Real World Data (RWD) to provide evidence where clinical trial data does not exist, but access to appropriate data sources is frequently cited as a barrier to RWD research. This paper discusses current RWD resources and how they can be accessed for cancer research.

There has been significant progress on facilitating RWD access in the last few years across a range of scales, from local hospital research databases, through regional care records and national repositories, to the impact of federated learning approaches on internationally collaborative studies. We use a series of case studies, principally from the UK, to illustrate how RWD can be accessed for research and healthcare improvement at each of these scales.

For each example we discuss infrastructure and governance requirements with the aim of encouraging further work in this space that will help to fill evidence gaps in oncology.

There are challenges, but real-world data research across a range of scales is already a reality. Taking advantage of the current generation of data sources requires researchers to carefully define their research question and the scale at which it would be best addressed.

Federated Learning (FL) enables collaborative model training while keeping data locally. Currently, most FL studies in radiology are conducted in simulated environments due to numerous hurdles impeding its translation into practice. The few existing real-world FL initiatives rarely communicate specific measures taken to overcome these hurdles. To bridge this significant knowledge gap, we propose a comprehensive guide for real-world FL in radiology. Minding efforts to implement real-world FL, there is a lack of comprehensive assessments comparing FL to less complex alternatives in challenging real-world settings, which we address through extensive benchmarking.

We developed our own FL infrastructure within the German Radiological Cooperative Network (RACOON) and demonstrated its functionality by training FL models on lung pathology segmentation tasks across six university hospitals. Insights gained while establishing our FL initiative and running the extensive benchmark experiments were compiled and categorized into the guide.

The proposed guide outlines essential steps, identified hurdles, and implemented solutions for establishing successful FL initiatives conducting real-world experiments. Our experimental results prove the practical relevance of our guide and show that FL outperforms less complex alternatives in all evaluation scenarios.

Our findings justify the efforts required to translate FL into real-world applications by demonstrating advantageous performance over alternative approaches. Additionally, they emphasize the importance of strategic organization, robust management of distributed data and infrastructure in real-world settings. With the proposed guide, we are aiming to aid future FL researchers in circumventing pitfalls and accelerating translation of FL into radiological applications.

Artificial intelligence (AI) radiation therapy (RT) planning holds promise for enhancing the consistency and efficiency of the RT planning process. Despite technical advancements, the widespread integration of AI into RT treatment planning faces challenges. The transition from controlled retrospective environments to real-world clinical settings introduces heightened scrutiny from clinical end users, potentially leading to decreased clinical acceptance. Key considerations for implementing AI RT planning include ensuring the AI model performance aligns with clinical standards, using high-quality training data, and incorporating sufficient data variation through meticulous curation by clinical experts. Beyond technical aspects, factors such as potential biases and the level of trust clinical end users place in AI may present unforeseen obstacles for real-world clinical use. Addressing these challenges requires bridging education and expertise gaps among clinical end users, enabling them to confidently embrace and utilize AI for routine RT planning. By fostering a better understanding of AI capabilities, building trust, and providing comprehensive training, the promises of AI RT planning can be a reality in the clinical setting. This article assesses the current clinical use of AI RT planning and explores challenges and considerations for bridging gaps in knowledge and expertise for AI operationalization, with focus on training data curation, workflow integration, explainability, bias, and domain knowledge. Remaining challenges in clinical implementation of AI RT treatment planning are examined in the context of trust building approaches.

Data-driven medicine is essential for enhancing the accessibility and quality of the healthcare system. The availability of data plays a crucial role in achieving this goal.

We propose implementing a robust data infrastructure of FAIRification and data fusion for clinical, genomic, and imaging data. This will be embedded within the framework of a distributed analytics platform for healthcare data analysis, utilizing the Personal Health Train paradigm.

This infrastructure will ensure the findability, accessibility, interoperability, and reusability of data, metadata, and results among multiple medical centers participating in the BETTER Horizon Europe project. The project focuses on studying rare diseases, such as intellectual disability and inherited retinal dystrophies.

The anticipated impacts will benefit a wide range of healthcare practitioners and potentially influence health policymakers.

The objective of this study was to develop a two-year overall survival model for inoperable stage I-III non-small cell lung cancer (NSCLC) patients using routine radiation oncology data over a federated (distributed) learning network and evaluate the potential of decision support for curative versus palliative radiotherapy.

A federated infrastructure of data extraction, de-identification, standardisation, image analysis, and modelling was installed for seven clinics to obtain clinical and imaging features and survival information for patients treated in 2011-2019. A logistic regression model was trained for the 2011-2016 curative patient cohort and validated for the 2017-2019 cohort. Features were selected with univariate and model-based analysis and optimised using bootstrapping. System performance was assessed by the receiver operating characteristic (ROC) and corresponding area under curve (AUC), C-index, calibration metrics and Kaplan-Meier survival curves, with risk groups defined by model probability quartiles. Decision support was evaluated using a case-control analysis using propensity matching between treatment groups.

1655 patient datasets were included. The overall model AUC was 0.68. Fifty-eight percent of patients treated with palliative radiotherapy had a low-to-moderate risk prediction according to the model, with survival times not significantly different (p = 0.87 and 0.061) from patients treated with curative radiotherapy classified as high-risk by the model. When survival was simulated by risk group and model-indicated treatment, there was an estimated 11% increase in survival rate at two years (p < 0.01).

Federated learning over multiple institution data can be used to develop and validate decision support systems for lung cancer while quantifying the potential impact of their use in practice. This paves the way for personalised medicine, where decisions can be based more closely on individual patient details from routine care.

The development of platforms for distributed analytics has been driven by a growing need to comply with various governance-related or legal constraints. Among these platforms, the so-called Personal Health Train (PHT) is one representative that has emerged over the recent years. However, in projects that require data from sites featuring different PHT infrastructures, institutions are facing challenges emerging from the combination of multiple PHT ecosystems, including data governance, regulatory compliance, or the modification of existing workflows. In these scenarios, the interoperability of the platforms is preferable. In this work, we introduce a conceptual framework for the technical interoperability of the PHT covering five essential requirements: Data integration, unified station identifiers, mutual metadata, aligned security protocols, and business logic. We evaluated our concept in a feasibility study that involves two distinct PHT infrastructures: PHT-meDIC and PADME. We analyzed data on leukodystrophy from patients in the University Hospitals of Tübingen and Leipzig, and patients with differential diagnoses at the University Hospital Aachen. The results of our study demonstrate the technical interoperability between these two PHT infrastructures, allowing researchers to perform analyses across the participating institutions. Our method is more space-efficient compared to the multi-homing strategy, and it shows only a minimal time overhead.

Hospitals and healthcare providers should assess and compare the quality of care given to patients and based on this improve the care. In the Netherlands, hospitals provide data to national quality registries, which in return provide annual quality indicators. However, this process is time-consuming, resource intensive and risks patient privacy and confidentiality. In this paper, we presented a multicentric 'Proof of Principle' study for federated calculation of quality indicators in patients with colorectal cancer. The findings suggest that the proposed approach is highly time-efficient and consume significantly lesser resources.

Two quality indicators are calculated in an efficient and privacy presevering federated manner, by i) applying the Findable Accessible Interoperable and Reusable (FAIR) data principles and ii) using the Personal Health Train (PHT) infrastructure. Instead of sharing data to a centralized registry, PHT enables analysis by sending algorithms and sharing only insights from the data.

ETL process extracted data from the Electronic Health Record systems of the hospitals, converted them to FAIR data and hosted in RDF endpoints within each hospital. Finally, quality indicators from each center are calculated using PHT and the mean result along with the individual results plotted.

PHT and FAIR data principles can efficiently calculate quality indicators in a privacy-preserving federated approach and the work can be scaled up both nationally and internationally. Despite this, application of the methodology was largely hampered by ELSI issues. However, the lessons learned from this study can provide other hospitals and researchers to adapt to the process easily and take effective measures in building quality of care infrastructures.

The recurrence of low-stage lung cancer poses a challenge due to its unpredictable nature and diverse patient responses to treatments. Personalized care and patient outcomes heavily rely on early relapse identification, yet current predictive models, despite their potential, lack comprehensive genetic data. This inadequacy fuels our research focus-integrating specific genetic information, such as pathway scores, into clinical data. Our aim is to refine machine learning models for more precise relapse prediction in early-stage non-small cell lung cancer. To address the scarcity of genetic data, we employ imputation techniques, leveraging publicly available datasets such as The Cancer Genome Atlas (TCGA), integrating pathway scores into our patient cohort from the Cancer Long Survivor Artificial Intelligence Follow-up (CLARIFY) project. Through the integration of imputed pathway scores from the TCGA dataset with clinical data, our approach achieves notable strides in predicting relapse among a held-out test set of 200 patients. By training machine learning models on enriched knowledge graph data, inclusive of triples derived from pathway score imputation, we achieve a promising precision of 82% and specificity of 91%. These outcomes highlight the potential of our models as supplementary tools within tumour, node, and metastasis (TNM) classification systems, offering improved prognostic capabilities for lung cancer patients. In summary, our research underscores the significance of refining machine learning models for relapse prediction in early-stage non-small cell lung cancer. Our approach, centered on imputing pathway scores and integrating them with clinical data, not only enhances predictive performance but also demonstrates the promising role of machine learning in anticipating relapse and ultimately elevating patient outcomes.

Predictive modelling of cancer outcomes using radiomics faces dimensionality problems and data limitations, as radiomics features often number in the hundreds, and multi-institutional data sharing is ()often unfeasible. Federated learning (FL) and feature selection (FS) techniques combined can help overcome these issues, as one provides the means of training models without exchanging sensitive data, while the other identifies the most informative features, reduces overfitting, and improves model interpretability. Our proposed FS pipeline based on FL principles targets data-driven radiomics FS in a multivariate survival study of non-small cell lung cancer patients. The pipeline was run across datasets from three institutions without patient-level data exchange. It includes two FS techniques, Correlation-based Feature Selection and LASSO regularization, and Cox Proportional-Hazard regression with Overall Survival as endpoint. Trained and validated on 828 patients overall, our pipeline yielded a radiomic signature comprising "intensity-based energy" and "mean discretised intensity". Validation resulted in a mean Harrell C-index of 0.59, showcasing fair efficacy in risk stratification. In conclusion, we suggest a distributed radiomics approach that incorporates preliminary feature selection to systematically decrease the feature set based on data-driven considerations. This aims to address dimensionality challenges beyond those associated with data constraints and interpretability concerns.

Distributed computations facilitate multi-institutional data analysis while avoiding the costs and complexity of data pooling. Existing approaches lack crucial features, such as built-in medical standards and terminologies, no-code data visualizations, explicit disclosure control mechanisms, and support for basic statistical computations, in addition to gradient-based optimization capabilities.

We describe the development of the Collaborative Data Analysis (CODA) platform, and the design choices undertaken to address the key needs identified during our survey of stakeholders. We use a public dataset (MIMIC-IV) to demonstrate end-to-end multi-modal FL using CODA. We assessed the technical feasibility of deploying the CODA platform at 9 hospitals in Canada, describe implementation challenges, and evaluate its scalability on large patient populations.

The CODA platform was designed, developed, and deployed between January 2020 and January 2023. Software code, documentation, and technical documents were released under an open-source license. Multi-modal federated averaging is illustrated using the MIMIC-IV and MIMIC-CXR datasets. To date, 8 out of the 9 participating sites have successfully deployed the platform, with a total enrolment of >1M patients. Mapping data from legacy systems to FHIR was the biggest barrier to implementation.

The CODA platform was developed and successfully deployed in a public healthcare setting in Canada, with heterogeneous information technology systems and capabilities. Ongoing efforts will use the platform to develop and prospectively validate models for risk assessment, proactive monitoring, and resource usage. Further work will also make tools available to facilitate migration from legacy formats to FHIR and DICOM.

Data-driven machine learning, as a promising approach, possesses the capability to build high-quality, exact, and robust models from ophthalmic medical data. Ophthalmic medical data, however, presently exist across disparate data silos with privacy limitations, making centralized training challenging. While ophthalmologists may not specialize in machine learning and artificial intelligence (AI), considerable impediments arise in the associated realm of research. To address these issues, we design and develop FedEYE, a scalable and flexible end-to-end ophthalmic federated learning platform. During FedEYE design, we adhere to four fundamental design principles, ensuring that ophthalmologists can effortlessly create independent and federated AI research tasks. Benefiting from the design principles and architecture of FedEYE, it encloses numerous key features, including rich and customizable capabilities, separation of concerns, scalability, and flexible deployment. We also validated the applicability of FedEYE by employing several prevalent neural networks on ophthalmic disease image classification tasks.

With the advent of the big data era, data security issues are becoming more common. Healthcare organizations have more data to use for analysis, but they lose money every year due to their inability to prevent data leakage. To overcome these challenges, research on the use of data protection technologies in healthcare is actively underway, particularly research on state-of-the-art technologies, such as federated learning announced by Google and blockchain technology, which has recently attracted attention. To learn about these research efforts, we explored the research, methods, and limitations of the most widely used privacy technologies. After investigating related papers published between 2017 and 2023 and identifying the latest technology trends, we selected related papers and reviewed related technologies. In the process, four technologies were the focus of this study: blockchain, federated learning, isomorphic encryption, and differential privacy. Overall, our analysis provides researchers with insight into privacy technology research by suggesting the limitations of current privacy technologies and suggesting future research directions.

Investigating low-prevalence diseases such as multiple sclerosis is challenging because of the rather small number of individuals affected by this disease and the scattering of real-world data across numerous data sources. These obstacles impair data integration, standardization, and analysis, which negatively impact the generation of significant meaningful clinical evidence.

This study aims to present a comprehensive, research question-agnostic, multistakeholder-driven end-to-end data analysis pipeline that accommodates 3 prevalent data-sharing streams: individual data sharing, core data set sharing, and federated model sharing.

A demand-driven methodology is employed for standardization, followed by 3 streams of data acquisition, a data quality enhancement process, a data integration procedure, and a concluding analysis stage to fulfill real-world data-sharing requirements. This pipeline's effectiveness was demonstrated through its successful implementation in the COVID-19 and multiple sclerosis global data sharing initiative.

The global data sharing initiative yielded multiple scientific publications and provided extensive worldwide guidance for the community with multiple sclerosis. The pipeline facilitated gathering pertinent data from various sources, accommodating distinct sharing streams and assimilating them into a unified data set for subsequent statistical analysis or secure data examination. This pipeline contributed to the assembly of the largest data set of people with multiple sclerosis infected with COVID-19.

The proposed data analysis pipeline exemplifies the potential of global stakeholder collaboration and underlines the significance of evidence-based decision-making. It serves as a paradigm for how data sharing initiatives can propel advancements in health care, emphasizing its adaptability and capacity to address diverse research inquiries.

Ensuring safe and healthy food is a big challenge due to the complexity of food supply chains and their vulnerability to many internal and external factors, including food fraud. Recent research has shown that Artificial Intelligence (AI) based algorithms, in particularly data driven Bayesian Network (BN) models, are very suitable as a tool to predict future food fraud and hence allowing food producers to take proper actions to avoid that such problems occur. Such models become even more powerful when data can be used from all actors in the supply chain, but data sharing is hampered by different interests, data security and data privacy. Federated learning (FL) may circumvent these issues as demonstrated in various areas of the life sciences. In this research, we demonstrate the potential of the FL technology for food fraud using a data driven BN, integrating data from different data owners without the data leaving the database of the data owners. To this end, a framework was constructed consisting of three geographically different data stations hosting different datasets on food fraud. Using this framework, a BN algorithm was implemented that was trained on the data of different data stations while the data remained at its physical location abiding by privacy principles. We demonstrated the applicability of the federated BN in food fraud and anticipate that such framework may support stakeholders in the food supply chain for better decision-making regarding food fraud control while still preserving the privacy and confidentiality nature of these data.

Lung cancer exhibits unpredictable recurrence in low-stage tumors and variable responses to different therapeutic interventions. Predicting relapse in early-stage lung cancer can facilitate precision medicine and improve patient survivability. While existing machine learning models rely on clinical data, incorporating genomic information could enhance their efficiency. This study aims to impute and integrate specific types of genomic data with clinical data to improve the accuracy of machine learning models for predicting relapse in early-stage, non-small cell lung cancer patients.

The study utilized a publicly available TCGA lung cancer cohort and imputed genetic pathway scores into the Spanish Lung Cancer Group (SLCG) data, specifically in 1348 early-stage patients. Initially, tumor recurrence was predicted without imputed pathway scores. Subsequently, the SLCG data were augmented with pathway scores imputed from TCGA. The integrative approach aimed to enhance relapse risk prediction performance.

The integrative approach achieved improved relapse risk prediction with the following evaluation metrics: an area under the precision-recall curve (PR-AUC) score of 0.75, an area under the ROC (ROC-AUC) score of 0.80, an F1 score of 0.61, and a Precision of 0.80. The prediction explanation model SHAP (SHapley Additive exPlanations) was employed to explain the machine learning model's predictions.

We conclude that our explainable predictive model is a promising tool for oncologists that addresses an unmet clinical need of post-treatment patient stratification based on the relapse risk while also improving the predictive power by incorporating proxy genomic data not available for specific patients.

Building on a strong foundation of philosophy, theory, methods and computation over the past three decades, Bayesian approaches are now an integral part of the toolkit for most statisticians and data scientists. Whether they are dedicated Bayesians or opportunistic users, applied professionals can now reap many of the benefits afforded by the Bayesian paradigm. In this paper, we touch on six modern opportunities and challenges in applied Bayesian statistics: intelligent data collection, new data sources, federated analysis, inference for implicit models, model transfer and purposeful software products. This article is part of the theme issue 'Bayesian inference: challenges, perspectives, and prospects'.

Lymph node metastases (pN+) in presumed early-stage cervical cancer negatively impact prognosis. Using federated learning, we aimed to develop a tool to identify a group of women at low risk of pN+, to guide the shared decision-making process concerning the extent of lymph node dissection.

Women with cervical cancer between 2005 and 2020 were identified retrospectively from population-based registries: the Danish Gynaecological Cancer Database, Swedish Quality Registry for Gynaecologic Cancer and Netherlands Cancer Registry. Inclusion criteria were: squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma; The International Federation of Gynecology and Obstetrics 2009 IA2, IB1 and IIA1; treatment with radical hysterectomy and pelvic lymph node assessment. We applied privacy-preserving federated logistic regression to identify risk factors of pN+. Significant factors were used to stratify the risk of pN+.

We included 3606 women (pN+ 11%). The most important risk factors of pN+ were lymphovascular space invasion (LVSI) (odds ratio [OR] 5.16, 95% confidence interval [CI], 4.59-5.79), tumour size 21-40 mm (OR 2.14, 95% CI, 1.89-2.43) and depth of invasion>10 mm (OR 1.81, 95% CI, 1.59-2.08). A group of 1469 women (41%)-with tumours without LVSI, tumour size ≤20 mm, and depth of invasion ≤10 mm-had a very low risk of pN+ (2.4%, 95% CI, 1.7-3.3%).

Early-stage cervical cancer without LVSI, a tumour size ≤20 mm and depth of invasion ≤10 mm, confers a low risk of pN+. Based on an international privacy-preserving analysis, we developed a useful tool to guide the shared decision-making process regarding lymph node dissection.

Among medical specialties, laboratory medicine is the largest producer of structured data and must play a crucial role for the efficient and safe implementation of big data and artificial intelligence in healthcare. The area of personalized therapies and precision medicine has now arrived, with huge data sets not only used for experimental and research approaches, but also in the "real world". Analysis of real world data requires development of legal, procedural and technical infrastructure. The integration of all clinical data sets for any given patient is important and necessary in order to develop a patient-centered treatment approach. Data-driven research comes with its own challenges and solutions. The Findability, Accessibility, Interoperability, and Reusability (FAIR) Guiding Principles provide guidelines to make data findable, accessible, interoperable and reusable to the research community. Federated learning, standards and ontologies are useful to improve robustness of artificial intelligence algorithms working on big data and to increase trust in these algorithms. When dealing with big data, the univariate statistical approach changes to multivariate statistical methods significantly shifting the potential of big data. Combining multiple omics gives previously unsuspected information and provides understanding of scientific questions, an approach which is also called the systems biology approach. Big data and artificial intelligence also offer opportunities for laboratories and the In Vitro Diagnostic industry to optimize the productivity of the laboratory, the quality of laboratory results and ultimately patient outcomes, through tools such as predictive maintenance and "moving average" based on the aggregate of patient results.

Heart failure (HF) is a multifaceted clinical syndrome characterized by different etiologies, risk factors, comorbidities, and a heterogeneous clinical course. The current model, based on data from clinical trials, is limited by the biases related to a highly-selected sample in a protected environment, constraining the applicability of evidence in the real-world scenario. If properly leveraged, the enormous amount of data from real-world may have a groundbreaking impact on clinical care pathways. We present, here, the development of an HF DataMart framework for the management of clinical and research processes.

Within our institution, Fondazione Policlinico Universitario A. Gemelli in Rome (Italy), a digital platform dedicated to HF patients has been envisioned (GENERATOR HF DataMart), based on two building blocks: 1. All retrospective information has been integrated into a multimodal, longitudinal data repository, providing in one single place the description of individual patients with drill-down functionalities in multiple dimensions. This functionality might allow investigators to dynamically filter subsets of patient populations characterized by demographic characteristics, biomarkers, comorbidities, and clinical events (e.g., re-hospitalization), enabling agile analyses of the outcomes by subsets of patients. 2. With respect to expected long-term health status and response to treatments, the use of the disease trajectory toolset and predictive models for the evolution of HF has been implemented. The methodological scaffolding has been constructed in respect of a set of the preferred standards recommended by the CODE-EHR framework.

Several examples of GENERATOR HF DataMart utilization are presented as follows: to select a specific retrospective cohort of HF patients within a particular period, along with their clinical and laboratory data, to explore multiple associations between clinical and laboratory data, as well as to identify a potential cohort for enrollment in future studies; to create a multi-parametric predictive models of early re-hospitalization after discharge; to cluster patients according to their ejection fraction (EF) variation, investigating its potential impact on hospital admissions.

The GENERATOR HF DataMart has been developed to exploit a large amount of data from patients with HF from our institution and generate evidence from real-world data. The two components of the HF platform might provide the infrastructural basis for a combined patient support program dedicated to continuous monitoring and remote care, assisting patients, caregivers, and healthcare professionals.

Bone tumours are relatively rare and, as a consequence, treatment in a centre with expertise is required. Current treatment guidelines also recommend review by a specialised pathologist. Here we report on international consensus-based datasets for the pathology reporting of biopsy and resection specimens of bone sarcomas. The datasets were produced under the auspices of the International Collaboration on Cancer Reporting (ICCR), a global alliance of major (inter-)national pathology and cancer organisations.

According to the ICCR's process for dataset development, an international expert panel consisting of pathologists, an oncologic orthopaedic surgeon, a medical oncologist, and a radiologist produced a set of core and noncore data items for biopsy and resection specimens based on a critical review and discussion of current evidence. All professionals involved were bone tumour experts affiliated with tertiary referral centres. Commentary was provided for each data item to explain the rationale for selecting it as a core or noncore element, its clinical relevance, and to highlight potential areas of disagreement or lack of evidence, in which case a consensus position was formulated. Following international public consultation, the documents were finalised and ratified, and the datasets, including a synoptic reporting guide, were published on the ICCR website.

These first international datasets for bone sarcomas are intended to promote high-quality, standardised pathology reporting. Their widespread adoption will improve the consistency of reporting, facilitate multidisciplinary communication, and enhance comparability of data, all of which will help to improve management of bone sarcoma patients.

Machine learning (ML) has succeeded in improving our daily routines by enabling automation and improved decision making in a variety of industries such as healthcare, finance, and transportation, resulting in increased efficiency and production. However, the development and widespread use of this technology has been significantly hampered by concerns about data privacy, confidentiality, and sensitivity, particularly in healthcare and finance. The "data hunger" of ML describes how additional data can increase performance and accuracy, which is why this question arises. Federated learning (FL) has emerged as a technology that helps solve the privacy problem by eliminating the need to send data to a primary server and collect it where it is processed and the model is trained. To maintain privacy and improve model performance, FL shares parameters rather than data during training, in contrast to the typical ML practice of sending user data during model development. Although FL is still in its infancy, there are already applications in various industries such as healthcare, finance, transportation, and others. In addition, 32% of companies have implemented or plan to implement federated learning in the next 12-24 months, according to the latest figures from KPMG, which forecasts an increase in investment in this area from USD 107 million in 2020 to USD 538 million in 2025. In this context, this article reviews federated learning, describes it technically, differentiates it from other technologies, and discusses current FL aggregation algorithms. It also discusses the use of FL in the diagnosis of cardiovascular disease, diabetes, and cancer. Finally, the problems hindering progress in this area and future strategies to overcome these limitations are discussed in detail.

Scientific advances, especially in the healthcare domain, can be accelerated by making data available for analysis. However, in traditional data analysis systems, data need to be moved to a central processing unit that performs analyses, which may be undesirable, e.g. due to privacy regulations in case these data contain personal information. This paper discusses the Personal Health Train (PHT) approach in which data processing is brought to the (personal health) data rather than the other way around, allowing (private) data accessed to be controlled, and to observe ethical and legal concerns. This paper introduces the PHT architecture and discusses the data staging solution that allows processing to be delegated to components spawned in a private cloud environment in case the (health) organisation hosting the data has limited resources to execute the required processing. This paper shows the feasibility and suitability of the solution with a relatively simple, yet representative, case study of data analysis of Covid-19 infections, which is performed by components that are created on demand and run in the Amazon Web Services platform. This paper also shows that the performance of our solution is acceptable, and that our solution is scalable. This paper demonstrates that the PHT approach enables data analysis with controlled access, preserving privacy and complying with regulations such as GDPR, while the solution is deployed in a private cloud environment.

Advances in artificial intelligence deep learning (DL) have made tremendous impacts on the field of ocular imaging over the last few years. Specifically, DL has been utilised to detect and classify various ocular diseases on retinal photographs, optical coherence tomography (OCT) images, and OCT-angiography images. In order to achieve good robustness and generalisability of model performance, DL training strategies traditionally require extensive and diverse training datasets from various sites to be transferred and pooled into a "centralised location". However, such a data transferring process could raise practical concerns related to data security and patient privacy. Federated learning (FL) is a distributed collaborative learning paradigm which enables the coordination of multiple collaborators without the need for sharing confidential data. This distributed training approach has great potential to ensure data privacy among different institutions and reduce the potential risk of data leakage from data pooling or centralisation. This review article aims to introduce the concept of FL, provide current evidence of FL in ocular imaging, and discuss potential challenges as well as future applications.

Federated learning has the potential to perfrom analysis on decentralised data; however, there are some obstacles to survival analyses as there is a risk of data leakage. This study demonstrates how to perform a stratified Cox regression survival analysis specifically designed to avoid data leakage using federated learning on larynx cancer patients from centres in three different countries.

Data were obtained from 1821 larynx cancer patients treated with radiotherapy in three centres. Tumour volume was available for all 786 of the included patients. Parameter selection among eleven clinical and radiotherapy parameters were performed using best subset selection and cross-validation through the federated learning system, AusCAT. After parameter selection, β regression coefficients were estimated using bootstrap. Calibration plots were generated at 2 and 5-years survival, and inner and outer risk groups' Kaplan-Meier curves were compared to the Cox model prediction.

The best performing Cox model included log(GTV), performance status, age, smoking, haemoglobin and N-classification; however, the simplest model with similar statistical prediction power included log(GTV) and performance status only. The Harrell C-indices for the simplest model were for Odense, Christie and Liverpool 0.75[0.71-0.78], 0.65[0.59-0.71], and 0.69[0.59-0.77], respectively. The values are slightly higher for the full model with C-index 0.77[0.74-0.80], 0.67[0.62-0.73] and 0.71[0.61-0.80], respectively. Smoking during treatment has the same hazard as a ten-years older nonsmoking patient.

Without any patient-specific data leaving the hospitals, a stratified Cox regression model based on data from centres in three countries was developed without data leakage risks. The overall survival model is primarily driven by tumour volume and performance status.

This article offers a brief overview of 'privacy-by-design (or data-protection-by-design) research environments', namely Trusted Research Environments (TREs, most commonly used in the United Kingdom) and Personal Health Trains (PHTs, most commonly used in mainland Europe). These secure environments are designed to enable the safe analysis of multiple, linked (and often big) data sources, including sensitive personal data and data owned by, and distributed across, different institutions. They take data protection and privacy requirements into account from the very start (conception phase, during system design) rather than as an afterthought or 'patch' implemented at a later stage on top of an existing environment. TREs and PHTs are becoming increasingly important for conducting large-scale privacy-preserving health research and for enabling federated learning and discoveries from big healthcare datasets. The paper also presents select examples of successful TRE and PHT implementations and of large-scale studies that used them.

The mining of personal data collected by multiple organizations remains challenging in the presence of technical barriers, privacy concerns, and legal and/or organizational restrictions. While a number of privacy-preserving and data mining frameworks have recently emerged, much remains to show their practical utility. In this study, we implement and utilize a secure infrastructure using data from Statistics Netherlands and the Maastricht Study to learn the association between Type 2 Diabetes Mellitus (T2DM) and healthcare expenses considering the impact of lifestyle, physical activities, and complications of T2DM. Through experiments using real-world distributed personal data, we present the feasibility and effectiveness of the secure infrastructure for practical use cases of linking and analyzing vertically partitioned data across multiple organizations. We discovered that individuals diagnosed with T2DM had significantly higher expenses than those with prediabetes, while participants with prediabetes spent more than those without T2DM in all the included healthcare categories to different degrees. We further discuss a joint effort from technical, ethical-legal, and domain-specific experts that is highly valued for applying such a secure infrastructure to real-life use cases to protect data privacy.

Emerging evidence suggests that data-driven support tools have found their way into clinical decision-making in a number of areas, including cancer care. Improving them and widening their scope of availability in various differing clinical scenarios, including for prognostic models derived from retrospective data, requires co-ordinated data sharing between clinical centres, secondary analyses of large multi-institutional clinical trial data, or distributed (federated) learning infrastructures. A systematic approach to utilizing routinely collected data across cancer care clinics remains a significant challenge due to privacy, administrative and political barriers.

An information technology infrastructure and web service software was developed and implemented which uses machine learning to construct clinical decision support systems in a privacy-preserving manner across datasets geographically distributed in different hospitals. The infrastructure was deployed in a network of Australian hospitals. A harmonized, international ontology-linked, set of lung cancer databases were built with the routine clinical and imaging data at each centre. The infrastructure was demonstrated with the development of logistic regression models to predict major cardiovascular events following radiation therapy.

The infrastructure implemented forms the basis of the Australian computer-assisted theragnostics (AusCAT) network for radiation oncology data extraction, reporting and distributed learning. Four radiation oncology departments (across seven hospitals) in New South Wales (NSW) participated in this demonstration study. Infrastructure was deployed at each centre and used to develop a model predicting for cardiovascular admission within a year of receiving curative radiotherapy for non-small cell lung cancer. A total of 10417 lung cancer patients were identified with 802 being eligible for the model. Twenty features were chosen for analysis from the clinical record and linked registries. After selection, 8 features were included and a logistic regression model achieved an area under the receiver operating characteristic (AUROC) curve of 0.70 and C-index of 0.65 on out-of-sample data.

The infrastructure developed was demonstrated to be usable in practice between clinical centres to harmonize routinely collected oncology data and develop models with federated learning. It provides a promising approach to enable further research studies in radiation oncology using real world clinical data.