Random forest and elastic net logistic regression yield higher discriminative performance in (chemo)radiotherapy outcome and toxicity prediction than other studied classifiers. Thus, one of these two classifiers should be the first choice for investigators when building classification models or to benchmark one's own modeling results against. Our results also show that an informed preselection of classifiers based on existing datasets can improve discrimination over random selection.

Background and purpose: Access to healthcare data is indispensable for scientific progress and innovation. Sharing healthcare data is time-consuming and notoriously difficult due to privacy and regulatory concerns. The Personal Health Train (PHT) provides a privacy-by-design infrastructure connecting FAIR (Findable, Accessible, Interoperable, Reusable) data sources and allows distributed data analysis and machine learning. Patient data never leaves a healthcare institute. Materials and methods: Lung cancer patient-specific databases (tumor staging and post-treatment survival information) of oncology departments were translated according to a FAIR data model and stored locally in a graph database. Software was installed locally to enable deployment of distributed machine learning algorithms via a central server. Algorithms (MATLAB, code and documentation publicly available) are patient privacy-preserving as only summary statistics and regression coefficients are exchanged with the central server. A logistic regression model to predict post-treatment two-year survival was trained and evaluated by receiver operating characteristic curves (ROC), root mean square prediction error (RMSE) and calibration plots. Results: In 4 months, we connected databases with 23 203 patient cases across 8 healthcare institutes in 5 countries (Amsterdam, Cardiff, Maastricht, Manchester, Nijmegen, Rome, Rotterdam, Shanghai) using the PHT. Summary statistics were computed across databases. A distributed logistic regression model predicting post-treatment two-year survival was trained on 14 810 patients treated between 1978 and 2011 and validated on 8 393 patients treated between 2012 and 2015. Conclusion:The PHT infrastructure demonstrably overcomes patient privacy barriers to healthcare data sharing and enables fast data analyses across multiple institutes from different countries with different regulatory regimens. This infrastructure promotes global evidence-based medicine while prioritizing patient privacy.

A statistical hypothesis is a statement that can be tested by collecting data and making observations. Before you start data collection and perform your research, you need to formulate your hypothesis. An example hypothesis could be for instance: "If I increase the prescribed radiation dose to the tumor, this will also lead to an increase of side-effects in surrounding healthy tissues". The purpose of statistical hypothesis testing is to find out whether the observations are meaningful or can be attributed to noise or chance.