Multi-centre radiomics for prediction of recurrence following radical radiotherapy for head and neck cancers: Consequences of feature selection, machine learning classifiers and batch-effect harmonization.

Background and purpose: Radiomics models trained with limited single institution data are often not reproducible and generalisable. We developed radiomics models that predict loco-regional recurrence within two years of radiotherapy with private and public datasets and their combinations, to simulate small and multi-institutional studies and study the responsiveness of the models to feature selection, machine learning algorithms, centre-effect harmonization and increased dataset sizes. Materials and methods: 562 patients histologically confirmed and treated for locally advanced head-and-neck cancer (LA-HNC) from two public and two private datasets; one private dataset exclusively reserved for validation. Clinical contours of primary tumours were not recontoured and were used for Pyradiomics based feature extraction. ComBat harmonization was applied, and LASSO-Logistic Regression (LR) and Support Vector Machine (SVM) models were built. 95% confidence interval (CI) of 1000 bootstrapped area-under-the-Receiver-operating-curves (AUC) provided predictive performance. Responsiveness of the models' performance to the choice of feature selection methods, ComBat harmonization, machine learning classifier, single and pooled data was evaluated. Results: LASSO and SelectKBest selected 14 and 16 features, respectively; three were overlapping. Without ComBat, the LR and SVM models for three institutional data showed AUCs (CI) of 0.513 (0.481-0.559) and 0.632 (0.586-0.665), respectively. Performances following ComBat revealed AUCs of 0.559 (0.536-0.590) and 0.662 (0.606-0.690), respectively. Compared to single cohort AUCs (0.562-0.629), SVM models from pooled data performed significantly better at AUC = 0.680. Conclusions: Multi-institutional retrospective data accentuates the existing variabilities that affect radiomics. Carefully designed prospective, multi-institutional studies and data sharing are necessary for clinically relevant head-and-neck cancer prognostication models.