Bi-Centric Independent Validation of Outcome Prediction after Radioembolization of Primary and Secondary Liver Cancer

Background: Yttrium-90 radioembolization (RE) plays an important role in the treatment of liver malignancies. Optimal patient selection is crucial for an effective and safe treatment. In this study, we aim to validate the prognostic performance of a previously established random survival forest (RSF) with an external validation cohort from a different national center. Furthermore, we compare outcome prediction models with different established metrics. Methods: A previously established RSF model, trained on a consecutive cohort of 366 patients who had received RE due to primary or secondary liver tumor at a national center (center 1), was used to predict the outcome of an independent consecutive cohort of 202 patients from a different national center (center 2) and vice versa. Prognostic performance was evaluated using the concordance index (C-index) and the integrated Brier score (IBS). The prognostic importance of designated baseline parameters was measured with the minimal depth concept, and the influence on the predicted outcome was analyzed with accumulated local effects plots. RSF values were compared to conventional cox proportional hazards models in terms of C-index and IBS. Results: The established RSF model achieved a C-index of 0.67 for center 2, comparable to the results obtained for center 1, which it was trained on (0.66). The RSF model trained on center 2 achieved a C-index of 0.68 on center 2 data and 0.66 on center 1 data. CPH models showed comparable results on both cohorts, with C-index ranging from 0.68 to 0.72. IBS validation showed more differentiated results depending on which cohort was trained on and which cohort was predicted (range: 0.08 to 0.20). Baseline cholinesterase was the most important variable for survival prediction. Conclusion: The previously developed predictive RSF model was successfully validated with an independent external cohort. C-index and IBS are suitable metrics to compare outcome prediction models, with IBS showing more differentiated results. The findings corroborate that survival after RE is critically determined by functional hepatic reserve and thus baseline liver function should play a key role in patient selection.