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Purpose: Radiotherapy planning based only on positron emission tomography/magnetic resonance imaging (PET/MRI) lacks computed tomography (CT) information required for dose calculations. In this study, a previously developed deep learning model for creating synthetic CT (sCT) from MRI in patients with head and neck cancer was evaluated in 2 scenarios: (1) using an independent external dataset, and (2) using a local dataset after an update of the model related to scanner software-induced changes to the input MRI., Methods and Materials: Six patients from an external site and 17 patients from a local cohort were analyzed separately. Each patient underwent a CT and a PET/MRI with a Dixon MRI sequence over either one (external) or 2 (local) bed positions. For the external cohort, a previously developed deep learning model for deriving sCT from Dixon MRI was directly applied. For the local cohort, we adapted the model for an upgraded MRI acquisition using transfer learning and evaluated it in a leave-one-out process. The sCT mean absolute error for each patient was assessed. Radiotherapy dose plans based on sCT and CT were compared by assessing relevant absorbed dose differences in target volumes and organs at risk., Results: The MAEs were 78 ± 13 HU and 76 ± 12 HU for the external and local cohort, respectively. For the external cohort, absorbed dose differences in target volumes were within ± 2.3% and within ± 1% in 95% of the cases. Differences in organs at risk were <2%. Similar results were obtained for the local cohort., Conclusions: We have demonstrated a robust performance of a deep learning model for deriving sCT from MRI when applied to an independent external dataset. We updated the model to accommodate a larger axial field of view and software-induced changes to the input MRI. In both scenarios dose calculations based on sCT were similar to those of CT suggesting a robust and reliable method., (© 2021 The Authors.)