Validation of the

Previously, PET image biomarkers (PET-IBMs) - the 90thpercentile standardized uptake value (P90-SUV) and the Mean SUV (Mean-SUV) ofthe contralateral parotid gland (cPG) - were identified as predictors for late-xerostomiafollowing head and neck cancer (HNC) radiotherapy. The aim of the current study wasto assess in an independent validation cohort whether these pre-treatment PET-IBMscan improve late-xerostomia prediction compared to the prediction with baselinexerostomia and mean cPG dose alone.The prediction endpoint was patient-rated moderate-to-severe xerostomia at 12 months after radiotherapy. The PET-IBMs were extracted frompre-treatment 18 F-FDG PET images. The performance of the model (base model)with baseline xerostomia and mean cPG dose alone and models with additionallyP90-SUV or Mean-SUV were tested in the current independent validation cohort.Specifically, model discrimination (area under the curve: AUC) and calibration(calibration plot) were evaluated.The current validation cohort consisted of 137 patients of which 40% developed moderate-to-severe xerostomia at 12 months. Both the PET-P90 model (AUC PET-P90 =0.71) and the PET-Mean model (AUC PET-Mean =0.70) performed well in the current validation cohort. Moreover, their performance was improved compared to the base model (AUC base =0.68). The calibration plots showed a good fit of the prediction to the actual rates for all tested models.PET-IBMs showed an improved prediction of late-xerostomia when added to the base model in this validation cohort. This contributed to the published hypothesis that PET-IBMs include individualized information and can serve as a pre- treatment risk factor for late-xerostomia.