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Dose-response modeling for radiotherapy-induced xerostomia in head and neck cancer (HN) patients is a promising frontier for personalized therapy. Feature extraction from diagnostic and therapeutic images (radiomics and dosiomics features) can be used for data-driven response modeling. The aim of this study is to develop xerostomia predictive models based on radiomics-dosiomics features. Data from the cancer imaging archive (TCIA) for 31 HN cancer patients were employed. For all patients, parotid CT radiomics features were extracted, utilizing Lasso regression for feature selection and multivariate modeling. The models were developed by selected features from pretreatment (CT 1 ), mid-treatment (CT 2 ), post-treatment (CT 3 ), and delta features (ΔCT 2-1 , ΔCT 3-1 , ΔCT 3-2 ). We also considered dosiomics features extracted from the parotid dose distribution images (Dose model). Thus, combination models of radio-dosiomics (CT + dose &amp; ΔCT + dose) were developed. Moreover, clinical, and dose-volume histogram (DVH) models were built. Nested 10-fold cross-validation was used to assess the predictive classification of patients into those with and without xerostomia, and the area under the receiver operative characteristic curve (AUC) was used to compare the predictive power of the models. The sensitivity and accuracy of models also were obtained. In total, 59 parotids were assessed, and 13 models were developed. Our results showed three models with AUC of 0.89 as most predictive, namely ΔCT 2-1  + Dose (Sensitivity 0.99, Accuracy 0.94 &amp; Specificity 0.86), CT 3  model (Sensitivity 0.96, Accuracy 0.94 &amp; Specificity 0.86) and DVH (Sensitivity 0.93, Accuracy 0.89 &amp; Specificity 0.84). These models were followed by Clinical (AUC 0.89, Sensitivity 0.81, Accuracy 0.97 &amp; Specificity 0.89) and CT 2  &amp; Dose (AUC 0.86, Sensitivity 0.97, Accuracy 0.87 &amp; Specificity 0.82). The Dose model (developed by dosiomics features only) had AUC, Sensitivity, Specificity, and Accuracy of 0.72, 0.98, 0.33, and 0.79 respectively. Quantitative features extracted from diagnostic imaging during and after radiotherapy alone or in combination with dosiomics markers obtained from dose distribution images can be used for radiotherapy response modeling, opening up prospects for personalization of therapies toward improved therapeutic outcomes.

Radiomics and dosiomics-based prediction of radiotherapy-induced xerostomia in head and neck cancer patients