Validation of the 18F-FDG PET Image Biomarker Model Predicting Late Xerostomia after Head and Neck Cancer Radiotherapy

Abstract

<h3>Purpose/Objective(s)</h3> PET image biomarkers can improve the prediction of radiation-induced late xerostomia in head and neck cancer (HNC) patients [1,2]. A PET image biomarker, the 90^th percentile (<i>P90</i>) of the standardized uptake value was identified as a promising predictor for late xerostomia, where HNC patients with lower metabolic activity in the pre-radiation parotid gland (<i>PG</i>) were more at risk of developing late xerostomia after radiation [2]. Addition of <i>P90</i> improved model performance of the reference model based on baseline xerostomia (<i>Xer-base</i>) and <i>PG</i> mean dose. The aim of the current study was to validate the pre-treatment <i>PET-P90 model</i> in an external HNC validation cohort. <h3>Materials/Methods</h3> HNC patients were treated with primary (chemo-)radiation with curative intent. ¹⁸F-FDG PET/CT images were acquired 2 weeks before radiotherapy. The main endpoint was patient-rated moderate-to-severe xerostomia 12 months after radiotherapy which was assessed via the EORTC QLQ-H&N35 questionnaire. The <i>P90</i> and <i>PG</i> mean dose of contralateral <i>PG</i> were extracted from PET images and radiation dose distribution, respectively. We validated the reference model that was based on <i>Xer-base</i> and <i>PG</i> mean dose only, as well as the PET-P90 model, which had the <i>P90</i> as an additional variable. The closed testing procedure was used to test whether the original coefficients (see [2]) of these models needed to be updated or revised in the current external validation cohort. Finally, model performance (AUC, R²) was evaluated and compared for the reference model and the PET-P90 model. Calibration was tested with the Hosmer-Lemeshow test (HL test). <h3>Results</h3> The current external validation cohort consisted 127 patients of which 40% developed moderate-to-severe xerostomia. The closed testing procedure indicated that all original coefficients of the models did not require any update or revision in the current cohort. Compared to reference model (Table 1. AUC_ref=0.67, R²_ref=0.13), the PET-P90 model showed better predictive performance (AUC_P90=0.71, R²_P90=0.18). Calibration was both good for the reference model and the PET-P90 model in current external cohort (HL test: <i>p</i>_ref=0.09, <i>p</i>_P90=0.09). <h3>Conclusion</h3> The PET-P90 model performed well in this external validation cohort, and outperformed the reference model. This contributes to the hypothesis that lower <i>PG</i> metabolic activity is a pre-treatment risk factor for late xerostomia.