18FDG Positron Emission Tomography Mining for Metabolic Imaging Biomarkers of Radiation-induced Xerostomia in Patients with Oropharyngeal Cancer

Abstract

Purpose Head and neck cancers (HNC) radiotherapy (RT) is associated with inevitable injury to parotid glands and subsequent xerostomia. We investigated the utility of standardized uptake values (SUV) derived from routinely performed 18-fluorodeoxygluocose positron-emission tomography (18FDG-PET) to develop metabolic imaging biomarkers (MIBs) of RT-related parotid injury. Methods Data for oropharyngeal cancer (OPC) patients treated with RT at our institution between 2005-2015 with available planning computed tomography (CT), dose grid, pre- & first post-RT 18FDG-PET-CT scans, and physician-reported xerostomia assessment at 3-6 months post-RT (Xero 3-6ms) per CTCAE, was retrieved, following an IRB approval. A CT-CT deformable image co-registration followed by voxel-by-voxel resampling of pre & post-RT 18FDG activity and dose grid were performed. Ipsilateral (Ipsi) and contralateral (contra) parotid glands were sub-segmented based on the received dose in 5 Gy increments, i.e. 0-5 Gy, 5-10 Gy sub-volumes, etc. Median and dose-weighted SUV were extracted from whole parotid volumes and sub-volumes on pre- & post-RT PET scans, using in-house code that runs on MATLAB. Wilcoxon signed-rank and Kruskal-Wallis tests were used to test differences pre- and post-RT. Results 432 parotid glands, belonging to 108 OPC patients treated with RT, were sub-segmented & analyzed. Xero 3-6ms was reported as: non-severe (78.7%) and severe (21.3%). SUV- median values were significantly reduced post-RT, irrespective of laterality (p=0.02). A similar pattern was observed in parotid sub-volumes, especially ipsi parotid gland sub-volumes receiving doses 10-50 Gy (p<0.05). A Kruskal-Wallis test showed a significantly higher mean planned RT dose in the contra parotid in the patients with more severe Xero 3-6mo (p= 0.03). Multiple logistic regression showed a combined clinical-dosimetric-metabolic imaging model could predict the severity of Xero 3-6mo; AUC=0.78 (95%CI:0.66-0.85;p<0.0001) Conclusion We sought to quantify pre- and post-RT 18FDG-PET metrics of parotid glands in patients with OPC. Temporal dynamics of PET-derived metrics can potentially serve as MIBs of RT-related xerostomia in concert with clinical and dosimetric variables. Keywords: Xerostomia; FDG-PET; radiotherapy; imaging biomarkers; predictive model; head and neck cancer