Impact of tumour region of interest delineation method for mid-treatment FDG-PET response prediction in head and neck squamous cell carcinoma undergoing radiotherapy

Background: The aim of this study was to evaluate the impact of tumour region of interest (ROI) delineation method on mid-treatment F-18-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) response prediction in mucosal head and neck squamous cell carcinoma during radiotherapy. Methods: A total of 52 patients undergoing definitive radiotherapy with or without systemic therapy from two prospective imaging biomarker studies were analysed. FDG-PET was performed at baseline and during radiotherapy (week 3). Primary tumour was delineated using a fixed SUV 2.5 threshold (MTV2.5), relative threshold (MTV40%) and a gradient based segmentation method (PET Edge). PET parameters SUVmax, SUVmean, metabolic tumour volume (MTV) and total lesion glycolysis (TLG) were calculated using different ROI methods. Absolute and relative change (Delta) in PET parameters were correlated to 2-year locoregional recurrence. Strength of correlation was tested using receiver operator characteristic analysis using area under the curve (AUC). Response was categorized using optimal cut-off (OC) values. Correlation and agreement between different ROI methods was determined using Bland-Altman analysis. Results: A significant difference in SUVmean, MTV and TLG values were noted between ROI delineation methods. When measuring relative change at week 3, a greater agreement was seen between PET Edge and MTV2.5 methods with average difference in Delta SUVmax, Delta SUVmean, Delta MTV and Delta TLG of 0.0%, 3.6%, 10.3% and 13.6% respectively. A total of 12 patients (22.2%) experienced locoregional recurrence. Delta MTV using PET Edge was the best predictor of locoregional recurrence (AUC =0.761, 95% CI: 0.573-0.948, P=0.001; OC Delta>50%). The corresponding 2-year locoregional recurrence rate was 7% vs. 35%, P=0.001. Conclusions: Our findings suggest that it is preferable to use gradient based method to assess volumetric tumour response during radiotherapy and offers advantage in predicting treatment outcomes compared with threshold-based methods. This finding requires further validation and can assist in future response-adaptive clinical trials.