Tumor Asphericity in FDG PET Is an Independent Prognostic Parameter Improving Risk Stratification in Patients with Head and Neck Squamous Cell Carcinoma

Tumor asphericity in ¹⁸F-FDG PET is a prognostic marker that has been investigated in small pilot studies of patients with head and neck squamous cell carcinoma (HNSCC). Here, we investigated the prognostic role of asphericity in a large multicenter database of patients with HNSCC treated with primary radiotherapy or chemoradiation and assessed its independent prognostic value. <b>Methods:</b> In total, 1,104 patients were included in this analysis. All received pretreatment ¹⁸F-FDG PET scans. Clinical risk factors were evaluated, and quantitative PET parameters SUV_max, metabolic tumor volume (MTV), total lesion glycolysis, and asphericity were calculated. Primary study endpoints were overall survival (OS) and locoregional control (LRC). Uni- and multivariate Cox regression analyses were performed. Additionally, asphericity was combined with the best-established quantitative PET parameter of MTV, and the combinatory approach of using asphericity and MTV was compared with the use of only asphericity or MTV by bootstrap analyses. <b>Results:</b> Asphericity showed only a modest correlation with the established PET parameters of MTV, SUV_max, and total lesion glycolysis. On univariate testing asphericity was strongly associated with the outcome of patients (LRC and OS with <i>P</i> < 0.001). In multivariate testing of all imaging parameters that were not highly correlated, both MTV and asphericity showed a significant association with LRC (<i>P</i> < 0.001 for MTV and <i>P</i> = 0.021 for asphericity) and OS (<i>P</i> < 0.001 for MTV and asphericity). Asphericity and MTV were binarized and combined for risk stratification, and the prognostic value of the combination was compared with the prognostic value of individual parameters. Bootstrapping revealed significantly better performance by the combinatory approach when compared with MTV (<i>P</i> = 0.012 for LRC and <i>P</i> < 0.001 for OS) and asphericity with regard to OS (<i>P</i> < 0.001) but not for LRC (<i>P</i> = 0.53). <b>Conclusion:</b> We were able to show that asphericity bears independent prognostic value and significantly improves risk stratification when combined with MTV in a comprehensive retrospective cohort of HNSCC patients.