Heterogeneity and irregularity of pretreatment ¹⁸F-fluorodeoxyglucose positron emission tomography improved prognostic stratification of p16-negative high-risk squamous cell carcinoma of the oropharynx

Objectives: Human papillomavirus-negative oropharyngeal squamous cell carcinoma (OPSCC) has unfavorable survival outcomes. Two outcomes have been identified based on smoking history and tumor stage. We investigate the prognostic role of pre-treatment positron emission tomography (PET) in high-risk OPSCC. Materials and Methods: We enrolled 147 M0 OPSCC patients with p16-negative staining and a history of heavy smoking (>10 pack-years) or T4 disease. All patients completed primary chemoradiotherapy, and 42% maximum standard uptake values (SUV_max) were used as the threshold for primary tumor. Patients were classified into training and validation cohorts with a ratio of 1:1.5 according to the PET date. Heterogeneity and irregularity indices were obtained. PET parameters with significant impact on progression-free survival (PFS) in receiver operating characteristic curves and univariate Cox models were identified and included in recursive partitioning analysis (RPA) for constructing a prognostic model. The RPA-based prognostic model was further tested in the validation cohort using multivariate Cox models. Results: Fifty-eight and 89 patients were in the training and validation groups, respectively. Heterogeneity parameter, SUV-entropy (derived from histogram analysis), and irregularity index, and asphericity were significantly associated with PFS. The RPA model revealed that patients with both high SUV-entropy and high asphericity experienced the worst PFS. Results were confirmed in the validation group. The overall concordance index for PFS of the model was 0.75, which was higher than the clinical stages, performance status, SUV_max, and metabolic tumor volume of PET. Conclusions: PET prognostic model provided useful prediction of PFS for patients with high-risk OPSCC.