Radiomics Predicts for Distant Metastasis in Locally Advanced Human Papillomavirus-Positive Oropharyngeal Squamous Cell Carcinoma

SIMPLE SUMMARY: There is strong evidence that locally advanced human papillomavirus positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) carries a significantly better prognosis than HPV negative OPSCC, suggesting the possibility of treatment de-escalation and, therefore, toxicity reduction in this patient population. The lack of success in clinical trials towards this end presses the need to risk stratify locally advanced HPV+ OPSCC patients who can safely have treatment de-escalated. The present study had recourse to radiomics for this purpose and showed that radiomics has the ability to discriminate patients with locally advanced HPV+ OPSCC who went on to develop distant metastasis after completion of definitive chemoradiation or radiation alone. The implications of this study aid in demonstrating the potential pivotal role of radiomics in predictive risk assessment and personalizing therapy for this patient population. ABSTRACT: (1) Background and purpose: clinical trials have unsuccessfully tried to de-escalate treatment in locally advanced human papillomavirus positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) with the goal of reducing treatment toxicity. The aim of this study was to explore the role of radiomics for risk stratification in this patient population to guide treatment. (2) Methods: the study population consisted of 225 patients with locally advanced HPV+ OPSCC treated with curative-intent radiation or chemoradiation therapy. Appearance of distant metastasis was used as the endpoint event. Radiomics data were extracted from the gross tumor volumes (GTVs) identified on the planning CT, with gray level being discretized using three different bin widths (8, 16, and 32). The data extracted for the groups with and without distant metastasis were subsequently balanced using three different algorithms including synthetic minority over-sampling technique (SMOTE), adaptive synthetic sampling (ADASYN), and borderline SMOTE. From these different combinations, a total of nine radiomics datasets were derived. Top features that minimized redundancy while maximizing relevance to the endpoint were selected individually and collectively for the nine radiomics datasets to build support vector machine (SVM) based predictive classifiers. Performance of the developed classifiers was evaluated by receiver operating characteristic (ROC) curve analysis. (3) Results: of the 225 locally advanced HPV+ OPSCC patients being studied, 9.3% had developed distant metastases at last follow-up. SVM classifiers built for the nine radiomics dataset using either their own respective top features or the top consensus ones were all able to differentiate the two cohorts at a level of excellence or beyond, with ROC area under curve (AUC) ranging from 0.84 to 0.95 (median = 0.90). ROC comparisons further revealed that the majority of the built classifiers did not distinguish the two cohorts significantly better than each other. (4) Conclusions: radiomics demonstrated discriminative ability in distinguishing patients with locally advanced HPV+ OPSCC who went on to develop distant metastasis after completion of definitive chemoradiation or radiation alone and may serve to risk stratify this patient population with the purpose of guiding the appropriate therapy.