Intra-Treatment PET/MRI Separates Intermediate Risk p16-Positive Oropharynx Cancer Patients into Favorable and Unfavorable Cohorts

Abstract

Although patients with low risk p16-positive oropharynx squamous cell carcinoma (LR p16+OPSCC) exhibit superior clinical outcomes than patients with p16+OPSCC and intermediate risk factors (T4, >N2b, and > 10 pack-years), there exists overlap in outcomes between the two groups. Metrics to define patients with IR p16+OPSCC that exhibit favorable outcomes remain to be defined. We evaluated the utility of early tumor response to definitive radiotherapy assessed by intra-treatment PET/MRI to define favorable and unfavorable IR p16+OPSCC cohorts. Patients with p16+OPSCC underwent pre-treatment PET/MRI and repeat imaging two weeks into definitive radiotherapy. Changes in volume, metabolic activity, and diffusion of the primary tumor and largest large lymph were evaluated. Standard T-test was used to assess the significance of observed changes. K-means clustering with Euclidean distance function and silhouette width were used to establish clusters. Thirteen patients were prospectively enrolled, 5 low risk and 8 intermediate risk. There was no significant difference in the intra-treatment response within the LR cohort. The IR group clustered into 2 groups. Five IR p16+OPSCC patients exhibited radiographic changes that were similar to the LR cohort and 3 IR patients exhibited changes that were significantly different from the LR cohort and the similarly responding IR cohort. All patients were disease free by PET/MRI at 3 months. We demonstrate the ability of intra-treatment PET/MRI responses to identify patients with IR p16+OPSCC that exhibit similar and dissimilar responses to definitive radiotherapy when compared to patients with LR disease. These data may provide a mechanism to determine in real-time the appropriateness for therapy escalation and de-intensification of IR p16+OPSCC undergoing definitive radiotherapy.