Apparent Diffusion Coefficient Magnetic Resonance Imaging as a Predictive Biomarker for Hypoxia, Treatment De-escalation, and Recurrence in Human Papillomavirus-Associated Oropharyngeal Cancer.

Abstract

To evaluate whether quantitative diffusion-weighted magnetic resonance imaging derived apparent diffusion coefficient (ADC) parametric values of nodal disease can identify nodal recurrence (NR) risk and distinguish patients with human papillomavirus-associated oropharyngeal cancer (HPV-OPC) suitable for radiation de-escalation following primary tumor resection. This secondary analysis of a prospective hypoxia-guided radiation de-escalation trial included 94 of 158 patients with HPV-OPC who underwent serial magnetic resonance imaging (MRI) scans and pre- and intratreatment ¹⁸F-fluoromisonidazole positron emission tomography hypoxia imaging. Patients with persistent hypoxia (pre- and intratreatment hypoxia) received standard 70 Gy chemoradiation, whereas those with baseline normoxia or resolved hypoxia received de-escalated 30 Gy treatment. All NR occurred in the 30 Gy arm. Nodal volume, mean ADC, and distribution parameters were quantified and correlated with hypoxia status and clinical outcomes. Random forest modeling assessed multiparametric MRI features for predicting treatment assignment. NRs exhibited larger intratreatment volume (weeks 2-4, P < .05) and mean ADC (weeks 3-4, P < .05) compared with nonrecurrent nodes. Baseline hypoxic tumors were significantly larger than normoxic tumors (P < .001). Analysis of an expanded panel of quantitative MRI (qMRI) features for prediction of hypoxia-based treatment assignment identified ADC skewness as significantly different between 30 Gy and 70 Gy arms (P < .05 pretreatment and week 1). Machine learning models incorporating multiple qMRI features achieved moderate predictive performance, with week 1 qMRI features performing best (area under the curve = 0.67). Intratreatment MRI features correlated with NR in patients with de-escalated HPV-OPC, whereas ADC skewness corresponded with hypoxia-based treatment assignment. These widely available and contrast-free imaging biomarkers warrant further exploration for guiding safe treatment adaptation in precision radiotherapy.