Apparent Diffusion Coefficient MRI as a Predictive Biomarker for Hypoxia, Treatment De-escalation, and Recurrence in HPV-Associated Oropharyngeal Cancer.
Authors
Affiliations (8)
Affiliations (8)
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY.
- Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY.
- Department of Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, NY.
- Department of Nuclear Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY.
- Department of Head and Neck Surgery, Memorial Sloan Kettering Cancer Center, New York, NY.
- Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY; Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY.
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY. Electronic address: [email protected].
Abstract
To evaluate whether quantitative diffusion-weighted magnetic resonance imaging (DW-MRI) derived apparent diffusion coefficient (ADC) parametric values of nodal disease can identify nodal recurrence (NR) risk and distinguish human papillomavirus-associated oropharyngeal cancer (HPV-OPC) patients 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 HPV-OPC patients who underwent serial MRI scans and pre- and intra-treatment <sup>18</sup>F-FMISO PET hypoxia imaging. Patients with persistent hypoxia (pre- and intra-treatment hypoxia) received standard 70Gy chemoradiation, while those with baseline normoxia or resolved hypoxia received de-escalated 30Gy treatment. All NR occurred in the 30Gy 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. Nodal recurrences exhibited larger intra-treatment volume (weeks 2-4, p<0.05) and mean ADC (weeks 3-4, p<0.05) compared to non-recurrent nodes. Baseline hypoxic tumors were significantly larger than normoxic tumors (p<0.001). Analysis of an expanded panel of quantitative MRI (qMRI) features for prediction of hypoxia-based treatment assignment identified ADC skewness as significantly different between 30Gy and 70Gy arms (p<0.05 pre-treatment and week 1). Machine learning models incorporating multiple qMRI features achieved moderate predictive performance, with week 1 qMRI features performing best (AUC=0.67). Intra-treatment MRI features correlated with NR in de-escalated HPV-OPC patients, while 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.