Adaptive Boost Target Definition in High-Risk Head and Neck Cancer Based on Multi-imaging Risk Biomarkers

Positron emission tomography with ¹⁸F-deoxyglucose (FDG), dynamic contrast-enhanced magnetic resonance imaging (MRI), and diffusion-weighted MRI each identify unique risk factors for treatment outcomes in head and neck cancer (HNC). Clinical trials in HNC largely rely on a single imaging modality to define targets for boosting. This study aimed to investigate the spatial correspondence of FDG uptake, perfusion, and the apparent diffusion coefficient (ADC) in HNC and their response to chemoradiation therapy (CRT) and to determine the implications of this overlap or lack thereof for adaptive boosting.

Forty patients with HNC enrolled in a clinical trial underwent FDG positron emission tomography-computed tomography before CRT and underwent dynamic contrast-enhanced and diffusion-weighted MRI scans before and during CRT. The gross tumor volume (GTV) of the primary tumor was contoured on post-gadolinium T1-weighted images. Tumor subvolumes with high FDG uptake, low blood volume (BV), and low ADC were created by using previously established thresholds. Spatial correspondences between subvolumes were analyzed using the Dice coefficient, and those between each pair of image parameters at voxel level were analyzed by Spearman rank correlation coefficients.

Prior to CRT, the median subvolumes of high FDG, low BV, and low ADC relative to the primary GTV were 20%, 21%, and 45%, respectively. Spearman correlation coefficients between BV and ADC varied from -0.47 to 0.22; between BV and FDG, from -0.08 to 0.59; and between ADC and FDG, from -0.68 to 0.25. Dice coefficients between subvolumes of FDG and BV, FDG and ADC, and BV and ADC were 10%, 46%, and 15%, respectively. The union of the 3 parameters was 64% of the GTV. The union of the subvolumes of BV and ADC was 56% of the GTV before CRT but was reduced significantly by 57% after 10 fractions of radiation therapy.

High FDG uptake, low BV, and low ADC as imaging risk biomarkers of HNC identify largely distinct tumor characteristics. A single imaging modality may not define the boosting target adequately.