Metabolic Imaging Biomarkers of Postradiotherapy Xerostomia

Abstract

Purpose Xerostomia is a major complication of head and neck radiotherapy. Available xerostomia measures remain flawed. FDG-PET/CT is routinely used for staging and response assessment of head and neck cancer. We investigated quantitative measurement of parotid gland FDG uptake as a potential biomarker for post-radiotherapy xerostomia. Methods and Materials Ninety-eight locally advanced head and neck cancer patients receiving definitive radiotherapy underwent baseline and post-radiotherapy FDG-PET/CT on a prospective imaging trial. A separate validation cohort of 14 patients underwent identical imaging while prospectively enrolled onto a second trial collecting sialometry and patient-reported outcomes. Radiation dose and pre/post-RT SUVs for all voxels contained within parotid gland regions-of-interest were deformably registered. Results Average whole gland or voxel-by-voxel models incorporating parotid DMet (defined as the pre-treatment parotid SUV weighted by dose) accurately predicted post-treatment changes in parotid FDG uptake (e.g. fractional parotid SUV). Fractional loss of parotid FDG uptake closely paralleled early parotid toxicity defined by post-treatment salivary output (p < 0.01) and RTOG/EORTC xerostomia scores (p < 0.01). Conclusions In this pilot series, loss of parotid FDG uptake strongly associates with acute clinical post-radiotherapy parotid toxicity. DMet may potentially be used to guide function-sparing treatment planning. Prospective validation of FDG-PET/CT as a convenient, quantifiable imaging biomarker of parotid function is warranted and ongoing.

18F-FDG PET image biomarkers improve prediction of late radiation-induced xerostomia

“…Other studies have shown that parotid gland SUVs decrease post-radiotherapy, and in addition that this change was associated with parotid gland dose [37,38]. Cannon et al [38] showed that mean 'SUV-weighted parotid gland dose (voxel-wise)' was significantly related to fractional-SUV (post-SUV/pre-SUV). In an additional small cohort (n = 8), they showed that fractional-SUV was significantly associated with fractional salivary flow and physician-rated xerostomia.…”

Early radiation‐induced changes evaluated by intravoxel incoherent motion in the major salivary glands

“…Similarly, a few studies have recently proposed novel models to quantify or predict normal tissue radiation toxicity using functional information from FDG‐PET , single photon emission computed tomography perfusion , and DCE‐MRI . These studies, that propose new metrics as the metabolic dose, functional dose or bio ‐dose, show an emerging interest toward an innovative approach to RT that integrates into the treatment strategies the individual differences in tumor biology and radiation sensitivity of normal tissues .…”

“…Studies have documented the utility of noninvasive imaging techniques, e.g., scintigraphy, [ 18 F]fluorodeoxyglucose-labeled positron emission tomography (FDG-PET), and ultrasound for quantitatively evaluating the salivary function (7,8). MR sialography, as well as dynamic contrast-enhanced MRI (DCE MRI), and diffusion-weighted imaging (DWI) have also been used to investigate the radiation damage to salivary glands (9)(10)(11)(12)(13)(14)(15).…”

Salivary hypofunction: An update on aetiology, diagnosis and therapeutics

“…In addition, the apoptotic response seen after irradiation was dependent on p53 expression. Cannon et al 149 demonstrated radiotherapy toxicity to the parotid gland by means of fluorodeoxyglucose-labelled positron emission tomography-computed tomography (FDG-PET-CT).…”