18FDG positron emission tomography mining for metabolic imaging biomarkers of radiation-induced xerostomia in patients with oropharyngeal cancer

Abstract

Head and neck cancers radiotherapy (RT) is associated with inevitable injury to parotid glands and subsequent xerostomia. We investigated the utility of SUV derived from 18 FDG-PET to develop metabolic imaging biomarkers (MIBs) of RT-related parotid injury. Methods: Data for oropharyngeal cancer (OPC) patients treated with RT at our institution between 2005 and 2015 with available planning computed tomography (CT), dose grid, pre-& first post-RT 18 FDG-PET-CT scans, and physician-reported xerostomia assessment at 3-6 months post-RT (Xero 3-6 ms) per CTCAE, was retrieved, following an IRB approval. A CT-CT deformable image co-registration followed by voxel-by-voxel resampling of pre & post-RT 18 FDG activity and dose grid were performed. Ipsilateral (Ipsi) and contralateral (contra) parotid glands were sub-segmented based on the received dose in 5 Gy increments, i.e. 0-5 Gy, 5-10 Gy sub-volumes, etc. Median and dose-weighted SUV were extracted from whole parotid volumes and sub-volumes on pre-& post-RT PET scans, using in-house code that runs on MATLAB. Wilcoxon signed-rank and Kruskal-Wallis tests were used to test differences pre-and post-RT. Results: 432 parotid glands, belonging to 108 OPC patients treated with RT, were sub-segmented & analyzed. Xero 3-6 ms was reported as: non-severe (78.7%) and severe (21.3%). SUV-median values were significantly reduced post-RT, irrespective of laterality (p = 0.02). A similar pattern was observed in parotid sub-volumes, especially ipsi parotid gland sub-volumes receiving doses 10-50 Gy (p < 0.05). Kruskal-Wallis test showed a significantly higher mean RT dose in the contra parotid in the patients with more severe Xero 3-6mo (p = 0.03).

Magnetic resonance biomarkers for timely diagnostic of radiation dose-rate effects

“…The prerequisites for effective markers to guide the course of therapy are: (i) yield responses on short time scales, ideally within few hours, (ii) be non-invasive, (iii) be translatable between bench and bedside to allow continuous research input for the clinic, and (iv) enable personalized treatment, being able toreflect individual metabolism. Molecular biomarkers for imaging radiotherapy effects can be rapid and non-invasive indicators of radiobiological effects in the targeted tumor and surrounding organs [4]. Endogenous magnetic resonance biomarkers are immediately translatable between in-vitro and in-vivo settings.…”

Biopsy-derived oral keratinocytes – A model to potentially test for oral mucosa radiation sensitivity

“…An accurate prediction of the radiation response of normal tissue would allow one to adapt treatment options. As yet no clinical biomarker for radiation mucositis is available [4] . One reason for the lack of biomarkers or adequate bioassays for mucosal tissue is that biomarkers or bioassays have mainly been tested in blood, but not in the target tissue where side effects occur.…”

“…In addition, oral mucosa is a mainly 2-dimensional tissue that can not be assessed by metabolic imaging in a way like other tissues at risk for radiation damage, e.g. salivary glands [4] . Therefore, acquisition of oral keratinocytes from individual patients where radiation response and additional cellular properties can be identified could help to better understand the pathophysiology of radiation-associated toxicity, and guide personalized treatment.…”