Evaluation of tumour hypoxia during radiotherapy using [F-18]HX4 PET imaging and blood biomarkers in patients with head and neck cancer

Increased tumour hypoxia is associated with a worse overall survival in patients with head and neck squamous cell carcinoma (HNSCC). The aims of this study were to evaluate treatment-associated changes in [F-18]HX4-PET, hypoxia-related blood biomarkers, and their interdependence. [F-18]HX4-PET/CT scans of 20 patients with HNSCC were acquired at baseline and after +/- 20Gy of radiotherapy. Within the gross-tumour-volumes (GTV; primary and lymph nodes), mean and maximum standardized uptake values, the hypoxic fraction (HF) and volume (HV) were calculated. Also, the changes in spatial uptake pattern were evaluated using [F-18]HX4-PET/CT imaging. For all patients, the plasma concentration of CAIX, osteopontin and VEGF was assessed. At baseline, tumour hypoxia was detected in 69 % (22/32) of the GTVs. During therapy, we observed a significant decrease in all image parameters. The HF decreased from 21.7 +/- 19.8 % (baseline) to 3.6 +/- 10.0 % (during treatment; P <0.001). Only two patients had a HV > 1 cm(3) during treatment, which was located for > 98 % within the baseline HV. During treatment, no significant changes in plasma CAIX or VEGF were observed, while osteopontin was increased. [F-18]HX4-PET/CT imaging allows monitoring changes in hypoxia during (chemo)radiotherapy whereas the blood biomarkers were not able to detect a treatment-associated decrease in hypoxia.