title: Evaluation of tumour hypoxia during radiotherapy using [18F]HX4 PET imaging and blood biomarkers in patients with head and neck cancer.
abstract: OBJECTIVE
  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 [18F]HX4-PET, hypoxia-related blood biomarkers, and their interdependence.
  
  
  METHODS
  [18F]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 [18F]HX4-PET/CT imaging. For all patients, the plasma concentration of CAIX, osteopontin and VEGF was assessed.
  
  
  RESULTS
  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 cm3during 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.
  
  
  CONCLUSIONS
  [18F]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.
authors.affiliation: Department of Radiation Oncology (MAASTRO), GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastro Clinic, Dr. Tanslaan 12, 6229ET, Maastricht, The Netherlands. karen.zegers@maastro.nl.
authors.forename: Catharina M L
authors.initials: CM
authors.lastname: Zegers
authors.affiliation: Department of Radiation Oncology (MAASTRO), GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastro Clinic, Dr. Tanslaan 12, 6229ET, Maastricht, The Netherlands.
authors.forename: Frank J P
authors.initials: FJ
authors.lastname: Hoebers
authors.affiliation: Department of Radiation Oncology (MAASTRO), GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastro Clinic, Dr. Tanslaan 12, 6229ET, Maastricht, The Netherlands.
authors.forename: Wouter
authors.initials: W
authors.lastname: van Elmpt
authors.affiliation: Central Diagnostic Laboratory, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Judith A
authors.initials: JA
authors.lastname: Bons
authors.affiliation: Department of Radiation Oncology (MAASTRO), GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastro Clinic, Dr. Tanslaan 12, 6229ET, Maastricht, The Netherlands.
authors.forename: Michel C
authors.initials: MC
authors.lastname: Öllers
authors.affiliation: Department of Radiation Oncology (MAASTRO), GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastro Clinic, Dr. Tanslaan 12, 6229ET, Maastricht, The Netherlands.|Helmholtz Zentrum Dresden-Rossendorf, Dresden, Germany.|OncoRay, Department of Radiation Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors.forename: Esther G C
authors.initials: EG
authors.lastname: Troost
authors.affiliation: Department of Radiation Oncology (MAASTRO), GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastro Clinic, Dr. Tanslaan 12, 6229ET, Maastricht, The Netherlands.
authors.forename: Daniëlle
authors.initials: D
authors.lastname: Eekers
authors.affiliation: Department of Radiation Oncology (MAASTRO), GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastro Clinic, Dr. Tanslaan 12, 6229ET, Maastricht, The Netherlands.
authors.forename: Leo
authors.initials: L
authors.lastname: Balmaekers
authors.affiliation: Department of Radiation Oncology (MAASTRO), GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastro Clinic, Dr. Tanslaan 12, 6229ET, Maastricht, The Netherlands.
authors.forename: Marlies
authors.initials: M
authors.lastname: Arts-Pechtold
authors.affiliation: Department of Nuclear Medicine, Maastricht University Medical Centre, Maastricht, The Netherlands.|Department of Nuclear Medicine, RWTH Aachen University, University Hospital, Aachen, Germany.
authors.forename: Felix M
authors.initials: FM
authors.lastname: Mottaghy
authors.affiliation: Department of Radiation Oncology (MAASTRO), GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastro Clinic, Dr. Tanslaan 12, 6229ET, Maastricht, The Netherlands.
authors.forename: Philippe
authors.initials: P
authors.lastname: Lambin
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D005260:Female; D006258:Head and Neck Neoplasms / Q000097:blood / Q000175:diagnosis / Q000532:radiotherapy*; D006801:Humans; D007093:Imidazoles; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016896:Treatment Outcome; D014230:Triazoles; D000072258:Tumor Hypoxia / Q000528:radiation effects*
chemical_list: D014408:Biomarkers, Tumor; C562168:HX4 compound; D007093:Imidazoles; D019275:Radiopharmaceuticals; D014230:Triazoles
keywords: CAIX; Hypoxia; Osteopontin; PET; VEGF