A prospective clinical study of 18 F-FAZA PET-CT hypoxia imaging in head and neck squamous cell carcinoma before and during radiation therapy
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Hypoxia in head and neck squamous cell carcinoma (HNSCC) is associated with poor prognosis and outcome. 18 F-Fluoroazomycin arabinoside (FAZA) is a positron emission tomography (PET) tracer developed to enable identification of hypoxic regions within tumor. The aim of this study was to evaluate the use of 18 F-FAZA-PET for assessment of hypoxia before and during radiation therapy.
Twelve patients with locally advanced HNSCC underwent 18 F-FAZA-PET scans before and at fraction 7 and 17 of concomitant chemo-radiotherapy. A hypoxic voxel was defined as a voxel expressing a standardized uptake value (SUV) equal or above the SUVmean of the posterior contralateral neck muscles plus three standard deviations. The fractional hypoxic volume fraction (FHV) and the spatial move of hypoxic volumes during treatment were analyzed.
A hypoxic volume could be identified in ten patients before treatment. FAZA-PET FHV varied from 0 to 54.3 % and from 0 to 41.4 % in the primary tumor and in the involved node, respectively. Six out of these ten patients completed all the FAZA-PET-computed tomography (CT) during the radiotherapy. In all patients, FHV and SUVmax values decreased. All patient presented a spatial move of hypoxic volume, but only three patients had newborn hypoxic voxels after 17 fractions.
This study indicated that 18 F-FAZA-PET could be used to identify and quantify tumor hypoxia before and during concomitant radio-chemotherapy in patients with locally advanced HNSCC. In addition to the information on prognostic value, the use of 18 F-FAZA-PET allowed the delineation of hypoxic volumes for dose escalation protocols. However, due to fluctuation of hypoxia during treatment, repeated scan will have to be performed (i.e. adaptive radiotherapy).
KeywordsPositron emission tomography (PET) 18F FAZA Hypoxia imaging Head and neck squamous cell carcinoma Radiotherapy
Conflict of interest
The authors declare that they have no conflict of interest.
- 2.Koukourakis MI, Bentzen SM, Giatromanolaki A, Wilson GD, Daley FM, Saunders MI, et al. Endogenous markers of two separate hypoxia response pathways (hypoxia inducible factor 2 alpha and carbonic anhydrase 9) are associated with radiotherapy failure in head and neck cancer patients recruited in the CHART randomized trial. J Clin Oncol. 2006;24(5):727–35.PubMedCrossRefGoogle Scholar
- 5.Lee DJ, Pajak TF, Stetz J, Order SE, Weissberg JB, Fischer JJ. A phase I/II study of the hypoxic cell sensitizer misonidazole as an adjunct to high fractional dose radiotherapy in patients with unresectable squamous cell carcinoma of the head and neck: a RTOG randomized study (#79-04). Int J Radiat Oncol, Biol, Phys. 1989;16(2):465–70.CrossRefGoogle Scholar
- 6.Villar A, Martinez JC, de Serdio JL. Chemoradiation for advanced head and neck cancer: potential for improving results to match those of current treatment modalities for early-stage tumors–long-term results of hyperfractionated chemoradiation with carbogen breathing and anemia correction with erythropoietin. Int J Radiat Oncol, Biol, Phys. 2008;70(5):1382–8.CrossRefGoogle Scholar
- 12.Busk M, Horsman MR, Jakobsen S, Keiding S, van der Kogel AJ, Bussink J, et al. Imaging hypoxia in xenografted and murine tumors with 18F-fluoroazomycin arabinoside: a comparative study involving microPET, autoradiography, PO2-polarography, and fluorescence microscopy. Int J Radiat Oncol, Biol, Phys. 2008;70(4):1202–12.CrossRefGoogle Scholar
- 24.Clausen MM, Hansen AE, Af Rosenschold PM, Kjaer A, Kristensen AT, McEvoy FJ, et al. Dose escalation to high-risk sub-volumes based on non-invasive imaging of hypoxia and glycolytic activity in canine solid tumors: a feasibility study. Radiat Oncol. 2013;8:262.PubMedCentralPubMedCrossRefGoogle Scholar
- 29.EudraLex TRGMPitEU. Good Manufacturing Practice Medicinal Products for Human and Veterinary Use. Volume 4; Annex 3 Manufacture of Radiopharmaceuticals.Google Scholar
- 35.Grosu AL, Souvatzoglou M, Roper B, Dobritz M, Wiedenmann N, Jacob V, et al. Hypoxia imaging with FAZA-PET and theoretical considerations with regard to dose painting for individualization of radiotherapy in patients with head and neck cancer. Int J Radiat Oncol, Biol, Phys. 2007;69(2):541–51.CrossRefGoogle Scholar
- 38.Gagel B, Piroth M, Pinkawa M, Reinartz P, Zimny M, Kaiser HJ, et al. pO polarography, contrast enhanced color duplex sonography (CDS), [18 F] fluoromisonidazole and [18 F] fluorodeoxyglucose positron emission tomography: validated methods for the evaluation of therapy-relevant tumor oxygenation or only bricks in the puzzle of tumor hypoxia? BMC Cancer. 2007;7:113.PubMedCentralPubMedCrossRefGoogle Scholar
- 39.Gagel B, Reinartz P, Dimartino E, Zimny M, Pinkawa M, Maneschi P, et al. pO(2) Polarography versus positron emission tomography ([(18)F] fluoromisonidazole, [(18)F]-2-fluoro-2'-deoxyglucose). An appraisal of radiotherapeutically relevant hypoxia. Strahlenther Onkol. 2004;180(10):616–22.PubMedCrossRefGoogle Scholar