Immunohistochemical overexpression of hypoxia-induced factor 1α associated with slow reduction in 18fluoro-2-deoxy-D-glucose uptake for chemoradiotherapy in patients with pharyngeal cancer

Abstract

Background: This study examined genomic factors associated with a reduction in ¹⁸fluoro-2-deoxy-D-glucose (FDG) uptake during positron emission tomography-computed tomography (PET-CT) for definitive chemoradiotherapy (CRT) in patients with pharyngeal cancer.

Methods: The pretreatment and interim PET-CT images of 25 patients with advanced pharyngeal cancers receiving definitive CRT were prospectively evaluated. The maximum standardized uptake value (SUV_max) of the interim PET-CT and the reduction ratio of the SUV_max (SRR) between the two images were measured. Genomic data from pretreatment incisional biopsy specimens (SLC2A1, CAIX, VEGF, HIF1A, BCL2, Claudin-4, YAP1, MET, MKI67, and EGFR) were analyzed using tissue microarrays. Differences in FDG uptake and SRRs between tumors with low and high gene expression were examined using the Mann-Whitney test. Cox regression analysis was performed to examine the effects of variables on local control.

Results: The SRR of the primary tumors (SRR-P) was 0.59 ± 0.31, whereas the SRR of metastatic lymph nodes (SRR-N) was 0.54 ± 0.32. Overexpression of HIF1A was associated with a high iSUV_max of the primary tumor (P < 0.001) and neck lymph node (P = 0.04) and a low SRR-P (P = 0.02). Multivariate analysis revealed that patients who had tumors with low SRR-P or high HIF1A expression levels showed inferior local control.

Conclusion: In patients with pharyngeal cancer requiring CRT, HIF1A overexpression was positively associated with high interim SUV_max or a slow reduction in FDG uptake. Prospective trials are needed to determine whether the local control rate can be stratified using the HIF1A level as a biomarker and SRR-P.

Keywords: 18Fluoro-2-deoxy-D-glucose; Chemoradiotherapy; Head and neck cancer; Hypoxia-inducible factor 1α; Positron emission tomography.