Immunohistochemical overexpression of hypoxia-induced factor 1α associated with slow reduction in18fluoro-2-deoxy-D-glucose uptake for chemoradiotherapy in patients with pharyngeal cancer.
BACKGROUND
This study examined genomic factors associated with a reduction in18fluoro-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 (SUVmax) of the interim PET-CT and the reduction ratio of the SUVmax(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 iSUVmaxof 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.


CONCLUSIONS
In patients with pharyngeal cancer requiring CRT, HIF1A overexpression was positively associated with high interim SUVmaxor 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.
Department of Radiation Oncology, China Medical University Hospital, Taichung, Taiwan.|School of Medicine, China Medical University, Taichung, Taiwan.|School of Medicine, Taipei Medical University, Taipei, Taiwan.
Shang-Wen
SW
Chen
Department of Radiation Oncology, China Medical University Hospital, Taichung, Taiwan.|The Ph.D. Program for Cancer Biology and Drug Discovery, China Medical University and Academia Sinica, Taichung, Taiwan.
Ying-Chun
YC
Lin
Department of Pathology, China Medical University Hospital, Taichung, Taiwan.
Rui-Yun
RY
Chen
Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung, Taiwan.|Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung, Taiwan.
Te-Chun
TC
Hsieh
Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung, Taiwan.|Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung, Taiwan.
Kuo-Yang
KY
Yen
Department of Radiation Oncology, China Medical University Hospital, Taichung, Taiwan.|Graduate Institute of Clinical Medical Science, School of Medicine, College of Medicine, China Medical University, No. 2, Yuh-Der Road, Taichung, 40447, Taiwan.
Ji-An
JA
Liang
Department of Radiation Oncology, China Medical University Hospital, Taichung, Taiwan.|Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung, Taiwan.
Shih-Neng
SN
Yang
Department of Radiation Oncology, China Medical University Hospital, Taichung, Taiwan.
Yao-Ching
YC
Wang
Graduate Institute of Cancer Biology, China Medical University, Taichung, Taiwan.|Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan.
Ya-Huey
YH
Chen
Department of Pathology, National Cheng Kung University, Tainan, Taiwan.
Nan-Haw
NH
Chow
Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung, Taiwan. d10040@mail.cmuh.org.tw.|Graduate Institute of Clinical Medical Science, School of Medicine, College of Medicine, China Medical University, No. 2, Yuh-Der Road, Taichung, 40447, Taiwan. d10040@mail.cmuh.org.tw.
Chia-Hung
CH
Kao
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009367:Neoplasm Staging; D010610:Pharyngeal Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology*; D000072078:Positron Emission Tomography Computed Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D015854:Up-Regulation
D014408:Biomarkers, Tumor; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18
18Fluoro-2-deoxy-D-glucose; Chemoradiotherapy; Head and neck cancer; Hypoxia-inducible factor 1α; Positron emission tomography