Shang-Wen Chen1,2,3, Ying-Chun Lin1,4, Rui-Yun Chen5, Te-Chun Hsieh6,7, Kuo-Yang Yen6,7, Ji-An Liang1,8, Shih-Neng Yang1,7, Yao-Ching Wang1, Ya-Huey Chen9,10, Nan-Haw Chow11, Chia-Hung Kao12,13. 1. Department of Radiation Oncology, China Medical University Hospital, Taichung, Taiwan. 2. School of Medicine, China Medical University, Taichung, Taiwan. 3. School of Medicine, Taipei Medical University, Taipei, Taiwan. 4. The Ph.D. Program for Cancer Biology and Drug Discovery, China Medical University and Academia Sinica, Taichung, Taiwan. 5. Department of Pathology, China Medical University Hospital, Taichung, Taiwan. 6. Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung, Taiwan. 7. Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung, Taiwan. 8. Graduate Institute of Clinical Medical Science, School of Medicine, College of Medicine, China Medical University, No. 2, Yuh-Der Road, Taichung, 40447, Taiwan. 9. Graduate Institute of Cancer Biology, China Medical University, Taichung, Taiwan. 10. Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan. 11. Department of Pathology, National Cheng Kung University, Tainan, Taiwan. 12. Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung, Taiwan. d10040@mail.cmuh.org.tw. 13. 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.
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 (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 iSUVmax 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 SUVmax 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.
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 (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 iSUVmax 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 SUVmax 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.
Entities:
Keywords:
18Fluoro-2-deoxy-D-glucose; Chemoradiotherapy; Head and neck cancer; Hypoxia-inducible factor 1α; Positron emission tomography
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