title: Correlation of pretreatment18F-FDG PET tumor textural features with gene expression in pharyngeal cancer and implications for radiotherapy-based treatment outcomes.
abstract: OBJECTIVE
  This study investigated the correlation of the matrix heterogeneity of tumors on18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) with gene-expression profiling in patients with pharyngeal cancer and determined the prognostic factors for radiotherapy-based treatment outcomes.
  
  
  METHODS
  We retrospectively reviewed the records of 57 patients with stage III-IV oropharyngeal or hypopharyngeal cancer who had completed definitive therapy. Four groups of the textural features as well as 31 indices were studied in addition to maximum standard uptake value, metastatic tumor volume, and total lesion glycolysis. Immunohistochemical data from pretreatment biopsy specimens (Glut1, CAIX, VEGF, HIF-1α, EGFR, Ki-67, Bcl-2, CLAUDIN-4, YAP-1, c-Met, and p16) were analyzed. The relationships between the indices and genomic expression were studied, and the robustness of various textural features relative to cause-specific survival and primary relapse-free survival was analyzed.
  
  
  RESULTS
  The overexpression of VEGF was positively associated with the increased values of the matrix heterogeneity obtained using gray-level nonuniformity for zone (GLNUz) and run-length nonuniformity (RLNU). Advanced T stage (p = 0.01, hazard ratio [HR] = 3.38), a VEGF immunoreactive score of >2 (p = 0.03, HR = 2.79), and a higher GLNUz value (p = 0.04, HR = 2.51) were prognostic factors for low cause-specific survival, whereas advanced T stage, a HIF-1α staining percentage of ≥80%, and a higher GLNUz value were prognostic factors for low primary-relapse free survival.
  
  
  CONCLUSIONS
  The overexpression of VEGF was associated with the increased matrix index of GLNUz and RLNU. For patients with pharyngeal cancer requiring radiotherapy, the treatment outcome can be stratified according to the textural features, T stage, and biomarkers.
authors.affiliation: 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.|Graduate Institute of Clinical Medical Science, School of Medicine, College of Medicine, China Medical University, No. 2, Yuh-Der Road, Taichung, 40447, Taiwan.
authors.forename: Shang-Wen
authors.initials: SW
authors.lastname: Chen
authors.affiliation: Cancer Center and Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan.|Department of Computer Science and Information Engineering, Asia University, Taichung, Taiwan.
authors.forename: Wei-Chih
authors.initials: WC
authors.lastname: Shen
authors.affiliation: 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.
authors.forename: Ying-Chun
authors.initials: YC
authors.lastname: Lin
authors.affiliation: Department of Pathology, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Rui-Yun
authors.initials: RY
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Te-Chun
authors.initials: TC
authors.lastname: Hsieh
authors.affiliation: 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.
authors.forename: Kuo-Yang
authors.initials: KY
authors.lastname: Yen
authors.affiliation: 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.|Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung, Taiwan. d10040@mail.cmuh.org.tw.|Department of Bioinformatics and Medical Engineering, Asia University, Taichung, Taiwan. d10040@mail.cmuh.org.tw.
authors.forename: Chia-Hung
authors.initials: CH
authors.lastname: Kao
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D010610:Pharyngeal Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy; D000072078:Positron Emission Tomography Computed Tomography; D019275:Radiopharmaceuticals; D011880:Radiotherapy Planning, Computer-Assisted; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D019275:Radiopharmaceuticals; D042461:Vascular Endothelial Growth Factor A; D019788:Fluorodeoxyglucose F18
keywords: 18F-fluorodeoxyglucose positron emission; Genomic expression; Head and neck cancer; Textural analysis