DOI: 10.1007/s00259-016-3580-5Pages: 567-580

Correlation of pretreatment 18F-FDG PET tumor textural features with gene expression in pharyngeal cancer and implications for radiotherapy-based treatment outcomes

1. China Medical University Hospital, Department of Radiation Oncology

2. China Medical University, School of Medicine

3. Taipei Medical University, School of Medicine

4. China Medical University, Graduate Institute of Clinical Medical Science, School of Medicine, College of Medicine

5. China Medical University, Cancer Center and Department of Medical Research, China Medical University Hospital

6. Asia University, Department of Computer Science and Information Engineering

7. China Medical University and Academia Sinica, The Ph.D. Program for Cancer Biology and Drug Discovery

8. China Medical University Hospital, Department of Pathology

9. China Medical University Hospital, Department of Nuclear Medicine and PET Center

10. China Medical University, Department of Biomedical Imaging and Radiological Science

11. Asia University, Department of Bioinformatics and Medical Engineering

Correspondence to:
Chia-Hung Kao
Tel: +886-4-2205-2121




This study investigated the correlation of the matrix heterogeneity of tumors on 18F-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.


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.


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.


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.

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  • Accepted: Nov 18, 2016
  • Online: Dec 20, 2016

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