Immunohistochemical biomarkers and volumetric parameters for predicting radiotherapy-based outcomes in patients with p16-negative pharyngeal cancer

// Rui-Yun Chen 1, * , Ying-Chun Lin 2, 3, * , Shang-Wen Chen 2, 4, 5, 6 , Tze-Yi Lin 1 , Te-Chun Hsieh 7, 8 , Kuo-Yang Yen 7, 8 , Ji-An Liang 2, 6 , Shih-Neng Yang 2, 8 , Yao-Ching Wang 2 , Ya-Huey Chen 9, 10 , Shu-Fen Chiang 11 and Chia-Hung Kao 6, 7, 12 1 Department of Pathology, China Medical University Hospital, Taichung, Taiwan 2 Department of Radiation Oncology, China Medical University Hospital, Taichung, Taiwan 3 The Ph.D. Program for Cancer Biology and Drug Discovery, China Medical University and Academia Sinica, Taichung, Taiwan 4 School of Medicine, China Medical University, Taichung, Taiwan 5 School of Medicine, Taipei Medical University, Taipei, Taiwan 6 Graduate Institute of Clinical Medical Science, School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan 7 Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung, Taiwan 8 Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung, Taiwan 9 Graduate Institute of Cancer Biology, China Medical University, Taichung, Taiwan 10 Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan 11 Cancer Center, China Medical University Hospital, Taichung, Taiwan 12 Department of Bioinformatics and Medical Engineering, Asia University, Taichung, Taiwan * Authors contributed equally to this work Correspondence to: Chia-Hung Kao, email: d10040@mail.cmuh.org.tw Shang-Wen Chen, email: D4634@mail.cmuh.org.tw Keywords: squamous cell carcinoma, p16-negative pharyngeal cancer, biomarker, positron emission tomography–computed tomography, gross tumor volume Received: May 07, 2017      Accepted: August 07, 2017      Published: August 21, 2017 ABSTRACT Background: This study determined the prognostic effects of immunohistochemical biomarkers and volumetric parameters predicting radiotherapy-based treatment in patients with p16-negative squamous cell carcinoma of the oropharynx or hypopharynx. Results: VEGF immunoreactivity > 2 and GLUT1 overexpression were prognostic factors for lower cause-specific survival. Moreover, both factors were associated with lower disease-free survival. The predictors of lower primary relapse-free survival were VEGF immunoreactivity > 2 and CT-based gross tumor volume > 16 mL. Materials and Methods: Immunohistochemical biomarkers in pretreatment biopsy specimens from 60 patients with p16-negative cancer were analyzed using tissue microarrays. Computed tomography (CT)-based and biological tumor volumes were retrieved through fluorodeoxyglucose positron emission tomography-CT. Correlations of cause-specific, disease-free, and primary relapse-free survival with volumetric parameters and the immunohistochemical biomarker score were investigated. Conclusions: For patients with p16-negative pharyngeal cancer receiving radiotherapy, treatment outcomes can be stratified by VEGF and GLUT1 expression and CT-based gross tumor volume.