Prognostic value of tissue necrosis, hypoxia-related markers and correlation with HPV status in head and neck cancer patients treated with bio- or chemo-radiotherapy

• Published in: Radiotherapy and oncology Vol. 126; no. 1; pp. 116 - 124
• Main Authors: Ou, Dan, Garberis, Ingrid, Adam, Julien, Blanchard, Pierre, Nguyen, France, Levy, Antonin, Casiraghi, Odile, Gorphe, Philippe, Breuskin, Ingrid, Janot, François, Temam, Stephane, Scoazec, Jean-Yves, Deutsch, Eric, Tao, Yungan
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.01.2018; Elsevier
• Subjects: Aged; Antigens, Neoplasm - biosynthesis; Biomarkers, Tumor - biosynthesis; CA-IX; Cancer; Carbonic Anhydrase IX - biosynthesis; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Carcinoma, Squamous Cell - therapy; Carcinoma, Squamous Cell - virology; CD34; Cell Hypoxia - physiology; Cetuximab - administration & dosage; Chemoradiotherapy; Cisplatin - administration & dosage; Female; Head and Neck Neoplasms - metabolism; Head and Neck Neoplasms - pathology; Head and Neck Neoplasms - therapy; Head and Neck Neoplasms - virology; Head-and-neck squamous cell carcinoma; Human papillomavirus; Humans; Life Sciences; Male; Middle Aged; Necrosis; Papillomaviridae - physiology; Papillomavirus Infections - metabolism; Papillomavirus Infections - pathology; Prognosis; Squamous Cell Carcinoma of Head and Neck; Treatment Outcome; Head-and-neck squamous cell carcinoma; CA-IX; Human papillomavirus; CD34; Necrosis
• ISSN: 0167-8140; 1879-0887
• DOI: 10.1016/j.radonc.2017.10.007

The aim of the present study was to investigate the role of three hypoxia-related biomarkers in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) treated with concurrent chemoradiotherapy (3-weekly cisplatin) or bioradiotherapy (weekly cetuximab). In tumor tissue material from 100 patients with known HPV status, we evaluated the extent of tumor necrosis, the expression level of CA-IX and the microvascular density (MVD) measured as the density of CD34+ vascular structures. The correlations between biomarker expressions and clinicopathological characteristics and treatment outcomes were analyzed. We found a significant correlation of MVD with UICC stage (p = 0.02) and T classification (p = 0.05), of CA-IX with UICC stage (p = 0.03) and N classification (p = 0.04) and a significant inverse correlation of MVD with CA-IX expression (r = −0.22, p = 0.03). Multivariate analysis showed that low MVD combined with high CA IX-expression was a significant independent prognostic factor for worse loco-regional control (HR = 2.6, 95%CI 1.1–5.0, p = 0.02) in the whole population but not in the p16+ subgroup. Patients treated with CRT had a better LRC than those with BRT independent of MVD or CA-IX expression. The combination of MVD and CA-IX expression might give additional prognostic information in HNSCC patients with known HPV status.