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Defining Cancer Cachexia in Head and Neck Squamous Cell Carcinoma

Authors' Affiliations: ¹ Doris Duke Clinical Research Fellowship, The Verne S. Caviness General Clinical Research Center, ² Department of Otolaryngology-Head and Neck Surgery, G0412 Neurosciences Hospital, ³ Lineberger Comprehensive Cancer Center, and ⁴ Department of Speech Pathology and Audiology, University of North Carolina School of Medicine; and ⁵ Department of Biostatistics, University of North Carolina School of Public Health, Chapel Hill, North Carolina

Requests for reprints: Carol G. Shores, Department of Otolaryngology-Head and Neck Surgery, University of North Carolina School of Medicine, CB#7070, Chapel Hill, NC 27599-7070. Phone: 919-843-3627; Fax: 919-843-3520; E-mail: shores{at}med.unc.edu.

Purpose: Cancer cachexia is a devastating and understudied illness in patients with head and neck squamous cell carcinoma (HNSCC). The primary objective was to identify clinical characteristics and serum levels of cytokines and cachexia-related factors in patients with HNSCC. The secondary objective was to detect the occurrence of cytokine and cachexia-related factor gene expression in HNSCC tumors.

Experimental Design: For the primary objective, cross-sectional data were obtained from prospectively recruited patients identified as cachexia cases and matching cachexia-free controls. For the secondary objective, a retrospective cohort design with matched controls was used.

Results: Clinical characteristics associated with cancer cachexia in HNSCC were T₄ status (P = 0.01), increased C-reactive protein (P = 0.01), and decreased hemoglobin (P < 0.01). Exploratory multiplex analysis of serum cytokine levels found increased interleukin (IL)-6 (P = 0.04). A highly sensitive ELISA confirmed the multiplex result for increased IL-6 in cachectic patients (P = 0.02). Quality of life was substantially reduced in patients with cachexia compared with noncachectic patients (P < 0.01). All tumors of HNSCC patients both with and without cachexia expressed RNA for each cytokine tested and the cachexia factor lipid-mobilizing factor. There were no statistically significant differences between the cytokine and cachexia factor RNA expression of cachectic and noncachectic patients (each P > 0.05). No tumors expressed the cachexia factor proteolysis-inducing factor.

Conclusion: We have identified clinical characteristics and pathophysiologic mechanisms associated with cancer cachexia in a carefully defined population of patients with HNSCC. The data suggest that the acute-phase response and elevated IL-6 are associated with this complex disease state. We therefore hypothesize that IL-6 may represent an important therapeutic target for HNSCC patients with cancer cachexia.