Defining cancer cachexia in head and neck squamous cell carcinoma.
OBJECTIVE
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.


METHODS
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 T(4) 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.


CONCLUSIONS
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.
Richey
Luke M
LM
Doris Duke Clinical Research Fellowship, Verne S. Caviness General Clinical Research Center, and Department of Otolaryngology-Head and Neck Surgery, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
George
Jonathan R
JR
Couch
Marion E
ME
Kanapkey
Brian K
BK
Yin
Xiaoying
X
Cannon
Trinitia
T
Stewart
Paul W
PW
Weissler
Mark C
MC
Shores
Carol G
CG
D000368:Aged; D002100:Cachexia / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000150:complications* / Q000473:pathology; D016207:Cytokines / Q000097:blood / Q000235:genetics / Q000378:metabolism; D005260:Female; D006258:Head and Neck Neoplasms / Q000150:complications* / Q000473:pathology; D006801:Humans; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism
D016207:Cytokines; D015850:Interleukin-6; D012333:RNA, Messenger