Defining Cancer Cachexia in Head and Neck Squamous Cell Carcinoma

Abstract

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 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. 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.

Nutrition impact symptoms: Key determinants of reduced dietary intake, weight loss, and reduced functional capacity of patients with head and neck cancer before treatment

“…1,4,6 The etiology of cancer anorexia is only partially understood, and it has been suggested that cancer anorexia results from the secretion of pro-inflammatory cytokines such as tumor necrosis factor-alpha, interleukin-6 and interleukin-8 acting as anorexigenic agents resulting in reduced dietary intake. [38][39][40] Additionally, disruptions in the signaling pathways of neuropetides such as leptin, ghrelin, and neuropeptide Y are proposed. 39,41 Anorexia is the target for a variety of orexigenic therapies such as dexamethasone and progestational agents.…”

“…The breakdown of the mucosal barrier of the mouth accelerates bacterial growth leading to the production of pro-inflammatory cytokines including tumor necrosis factor-alpha, interleukin-1 and interleukin-6 which in turn may lead to anorexia. 38,47 Similarly, mouth sores resulting from lack of saliva or dental problems, including ill fitting dentures and dental caries, may also influence food choices and eating behaviors. 11,16,35 Ultimately, the consequence of mouth sores increases the risk of weight loss in patients with head and neck cancer.…”

Muscle Atrophy in Response to Cytotoxic Chemotherapy Is Dependent on Intact Glucocorticoid Signaling in Skeletal Muscle

“…Inflammatory cytokines are present at increased levels in cancer patients and are believed to convey the catabolic signal via at least two distinct mechanisms [9], [10]. Cytokines act directly on skeletal myocytes to induce muscle atrophy via the engagement of surface receptors and the activation of NFκB [6], [11].…”

Critical weight loss is a major prognostic indicator for disease-specific survival in patients with head and neck cancer receiving radiotherapy

“…Patients with head and neck cancer are predominantly at risk for malnutrition due to anorexia, sequelae of the treatment that hamper food intake (e.g., xerostomia or dysphagia) and metabolic alterations as a result of inflammation, which can be induced by the tumour or the therapy (Van Cutsem and Arends, 2005; Baracos, 2006; Richey et al , 2007; Silver et al , 2007). Malnutrition is a subacute or chronic state in which a combination of varying degrees of undernutrition and inflammatory activity has led to a change in body composition and diminished function (Soeters et al , 2008).…”