Cancer cachexia syndrome in head and neck cancer patients: Part I. Diagnosis, impact on quality of life and survival, and treatment

Couch, Marion E.; Lai, Victor; Cannon, Trinitia; Guttridge, Denis C.; Zanation, Adam M.; George, Julia D.; Hayes, D. Neil; Zeisel, Steven H.; Shores, Carol G.

doi:10.1002/hed.20447

Cited by 131 publications

(129 citation statements)

References 59 publications

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“…Historically, high-risk patients would have a percutaneous endoscopic gastrostomy (PEG) placed prior to starting treatment in order to prevent decreased caloric intake, but more recently there has been movement away from using feeding tubes due to concerns about delayed recovery of swallowing post-CTRT [18][19][20]. Interestingly, the placement of a PEG, or increased caloric intake alone, does not alleviate all the weight loss experienced during CTRT [12,19,21].…”

Section: Main Textmentioning

confidence: 99%

“…However, decreased caloric intake is probably only partially responsible for sarcopenia and simply increasing calories may not address loss of muscle mass. In a review of sarcopenia and cachexia in patients with all stages of HNSCC, Couch and colleagues describe the dysregulated metabolism and the resulting sarcopenia seen in patients with HNSCC, suggesting that nutrition alone is not enough to counteract the impact of body composition [21]. In spite of this, numerous studies have tried to optimize nutritional support in patients undergoing CTRT.…”

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confidence: 99%

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A review of weight loss and sarcopenia in patients with head and neck cancer treated with chemoradiation

2016

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Background: Concurrent chemotherapy and radiation (CTRT) improves disease-free survival in locally advanced head and neck cancer but is associated with numerous acute and chronic toxicities resulting in substantial alterations in body mass and composition. We aim to summarize the current evidence on body composition changes experienced by patients undergoing CTRT, examine the impact of these changes on clinical outcomes and address potential interventions aimed at mitigating the loss. Main Body: Loss of 20 % of pre-CTRT weight predicts poorer treatment tolerance and 30-day mortality. While clinical practice focuses on body weight, emerging data indicates that CTRT causes profound adverse changes in lean body mass (sarcopenia). Higher prevalence of sarcopenia predicts poorer disease-free survival as well as overall survival, lower quality of life and functional performance. The magnitude of CTRT-induced sarcopenia is the equivalent to that observed in a decade of aging in a healthy adult. Alterations in body composition are only explained, in part, by decreased caloric intake; other significant predictors include body mass index, stage, and dysphagia. Lifestyle interventions aimed at preventing loss of whole-body and especially lean mass include nutritional counseling, nutritional supplements, dietary supplements and exercise training. Personalized nutritional counseling has been associated with improvement in quality of life, while the benefits of feeding tube placement are inconsistent. There are inconsistently reported benefits of resistance training in this population. Conclusion: Patients with head and neck cancer undergoing CTRT therapy experience dramatic shifts in body composition, including sarcopenia, which can negatively impact clinical outcomes. Efforts to understand the magnitude, clinical importance and mechanisms of sarcopenia are needed to inform a more personalized approach to mitigating the body composition changes associated with CTRT.

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confidence: 99%

Section: Main Textmentioning

confidence: 99%

A review of weight loss and sarcopenia in patients with head and neck cancer treated with chemoradiation

2016

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“…Cachexia is seen in as many as 80% of patients with advanced malignancy and, rather than tumor burden, accounts for an estimated 20 to 30% of all cancer related deaths [30,37,65]. Tumor-induced wasting also lowers patient response to chemotherapy, corresponding to a poorer prognosis and quality of life [20]. Despite the clinical significance of the problem, effective therapies targeting skeletal muscle loss in cancer cachexia are not currently available.…”

Section: Introductionmentioning

confidence: 99%

Selective Inhibition of NF-kappa-B with NBD Peptide Reduces Tumor- Induced Wasting in a Murine Model of Cancer Cachexia In vivo

Wysong¹,

Asher

Yin

et al. 2011

JCST

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Cancer cachexia is a severe wasting syndrome characterized by the progressive loss of lean body mass and systemic inflammation, which is seen in as many as 80% of patients with advanced malignancy. It accounts for an estimated 20-30% of all cancer-related deaths. The mechanism by which cancer induces skeletal muscle atrophy in cachexia involves tumor-derived cytokines, including TNFα, IL-1, and IL-6. Upon interaction with their unique receptors on skeletal muscle, these cytokines activate NF-kappaB, a transcription factor crucial for atrophy related sarcomere proteolysis to occur. The significance of NF-κB is highlighted in studies demonstrating that genetic inhibition of NF-κB ameliorates cancer-induced muscle loss in vivo. In the present study, we evaluate a selective NF-kappaB inhibitor (NBD peptide) which targets the IkappaB complex to prevent cancer-induced skeletal muscle atrophy in an established mouse model (C26 adenocarcinoma). We identified for the first time that NBD peptide can directly inhibit tumor-induced NFkappaB activation in skeletal muscle, resulting in a decrease loss of lean muscle. We also identified that NBD peptide reduces the expression of the tumor induced ubiquitin ligases MuRF-1 and MAFbx/Atrogin-1 necessary for atrophy. These findings highlight that NBD peptide may be a potential selective therapeutic agent for the treatment of cancer cachexia.

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“…An important distinction between starvation and cachexia is that the latter cannot be reversed with appropriate nutritional supplementation as the sole intervention. Additionally, cachexia is characterized by a disproportionate loss of lean mass in the setting of increased resting energy expenditure; however, in starvation lean mass is better preserved, and energy expenditure is normal or decreased (1). The clinical definition of cancer cachexia requires an unintentional weight loss of at least 5% premorbid weight occurring over 3 to 6 months.…”

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Defining Cancer Cachexia in Head and Neck Squamous Cell Carcinoma

Richey

George

Couch

et al. 2007

Clinical Cancer Research

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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.

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Cancer cachexia syndrome in head and neck cancer patients: Part I. Diagnosis, impact on quality of life and survival, and treatment

Cited by 131 publications

References 59 publications

A review of weight loss and sarcopenia in patients with head and neck cancer treated with chemoradiation

A review of weight loss and sarcopenia in patients with head and neck cancer treated with chemoradiation

Selective Inhibition of NF-kappa-B with NBD Peptide Reduces Tumor- Induced Wasting in a Murine Model of Cancer Cachexia In vivo

Defining Cancer Cachexia in Head and Neck Squamous Cell Carcinoma

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