Page 12 - Diagnosis and clinical consequences of cachexia in patients with advanced cancer Susanne Blauwhoff-Buskermolen

Chapter 1
General introduction
Cancer
Cancer is a prevalent and burdensome disease.The number of people living with cancer in the Netherlands was over 300.000 in 2013 and the prevalence increases with approximately twenty percent per ve years (3). At diagnosis, the cancer is staged based on the size of the tumor (T), the presence of lymph node metastases (N) and distant metastases (M). Between 30 to 75 percent of patients (dependent on tumor type and available screening programs) are diagnosed with synchronic lymph node or distant metastases: stage III or IV disease, also referred to as ‘advanced cancer’.Furthermore,a number of patients will eventually develop metastatic disease after their primary diagnosis (3).Treatment of patients with advanced cancer is mainly focused on prolonging life with speci c focus on reduction of symptoms and improvement or maintenance of quality of life. Improvement of quality of life can be achieved by reducing tumor burden and alleviating symptoms (4).Treatment to reduce tumor burden may consist of palliative surgery, hormonal treatment, chemotherapy, radiotherapy or treatment with biological agents (5). Alleviating symptoms can be reached by reducing tumor burden or directly treating symptoms with medication, for example medication to reduce nausea, or with other strategies, such as a celiac plexus block to reduce pain (4;6). Despite effor ts to reduce symptoms, patients with advanced cancer still suffer from multiple symptoms, ranging from 4 to 11 symptoms at the same time (7-9). The most prevalent symptoms are pain, fatigue, weakness, insomnia and appetite loss (anorexia). Many symptoms are nutrition-related, such as involuntary weight loss, anorexia, taste alterations and nausea/vomiting (7).These nutrition-related symptoms have been described to have a negative effect on quality of life of patients with advanced cancer (10-12).
Metabolic alterations in cancer
As a consequence of the presence of a malignant tumor, substantial metabolic alterations take place in cancer patients with direct or indirect effects on body weight, body composition and appetite (13). The tumor itself secretes substances such as proteolysis-inducing factor (PIF), activin A, zinc-alpha2-glycoprotein (ZAG) and parathyroid hormone-related protein (PTHrP). Elevated levels of PIF and activin A have been detected in respectively urine and serum of patients with cancer and weight loss (14;15). PIF and activin A are known to promote protein degradation and inhibit protein synthesis, leading to loss of muscle mass (13;16). ZAG, a lipid
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