Clinical Significance of Weight Loss in Cancer Patients: Rationale for the Use of Anabolic Agents in the Treatment of Cancer-Related Cachexia

Nutrition. 2001 Jan; 17(1 Suppl):S1-20. doi: 10.1016/s0899-9007(01)80001-0.
Langer, C. J., Hoffman, J. P., & Ottery, F. D.


The full spectrum of oncologic care ranges from prevention and cure to supportive palliation. The nutritional status of a given individual plays an integral role in determining risk of cancer development, as well as risk for compromised treatment response, therapy-related toxicity, and death. Classic prognostic indicators of clinical outcome in oncology include tumor histology, clinical and pathologic stage, and performance status. Degree of weight loss has been recognized as a predictor of medical outcome since the 1930s. Wasting and malnutrition in cancer patients have long been recognized as being predictive of poor outcome, but were quantified by clinicians in the Eastern Cooperative Oncology Group (ECOG) only in 1980. Significant weight loss at the time of diagnosis was correlated with decreased survival and impaired response to chemotherapeutic intervention. The following manuscript describes a philosophical and practical approach that integrates a number of these disparate prognostic parameters, with special emphasis on histology, performance status, and weight loss. It is widely appreciated that the finding of involuntary weight loss at disease presentation or as a result of treatment toxicity varies widely by tumor type and therapeutic modality. When one appreciates that weight loss in patients with cancer is disproportionately represented by a loss of muscle mass, the potential interaction between such loss and performance status (PS) is obvious. Performance status, as assessed by the Kamofsky or Zubrod scales, represents a patient’s ability to function in day-to-day activities. The recognized importance of this parameter is supported by the fact that only patients with relatively good PS are included in clinical trials. Nutritional deterioration and weight loss can be part of the patient’s presentation, as well as known complications of all therapeutic modalities in oncology. While the specifics of the nutritional deficit may vary across the spectrum of interventions - surgery, chemotherapy, biologics, and radiation therapy - there are common threads. In general, multimodality therapy induces the greatest risk for progressive nutritional deficit. Nutritional risk associated with single- or multimodality therapy is significantly affected by tumor location, especially with tumors involving or adjacent to the aerodigestive or gastrointestinal tracts. As a consequence of progressive weight loss and nutritional deterioration, cancer patients are at increased risk for infection, as well as compromised wound healing. Loss of lean body mass of >10% has been associated with lack of wound healing in nononcology settings. Patients become progressively weak, fatigued, and debilitated as a complication of weight loss and wasting. As a consequence, they are less active and may spend increasing amounts of time in bed or chair. Bed rest results in predictable consequences of increased risk of pulmonary embolus and decubitus ulcers. This inactivity can also contribute to further decreases in functional capacity, because of progressive disuse muscle atrophy. Stuart and colleagues have demonstrated that healthy volunteers experience significant functional and morphometric alterations following absolute bed rest for 7 days. Muscle volume loss of 1% to 4% in the back and lower extremities was quantified by magnetic resonance imaging, and lower extremity fat increased by 2% to 5%. In addition, metabolic derangements, including decreased glucose tolerance, incresed peripheral insulin resistance, and inhibited skeletal muscle protein synthesis, were observed as a direct result of bed rest. Finally, progressive cachexia can cause respiratory muscle weakness and deterioration of respiratory capacity, potentially contributing to respiratory failure and death. In addition to the common facets of nutritional complication during cancer treatment, each modality has additional specific complications. For surgical intervention, nutritional consequences may range from limited impact to frank malabsorption, dumping syndrome, gastric hypersecretion, water and electrolyte loss, or need for enterostomy and tube feedings. Nutrition impact symptoms related to chemotherapy most commonly include stomatitis, sensory changes in taste and smell. nausea, vomiting, diarrhea, and constipation. In addition, the specific toxicity profiles of biologic response moditiers include fever and an array of other catabolic effects that contribute to anabolic compromise. Nutritional deficit has specific adverse effects on immune competence. When this is combined with immunocompromise due to cytotoxic agents, the effect is often clearly synergistic. Onset and duration of radiation therapy-induced nutritional complications can be acute or span the time frame of decades. In general, degree of radiation injury is dependent on the anatomic site, portal size, fractionation schedule, total dose, comorbidities including malnutrition, and other concomitant therapies. One final consideration needs to be addressed in terms of potential impact of nutritional deficit on the outcomes of oncologic treatment. Impaired nutritional status. especially protein deficiency, can affect pharmacokinetic and pharmacodynamic parameters of chemotherapeutic agents, contributing to increased therapy toxicity.

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List of abbreviations

DGEM German Society for Nutritional Medicine (German Deutsche Gesellschaft für Ernährungsmedizin)
GESKES  Swiss Society for Clinical Nutrition (German Gesellschaft für klinische Ernährung der Schweiz) 
ESPEN European Society of Clinicl Nutrition and Metabolism