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Departments of Clinical Nutrition and * Surgery, Göteborg University, Sahlgrenska University Hospital, S-413 45 Göteborg, Sweden
2To whom correspondence should be addressed. E-mail: ingvar.bosaeus{at}nutrition.gu.se.
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONLITERATURE CITED |
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KEY WORDS: • cancer cachexia • dietary intake • energy expenditure • weight loss • survival
Weight loss, anorexia and increased resting energy expenditure (REE)3
are frequent findings in advanced cancer. The mechanisms of cancer cachexia have been extensively studied but not fully clarified (1
). In terms of energy balance, progressive wasting can be attributed to changes in dietary intake, energy expenditure or both, mediated by metabolic alterations. Several aspects of the energy balance equation in advanced cancer are not well known. Although anorexia is very common in progressive cancer disease, we have not found many quantitative measurements of dietary intake in clinical cancer reported in the literature. Increased REE is frequently found, and a large span in REE from hypometabolism to hypermetabolism has been reported in malnourished patients with cancer. Sustained hypermetabolism over a long period of disease progression can make a large contribution to negative energy balance and wasting if not compensated for by an increase in energy intake. Hypermetabolism and diminished energy intake due to anorexia may thus constitute a vicious cycle in the development of cancer cachexia.
We studied dietary intake, REE and weight loss in unselected patients with generalized malignant disease of a solid tumor type, mainly gastrointestinal tumors. Inclusion criteria were generalized malignant disease with a solid tumor type, no other efficient or established tumor treatment available to the patient and expected survival of 
6 mo. Patients were examined at entry to an outpatient palliative care program that included anti-inflammatory treatment with indomethacin (2
), treatment of anemia with erythropoietin (3
), dietary advice and nutritional support.
REE by indirect calorimetry, height, weight and weight loss were recorded for 297 patients with cancer. REE was determined in the morning after an overnight fast by indirect calorimetry (Deltatrac; Datex, Helsinki, Finland). Predicted basal metabolic rate was calculated using the Harris-Benedict equation. Patients were classified as hypermetabolic if measured REE was >10% above predicted metabolic rate. Body weight was recorded in light indoor clothing on a digital electronic scale. We asked for habitual weight before the onset of disease. Body height was measured to the nearest centimeter using a wall-mounted stadiometer. Patients were regarded as weight stable if actual weight was within 5% of habitual weight and as weight losing if >10% of habitual weight was lost. Patients were classified as underweight if body mass index was <18.5, as normal weight if it was between 18.5 and 25 and as overweight if it was >25 kg/m2.
Dietary intake of energy and macronutrients was obtained from a 4-d food record. Patients were instructed by the team dietitian to complete the record in their homes. The amounts of all food and beverages consumed were recorded in household measures. In addition, meal pattern and preparation procedures were noted. When the food record was returned, the dietitian interviewed the patient to check for incomplete recordings and to estimate serving sizes. The estimation of serving sizes and conversion to weight units were aided by the use of a previously validated meal model. The nutrient database used was the Swedish National Food Composition Tables, which take into account average nutrient loss during food preparation. Protein intake was validated against 24-h urine nitrogen in a subgroup of 53 patients, and no indication of systematic misreporting was found. Survivors were reexamined after 4 mo during palliative care, and survival time from entry was recorded.
Correlation between variables was calculated with Pearson’s regression coefficient. Differences between two mean values were assessed by t test and between three or more means by one-way analysis of variance, with post hoc differences assessed by the method of Tukey. Relations between predictive variables and survival were assessed using Cox regression analysis. A value of P 
0.05 was considered statistically significant.
We previously reported (4
) that at entry, weight loss of >10% was present in 43% of the patients and elevated REE (>110% of predicted) was present in 48%. Mean dietary intake was low: 26 ± 10 kcal/(kg · d). Dietary intake did not differ between normometabolic and hypermetabolic patients, nor was tumor type or gender related to energy and protein intake. The proportions of macronutrients were not different from those of a healthy population living in the same area.
Weight loss could not be accounted for by diminished dietary intake because energy intake in absolute amounts was not different and intake per kilogram body weight was higher in weight-losing patients than in weight-stable patients. Thus dietary intake of energy was low. Weight loss and hypermetabolism were frequent and not compensated for by an increase in spontaneous food intake. These findings indicate that feedback regulation of dietary intake in relation to energy expenditure is frequently lost in patients with cancer.
At follow-up, mean survival time was 8 mo. Hypermetabolism and weight loss were associated with decreased survival; 189 patients survived 4 mo, of whom 153 could be reexamined. Reasons for nonparticipation at follow-up were mainly unwillingness to participate in further investigations and terminal illness.
At the 4-mo follow-up during palliative care, group mean weight was nearly maintained, with large individual variations (mean difference, -0.3 ± 4.4 kg). Weight loss during follow-up predicted decreased survival. Energy intake increased slightly, also with large variation (mean difference, 146 ± 661 kcal/d). Increased energy intake predicted increased survival. Group mean REE was unchanged (mean difference, 15 ± 162 kcal/d). Hypermetabolism at follow-up remained associated with decreased survival. Thus hypermetabolism and weight loss were associated with decreased survival, whereas an increase in energy intake during follow-up was associated with increased survival.
The metabolic alterations in advanced cancer have many parallels with a chronic systemic inflammatory response and differ considerably from the metabolic changes in starvation (1
). Artificial nutrition alone does not appear to affect overall survival in advanced cancer. Appetite stimulants such as high-dose progestins can improve anorexia and, to a lesser extent, promote weight gain, but timing, duration and dosage for optimal therapeutic effect are still unclear (5
). Therapeutic strategies aimed at modulating the mediators of the catabolic response, such as cytokines and eicosanoids (6
), or metabolic regulation, such as with anabolic and anticatabolic agents, may offer more promise in the future. Also, early detection and intervention may be more effective. Thus strategies to counteract hypermetabolism and anorexia may be important for the survival of patients with cancer and should be further explored in interventional studies.
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FOOTNOTES |
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3 Abbreviation used: REE, resting energy expenditure.
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LITERATURE CITED |
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TOPABSTRACTINTRODUCTIONLITERATURE CITED |
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1. Kotler, D. P. (2000) Cachexia. Ann. Intern. Med. 133:622-634.
2. Lundholm, K., Gelin, J., Hyltander, A., Lönnroth, C., Sandström, R. & Svaninger, G. (1994) Anti-inflammatory treatment may prolong survival in undernourished patients with metastatic solid tumours. Cancer Res. 54:5602-5606.
3. Daneryd, P., Svanberg, E., Körner, U., Lindholm, E., Sandström, R., Brevinge, H., Pettersson, C., Bosaeus, I. & Lundholm, K. (1998) Protection of metabolic and exercise capacity in unselected weight-losing patients with cancer following treatment with recombinant erythropoietin: a randomized prospective study. Cancer Res. 58:5374-5379.
4. Bosaeus, I., Daneryd, P., Svanberg, E. & Lundholm, K. (2001) Dietary intake and resting energy expenditure in relation to weight loss in unselected patients with cancer. Int. J. Cancer 93:380-383.[Medline]
5. Maltoni, M., Nanni, O., Scarpi, E., Rossi, D., Serra, P. & Amadori, D. (2001) High-dose progestins for the treatment of cancer anorexia-cachexia syndrome: a systematic review of randomised clinical trials. Ann. Oncol. 12:289-300.
6. Ross, J. A. & Fearon, K. C. H. (2002) Eicosanoid-dependent cancer cachexia and wasting. Curr. Opin. Clin. Nutr. Metab. Care 5:241-248.[Medline]
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