Marnie G. Dobbin
While only effective cancer treatment can reverse the symptoms of cancer cachexia, nutritional deficits and weight loss in patients with cancer can be minimized with timely nutritional intervention and pharmacologic management.
INCIDENCE AND IMPACT OF MALNUTRITION
■More than 40% of oncology patients develop signs of malnutrition during treatment.
■Malnourished patients incur higher costs for their care, have impaired responses to treatment, greater risk of drug toxicity, and increased rates of morbidity and mortality compared to patients with normal nutritional status.
■As many as 20% of oncology patients die from nutritional complications rather than from their primary diagnosis.
CANCER CACHEXIA
■Nearly two-thirds of patients with cancer develop cancer cachexia characterized by systemic inflammation, anorexia, immunosuppression, and metabolic derangements. These can lead to unintentional weight loss and failure to preserve muscle and fat mass.
■There is no consistent relationship between tumor type, tumor burden, anatomic site of involvement, and cancer cachexia.
■Hypermetabolism is not uniformly present.
■Tumor-induced changes in host production of proinflammatory cytokines (TNF, IL-1, IL-6, and IFN) can lead to hypermetabolism and to anorexia due to changes in gherlin, seratonin, and leptin production. Tumor production of proteolysis-inducing factor and lipid-mobilizing factor contribute to loss of muscle and fat mass. Inefficient energy metabolism and insulin resistance lead to further depletion of lean body mass.
■Patients with cancer cachexia may not be able to sustain their weight despite adequate nutritional intake.
■Overfeeding is likely to worsen metabolic dysregulation and will not result in weight gain.
SCREENING FOR NUTRITIONAL RISK
■Nutritional deterioration can be minimized if patients are screened at each visit, so that problems can be identified and interventions provided when they can have the most impact. The Joint Commission on Healthcare Accreditation standards state that inpatients are to be screened for nutritional risk within 1 day of admission. Validated screening tools such as the Subjective Global Assessment (SGA) form, developed by Jeejeebhoy et al. (1987) and adapted for use with oncology patients by Dr. Faith Ottery (www.ons.org/webcasts/downloads/pg-sga.pdf), may be especially helpful in the outpatient setting. Patients can complete the form in a few minutes during their medical appointments. The form covers questions about weight change, dietary intake, gastrointestinal symptoms, and functional capacity.
■Members of the healthcare team then gather additional data about metabolic demand (presence of fever, use of corticosteroids, etc.) and complete a nutrition-related physical assessment. The patient-generated tool (PG-SGA) not only aids in identifying the need for nutritional counseling and/or pharmacologic intervention, but also conveys to the patient that nutrition is a primary concern of the medical team.
NUTRITIONAL ASSESSMENT
■Registered dietitians (RD) use anthropometric data, biochemical indices, nutritional physical assessment, and dietary and medical histories to assess the nutritional status of patients and to determine appropriate intervention.
■Rate of weight change is the most useful parameter for identifying patients at nutritional risk. An unintentional weight loss of >5% per month, >2% per week, >7.4% in 3 months, or >10% in 6 months is associated with severe risk of malnutrition. Comparison of current weight to usual weight is more useful than comparing current weight to an ideal or desirable weight. Loss of more than 15% of usual weight may indicate a risk of protein–energy malnutrition.
BODY COMPOSITION
■Obtaining baseline measurements of body composition and comparing these measurements over time can be helpful for monitoring nutritional status. Measures of muscle mass include the use of skin calipers to measure mid-arm circumference (MAC) and mid-arm muscle circumference (MAMC). Triceps skinfold measurements can be used to estimate fat stores.
■Bioelectric impedance (BIA) is an inexpensive, noninvasive method for measuring body fat and fat-free mass, based on the principle that lean tissue has greater conduction and lower impedance than fatty tissue.
■Body mass index (BMI) correlates well with body fat, morbidity, and mortality (Table 39.1). However, BMI could incorrectly categorize highly muscled patients or those with edema or ascites as having excess fat stores. A BMI correlation of <18.5 is associated with protein–energy malnutrition.
PROTEIN
■If energy intake is inadequate, catabolism of protein will occur, especially as tumors preferentially metabolize protein. Limiting cancer patients’ protein intake has not been shown to interfere with tumor growth and may lead to protein malnutrition and impaired immunity.
■Protein turnover in patients with cancer is similar to that of patients with infection or injury, and their protein requirements are 50% above those of healthy individuals.
■Transport proteins (such as albumin and thyroxin-binding prealbumin) are negative acute-phase proteins that decrease in the presence of inflammation, regardless of a patient’s protein status. Earlier studies incorrectly correlated these proteins with nutritional status, not accounting for their role as inflammatory markers. Inflammatory processes can lead to loss of lean body mass, and low levels of transport proteins are correlated with poor clinical outcome, but the relationship with nutritional status is indirect. Dietary history and nitrogen balance measurements are more reliable measures of protein adequacy.
NUTRITIONAL REQUIREMENTS
■Indirect calorimetry, the preferred method for estimating resting energy expenditure, measures O2 consumed (VO2) and volume of carbon dioxide produced (VCO2) to determine respiratory quotient (RQ). This can be done with a portable metabolic cart operated by a respiratory therapist, or by a handheld device recently approved by the FDA.
■There are a variety of recommended calculations for estimating energy, fluid, and protein requirements (Table 39.2). However, formulas that rely on stress and activity factors, or calculations such as >45 kcal/kg “for stress,” have been shown to overestimate requirements. It is important not to overfeed cancer patients. Overfeeding can increase infection and induce respiratory distress, hyperglycemia, and fatty liver.
■The initial calorie goal for critically ill patients should be to meet their estimated resting energy expenditure (Table 39.3).
NUTRITIONAL INTERVENTION
■Nutritional counseling by an RD is associated with improvement in quality of life scores and nutritional parameters, and with success of oral nutritional intervention for oncology patients. Continual reassessment, pharmacologic management, and nutritional counseling can often help avoid costly, risky nutritional support options.
■Nutritional intervention by an RD may include education on individualized nutritional goals for energy, protein, and micronutrients, modification of foods and feeding schedules, fortification of foods with modular nutritional products, supplementation with meal-replacement products, or recommendations for appropriate nutritional support (Tables 39.4 and 39.5).
■Self-imposed diets and the use of dietary supplements should be evaluated by an RD for possible risks to the patient and for their potential to confound protocol results.
■A national registry of RDs is available from the Academy of Nutrition and Dietetics (eatright.org).
MICRONUTRIENT CONSIDERATIONS
■Although two-thirds of American adults are overweight or obese (BMI >25), the majority do not meet their requirements for magnesium, vitamin B6, zinc, and calcium. Optimal dietary intake of vitamins A, C, and E is rare, and patients often take excessive amounts of supplementary antioxidants. Use of dietary supplements should be evaluated as part of a nutritional assessment.
■When treatment involves oxidation (such as radiation therapy), pharmacologic doses of antioxidants might interfere with the treatment objective and may protect the tumor. A diet including foods that are good sources of antioxidants, along with a multivitamin providing 100% to 200% of recommended levels for most nutrients, has not been shown to be harmful and is recommended for patients on limited diets who are undergoing cancer treatment.
■Patients with low levels of ionized calcium, elevated AlkP, and a history of corticosteroid use and risk for osteoporosis should have their vitamin D levels assessed by measuring levels of cholecalciferol [25(OH)D]. Calcitrol, the 1,25 dihydroxy form of vitamin D, is not a reliable indicator of vitamin D status due to its short half-life and dysregulation in the presence of deficiency. The best available current data indicate that a serum 25(OH)D level of >32 ng/mL (80 mmol/L) is a supportable goal.
■Repleting vitamin D stores is associated with improved insulin sensitivity, enhanced immunity, improved musculoskeletal function (reduced falls and fractures), and a beneficial effect on bone mineral density. Low levels of cholecalciferol are commonly found in the elderly, dark-skinned individuals, the obese, and those with malabsorption syndromes and osteoporosis.
NUTRITIONAL SUPPORT
Although tumor growth is stimulated by a variety of nutrients, limiting the nutrients preferred by tumors can be detrimental to the patient. If patients have moderate to severe malnutrition and are unable to meet their nutritional needs with oral intake alone, specialized nutrition support such as parenteral or enteral nutrition is indicated (Table 39.6).
Enteral Nutrition
■Reviews of nutritional support practices indicate that parenteral nutrition (PN) is often instituted even when safer, more physiologic enteral nutritional (EN) support could have been provided. The benefits of EN over PN have been well demonstrated, including fewer infections, decreased catabolic hormones, improved wound healing, shorter hospital stay, and maintenance of gut integrity. In other words, if the gut works, use it.
■To be successful, EN should be implemented as soon as possible. Surgeons may approve of enteral feeding within 4 hours of placement of gastrostomy tubes and immediately after jejunostomy (because bowel sounds are not needed). Prophylactic placement of gastrointestinal tubes can considerably reduce weight loss during radiotherapy and may reduce the need for hospitalization due to dehydration, weight loss, or other complications of mucositis.
Parenteral Nutrition
■PN (Table 39.7) can be beneficial to cancer patients when response to treatment is good but associated nutritional morbidity is high, and when the GI tract is unavailable to support nutrition. Perioperative PN should be limited to patients who are severely malnourished, with surgery expected to prevent oral intake for more than 10 days after surgery.
■For the families of cancer patients, feeding is often synonymous with caring. However, end-stage patients who are encouraged to eat and drink as desired may have better quality of life than if specialized nutrition support is provided (which could contribute to incontinence, fluid imbalance, and respiratory compromise). The risks and benefits of PN must be addressed individually and evaluated for each case with patient and family input. In general, PN is not usually indicated in patients with an expected survival of less than 3 months.
COMPLICATIONS OF NUTRITIONAL SUPPORT
Refeeding Syndrome
Feeding after starvation is associated with increased intravascular volume, cardiopulmonary compromise, and plummeting levels of phosphorus, magnesium, and potassium due to the intracellular movement of electrolytes during anabolism. Malnourished individuals with severe weight loss, negligible intake for >7 days, a history of alcoholism, recent surgery, electrolyte losses due to diarrhea, high-output fistulas, or vomiting are especially vulnerable. Initially, no more than 50% of estimated needs (~15 kcal/kg/day and no more than 150 g dextrose/day) are recommended. Because thiamin is an important coenzyme for carbohydrate metabolism, the addition of 10 to 100 mg of thiamin is warranted.
Hypertriglyceridemia
For individuals receiving PN who have preexisting hyperlipidemia and obesity, or for those taking sirolimus, cyclosporine, and other medications associated with increased triglyceride (TG) levels, the goal is to keep TG <300 mg/dL. Ensure that blood is drawn 4 hours after lipid infusion or before lipids are hung, to avoid falsely elevated TG. Lipid dose should be reduced if TG is >300 mg/dL (but <600 mg/dL); however, stopping lipid altogether can worsen liver dysfunction. Slowing the rate of infusion of intravenous fat emulsion (IVFE) to between 6 and 12 hours may help with TG clearance. Five hundred milliliters per week of 20% IVFE can prevent essential fatty acid deficiency in adults.
Parenteral Nutrition–Associated Liver Disease
Hepatic fat accumulation is most common in adults and usually resolves within 2 weeks, even if PN continues. It typically presents within 2 weeks of PN with moderate elevations in serum aminotranferase concentrations. Parenteral nutrition–associated liver disease (PNALD) is usually a complication of overfeeding; it has become less common in the last 10 years, since calories provided via PN have become more appropriate.
Parenteral Nutrition–Associated Cholestasis
■Parenteral nutrition–associated cholestasis (PNAC) is primarily a result of excess calories in PN. Overfeeding contributes to fat deposition in the liver by stimulating insulin release, which promotes lipogenesis and inhibits fatty acid oxidation. PNAC occurs most often in children. It is associated with elevated serum conjugated bilirubin (>2 mg/dL) and may progress to cirrhosis and liver failure. Factors unrelated to PN that have been misattributed to PNAC include bacterial and fungal infections.
■Fat-free PN formulations have also been implicated in the development of fatty liver, since a high percentage of calories from carbohydrates can lead to fat deposition in the liver. Providing a balance of calories from dextrose and fat seems to decrease the incidence of steatosis, possibly by decreasing hepatic TG uptake and promoting fatty oxidation.
■IVFE exceeding 1 g/kg/day is associated with chronic PNAC and severe PNALD (5 mL of 20% IVFE = 1 g fat). Cyclic PN (generally 8 to 12 hours) has shown better results in terms of improved liver enzymes and conjugated bilirubin concentrations compared to continuous PN infusions. Fat emulsions containing a combination of medium-chain and long-chain TGs (not yet available in the United States) may reduce liver complications as well.
REVIEW QUESTIONS
1.A patient presents with cachexia and more than 7% weight loss in the past month. He reports that his food intake has been constant even while his weight continues to decrease. He has no gastrointestinal symptoms or fever. The most likely reason for his weight loss is
A.The patient has an inaccurate perception of his recent intake.
B.Energy expenditure and nitrogen losses are increased in those with cancer.
C.Lipolysis has occurred as a result of a preferential use of fat for energy which spares lean body mass.
D.There is increased turnover of free fatty acids, glucose, and protein.
2.A moderately malnourished patient with stomach cancer is admitted for a gastrectomy to be followed by chemotherapy (leucovorin + 5FU + oxaliplatin). Resting energy expenditure is 1,800 kcal. The patient has been drinking oral nutrition products formulated for postgastrectomy patients, but 1 week after surgery the patient is still unable to tolerate more than 300 kcal a day by mouth. Which is the most appropriate nutrition intervention?
A.PN should be initiated
B.A trial of EN via jejunostomy
C.Track intake; encourage continued use of postgastrectomy oral nutrition product
D.B and C
3.A woman with end-stage breast cancer and bony metastases has begun treatment for hypercalcemia of malignancy. Her usual diet includes foods high in calcium. Which of the following is NOT indicated?
A.A low calcium diet to limit exogenous sources of calcium
B.Discontinuation of drugs that contain vitamin D, calcium, or vitamin A
C.Rehydration to correct calciuresis-related dehydration
D.Diuresis to manage or prevent fluid overload
4.What are the most likely reasons for a patient’s serum albumin and prealbumin levels to decrease from near normal levels at the time of admission to below reference range 1 week after admission?
A.Inadequate protein intake
B.An acute-phase protein response as seen during a fever
C.Intravascular dilution
D.Both B and C
Suggested Readings
1.August DA, Huhmann MB. A.S.P.E.N. clinical guidelines: nutrition support therapy during adult anticancer treatment and in hematopoietic cell transplantation. J Parenter Enteral Nutr. 2009;33(5):472-500.
2.Bischoff-Ferrari HA. Optimal serum 25-hydroxyvitamin D levels for multiple health outcomes. Adv Exp Med Biol. 2008;624:55-71.
3.Boateng AA, Sriram K, Meguid MM, Crook M. Refeeding syndrome: treatment considerations based on collective analysis of literature case reports, Nutrition. 2010;26:156-167.
4.Bozzetti F, Boracchi P, Costa A, et al. Relationship between nutritional status and tumor growth in humans. Tumori. 1995;81:1-6.
5.Elliott L, Molseed LL, McCallum PD, Grant B, eds. The Clinical Guide to Oncology Nutrition. 2nd ed. Oncology Nutrition Dietetic Practice Group. Chicago, IL: American Dietetic Association; 2006.
6.Gariballa S. Refeeding syndrome: a potentially fatal condition but remains underdiagnosed and undertreated. Nutrition. 2008;24:604-606.
7.Gottschlich MM, ed. The A.S.P.E.N. Nutrition Support Core Curriculum: A Case-Based Approach—The Adult Patient. Silver Spring, MD: American Society for Parenteral and Enteral Nutrition; 2007.
8.Heaney RP. The vitamin D requirement in health and disease. J Steroid Biochem Mol Biol. 2005;97:13-19.
9.Jeejeebhoy KN. Permissive underfeeding of the critically ill patient. Nutr Clin Pract. 2004;19(5):477-480.
10.Johnson G, Salle A, Lorimier G, et al. Cancer cachexia: measured and predicted resting energy expenditures for nutritional needs evaluation. Nutrition. 2008;24:443-450.
11.Marian M, Robert S. Clinical Nutrition for Oncology Patients. Clinical Nutrition for Oncology Patients is Sudberry, MA (USA, 01776). Jones & Bartlett Publishers; 2010.
12.Moynihan T, Kelly DG, Fisch MJ. To feed or not to feed: is that the right question? J Clin Oncol. 2005;23:6256-6259.
13.Mueller CM. The A.S.P.E.N. Adult Nutrition Support Core Curriculum. 2nd ed. American Society for Parenteral and Enteral Nutrition; 2012.
14.National Cancer Institute: PDQ Hypercalcemia. Bethesda, MD: National Cancer Institute; 2011. Available at: http://cancer.gov/cancertopics/pdq/supportivecare/hypercalcemia/Health Professional. Accessed November 16, 2012.
15.National Heart Lung and Blood Institute. Calculate Your Body Mass Index. Available at: http://www.nhlbisupport.com/bmi/bmicalc.htm
16.Tisdale MJ. Pathogenesis of cancer cachexia. J Support Oncol. 2003;1:159-168.