Considerations in Head and Neck Cancer
SOURCE: Dept. of Otolaryngology, UTMB, Grand Rounds Presentation
DATE: December 09, 1998
RESIDENT PHYSICIAN: Karen L. Stierman, M.D.
FACULTY PHYSICIAN: Francis B. Quinn, Jr., M.D.
SERIES EDITOR: Francis B. Quinn, Jr., M.D.
|Return to Grand Rounds Index|
"This material was prepared by resident physicians in partial fulfillment of educational requirements established for the Postgraduate Training Program of the UTMB Department of Otolaryngology/Head and Neck Surgery and was not intended for clinical use in its present form. It was prepared for the purpose of stimulating group discussion in a conference setting. No warranties, either express or implied, are made with respect to its accuracy, completeness, or timeliness. The material does not necessarily reflect the current or past opinions of members of the UTMB faculty and should not be used for purposes of diagnosis or treatment without consulting appropriate literature sources and informed professional opinion."
Significant malnutrition is present in approximately 20% of patients with cancer in the head and neck. Severity of malnutrition correlates with increased rates of postoperative sepsis and depressed cell mediated immunity.
Classification of Malnutrition
A universal definition of malnutrition does not exist. In general, malnutrition is weight loss greater than 10% of ideal body weight that is associated with loss of muscle. Mild to moderate malnutrition is weight loss of 6 to 12% of the ideal body weight. Severe malnutrition is weight loss of more than 12 percent with decreased albumin and/or transferrin levels. The two types of malnutrition are marasmus and kwashiorkor. Marasmus is secondary to total caloric deprivation and is associated with normal serum protein levels. Kwashiorkor is associated with loss of protein calories and is associated with head and neck cancer.
Pathogenesis of Malnutrition
Three mechanisms take part in producing malnutrition in a cancer patient. These include: reduced caloric intake, anorexia, and cachexia. Alcohol and tobacco play a role in reducing calories and anorexia. Alcohol provides mainly simple carbohydrates and results in vitamin and mineral deficiencies due to malabsorption. Poor dentition and local tumor effects(such as with bulky tumors) can cause decreased caloric intake secondary to physical limitations. These include inability to manipulate the food bolus and aspiration. Radiation induced mucositis and progression of dental disease and chemotherapy side effects can also reduce caloric intake.
The causes of anorexia appear to be multifactorial and not understood fully. Animal models have shown an association between tumor growth and food aversion. Deficits of olfactory and gustatory function associated with radiation or chemotherapy can also contribute to anorexia.
Cachexia that is cancer induced is based on the fact that solid tumors derive their energy from the anaerobic(Cori) cycle where glucose is metabolized to lactate . Regular cells derive their energy from the aerobic(Krebs) cycle when glucose is broken down into CO2 and water. Tumor cells are not able to use fat as a source of energy and must use glucose. In addition, severe malnutrition by itself is associated with reduced insulin secretion, decreased insulin receptor affinity, and glucose intolerance. When glucose stores run out or when the cells cannot take up glucose, amino acids can be sacrificed from muscle stores in order to manufacture glucose. Tumor patients also have an increased level of free fatty acids which impairs tissue response to insulin. This causes the body to think it needs more glucose and it continues to convert protein into sugar.
Dietary Risks Factors for Cancer
Low serum levels of vitamin A or B-carotene are associated with cancer of the head and neck and lung cancer. Increased levels of selenium is associated with a decreased risk of esophageal cancer. Epidemiological studies have shown that low intake of fruits and vegetables are associated with increased risk of lung cancer.
In dealing with cancer patients, it is important to assess the type of diet the patient follows, any recent weight loss, and the quantity of alcohol the patient consumes. Patients that lose more than 12 to 20% of their ideal body weight are at a high risk for development of septic complications following surgery. Patients with weight loss of 6-12% are at intermediate risk.
When examining the cancer patient it is important to look for evidence of loss of subcutaneous fat and muscle wasting. This can be accomplished by looking at the amount of subcutaneous fat at the triceps region, the interosseous and palmer areas of the hand, and the deltoid region of the shoulder. Muscle wasting can be determined by examining the deltoid and the quadriceps muscles. Edema can be indicative of a low protein state and is best appreciated in the pretibial and sacral areas. Cheilosis, stomatitis, and dry scaling skin can be indicative of vitamin deficiencies. An obese body habitus can cause a patient with protein depletion to look well nourished. In these cases, anthropometric measurements allow calculation of the body fat content from which total lean body mass can be determined. Although anthropometric measurements are an accurate way of determining nutritional status, the subjective global assessment(SGA) is a good predictor of postoperative complications. The SGA combines information from the history and exam to categorize the patients nutritional status.
Characterization of nutritional status can also be determined by the prognostic nutritional index(PNI). This index is based on serum albumin, serum transferrin, triceps skin fold measurement, and the presence of delayed hypersensitivity.
The most common test of the bodyís protein reserve is serum albumin. Patientís with serum albumin levels less than 3.0 g/dL have increased perioperative morbidity. Albumin levels are influenced by two factors. First, the albumin level is dependent on the hydration status of the patient. Secondly, the half-life of albumin is 20 days therefore the level may not provide the most recent information about a patientís nutritional status. Other protein such as serum transferrin, prealbumin, and retinol binding protein have a shorter half-life and may provide more recent information. However, transferrin can be artificially elevated with infection or inflammation. Transferrin levels less than 200 mg/dL can increase perioperative morbidity. The other protein levels can be difficult and expensive to measure.
Measurements of cell-mediated immunity can also estimate the patients nutritional status. Recall that depressed cell mediated immunity can signify severe malnutrition. An anergy skin test and total lymphocyte count(TLC) help measure cell mediated immunity. The anergic patient undergoing elective surgery develops septic complications one third of the time versus one twentieth of the time with immunocompetent hosts. Patients with a TLC less than 1,700/uL have a five time increase in their rate of wound infection.
Caloric needs of patients with head and neck cancer are calculated by adding needs due to the illness to the basal metabolic edict form needs of the patient. The Harrison-Benedict formula can be used to calculate caloric requirements. The daily caloric intake for a normal adult is 25 to 35 kcal/kg of body weight/day. Protein intake is usually 0.8 g/kg/day. Patients who are ill may need 1.2 to 2.0 g/kg/day of protein. Usually, caloric requirements are 150% more than the basal energy expenditure. Patients undergoing major surgery with complications may require up to 50% greater calories. Patients undergoing uncomplicated surgery generally do not have increased caloric needs. According to Moore, there are four phases following surgery. Phase I is the catabolic phase lasting 3-7 days where there is increased protein consumption. Phase II is the point at which protein consumption and production are equal. Phase III is the anabolic phase where protein production exceeds production. Phase IV is defined by the restoration of lipid stores. Currently the concepts of nutritional requirements in disease states is changing. Some measurements note that energy expenditure in adults is usually 1700-2500 kcal/day regardless of their preoperative or postoperative status. Therefore, current guidelines could result in overfeeding of patients.
Calories must be given in an appropriate calorie to protein ratio to avoid malnutrition. The ratio in surgical patients should be between 120:1 and 180:1. There are also specific requirements for amino acids, fats, vitamins, and micronutrients. Animal studies have shown significant differences in the amino acid profile of tumor versus non-tumor bearing animals. For example, arginine has been demonstrated to be decreased in animals with tumors. It has been suggested that arginine supplementation may be beneficial to the immune system and for collagen synthesis.
Fats provide 9 kcal/g which makes them a very efficient energy source. Giving the surgical patient fat in their diets may help preserve protein stores. Two to three percent of the total caloric intake should be made up of free fatty acids. The lipid composition of tumor cell membranes responds to dietary manipulation. The fatty acids of tumor cell membranes are derived from circulating fatty acids. By increasing a patients intake of polyunsaturated fatty acids(PUFA), tumor cells can be made more sensitive to chemotherapy and hyperthermia. Changes in the tumor cell membranes may also make them more susceptible to immune cell destruction. The major dietary PUFA in the American diet is an n-6 PUFA(linoleic acid). Diets high in n-6 PUFA result in production of arachidonic acid metabolites which can have an immunosuppressive effect. Consideration should be given to diets high in n-3 PUFAís which can be derived from fish oils. Carbohydrate intake is also important. Diets that are high in carbohydrates may result in excessive carbon dioxide production. This can be bad for patients with COPD especially when trying to wean them from the ventilator.
Micronutrients are also an important consideration in diet. Phosphorus is essential for energy metabolism. Therefore, it is important to identify and correct hypophosphatemia in the head and neck cancer patient. Trace metals such as iron, copper, zinc, manganese, iodine, selenium, chromium, and molybdenum are also important to provide as they are important in the bodyís enzyme systems. Some studies have shown that patients with upper aerodigestive tract cancers are deficient in selenium. Selenium deficiency can affect immune function. Zinc has been found to be deficient in many head and neck cancer patients. In a study by Doerr, et. al., patients who had a PNI of 60 were evaluated for their baseline zinc status based on cellular methods. They noted baseline zinc status to be a significant indicator of tumor size and stage of disease. They did not see a correlation between tumor size and stage of disease and the PNI.
Techniques of Delivery
Oral intake of nutrients is the best for the patient. Patients with head and neck cancer frequently have impairment of mastication and swallowing. If oral intake cannot be accomplished, enteral feedings at other locations within the alimentary tract is the next best option. Nasogastric feeding for short-term feeding versus percutaneous endoscopic gastrostomy(PEG) or an open G-tube for long term feeding should be considered. Jejunostomy should be considered in patients undergoing laryngopharyngoespophagectomy with gastric pull-up, patients reconstructed with jejunal free flap transfer, or in patients with severe gastric disease. A G-J tube is also a consideration in patients with gastric disease. One study by Lee, et. al suggested use of prophylactic gastrostomy tubes in patients receiving high dose radiotherapy. The noted the prophylactic use of the tubes to decrease dehydration and malnutrition associated with severe radiation induced mucositis.
Parenteral hyperalimentation is a third route to provide rapid nutrition without use of the alimentary tract. It may be the best option for patients with obstructive gastrointestinal disease or in patients with malabsorption. The two types of parenteral nutrition(PN) are PPN(peripheral) and TPN(total). PPN is not meant for total nutritional replacement long term because it is not good to use hyperosmolar solutions in peripheral veins long term. TPN, which is delivered through a central vein, has the advantage of delivering rapid nutritional support long term. Risks of TPN include the risk of having and placing a central line including line sepsis, pneumothorax and hemorrhage. There is also a need for close monitoring of the patients serum osmolarity and electrolytes to avoid imbalance and a hyperosmolar or hyperglycemic state.
There are many different nutritional formulas available to match the needs of a specific patient. Things to consider include lactose intolerance, serum osmolality, and cost. Volume restriction needs to be considered in patients with renal problems and respiratory difficulty. Elemental diets are usually reserved for patients with malabsorption. Enteral tube feedings may be given on a continuous, intermittent, or bolus schedule.
Review of Studies on the Efficacy of Nutritional Replacement
Much of the studies on the efficacy of nutritional replacement in head and neck cancer patients has been retrospective. Patients with mild to moderate malnutrition can undergo nutritional supplementation in the postoperative period. In the case of severe malnutrition, nutritional replacement should begin 7 to 10 days prior to surgery. Mullen et. al. noted that the use of preoperative TPN for 1 week significantly decreased postoperative morbidity and mortality in a group of 145 general surgical patients. This study was confirmed by other studies involving patients undergoing cancer surgery in general. A meta-analysis of the prospective clinical trials in general surgery literature has noted that a 10 day course of preoperative TPN in malnourished patients results in a reduction of postoperative complications and fatalities by 21% to 32%. This was translated into a savings of $2,000 per patient. Sako and colleagues looked at a group of 69 head and neck cancer patients who were noted to be malnourished based on weight loss alone. These patients got preoperative TPN or enteral nutrition for 8 to 32 days. No significant differences in postoperative morbidity or mortality could be shown. The maintenance of weight and nitrogen balance was noted to be better in the group receiving TPN. Critical analysis of this study shows it to be based on a small sample size which was incompletely randomized and based on an inadequate definition of malnutrition.
Although other studies have shown efficacy between parenteral and enteral nutrition, there are many reasons to choose enteral nutrition over TPN. The enteral route is safer, more convenient, and less costly. In addition, nutrients delivered enterally are better utilized than those administered parenterally. Enteral nutrition also prevents gastrointestinal mucosal atrophy, lessens the stress response, maintains immunocompetence, and maintains the normal gut flora. TPN has also been noted to have an effect on the tumor cell cycle of sqamous cell carcinoma (SCCA) of the head and neck. It has been shown to increase the number of hyperdiploid cells. The relationship of TPN on tumor growth and patient survival however has not been thoroughly investigated and requires further studies.
Postoperative controlled studies of nutritional support patients have shown improved nutritional status when compare to control patients. This can be translated into reduced surgical morbidity and mortality. Advantages were noted when enteral nutrition versus oral nutrition were provided.
In chemotherapy patients, a meta-analysis of prospective randomized controlled trials of parenteral nutrition did not show an influence of survival rate, treatment toxicity, or response of tumor to therapy. Similar findings were noted in studies of patients undergoing radiotherapy.
Many patients with head and neck cancer are malnourished. Perioperative nutritional support decreases morbidity and mortality associated with malnutrition. This can decrease cost to the patient. Further studies are necessary in order to determine the correct nutritional management of patients with head and neck cancer.
Bumpous, J. M. and Snyderman, C. H., Nutritional considerations in patients with cancer of the head and neck. Cancer of the Head and Neck. New York. Churchill-Livingstone, Third Edition, 105-115.
Bailey, B.J., et. al. Perioperative management issues. Head & neck surgery - Otolaryngology. Second edition, 1998, 243-244.
Doerr, T.D., et al. Effects of zinc and nutritional status on clinical outcomes in head and neck cancer. Nutrition. June 1998, 14(6):489-95 .
Lee, J. H., et al. Prophylactic gastrostomy tubes in patients undergoing intensive irradiation for cancer of the head and neck. Archives of Otolaryngology - Head and Neck Surgery, 1998 Aug., 124(8):871-5.
Doerr, T.D. et al., Zinc deficiency in head and neck cancer patients. Journal of the American College of Nutrition, Oct 1997, 16(5):418-22.
Tayek, J. A. et al. Insulin secretion, glucose production, and insulin sensitivity in underweight and normal weight cancer patients. Metabolism: Clinical and Experimental, Feb 1997, 46(2)140-5.
Himberlin, C. et. al. Prognostic significance of routine clinical and laboratory data in advanced head and neck cancer. Anticancer Research. March 1996 16(2)1005-10.
Sako, K., et al. Parental hyperalimentation in surgical patients with head and neck cancer: A Randomized study. Journal of Surgical Oncology, 1981, 16, 391-409.
Moore, F. A., et. al. Early enteral feeding, compared with parenteral reduces postoperative septic complications. Annals of Surgery, 1992., 216(2), 172-182.
Key, T., Micronutrients and cancer aetiology:the epidemiological evidence. Proceedings of the Nutrition Society, 1994, 53, 605-614.
Mullen, J.L., et al, Reduction of Operative Morbidity and Mortality by Combined Preoperative and Postoperative Nutritional support., Annals of Surgery, Nov 1980, 604-612.