Nutritional Support of Patients Undergoing Radiation Therapy for Head and Neck Cancer

Malnutrition plays a key role in the morbidity of head and neck cancer patients receiving surgery, chemotherapy, radiotherapy, or combined- modality therapy. In addition to weight lost prior to the diagnosis of head and neck cancer, the patient may lose an additional 10% of pretherapy body weight during radiotherapy or combined-modality treatment. A reduction of greater than 20% of total body weight results in an increase in toxicity and mortality. Severe toxicity can result in prolonged treatment time, which has been implicated in poor clinical outcome. Early intervention with nutritional supplementation can reduce the chance of inferior outcome in patients at high risk of weight loss. The preferred route of nutritional support for these patients is enteral nutrition. Two commonly used methods for enteral feedings are nasoenteric and percutaneous endoscopic gastrostomy. It is important to take into account the ethical considerations involved in providing long-term nutritional support, particularly for patients with terminal conditions. Nutritional directives are best evaluated through multidisciplinary efforts, including input from the patient as well as members of the nursing, nutritionist, and medical staff.

Commonly observed manifestations of cancer and its treatment include hypermetabolism, cachexia, and anorexia. Patients undergoing treatment for head and neck cancer are particularly prone to weight loss, both secondary to the disease process and due to treatment side effects. There is a direct correlation between more aggressive therapeutic modalities and progressive malnutrition, resulting in a diminished quality of life and poor outcome. Therefore, nutritional support can significantly benefit the malnourished patient who may then have a positive response to therapy. Appropriate nutritional support and early interven tion with temporary enteral access can result in improved nutritional status[1] and therapy tolerance.[2] This correlates with decreased hospitalizations,[3] enhanced quality of life,[4] and a reduction in morbidity and mortality.[5,6]

Etiology of Malnutrition

Patients with head and neck cancer have multiple etiologies for malnutrition as a consequence of the imbalance between nutrient intake and demand. Decreased nutrient intake may be associated with localized tumor effect[7,8] or the toxicities of treatment. Typically, the patient has lost weight prior to beginning therapy. Local tumor effect may obstruct the aerodigestive tract, impede mastication, or hinder deglutition. Patientrelated factors, such as poor dentition, unique anatomy, and nutritional history may also exacerbate the local tumor effect.

Lees reported on weight change in 100 consecutive patients with head and neck carcinoma prior to the start of radical or palliative radiotherapy.[9] Approximately 57% had lost weight, whereas only 12% had gained weight prior to the start of radiotherapy. The mean weight loss was approximately 10% of total body weight and was considered unintentional in 95% of patients. Dry mouth and the inability to wear dentures secondary to mouth discomfort were the most common causative factors of weight loss.

Treatment modalities for head and neck cancer may include surgery, chemotherapy, radiotherapy, or combination therapy. Each of these treatment modalities may result in side effects that could affect nutritional status. Postsurgical changes may result in localized pain or difficulty with mastication and deglutition. Chemotherapy may induce mucositis, nausea, vomiting, stomatitis, fatigue, or neutropenia leading to infection that may contribute to a poor nutritional status. Radiotherapy can induce mucositis, dysgeusia, xerostomia, change in viscosity of saliva, fistula formation, infection, fatigue, stricture, gustatory dysfunction, or olfactory dysfunction that can also significantly impair nutritional status. The addition of concurrent chemotherapy to radiotherapy may significantly exacerbate these effects.

Clinical Experience

It has been well documented that standard radiotherapy fractionation schedules (2 Gy/d, 5 days per week to at least 60 Gy) result in an increased risk of weight loss both during and following treatment. Johnston et al reported on 31 patients receiving standard fractionated radiotherapy for localized head and neck cancer. This prospective study revealed that pretreatment dietary habits, serum albumin, or anthropometric measurements were not predictive for weight loss; however, weight loss could be predicted on the basis of field size and site irradiated.[10] Tyldesley et al reported on 76 patients with head and neck cancer treated with radiotherapy alone who received gastrostomy tubes either electively (inserted during week 1), or only if a severe reaction occurred (inserted during week 3 on average) and compared them to a control group that did not receive a gastrostomy tube (G-tube). Initial weight loss and weight loss at followup was significantly less for patients who underwent elective or nonelective G-tube placement, which corresponded to fewer days hospitalized.[11]

Peters et al reported on 240 patients with advanced stage head and neck cancer treated with surgical resection and randomized to receive escalating doses of postoperative radiotherapy.[12] Three dose levels were analyzed, ranging from 52.2 to 68.4 Gy (field reduction at 57.6 Gy) in daily 1.8-Gy fractions. Overall, only 3.8% developed acute reactions that required a treatment interruption greater than 2 days (maximum interruption was 6 days). The average weight loss was 2.6 kg.

Radiotherapy Strategies

Novel radiotherapy technique and fractionation schedules continue to be investigated to improve local control and survival[13,14] with acceptable quality of life or organ preservation.[15] However, most altered fractionation schedules and combinedmodality therapies have shown improved outcome at the cost of increased morbidity.[16,17]

Fu et al reported on the RTOG 9003 phase III trial that compared standard fractionation techniques with hyperfractionation and two variants of accelerated fractionation.[18] This analysis involved 1,073 patients with locally advanced head and neck cancer. The study showed an improved locoregional control and a trend toward increased disease-free survival for patients who underwent the hyperfractionation technique (1.2 Gy per fraction twice daily for 5 days per week, to a total of 81.6 Gy) and accelerated fractionation with concomitant boost (1.8 Gy per fraction for 5 days per week with 1.5 Gy/d to a boost field for the last 12 treatments, to a total of 72 Gy) compared with standard fractionation (2 Gy per fraction for 5 days per week, to a total of 70 Gy) and accelerated fractionation with split (1.6 Gy per fraction twice daily for 5 days a week, to a total of 67.2 Gy with a 2-week break at 38.4 Gy).

Weight loss data were not reported for this study. The most common site of acute side effects included the mucous membranes and pharynx, whereas the most common site of late effects included the pharynx and salivary glands. The hyperfractionation technique and two variants of accelerated fractionation had significantly increased grade 3 or worse acute side effects compared to standard fractionation techniques. Only the accelerated fractionation with concomitant boost had a significant increase in grade 3 or worse late effects.

Concurrent Chemotherapy/ Radiotherapy

The addition of concurrent chemotherapy to radiotherapy for head and neck neoplasms has been shown to improve both local control and overall survival, but at the cost of increased severity and duration of acute side effects. Newman et al reported on 47 head and neck cancer patients who underwent concurrent radiotherapy (1.8-2.0 Gy daily fractions) with intra-arterial cisplatin and parenteral sodium thiosulfate.[17] Prior to the start of treatment, 53% of patients already had impaired swallowing and 9% were dependent on tube feedings. Investigators found a mean 10% reduction in total body weight during treatment and no significant changes in weight following treatment. No correlation between weight loss and tumor stage was seen. In a subgroup analysis, the 9% of patients who had a G-tube prior to treatment did not lose significant weight. During treatment, the cohort of patients with difficulty swallowing increased from 62% to 79%, which correlated with an increase of G-tubes from 9% to 26% by the end of treatment. However, swallowing difficulty was reported in only 28% of patients at 18 months after treatment.

Brizel et al reported on 116 patients with advanced head and neck cancer who were treated with a hyperfractionated radiotherapy technique and randomized to concurrent chemotherapy (cisplatin and fluorouracil [5-FU]) or no chemotherapy.[19] Locoregional control and overall sur vival was significantly improved with combined-modality therapy, and the investigators found no significant difference in the incidence of mucositis, although the mucositis took longer to resolve in the combined-modality group (6 weeks) than in the hyperfractionation radiotherapy-alone group (4 weeks). There was no significant difference in weight loss; however, 44% of patients in the combined-modality group had a temporary feeding tube placed (nasogastric or G-tubes), compared to 29% of the patients who received hyperfractionated radiotherapy only. In addition, the combined-modality therapy arm resulted in continued treatment sequelae a year after treatment, causing dietary restrictions, but this did not correlate with a significant change in quality of life.[20]

Calais et al analyzed 226 patients in a phase III randomized trial that compared radiation therapy vs concurrent radiation therapy and chemotherapy (carboplatin and 5-FU) for advanced-stage oropharyngeal cancer.[16] This revealed a significant improvement in local control and overall survival; however, there was also a significant increase in grade 3/4 mucositis in the combined-modality arm (71%) vs radiotherapy alone (39%). The nutritional status of the combined-modality arm was poor, based on a higher proportion of patients who lost more than 10% body mass. Moreover, the combinedmodality arm had an increased requirement for temporary G-tube or nasogastric feeding tubes.

Chan et al reported on a phase III randomized trial that compared radiotherapy vs concurrent chemotherapy and radiotherapy for the treatment of locoregionally advanced nasopharyngeal carcinoma. In this study, weight loss was significantly more pronounced in the combined-modality arm, which included 74% of patients losing more than 10% of body weight and 11% losing more than 20% of body weight, compared to 50% and 6% in the radiotherapy-alone arm. The combined-modality arm also showed a statistically significant increase in anemia, leukopenia, thrombocytopenia, nausea, vomiting, and stomatitis. This study demonstrated an improved progression-free survival for advanced tumor and nodal stages only in subgroup analysis.[21]

In contrast, the results of the Intergroup study 0099 revealed improved overall and progression-free survival in the combined-modality arm. The Intergroup study concluded that combined modality is superior to radiotherapy alone for stage III/IV nasopharyngeal cancers. However, both studies agree that toxicity, including weight loss, is worse in the combinedmodality group.[22]

Weight Loss and Other Metabolic Effects

Studies have revealed an association between weight loss and inferior outcome for the head and neck cancer patient.[23] Bosaeus et al reviewed 297 cancer patients involved in an outpatient palliative care program and noted that a weight loss greater than 10% was present in 43% of the patients, while hypermetabolism was present in 48%. Hypermetabolism and weight loss were significant factors associated with decreased survival.[6] Also, the sequelae of radiotherapyinduced toxicity including impaired nutrition may cause treatment delays and a prolonged treatment course that has been shown to affect local control[24] and survival.[4,25]

Weight loss in the head and neck cancer patient is not caused exclusively by decreased nutritional intake. Surgery, radiotherapy, and chemotherapy also lead to acute metabolic stress and amplified nutrient demands. In addition, the increased nutrient demand may be associated with the systemic effect of the tumor,[26-29] which competes with the host for nutrients, resulting in metabolic disturbances leading to anorexia, increased basal metabolic rate, and abnormal metabolism of nutrients. Tumor necrosis factor-alpha, possibly with other cytokines such as interleukin-6 or interferon-gamma, have been implicated in cachexia in animal models and may be, in part, regulated by NF-kappaB.[30-33] A combination of cytokines from the host and tumor are released, causing abnormalities in carbohydrate, fat, and lipid metabolism. Muscle wasting is found in skeletal, cardiac, and smooth muscle types. Muscle loss can cause generalized weakness, reduced cardiac function, or decreased respiratory function.

Tube Placement and Technique

TABLE 1

American Society for Gastrointestinal Endoscopy Guidelines for Selecting Patients for Tube Feeding

Providing adequate nutrition to this group of patients can be very challenging, despite the use of enteral supplementation, appetite stimulation, and dietary counseling. This has led to the role for enteral access and tube feeding to provide calories, fluids, and medications. Enteral nutrition is preferred over parenteral nutrition, because it preserves gut integrity, function, and immune mechanisms, and is also associated with lower risks and costs. Tube feeding should be considered for patients who have a functional gut but cannot or will not eat, and for whom a safe method of access is possible (Table 1).

Temporary enteral access can be obtained using nasogastric (NG) or nasojejunal (NJ) feeding tubes, and is particularly useful in patients who need short-term (< 30 days) nutritional support. These tubes have the benefit of easy placement and removal but are limited by becoming dislodged, easily clogged, or irritating to the upper aerodigestive tract in the head and neck cancer patient. Such problems have led to the development of more permanent endoscopically, radiologically, or surgically placed enteral access such as gastrostomy, gastrojejunostomy, or jejunostomy feeding tubes. These tubes are especially useful for patients who will need tube feeding for more than 30 days.

Gastrostomy

TABLE 2

American Society for Gastrointestinal Endoscopy Contraindications to PEG Placement

Over 216,000 percutaneous endoscopic gastrostomy (PEG) procedures are performed annually in the United States.[34] Although the evidence base is limited, the available data support the use of PEG in patients with head and neck cancer. The absolute contraindications to PEG placement are the same as those of endoscopy, which include an inability to transilluminate the abdominal wall and appose the anterior gastric wall. Relative contraindications include ascites, coagulopathy, gastric varices, morbid obesity, and neoplastic, infiltrative, or inflammatory disease of the gastric or abdominal wall (Table 2).

Commercially available PEG tubes are sized 18F to 28F, made of polyurethane or silicone, and can last from 24 to 48 months. In most cases, preprocedure prophylactic antibiotics such as cefazolin are given to prevent infection. The procedure involves an initial endoscopy using conscious sedation to exclude gastric or duodenal obstruction, followed by the combined use of transillumination and finger indentation of the anterior abdominal wall to identify a suitable site. Once identified, the site is anesthetized with lidocaine, and a sounding needle is advanced from the anterior abdominal wall into the stomach lumen with endoscopic guidance.

This is followed by a 1-cm incision at the site and the passage of a trocar through the incision into the stomach, so that a guidewire can be passed into the stomach. An endoscopic snare or forceps is then used to grasp the wire and pull it out of the mouth while the trocar is removed. Once the guidewire is released, a PEG tube is either fastened to the guidewire and pulled into position or pushed over the guidewire into position. An external bolster is then placed to keep the PEG tube in place. PEG tubes can be used for feeding within 3 to 4 hours of placement.

Variations of this technique include the push introducer (Russell), Versa (a combination of the push and introducer technique), and primary button methods. When there is esophageal obstruction, the PEG can also be placed radiologically under fluoroscopic guidance. Surgical placement is comparable to PEG but is more expensive (as general anesthesia is required) and requires more recovery time before use.[35]

Other reported surgical techniques in the literature include laparoscopic gastrostomy,[36] cervical esophagostomy used in patients with oropharyngeal cancer,[37] and percutaneous needle pharyngostomy.[38] Transnasal, straight laryngoscopic or intraoperative open (pharyngeal) endoscopy techniques have also been used to facilitate PEG tube placement in head and neck cancer patients, in whom partial or complete trismus and/or stenosis of the upper aerodigestive tract prevented oral insertion of the endoscope into the esophagus.[39] Local expertise and accessibility should determine which approach to gastrostomy is performed; however, for gastric access using conscious sedation, the endoscopic approach is the most common.

Complications of gastrostomy tube placement in some series suggest a 17% morbidity rate, of which 3% were considered serious.[40] The minor complications include pneumoperitoneum, temporary ileus, wound bleeding, wound infection, cutaneous or gastric ulceration, peristomal leakage, and tube clogging. Major complications include necrotizing fascitis, peritonitis, aspiration, septicemia, dislodgement, esophageal perforation, gastric perforation, bowel perforation, gastrocolocutaneous fistulae, inadvertent PEG removal and buried bumper syndrome. Buried bumper syndrome occurs when the external bolster of the PEG tube is placed too firmly against the abdominal wall, causing the internal bolster device to slowly erode into the gastric wall and resulting in pain and difficulty infusing tube feeds. Metastatic tumor deposits have also been reported at the PEG site. The mortality rate associated with the procedure is < 1%.

Jejunal Access

Jejunal access is primarily useful in patients with ileus, gastric feeding intolerance, tube feeding-related reflux esophagitis, gastroparesis, insufficient stomach from a prior resection, aspiration pneumonia, or chronic pancreatitis, and is occasionally useful in patients with an unresectable gastric or pancreatic malignancy. However, further evidence is required to confirm the long-term impact of jejunal feeding.

Jejunal enteral access can be achieved either by initially performing an 18-28F gastrostomy and then placing a 9-12F jejunal attachment endoscopically over a guidewire (PEG/J), or by endoscopic (DPEJ), radiologic, or surgical placement directly into the jejunum. PEG/J tubes are associated with a tube malfunction rate in 53% to 84% of cases, and aspiration in 17% to 60% of cases.[41] The technique for DPEJ is an adaptation of a PEG, where an enteroscope or pediatric colonoscope is advanced to the jejunum, and then a similar method using a trocar and transillumination is performed.

Placement of a DPEJ is successful in 72% to 88% of patients[42] and appears to provide superior jejunal access compared to the PEG/J[43] but is technically considerably more difficult than a PEG. DPEJ placement is associated with major complications needing surgery in 2% of cases (including abdominal wall abscesses, bleeding, and colon perforations). Minor complications such as leakage, peristomal infections, and enteric ulcers occur in 8%, 7%, and 5% of patients, respectively. Aspiration of tube feeds with DPEJ is highly unlikely.[42]

Overall, multiple safe and efficient endoscopic, radiologic, and surgical techniques are available to obtain enteral access and ensure adequate nutritional support in patients with head and neck cancer. However, although there is evidence suggesting advantages of enteral support, larger prospective studies are required to confirm this benefit.

Nutrition

Once the decision is made regarding type of tube, there are three main methods by which the enteral supplement can be delivered: (1) the continuous drip, which can be either a 24-hour administration or cyclic, (2) intermittent delivery, which can also be performed over 24 hours without night feedings, and (3) bolus delivery, which gives flexibility in feedings to the alert and oriented patient.

Energy Requirements

The next issues to consider are the amount of formula and the type of formula to be used. Energy requirements can be calculated using indirect calorimetry, which gives the most precise estimate of resting energy expenditure. Due to financial constraints, however, the Harris and Benedict equation is more practical and reliable for measuring metabolic rate. The equation is used to estimate the basal energy expenditure (BEE) based on weight, height, and age.

In men:
BEE = 66.5 + (13.75 × kg) + (5.003 × cm) − (6.775 × age).

In women:
BEE = 655.1 + (9.563 × kg) + (1.850 × cm) − (4.676 × age).

These formulas were first published in 1919 and are still used extensively today for the calculation of BEE.[44] The results from this equation have been verified in validation studies comparing actual measurements and the predicted values of healthy individuals, with a mean difference of 4%.[45] One must keep in mind that these calculations are estimates and not based on actual calories expended; thus, monitoring of patient response is crucial. Monitoring by both weight profile and biochemical parameters can be useful in determining whether the patient's nutritional status is improving. Biochemical observation of serum albumin, serum transferrin, and prealbumin can provide necessary information for assessing patients both acutely and chronically.

Key Formula Components

• Protein-Protein quantity and quality are essential components in the selection of formula. Cancer patients have an accelerated protein turnover and a derangement in protein metabolism.[46] Requirements for protein are determined by calculations based on the patient's ideal body weight by utilizing the Metropolitan Height-Weight Tables. For individuals with a mild level of stress, the protein needs are 0.8 to 1.0 g of protein/kg of ideal body weight. Individuals who are determined to have mild to moderate depletion and are under metabolic stress require 1.5 to 2.0 g of protein/kg of ideal body weight. Weight gain and nitrogen equilibrium are the best methods for determining that adequate protein needs are being met.[47] Protein is considered to be the most important component of enteral formulas.

• Carbohydrates-The carbohydrate component of formulas provides 30% to 90% of total calories and in most cases is the principal energy source. The form in which carbohydrate is provided can range from starch to simple glucose, and these forms contribute to the osmolality and disgestibility of the formula. In most cases, the longer carbohydrate molecules exert less osmotic pressure and require more digestion than shorter ones.[48]

The most commonly used forms of carbohydrates in enteral formulas are oligosaccharides and polysaccharides. These require pancreatic enzymatic breakdown for digestion and rarely cause intolerance. The major drawback to the starch-rich formulas is greater osmolality. Disaccharides are sugars composed of two monosaccharides that require specific enzymes in the small bowel mucosa for digestion to occur. Most enteral formulas are lactose-free, as lactose is a disaccharide and lactase deficiency is the most prevalent of all enzymatic deficiencies. The monosaccharides are simple sugars, which cannot be hydrolyzed into a smaller form. They are found in enteral formulas in the form of glucose and fructose. Hydrolysis is not required for digestion, but tolerance may be limited by the absorptive capacity of the small bowel.[48,49]

• Fat-The third macronutrient component of enteral formulas, fat provides the calorie-dense energy source and a vehicle for fat-soluble vitamins and essential fatty acids. The fat calorie content in enteral formulas can range from 2% to 55%, with the average being 30%. Most commonly used fat sources are soybean, corn, safflower, and canola oil, medium-chain triglyceride, lecithin, and milk fat. Other emerging fat sources that provide not only important nutrients but also immune regulators are fish oil, structured lipids, and short-chain fatty acids.

• Vitamins and Minerals-Minerals-Most enteral formulas contain adequate vitamins and minerals in a volume of formula to meet energy and protein needs. Supplementation of additional vitamins and minerals may be indicated for patients who are fed incomplete or diluted formulas, and additional fatsoluble vitamins should be included for those with fat malabsorption.

• Fluids-Total body water accounts for 45% to 60% of adult body weight. The normal adult loses about 2,600 mL of fluid daily, which is usually offset by endogenous water production and metabolism or intake of exogenous fluids. When an individual relies on enteral nutrition, this amount of water must be supplied. Monitoring of daily weight, intake, and output can be helpful in assessing adequate hydration.[50] A 1.0-kcal/mL formula contains 75% free water, and a 2.0-kcal/mL formula contains 69% free water. When fluid recommendations are made these numbers must be taken into account.

Other Components

The final components of the formula involve the physical characteristics, ie, osmolality, renal solute load, hydrogen ion concentration, and lastly, calorie density. Osmolality is a measure of the concentration of free particles, molecules, or ions-e, protein/ amino acids, electrolytes, minerals, and carbohydrates-in a given solution in water. This parameter is measured by determining the number of particles or solute present per unit weight of water and is expressed in milliosmoles per kilogram of water (mOsm/kg).[51] Osmolality is important because of its role in maintaining the balance between intracellular and extracellular fluids. The average osmolality of enteral formulas ranges from 270 to 700 mOsm/kg.

The renal solute load refers to the constituents in the formula that must be excreted by the kidneys. The major constituents that contribute to renal solute load are protein, sodium, potassium, and chloride. This is important because as the formula becomes more concentrated or the renal solute load increases, the patient requires more water.[52]

Hydrogen ion concentration affects gastric motility when the pH is lower than 3.5.[53] However, the pH level of most enteral formulas is above 3.5.

The final component is caloric density, which determines not only how many calories the patient receives, but also the density of many other nutrients. The more nutrient-dense the formula, the less the moisture or water content. Gastric emptying rate may be slowed by high-caloric density formulas.[54]

Specialized Formulas

Specialized formula may be warranted for unique disease processes. For example, there are formulas designed for patients with pulmonary disease, where the goals are adequate nutritional support without overfeeding. Overfeeding patients with pulmonary disease produces a substantially greater increase in CO₂ production, since the respiratory quotient for converting carbohydrates to fat exceeds 1.0. In patients with CO₂ retention and pulmonary failure, the ratio of carbohydrate to fat calories within an enteral formulation may have some impact.[55]

Patients suffering from declining renal function may benefit from the same formulas that would be used in patients with renal failure.[56] These formulas are low in protein, phosphorus, magnesium, potassium, and sodium. A common comordibity, glucose intolerance, may also require a specialized formula that uses a carbohydrate component with a low gylcemic response. However, balanced polymeric formulas are appropriate for most patients, including those with mild to moderate gastrointestinal impairment.[57]

Complications of Enteral Nutrition

There are three main categories of complications during enteral nutrition: (1) mechanical problems related to the placement of the feeding tube and the formula delivery method, (2) clinical and metabolic problems, and (3) nutritional problems.

Mechanical Problems

Mechanical complications can be related to displacement of the tube via purposeful removal by the patient or by an inadvertent displacement from coughing, retching, or vomiting. The most common mechanical complication, however, is related to clogging of the tube. Simple actions are recommended to prevent clogging. The primary preventive measure is to flush with enough water to clear the tube. Even during continuous feeding, tubes should be routinely flushed with water every 4 hours, whenever the feeding is stopped, and whenever medications must be given through the feeding tube.

In the clinical setting, many types of fluids are used to "open up" feeding tubes, the most common being cola beverages, cranberry juice, and warm tea. Unfortunately these rinsing agents may actually produce a dried residue that can further diminish the effective lumen of the tube and can actually contribute to further clogging. The best solvent and rinsing agent is water, which leaves little or no residue.[54] The steps to prevent clogging are as follows[51]:

• With continuous feeding, routinely flush feeding tubes every 4 hours.
• Flush feeding tubes with water whenever feedings are stopped.
• Flush feeding tubes before and after gastrointestinal contents are withdrawn.
• Avoid giving powdered, crushed, highly acidic, or alkaline additives.
• If medications must be given through the tube, flush it with water before and after.
• Prevent contamination of enteral feeding.
• Avoid passing viscous foods and fiber supplements through small tubes.
• If blended foods are used, be sure foods are finely divided, and use larger tubes.

Clinical/Metabolic Problems

• Diarrhea-The first of the clinical problems associated with enteral nutrition is diarrhea. There is a long list of causes and contributors to diarrhea in the enterally fed individual, including medications, rate of delivery, composition of the feeding formula, malnutrition, aggressive refeeding, intercurrent gastrointestinal disorders, and opportunistic infection. In the acute care setting, most cases of diarrhea can probably be related to medications, either directly or indirectly.

The management of diarrhea involves first the assessment of severity, duration, and pattern, and then a detailed history to investigate all possible causes. When possible and if appropriate, the physician should withdraw offending medications; reduce the feeding rate, concentration, or volume; switch from bolus to intermittent or continuous feedings; remove the offending ingredient from the feeding; or relieve impaction. After all the preventable causes of diarrhea have been addressed, medications may be used to reduce or resolve many cases of mild to moderate diarrhea. More severe diarrhea may indicate malabsorption, maldigestion, or a secretory or infectious cause. Malabsorption might respond to a change in the concentration or rate of the formula, its composition or lipid content, or to adding pancreatic enzymes.[58-61]

• Aspiration-Aspiration is one of the most serious and life-threatening complications of tube feeding.[6] There are many components to the mechanics of aspiration: The position of the patient, the position of the tube, medications, surgical procedures, neuromuscular problems, delayed gastric emptying, or even reduced esophageal sphincter function can all increase the risk of reflux and aspiration.

Several measures have been advocated for reducing aspiration, but each has its own limitations. These include positioning of the tube-fed patient, elevating the head of the bed to at least 30°, checking residual volume,[6] and use of prokinetic agents to enhance gastric emptying. In general, aspiration is less frequent during continuous feeds rather than in bolus or intermittent feeds. The volume of gastric residuum to use as a cut point for deciding to delay or slow subsequent feedings is not completely clear; recommendations range from 100 to 200 mL, depending on the clinical situation.[20,62]

Nutritional Problems

Underfeeding occurs when a patient receives less than the prescribed or desired amount of feeding. Most commonly, underfeeding occurs because of interruptions in the feeding schedule, and therefore, awareness by patient or the patient's caretaker is essential. Overfeeding may result in abdominal bloating, cramping, diarrhea, or reflux, especially in a malnourished patient whose gastrointestinal function is compromised. Side effects of overfeeding include but are not limited to weight gain in the form of fat mass, and hyperglycemia. Overfeeding can also manifest as increased metabolic rate, cardiac demand, respirations, and carbon dioxide production. Concern for overfeeding is usually directed to patients with chronic obstructive pulmonary disease or those on ventilators. Reducing excessive caloric intake is more beneficial than reducing carbohydrate content of the feeding. Overfeeding syndrome potentially can be avoided by ensuring that feedings begin slowly at calorie levels below maintenance needs and are gradually advanced to maintenance needs.

Tube feeding syndrome is a set of symptoms, including azotemia, hypernatremia, and dehydration, that result from high-protein tube feedings especially in association with inadequate amounts of water. Prevention of this problem requires adequate fluid (at least 1 mL/cal plus any unusual respiratory, renal, or gastrointestinal losses) and the avoidance of protein loads greater than 1.5 g/kg of desirable body weight.

It is crucial that the medical team identify the degree of malnutrition and implement aggressive and sometimes invasive methods of nutritional support in patients who are at risk. In most patients, by providing enteral support, quality of life is improved through restoration of strength and energy and by reducing the pressure associated with "forced" feeding.

Summary

Malnutrition plays a key role in the morbidity of head and neck cancer patients receiving surgery, chemotherapy, radiotherapy, or combinedmodality therapy. Typically, the patient has already lost weight prior to the diagnosis of head and neck cancer.[7,63] Following diagnosis, an additional 10% of pretherapy body weight may be lost during radiotherapy or combined-modality treatment.[10,17,64] It is difficult to discern whether poor nutrition results in poor outcome because patients who receive more aggressive treatment experience greater toxicity, resulting in poor nutrition and weight loss. It has been established, however, that a reduction of greater than 20% of total body weight results in an increase in toxicity and mortality.[4]

In addition, the literature suggests that severe toxicity can result in prolonged treatment times because of poor nutritional status, and prolonged treatment time has been implicated in poor clinical outcome. Therefore, early intervention with nutritional supplementation can reduce the chance of inferior outcome in patients at high risk of weight loss, such as those with poor nutritional status prior to the initiation of therapy, those with a large tumor burden, those undergoing concurrent radiation therapy/chemotherapy, or those managed with radiotherapy fields that encompass large volumes of oropharyngeal mucosa.

The preferred route of nutritional support for these patients is enteral nutrition, which is more "physiologic," less expensive, safer, and associated with fewer side effects than the more aggressive approach of parenteral nutrition. Enteral nutrition is indicated in individuals who have an inability to orally ingest adequate nutrients, to meet the metabolic demands related to their treatment and disease. They must have a gastrointestinal tract that is functional. Enteral nutrition is contraindicated in individuals with a complete mechanical obstruction, intestinal hypomotility, severe pancreatitis, intractable vomiting, severe diarrhea, or any other situation where the gastrointestinal tract cannot be used safely.

Two commonly used methods for enteral feedings are nasoenteric and PEG. Nasoenteric feedings are the least invasive of all feeding methods and generally indicated for use in those who require short-term or supplemental nocturnal feedings. Generally, the nasoenteric method can be used for both bolus administration and continuous feeding. For patients who require long-term nutritional support, a PEG tube is preferred.[65]

It is important to take into account the ethical considerations involved in providing long-term nutritional support, particularly when considering patients with terminal conditions. Evaluation of eventual nutritional directives is best accomplished through multidisciplinary efforts, including input from the patient as well as members of the nursing, nutritionist, and medical staff.

Disclosures:

The authors have no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.

References:

1. Parshad R, Misra MC, Joshi, YK, et al: Role of enteral hyperalimentation in patients of carcinoma oesophagus. Indian J Med Res 98:165-169, 1993.
2. Nayel H, el-Ghoneimy E, el-Haddad S: Impact of nutritional supplementation on treatment delay and morbidity in patients with head and neck tumors treated with irradiation. Nutrition 8:13-18, 1992.
3. Daly JM, Weintraub FN, Shou J, et al: Enteral nutrition during multimodality therapy in upper gastrointestinal cancer patients. Ann Surg 221:327-338, 1995.
4. Goodwin WJ Jr, Byers PM: Nutritional management of the head and neck cancer patient. Med Clin North Am 77:597-610, 1993.
5. Heys SD, Park KG, Garlick PJ, et al: Nutrition and malignant disease: Implications for surgical practice. Br J Surg 79:614-623, 1992.
6.Bosaeus I, Daneryd P, Lundholm K: Dietary intake, resting energy expenditure, weight loss and survival in cancer patients. J Nutr 132:3465S-3466S, 2002.
7. Saito T, Kuwahara A, Shigemitsu Y, et al: Factors related to malnutrition in patients with esophageal cancer. Nutrition 7:117-121, 1991.
8. Belghiti J, Langonnet F, Bourstyn E, et al: Surgical implications of malnutrition and immunodeficiency in patients with carcinoma of the oesophagus. Br J Surg 70:339-341, 1983.
9. Lees J: Incidence of weight loss in head and neck cancer patients on commencing radiotherapy treatment at a regional oncology centre. Eur J Cancer Care 8:133-136, 1999.
10. Johnston CA, Keane TJ, Prudo SM: Weight loss in patients receiving radical radiation therapy for head and neck cancer: A prospective study. J Parenter Enteral Nutr 6:399- 402, 1982.
11. Tyldesley S, Sheehan F, Munk P, et al: The use of radiologically placed gastrostomy tubes in head and neck cancer patients receiving radiotherapy. Int J Radiat Oncol Biol Phys 36:1205-1209, 1996.
12. Peters LJ, Goepfert H, Ang KK, et al: Evaluation of the dose for postoperative radiation therapy of head and neck cancer: First report of a prospective randomized trial. Int J Radiat Oncol Biol Phys 26:3-11, 1993.
13. Pignon JP, Bourhis J, Domenge C, et al: Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: Three meta-analyses of updated individual data. MACH-NC Collaborative Group. Meta- Analysis of Chemotherapy on Head and Neck Cancer. Lancet 355:949-955, 2000.
14. Niibe Y, Karasawa K, Mitsuhashi T, et al: Hyperfractionated radiation therapy for hypopharyngeal carcinoma compared with conventional radiation therapy: Local control, laryngeal preservation and overall survival. Jpn J Clin Oncol 33:450-455, 2003.
15. Jeremic B, Shibamoto Y, Milicic B, et al: Hyperfractionated radiation therapy with or without concurrent low-dose daily cisplatin in locally advanced squamous cell carcinoma of the head and neck: A prospective randomized trial. J Clin Oncol 18:1458-1464, 2000.
16. Calais G, Alfonsi M, Bardet E, et al: Randomized trial of radiation therapy vs concomitant chemotherapy and radiation therapy for advanced-stage oropharynx carcinoma. J Natl Cancer Inst 91:2081-2086, 1999.
17. Newman LA, Vieira F, Schwiezer V, et al: Eating and weight changes following chemoradiation therapy for advanced head and neck cancer. Arch Otolaryngol Head Neck Surg 124:589-592, 1998.
18. Fu KK, Pajak TF, Trotti A, et al: A Radiation Therapy Oncology Group (RTOG) phase III randomized study to compare hyperfractionation and two variants of accelerated fractionation to standard fractionation radiotherapy for head and neck squamous cell carcinomas: First report of RTOG 9003. Int J Radiat Oncol Biol Phys 48:7-16, 2000.
19. Brizel DM, Albers ME, Fisher SR, et al: Hyperfractionated irradiation with or without concurrent chemotherapy for locally advanced head and neck cancer. N Engl J Med 338:1798- 1804, 1998.
20. List MA, Mumby P, Haraf D, et al: Performance and quality of life outcome in patients completing concomitant chemoradiotherapy protocols for head and neck cancer. Qual Life Res 6:274–284, 1997.
21. Chan AT, Teo PM, Ngan RK, et al: Concurrent chemotherapy-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: Progression- free survival analysis of a phase III randomized trial. J Clin Oncol 20:2038-2044, 2002.
22. Al-Sarraf M, LeBlanc M, Giri PG, et al: Chemoradiotherapy vs radiotherapy in patients with advanced nasopharyngeal cancer: Phase III randomized Intergroup study 0099. J Clin Oncol 16:1310-1317, 1998.
23. Lopez MJ, Robinson P, Madden T, et al: Nutritional support and prognosis in patients with head and neck cancer. J Surg Oncol 55:33- 36, 1994.
24. Barton MB, Keane TJ, Gadalla T, et al: The effect of treatment time and treatment interruption on tumour control following radical radiotherapy of laryngeal cancer. Radiother Oncol 23:137-143, 1992.
25. Alden ME, O’Reilly RC, Topham A, et al: Elapsed radiation therapy treatment time as a predictor of survival in patients with advanced head and neck cancer who receive chemotherapy and radiation therapy. Radiology 201:675-680, 1996.
26. Burt ME, Brennan MF: Nutritional support of the patient with esophageal cancer. Semin Oncol 11:127-135, 1984.
27. DeWys WD: Anorexia as a general effect of cancer. Cancer 43:2013-2019, 1979.
28. Belghiti J, Bourstyn E, Fekete F: Anorexia in oesophageal carcinoma. Eur J Surg Oncol 13:405-407, 1987.
29. Shaw JH, Humberstone DA, Holdaway C: Weight loss in patients with head and neck cancer: Malnutrition or tumour effect? Aust N Z J Surg 58:505-509, 1988.
30. Llovera M, Garcia-Martinez C, Lopez- Soriano J, et al: Role of TNF receptor 1 in protein turnover during cancer cachexia using gene knockout mice. Mol Cell Endocrinol 142:183- 189, 1998.
31. Garcia-Martinez C, Costelli P, Lopez- Soriano FJ, et al: Is TNF really involved in cachexia? Cancer Invest 15:47-54, 1997.
32. Oliff A, Defeo-Jones D, Boyer M, et al: Tumors secreting human TNF/cachectin induce cachexia in mice. Cell 50:555-563, 1987.
33. Zhou W, Jiang ZW, Tian J, et al: Role of NF-kappaB and cytokine in experimental cancer cachexia. World J Gastroenterol 9:1567- 1570, 2003.
34. Gauderer MW: Percutaneous endoscopic gastrostomy-20 years later: A historical perspective. J Pediatr Surg 36:217-219, 2001.
35. Grant MD, Rudberg MA, Brody JA: Gastrostomy placement and mortality among hospitalized Medicare beneficiaries. JAMA 279:1973, 1998.
36. Edelman DS, Unger SW: Laparoscopic gastrostomy. Surg Gynecol Obstet 173:401, 1991.
37. Klopp CT: Cervical esophagostomy. J Thorac Surg 21:490-491, 1951.
38. Bucklin DL, Gilsdorf RB: Percutaneous needle pharyngostomy JPEN 9:68-70, 1985.
39. Taller A, Horvath E, Ilias L, et al: Technical modifications for improving the success rate of PEG tube placement in patients with head and neck cancer. Gastrointest Endosc 54:633-636, 2001.
40. Safadi BY, Marks JM, Ponsky JL: Percutaneous endoscopic gastrostomy. Gastrointest Endosc Clin N Am 8:551-568, 1998.
41. DiSario JA, Foutch PG, Sanowski RA: Poor results with percutaneous endoscopic jejunostomy. Gastrointest Endosc 36:257-260, 1990.
42. Shike M, Latkany L: Direct percutaneous endoscopic jejunostomy. Gastrointest Endosc Clin N Am 8:569, 1998.
43. Fan AC, Baron TH, Rumalla A, et al: Comparison of direct percutaneous endoscopic jejunostomy and PEG with jejunal extension. Gastrointest Endosc 56:890, 2002.
44. Harris J, Benedict F: A biometric study of basal metabolism in man. Washington, DC; Carnegie Institution; publication 279:40-44, 1919.
45. Shike M: Nutrition therapy for the cancer patient. Hematol Oncol Clin North Am. 10221-10234, 1996.
46. Buzby K: Overview: Screening, assessing, and monitoring, in Bloch AS (ed): Nutrition Management of the Cancer Patient, pp 15- 22. Rockville, Md; Aspen Publishers, Inc; 1990.
47. MacBurney MM, Russell C, Young LS: Formulas, in Rombeau JL, Caldwell MD (eds): Clinical Nutrition: Enteral and Tube Feeding, 2nd ed, pp 149-170. Philadelphia, WB Saunders, 1990.
48. Mayes PA: Carbohydrates, in Martin DW, Mayes PA, Radwell VW, et al (eds): Harper’s Review of Biochemistry, 20th ed, pp 147-157. Los Altos, Calif; Lange; 1985.
49. Hauff K: Water-the forgotten nutrient. Support Line 13:11-16, 1991.
50. Trujillo EB: Enteral nutrition: A comprehensive overview, in Matarese LE, Gottschlich MM (eds): Contemporary Nutrition Support Practice: A Clinical Guide, pp 192-199. Philadelphia, WB Saunders, 1998.
51. Hunt JN, Stubbs DF: The volume and energy content of meals as determinants of gastric emptying. J Physiol 245:209-225, 1975.
52. Smith CE, Marien L, Brogdon C, et al: Diarrhea associated with tube feeding in mechanically ventilated critically ill patients. Nurs Res 39:148-152, 1990.
53. Eisenberg PG: Causes of diarrhea in tubefed patients: A comprehensive approach to diagnosis and management. Nutr Clin Pract 8:119-123, 1993.
54. Roediger WEW: Metabolic basis of starvation, diarrhoea: Implications for treatment. Lancet 8489:1082-1083, 1986.
55. American Gastroenterological Association Medical Position Statement: Guidelines for the Use of Enteral Nutrition, p 22. Bethesda, Md; American Gastroenterological Association; 1995.
56. Abel RM, Beck CH Jr, Abbott WM, et al: Improved survival from acute renal failure after treatment with intravenous essential Lamino acids and glucose: Results of a prospective, double-blind study. N Engl J Med 288:695-699, 1973.
57. Charney P: Nutrition management for specific medical conditions-diabetes mellitus. Quick Reference to Clinical Dietetics, p 41. Gaithersburg, Md; Aspen Publishers; 1997.
58. Roediger WEW: Famine, fiber, fatty acids, and failed colonic absorption: Does fiber fermentation ameliorate diarrhea? J Parenter Enteral Nutr 18:4-8, 1994.
59. Coben R, Weintraub A, DiMarino A: Gastroesophageal reflux during gastrostomy feeding. Gastroenterology 106:13-18, 1994.
60. Metheny N: Minimizing respiratory complications of nasogastric tube feedings: State of the science. Heart Lung 22:213-223, 1992.
61. McClave SA, Snider HL, Lowen CC, et al: Use of residual volume as a marker for enteral feeding intolerance: Prospective blinded comparison with physical examination and radiographic findings. J Parenter Enteral Nutr 16:99-105, 1992.
62. Stiegmann G, Goff J, VanWay C, et al: Operative vs endoscopic gastrostomy: Preliminary results of a prospective randomized trial. Am J Surg 155:88-92, 1988.
63. Chencharick JD, Mossman KL: Nutritional consequences of the radiotherapy of head and neck cancer. Cancer 51:811-815, 1983.
64. Beeken L, Calman F: A return to “normal eating” after curative treatment for oral cancer: What are the long-term prospects? Eur J Cancer B Oral Oncol 30B:387-392, 1994.
65. Long CL: Nutritional assessment of the critically ill patient, in Wright RA, Heymsfield S (eds): Nutritional Assessment, p 168. Boston, Blackwell Scientific Publications, 1984.