The nutrition status of patients with cancer can vary at presentation and through the continuum of cancer care. Many patients experience unintentional weight loss leading to a diagnosis of cancer.[1,2] Studies have reported malnutrition in 30% to 85% of patients with cancer.[3,4] Because there has previously been no universal definition of malnutrition, reports of malnutrition occurrence vary and may be under- or overreported in different populations. Historically, weight loss, low body mass index (BMI), and serum albumin levels have been used as surrogate markers for malnutrition.[5,6]
Emerging evidence supports that loss of lean body mass (sarcopenia) in patients with cancer is an independent risk factor for poorer outcomes; and that in the setting of obesity, unlike in other diseases where weight loss may be welcomed, inappropriate loss of weight may lead to loss of muscle mass and poorer outcomes.[1,2,7,8] However, there is no universal definition of sarcopenia, and there are no simple methods to identify the condition, limiting application in clinical practice.
The leading nutrition societies of the United States and Europe have developed consensus guidelines regarding standardized definitions of malnutrition, and the U.S. societies have developed criteria for assessment of malnutrition including weight loss.[6,10,11]
In 2010, the American Society for Parenteral and Enteral Nutrition (ASPEN) and the European Society for Clinical Nutrition and Metabolism published their proposed etiology-based definitions of malnutrition. These have been accepted by both groups and the Academy of Nutrition and Dietetics (the Academy).[6,10,12] The definitions and characteristics of malnutrition have also been accepted by the Academy's Oncology Nutrition Evidence Analysis Library Work Group.
Etiology-based definitions of malnutrition include the following:
In 2012, ASPEN and the Academy released a joint statement regarding assessment of malnutrition. The statement serves as a guide for nutrition assessment, including nutrition-focused physical assessment, to determine nutrition status. The assessment takes into consideration that obesity may mask malnutrition and that weight and BMI alone are not good surrogates for nutrition status. The consensus statement provides the criteria for evaluating each of the following six potential indicators of malnutrition, with the recommendation that if two or more characteristics are present, the diagnosis of malnutrition is warranted.
Significant Weight Loss
Weight loss is often used as a surrogate for malnutrition. It has been correlated with adverse outcomes, including increased incidence and severity of treatment side effects and increased risk of infection, thereby reducing chances for survival. Weight loss has been used as an indicator of poor prognosis in cancer patients. One limitation of using weight loss as a surrogate for malnutrition is that it does not take into account the time course of the weight loss or the type of tissue loss. In addition, weight may be affected by fluid shifts and may represent changes in hydration status, edema, or ascites rather than actual changes in fat and lean body mass.
The major nutrition societies of the United States have published criteria for the evaluation of weight loss over time and classifications as moderate or severe  (refer to Table 1). It is important that changes in weight be evaluated in the context of other clinical characteristics of under- or overhydration.
|Time||% Weight Loss for Non-Severe (Moderate) Malnutrition||% Weight Loss for Severe Malnutrition|
|a Adapted from White et al.|
Anorexia and Cachexia
Anorexia, the loss of appetite or desire to eat, is typically present in 15% to 25% of all patients with cancer at diagnosis and may also occur as a side effect of treatments or related to the tumor itself. In an observational study of patients in outpatient clinics, anorexia was reported by 26% of patients receiving chemotherapy. Anorexia can be exacerbated by chemotherapy and radiation therapy side effects such as taste and smell changes, nausea, and vomiting. Surgical procedures, including esophagectomy and gastrectomy, may produce early satiety, a premature feeling of fullness. Depression, loss of personal interests or hope, and anxious thoughts may be enough to bring about anorexia and result in malnutrition. Anorexia is an almost-universal symptom in individuals with widely metastatic disease [19,20] because of physiologic alterations in metabolism during carcinogenesis.
Anorexia can hasten the course of cachexia, a progressive wasting syndrome evidenced by weakness and a marked and progressive loss of body weight, fat, and muscle. It can develop in individuals who have adequate protein and calorie intake but have primary cachexia whereby tumor-related factors prevent maintenance of fat and muscle. Patients with diseases of the gastrointestinal tract are particularly at risk of developing anorexia. (Refer to the Tumor metabolism section in the Impediments to Adequate Nutrition section of this summary for more information.)
Sarcopenia is the condition of severe muscle depletion. The importance of lean body mass is shown in studies of sarcopenia in cancer. A meta-analysis of 38 studies found that a low skeletal muscle index at cancer diagnosis was associated with worse survival in patients with solid tumors. Other studies have also reported poorer overall survival and increased chemotherapy toxicity in patients with sarcopenia.[1,2,8] Sarcopenic obesity may represent a chronic low-level inflammatory state that, as with disease-related malnutrition, often limits the effectiveness of nutrition interventions and requires successful treatment of the underlying disease or condition. Sarcopenia is associated with increased toxicity of treatment and therefore treatment interruptions and dose reductions. It is reported to occur in 50% of patients with advanced cancer.[21,22,23]
Sarcopenic obesity is the presence of sarcopenia in individuals with a high BMI (≥25 kg/m2) often precipitated by the loss of skeletal muscle and gain of adipose tissue. Sarcopenic obesity is an independent risk factor for poor prognosis.[1,24,25]
It is important to identify and anticipate malnutrition and other nutrition impact symptoms early. (Nutrition impact symptoms are a range of side effects of cancer and cancer treatment that impede oral intake, e.g., alterations in taste and smell, mucositis, dysphagia, stomatitis, nausea, vomiting, diarrhea, constipation, malabsorption, pain, depression, and anxiety.) Nutrition intervention improves outcomes by helping a patient do the following:[4,5,15,21,26,27,28]
It is suggested that the treating clinician assess baseline nutrition status (refer to the Nutrition Screening and Assessment section of this summary for more information) and be aware of the possible implications of the various therapies. Patients receiving aggressive cancer therapies typically need aggressive nutrition management.
In this summary, unless otherwise stated, evidence and practice issues as they relate to adults are discussed. The evidence and application to practice related to children may differ significantly from information related to adults. When specific information about the care of children is available, it is summarized under its own heading.
Influences on nutrition status and risk of malnutrition include the following:
Treatment approaches, including surgery, chemotherapy, and radiation therapy, can have a direct (mechanical) negative effect and/or an indirect (metabolic) negative effect on nutrition status. The success of anticancer therapy is affected by the patient's nutrition status before and during treatment, which influences the patient's ability to tolerate therapy.
Oral intake is impeded by the following nutrition impact symptoms:
Preexisting comorbidities may also play a role in the development of cancer, e.g., alcohol abuse (head and neck cancer) and obesity (breast or prostate cancer), or may increase the risk of malnutrition at presentation.[3,4]
Tumor-Induced Effects on Nutrition Status
Tumors may have systemic or local effects that affect nutrition status, including hypermetabolism, malabsorption, dysmotility, and obstructions.
Nutrition complications are usually most notable and severe with tumors involving the digestive tract or head and neck, owing to mechanical obstruction or dysfunction. Refer to Table 2 for common side effects of tumor locations.
|Common Side Effects||Tumor Location|
|a Adapted from McGuire,Leser,Gill,Nguyen et al.,and Petzel.|
|Head/Neck||Esophagus, Stomach||Pancreas, Liver, Small Intestine||Large Intestine|
Nutrition status can be compromised in direct response to tumor-induced alterations in metabolism (i.e., cachexia). Tumor-induced weight loss occurs frequently in patients with solid tumors of the lung, pancreas, and upper gastrointestinal (GI) tract and less often in patients with breast cancer or lower GI cancer. Cachexia is also more common with more-advanced disease.
In 2011, an international group of experts developed a consensus definition of cachexia as "a multifactorial syndrome defined by an ongoing loss of skeletal muscle mass...that cannot be fully reversed by conventional nutrition support and leads to progressive functional impairment." They classified three stages of cachexia and provided diagnostic criteria:
Although anorexia may also be present, the energy deficit alone does not explain the pathogenesis of cachexia. The etiology of cancer cachexia is not entirely understood, but several factors have been proposed. Mediators, including cytokines, neuropeptides, neurotransmitters, and tumor-derived factors, are postulated to contribute to this syndrome. Products of host tissues (e.g., tumor necrosis factor-alpha, interleukin-1, interleukin-6, interferon-gamma, and leukemia inhibitor factor) have been identified as mediators of this complex syndrome; also, tumor products (e.g., lipid-mobilizing factor and proteolysis-inducing factor [not established as definite in humans]) have a direct catabolic effect on host tissues.
Altered metabolism of fats, proteins, and carbohydrates is evident in patients with cancer cachexia. Tumors may impair glucose uptake and glucose oxidation, leading to an increased glycolysis. Weight loss can occur from a decrease in energy intake and/or an increase in energy expenditure. Although anorexia is a common symptom of patients with cancer, studies have shown that increased caloric intake, whether by the oral route or by supplementation with total parenteral nutrition, has failed to counteract the wasting process. This aberrant metabolic rate appears to be a direct response by the tumor and immune system to disrupt the pathways that regulate the body-weight regulation homeostasis loop.
Treatment-Induced Effects on Nutrition Status
Cancer treatments may cause acute and chronic effects. Nutrition intervention is based on symptom management. Patients who maintain good nutrition are more likely to tolerate the side effects of treatment. Adequate calories and protein can help maintain patient strength and prevent body tissues from further catabolism. Side effects of cancer treatments vary among patients, depending on the type, length, and dose of treatments and the type of cancer being treated (refer to Table 3). Cancer treatment has toxic effects on the GI tract, including the following:
|a Adapted from Grantand American Cancer Society.|
|Chemotherapy||Radiation Therapy||Biotherapy||Hormone Therapy||Surgery|
Chemotherapy and hormone therapy
Chemotherapy and hormone therapy can be used as single agents or in combination, depending on the disease type and patient's health condition.[16,18] These agents are divided into several functional categories. For example, chemotherapy is a systemic treatment (not a localized treatment) that affects the whole body (not just a specific part)  and potentially causes more side effects when compared with localized treatments such as surgery and radiation therapy.
Common nutrition-related side effects include the following:
Because cancer and the side effects of chemotherapy can greatly affect nutrition status, health care providers must anticipate possible problems and formulate a plan with the patient to prevent malnutrition and weight loss (refer to the Nutrition Screening and Assessment section of this summary for more information). Malnutrition and weight loss can affect a patient's ability to regain health and acceptable blood counts between chemotherapy cycles; this can directly affect the patient's ability to stay on treatment schedules, which is important for achieving a successful outcome. (Refer to the Behavioral strategies for symptom management section in the Nutrition Therapy section of this summary for more information.)
Patients receiving hormone suppression therapies are at risk of weight gain rather than weight loss. These patients may benefit from directed education to minimize weight gain and help reduce the risk of developing comorbidities associated with excess body weight.
Radiation therapy causes localized symptoms. Some of the common nutrition-related side effects caused by irradiation include the following:
The side effects of radiation therapy depend on the area that is irradiated, total dose, fractionation, duration, and volume irradiated (refer to Table 4). Most side effects are acute, begin around the second or third week of treatment, and diminish 2 or 3 weeks after radiation therapy has been completed. Some side effects can be chronic and continue or occur after treatment has been completed. (Refer to the Behavioral strategies for symptom management section in the Nutrition Therapy section of this summary for more information.)
Nutrition support during radiation therapy is vital. The effect of radiation therapy on healthy tissue in the treatment field can produce changes in normal physiologic function that may ultimately diminish a patient's nutrition status by interfering with ingestion, digestion, or absorption of nutrients.
Many nutrition-related side effects result from radiation therapy. Quality of life and nutrition intake can be improved by managing these side effects through appropriate medical nutrition therapy and dietary modifications. For example, medications such as pilocarpine (Salagen) may be useful in treating the xerostomia that accompanies radiation therapy targeting the head and neck. This medicine may reduce the need for artificial saliva agents or other oral comfort agents such as hard candy or sugarless gum.
|a Adapted from Grant (tables 11-14–11-16),Romano,and Harris et al.|
|Xerostomia, mucositis, taste changes||Dysphagia, odynophagia, esophagitis||Nausea, vomiting||Diarrhea||Other acute||Late side effects|
|Brain||X||X||Loss of appetite||Dysphagia|
|Head and neck||X||X||Thick saliva||Trismus, dysphagia, xerostomia|
|Chest||X||X||Loss of appetite||Esophageal stenosis, fibrosis, or necrosis|
|Abdomen||X||X||Chronic enteritis/colitis, intestinal stricture or obstruction|
|Pelvis and rectum||X||X|
For patients with most types of solid tumors, surgery is the only chance for a cure. Although a tumor may be technically resectable, a meaningful recovery can depend on a patient's preoperative nutrition status. Patients who are malnourished at the time of surgery are at higher risk of postoperative morbidity and mortality and longer hospital stays.[25,26] If time permits or if the surgical procedure may be delayed safely, steps can be taken to identify patients who are moderately to severely malnourished before surgery (refer to the Nutrition Screening and Assessment section of this summary for more information) and to correct macronutrient and micronutrient deficiencies before surgery.[6,25] Choosing the best method to correct a nutrition deficiency depends on GI tract function; options include oral liquid nutrition supplements, and enteral or parenteral nutrition support.
Surgical treatment can increase occurrence of malnutrition or worsen malnutrition. Common side effects of surgery, especially to the GI tract or head and neck, include decreased appetite, decreased ability to take food by mouth, and early satiety, all of which can lead to worsening preexisting malnutrition or may cause previously adequately nourished patients to become malnourished after surgery.
Depending on the procedure, surgery can cause mechanical or physiologic barriers to adequate nutrition, such as a short gut that results in malabsorption after bowel resection. In addition to these mechanical barriers, surgery frequently leads to an immediate catabolic response and changes the nutrient requirements necessary for wound healing and recovery at a time when baseline needs and requirements are often not being met.
(Refer to the Nutrition support section in the Nutrition Therapy section of this summary for more information about approaches to nutrition intervention and the appropriate use of enteral and parenteral nutrition support.)
Biotherapy is treatment to boost the immune system to help enhance the body's own response against cancer or to help repair normal cells damaged as a side effect of treatment. Biotherapy includes growth factors, monoclonal antibodies, and vaccines. The symptoms of biotherapy that are most likely to impact nutrition status are fatigue, fever, nausea, vomiting, and diarrhea.
Hemopoietic cell transplantation (HCT)
HCT patients can have special nutrition requirements. Before cell transplant, patients receive high-dose chemotherapy and may be treated with total-body irradiation.[28,29] In addition to the medications used during transplantation, these treatments frequently result in nutrition-related side effects, including mucositis and significant diarrhea, which may affect the ability of patients to consume an adequate diet. Patients may also experience acute or chronic graft-versus-host disease (GVHD). GVHD may target the GI tract, liver, or skin, altering the body's ability to ingest and process adequate calories and protein.
The goal of nutrition support is to maintain adequate nutrition status and protein stores. The American Society for Parenteral and Enteral Nutrition recommends that patients undergoing HCT who are malnourished and anticipated to be unable to ingest or absorb adequate nutrients for a prolonged period of time (>7–14 days) receive nutrition support; if a patient has a functioning GI tract, enteral nutrition is recommended.[28,29]
In addition, transplant patients are at very high risk of neutropenia, an abnormally small number of neutrophils in the blood that increases susceptibility to multiple infections. To reduce the risk of infections related to HCT, patients can receive dietary counseling regarding safe food handling and avoidance of foods that may pose an infection risk.[28,29] (Refer to the Reducing Risk of Foodborne Illness in Cancer Patients section of this summary for more information about diet for immunocompromised patients.)
Optimizing nutrition for patients with cancer involves early detection of malnutrition or risk of malnutrition so that intervention may be initiated in the early stages of disease or treatment. The goal of nutrition screening is to rapidly identify patients who are at risk of developing malnutrition and refer them to a health care professional, ideally a registered dietitian, who can perform a complete nutrition assessment and implement a nutrition care plan.[1,2]
There are no standard definitions or indices of malnutrition. Historically, loss of weight or body mass index (BMI), low BMI, and low serum protein (e.g., albumin) have been used to identify patients with malnutrition. Without more context, these characteristics are not acceptable measures by which to determine malnutrition.[3,4,5] Weight changes alone cannot be used to determine nutrition status because weight changes do not account for fluid changes (dehydration, ascites, and edema) or disproportionate loss of lean body mass.[4,6] Likewise, evidence demonstrates that BMI is deceiving because it does not account for body composition (lean body mass vs. fat mass), and many patients with cancer may present with a normal or high body weight/BMI but have severe muscle depletion (i.e., sarcopenia). The use of albumin, which is now recognized as being significantly influenced by inflammation, is also a poor measure of nutrition status and more likely suggestive of disease severity, not nutrition status.[4,8] Standardized definitions and cutoff points that designate malnutrition or cachexia are being developed; however, the true prevalence of malnutrition in the oncology population is unknown.
A growing body of literature examines the prevalence of malnutrition in obese cancer patients. In a study of clinical data obtained from 1,469 patients with metastatic primary cancers, 41.9% were identified as overweight or obese. Upon assessment, 50% were at risk of being malnourished, and 12% were already malnourished at presentation. Malnutrition, even in the presence of obesity, has been found to be an independent predictor of survival, with patients presenting with sarcopenic obesity having the poorest prognosis. Therefore, these data suggest that the assessment of malnutrition among patients of every weight status is important.
Obesity has been shown to increase the risk of cancer recurrence, and it negatively impacts overall survival.[1,11,12] The prevalence of obesity is higher in adult cancer survivors than in those without a cancer history. Cancer survivors with the highest rates of increasing obesity are colorectal and breast cancer survivors and non-Hispanic blacks. Emerging evidence supports the efficacy of intentional weight loss in overweight or obese cancer patients and survivors to reduce the risk of recurrent disease and improve prognosis, particularly among breast cancer patients.[14,15,16] Similar research is under way for patients with other obesity-related cancers.
Early recognition of nutrition-related issues is necessary for appropriate nutrition management of cancer patients. Nutrition screening can be performed with a validated tool before treatment begins and at regular intervals over the course of treatment.
Nutrition screening can be a simple process that may be completed by hospital staff or members of the community/ambulatory health care team, with the goal of early identification of individuals with malnutrition or at risk of malnutrition.[1,5,17,18] Leading nutrition organizations—including the American Society for Parenteral and Enteral Nutrition, the European Society for Clinical Nutrition and Metabolism, and the Academy of Nutrition and Dietetics (the Academy)—recommend screening patients in both acute and ambulatory settings for risk of malnutrition.[8,17,18] The Academy's Oncology Nutrition Dietetic Practice Group, the Oncology Nursing Society, and the Association of Community Cancer Centers recommend screening all patients with cancer in the outpatient setting.[1,5] Because of a mandate from The Joint Commission that all patients admitted to the hospital undergo nutrition screening, most acute care facilities have a screening system set up, although such a system may not be specific to or validated in the oncology setting.
In the outpatient oncology setting, it is recommended that patients be screened initially before treatment begins and re-screened at planned intervals. Screening can most often coincide with the patient's treatment schedule, such as weekly during radiation therapy and as frequently as every 2 to 3 weeks during chemotherapy, before surgery, and at follow-up visits after completion of treatment or surgical recovery.[1,2,5]
However, only the MST and the PG-SGA have been validated for use in both inpatient and outpatient oncology settings. Several studies have validated the use of the abridged PG-SGA (abPG-SGA) or short-form PG-SGA (PG-SGAsf), each of which is simply the section of the PG-SGA completed by the patient.[25,26]
The Nutrition Risk Screening-2002 has not been validated in the oncology setting, but it has been used in several studies of oncology patients. Scores are correlated to general outcomes associated with malnutrition, such as hospital length of stay, complications, and mortality.[2,3,18,27,28]
The NUTRISCORE tool utilizes the MST as a base but has additional items, including tumor location and treatment, that help improve sensitivity (97.3% vs. 84%) and specificity (95.9% vs. 85.6%). The authors used the PG-SGA as the reference for validation in the outpatient oncology setting, also finding that it took less time to complete the NUTRISCORE than it did to complete the PG-SGA.
When a screening method is being chosen, it is recommended to consider who will be performing the screen, how much time may be devoted to the process, and what the process will be for referring the patient for a full nutrition assessment. It is also ideal to use a validated tool. The two tools validated for both inpatient and outpatient in oncology settings are presented in further detail below.
The MST is a short questionnaire comprising two questions. Depending on the answers to these questions, patients are stratified into two categories: at risk or not at risk. The advantage of the MST is that it is quick to perform and may be completed by health care or administrative staff. It is well validated and consistently shows high sensitivity and specificity in identifying patients at risk of malnutrition.
In screening, it is important to use a validated tool and to consider the needs of the clinical practice. In centers where a registered dietitian is readily available, the MST may be the screening tool of choice because it is quick and can be performed by many members of the office and practice staff. Patients found to be at risk may be referred to the dietitian for further assessment.
The PG-SGA is the most commonly accepted tool for screening and assessment, backed by many studies and validated in both inpatient and outpatient oncology settings.[2,29] It is an in-depth tool, and most of the items are completed by the patient. There are four sections comprising 17 data points evaluating the following:
The remainder of the PG-SGA is completed by a health care practitioner, accounting for information about disease and metabolic demand and the completion of a physical exam. The abPG-SGA and PG-SGAsf use only the section completed by the patient. Responses are then scored and, on the basis of the score, patients are stratified into the following four nutrition triage categories:[1,5]
The drawback is that the PG-SGA takes more time to administer and requires a trained health care practitioner to complete the physical assessment portion. With validation of the short form, the need for physical exam is eliminated, and the practitioner's administration time is reduced. The benefit of the PG-SGA (PG-SGAsf) is that it collects clinical information that can be helpful in the nutrition assessment.
In practices where a registered dietitian is not readily available, the PG-SGAsf may be more appropriate because it helps better determine which patients may receive sufficient information from the nurse, advanced-practice provider, or physician and which patients would best be referred to a registered dietitian for more in-depth assessment and intervention.
Nutrition assessment is a comprehensive approach to evaluating and diagnosing nutrition problems and designing interventions. A full nutrition assessment involves evaluation of the following six components:
The assessment of anthropometric measurements evaluates weight loss, takes into account the time frame of weight loss, and is considered in the context of physical findings such as dehydration or fluid retention. Evaluation of food- and nutrition-related history ideally involves a dietitian obtaining a diet history and comparing intake with the patient's calculated energy needs.[2,6] The nutrition-focused physical assessment evaluates loss of muscle mass and subcutaneous fat, fluid accumulation, and potential micronutrient deficiencies. The physical exam of the following areas determines loss of subcutaneous fat or muscle:
Subcutaneous fat loss
Subcutaneous muscle loss
Within the nutrition assessment, the following factors are considered in diagnosing malnutrition:
In addition to the issues described above, the oncology nutrition assessment also takes into account the following:
The goal of an oncology nutrition assessment is to collect the information necessary to determine current or anticipated nutrition issues and to formulate a plan with the patient, caregivers, and other members of the health care team involved with nutrition interventions. Additionally, this multidisciplinary team approach may also include metabolic, pharmacologic, and functional interventions to address and prevent the identified or anticipated nutrition issues.[1,5,30]
Goals of Nutrition Therapy
The goals of medical nutrition therapy are to do the following:
Goals must be individualized for each patient on the basis of the following:
Decisions about the best approach for therapy are informed by symptom severity and function of the gastrointestinal (GI) tract. Treatment could include multiple strategies based on these factors.
Nutrition goals during and after cancer therapy are integrated with goals related to nutrition status and the presence of malnutrition.Table 5 summarizes nutrition goals on the basis of nutrition status, malnutrition as defined by current guidelines, and stage of cancer treatment.
A healthy diet with an emphasis on plant-based foods, regular physical activity, and achievement of a healthy weight has been recommended for all patients after cancer treatment on the basis of extensive reviews of the evidence.[4,5] Evidence-based guidelines for a healthy diet for cancer risk reduction are available online from the American Institute for Cancer Research (AICR) and the American Cancer Society (ACS).
|Weight/Nutrition Status||During Treatment|
|a Adapted from Hamilton et al.,Kushi et al.,and Rock et al.|
|Healthy weight and nutrition status||Maintain lean body mass|
|Maintain healthy weight|
|– Acute disease related||Support vital organ function|
|Preserve host response though acute episode|
|May have increased energy and protein requirements|
|– Chronic disease related||Maintain and improve lean body mass and fat|
|Obesity (no malnutrition)||Maintain lean body mass|
|Consider modest weight reduction (≤2 lbs/wk)|
Methods of Nutrition Therapy
Prompt and aggressive nutrition intervention is required for patients with precachexia or cancer cachexia. Intervention is more likely to be effective when started early. Interventions include an individualized approach to oral, enteral, and parenteral nutrition using evidence-based recommendations, guidelines, and program and regulatory standards.
The dietitian works with the patient, caregivers, and members of the health care team to (1) improve compliance and the effectiveness of pharmacotherapy interventions prescribed to manage cancer and cancer treatment–related symptoms; and (2) counsel patients about behavioral strategies to alleviate nutrition impact symptoms.
Counseling by a registered dietitian
The registered dietitian/nutritionist is an integral member of the oncology team in hospital and ambulatory settings. The Association of Community Cancer Centers Cancer Program Guidelines  specify having a registered dietitian as the nutrition professional available to work with patients and their families, especially those at risk of developing nutrition problems. Registered dietitians work with the patient, family, and medical team to manage the nutrition and hydration status and maintain optimal nutrition status across the continuum of care through appropriate screening, assessment, and intervention.
A systematic review of randomized controlled trials led to the recommendation that patients be referred for nutrition counseling because of strong evidence of the beneficial effects it has on the prevention and reduction of malnutrition. Intensive, individualized nutrition counseling requires nutrition professionals with specific experience in oncology.[9,11]
Behavioral strategies for symptom management
Cancer and cancer treatment result in a range of side effects, described as nutrition impact symptoms, that impede oral intake. While some patients experience few of these effects, others may have multiple symptoms, including:
These symptoms can result in a decline in nutrition status and quality of life. Behavioral strategies are essential for alleviating the impact of these symptoms and promoting adequate nutrient intake; pharmacologic interventions may be used in combination with these strategies to minimize symptom severity.
The following lists describe behavioral strategies to help alleviate nutrition-related symptoms of cancer treatment. The information is based on the National Cancer Institute's (NCI's) Eating Hints: Before, During, and After Cancer Treatment and AICR's Dealing with Treatment Side Effects. Additional information about nutrition strategies during treatment is available from oncology-focused organizations such as ACS and AICR.[4,5,12]
Behavioral Strategies to Alleviate Nutrition-Related Symptoms
Oral nutrition supplements
Commercially available oral nutrition supplements (e.g., Boost, Ensure) are often used to improve the adequacy of nutrient intake. These medical food products are not intended to serve as the sole source of nutrition, but to supplement energy, protein, fat, carbohydrate, and/or fiber intake, and also contribute to vitamin and mineral intake. Recommendations for oral nutrition supplements are based on assessment of a patient's nutrition status, nutrient needs, GI function, clinical condition, diet, food preferences, comorbid conditions, and resources.
Patients with cancer need adequate protein to maintain and rebuild lean body mass. A systematic review of multinutrient, high-protein oral nutrition supplements found significant improvement in total energy and protein intake and reduced incidence of complications. Specialized products are also available for use in clinical conditions requiring diet modifications. Research related to oral nutrition supplements and cancer patients has primarily focused on products containing fish oil/omega-3 fatty acids.[14,15,16] A systematic review of 38 studies did not find evidence to support a benefit of fish oil (supplements or enriched oral nutrition drinks) for the treatment of cachexia in advanced cancer. A randomized trial evaluated the perioperative use of an oral nutrition drink enriched with eicosapentaenoic acid (EPA) (fish oil). In patients with resectable gastric cancer, supplementation did not change postoperative weight loss or complication rates.
Although supplements containing fish oil alone do not seem to be beneficial in cachexia or surgery recovery, studies of immune-enhancing (IE) formulas containing fish oil, as well as arginine and nucleotides, suggest benefit for individuals undergoing GI surgery. A 2012 Cochrane review found significant reduction in postoperative complications and infections when IE oral supplements or enteral feeding were given before GI surgery. A 2015 Bayesian network meta-analysis of randomized controlled trials also demonstrated reduction in postoperative infectious complications when IE formulas were used preoperatively. Studies of both preoperative and postoperative use found that noninfectious complications and hospital length of stay were also reduced.
There is concern that long-term use of oral nutrition supplements can result in taste fatigue and decreased compliance with recommendations. A systematic review of compliance with oral nutrition supplements suggested that compliance is good, especially with higher-energy-density supplements. Weaknesses of the review were that compliance was not the primary outcome variable of most of the evaluated studies, the analysis involved mean results from groups of subjects rather than individual compliance, and only 11% of the studies involved patients with cancer.
When oral supplements do not achieve nutrition goals, enteral and/or parenteral nutrition can be considered in the context of a patient's nutrition status and the overall medical treatment plan.[22,23]
Nutrition support is the delivery of nutrition that bypasses oral intake. Every measure is employed to sustain patients and improve their condition through oral intake before consideration is given to nutrition support.
The use of enteral and parenteral nutrition in the oncology population may be indicated when oral nutrition strategies are not possible or fail because of tumor location or severe side effects. Although nutrition support is not recommended as standard treatment, it may be beneficial for patients who are malnourished and expected to become unable to take in adequate nutrition by mouth for an extended period of time.[22,23] There are concerns that use of nutrition support will stimulate tumor growth and metastasis, but studies in humans are limited and show mixed results. However, if nutrition support is clinically indicated, it should not be withheld because of concerns about tumor promotion.[22,24]
Enteral nutrition is preferred over parenteral nutrition in most instances. Enteral nutrition continues to use the gut, is associated with fewer infectious complications, is often easier to administer, and is more cost-effective than parenteral nutrition.[22,24,25] Parenteral nutrition is indicated for patients with a malfunctioning GI tract, malabsorptive conditions, mechanical obstructions, severe bleeding, severe diarrhea, intractable vomiting, GI fistulas in locations difficult to bypass with an enteral tube, or inflammatory bowel processes such as prolonged ileus and severe enterocolitis.[24,25]
Providing nutrition support routinely to patients undergoing chemotherapy or radiation therapy is not recommended; rather, nutrition support is reserved for patients who meet any of the criteria listed above. It is sometimes difficult to know which patients will have a prolonged period of inadequate oral intake or malabsorption and will benefit from nutrition support. For patients undergoing head and neck radiation, investigators have validated an evidenced-based protocol for determining which patients are at high risk of nutrition deficiency and therefore proactive placement of a gastrostomy tube.[27,28]
Although aggressive nutrition support has been shown to improve quality of life in patients with advanced cancer, it is generally not recommended if life expectancy is shorter than 40 to 60 days. For some patients who have incurable disease and are undergoing anticancer treatment—such as those with bowel obstruction—nutrition support may be appropriate.
Investigators have suggested the following additional criteria for withholding nutrition support in patients with advanced disease:
Enteral route and administration
Several effective methods for the delivery of enteral nutrition exist. Factors affecting a choice of the enteral route include the following:
Assessment of need is best performed early. If a malnourished patient requires surgery for an unrelated event, a feeding tube may be placed at that time to avoid an additional procedure.
For short-term feeding (<2 weeks), a nasoenteric tube may be best. The risk of aspiration is considered in the determination of the proper termination point of the tube, as follows:
Tubes are constructed of silicone or polyurethane and can vary in length from 30 to 43 inches, with the shorter tubes used for nasogastric feedings. Diameters range from 5F catheters to 16F catheters. Tubes may have weighted tips to help passage through the gut. If a patient with cancer is at very high risk of aspiration, enteral nutrition may be contraindicated, and parenteral nutrition can be considered. Immunocompromised patients with mucositis, esophagitis, and/or herpetic, fungal, or candidiasis lesions in the mouth or throat may not be able to tolerate the presence of a nasoenteric tube.
For longer-term feeding (>4 weeks), direct enteral access is recommended. Percutaneous tubes may be placed endoscopically, surgically, or with fluoroscopy by interventional radiology.
Percutaneous tube placement has a number of advantages, including the following:
Conversion to a skin-level button gastrostomy or jejunostomy may also be considered when longer-term support is anticipated.
Infusion methods and formulas
Administration methods vary depending on where in the GI tract the tube terminates and may be affected by treatment side effects.
For tubes terminating in the stomach, a bolus or intermittent (gravity) drip may be possible and is preferable because it mimics normal feeding, requires less time and equipment, and offers greater flexibility to the patient. For tubes terminating in the duodenum or jejunum, an infusion pump is required because a slower administration rate is necessary. Feedings via a pump may be administered cyclically (<24 hours per day) or continuously.
The following lists summarize infusion methods and considerations for initiation and administration of enteral nutrition.
Bolus and Intermittent Feeding
Continuous or Cyclic Drip Feeding
Enteral formulas vary in nutrient composition and source. Most commercially available formulas are lactose free, kosher, and halal. Standard/polymeric formulations are appropriate for most patients. Semi-elemental and elemental formulas are available for patients with malabsorption who do not or will not tolerate standard formulas. In some cases, disease-specific (renal, pulmonary, and diabetic) formulas may be appropriate and are available but in general are not necessary unless the patient has a demonstrated "failure" with standard formulas.
The use of whole-food blenderized formulas is gaining in popularity. Some products are commercially available, and there are published recipes for home-made formula. It is important for a dietitian to thoroughly review the nutrient content of these home-blenderized formulas to ensure adequacy.
For patients in the perioperative setting, evidence supports the use of IE formulas. The most widely studied formula in this category contains a combination of arginine, omega-3 fatty acids, and nucleotides.[22,26] Studies suggest that use of these formulas for a very narrow period of time can reduce the incidence of surgical complications (infectious and noninfectious) and decrease the length of hospital stays.[19,22,32]
Parenteral route and administration
If parenteral nutrition is determined to be beneficial and appropriate, it can be administered via central or peripheral venous access. Many patients with cancer already have central IV catheters to accommodate multiple IV therapies. For patients who do not already have central line access or will not have it for a period of time, a peripheral catheter can be placed; however, care must be taken to avoid overuse of the peripheral IVs, as this can result in vessel sclerosis. To minimize venous complications, the use of peripheral parenteral nutrition is limited.
Parenteral nutrition is a combination of dextrose (carbohydrate), amino acids (protein), and lipid emulsions (fat) with added electrolytes, vitamins, and trace elements. It is recommended that parenteral nutrition management include clinicians with expertise in nutrition support and be made up of a multidisciplinary team, including a registered dietitian and clinical pharmacist.
Parenteral nutrition is typically initiated as a 24-hour infusion. After tolerance is established and generally after daily macronutrient goals are achieved, parenteral nutrition may be cycled (typically to an infusion time of 10–14 hours). For patients who will be receiving home parenteral nutrition, a cyclic infusion is preferred. It is generally recommended that parenteral nutrition be initiated in the hospital and not at home. Only if the benefits of home initiation far outweigh the risks should it be considered, and only for patients who are hemodynamically stable, at low risk of refeeding syndrome, and nondiabetic.
Pharmaceutical management of cancer-associated cachexia and weight loss
Many treatments have been suggested for cachexia-anorexia syndrome (CAS), but few of these treatments have resulted in consistent improvement, probably because of the multifactorial mechanisms involved.[35,36,37] Treatment must both reverse the metabolic disturbances in carbohydrate, lipid, and protein metabolism and treat the associated decrease in caloric intake. Although most studies have examined single agents targeting one part of the multifactorial issues associated with CAS, many investigators have suggested that a multidrug approach might be more beneficial.[38,39,40] A summary of selected agents can be found in Table 6.
The first issue widely studied for treatment has been anorexia associated with CAS. The use of agents that improve appetite and resultant caloric intake have been widely studied; these agents include corticosteroids, progesterone analogs, androgens, cannabinoids, and cyproheptadine.
Perhaps the earliest agents studied for the management of cancer cachexia are dexamethasone and prednisolone. Used in cancer treatment for their anti-inflammatory, antimalignancy, and antiemetic properties, steroids have produced side effects such as increased appetite and weight gain, probably because of their effects in the hypothalamus.
Several large placebo-controlled studies have shown increases in appetite and weight gain associated with steroid use in this setting. However, the palliative effects on CAS have typically been short lived, and prolonged use is associated with significant side effects such as furthering catabolic effects on muscle, myopathy, joint disease, hyperglycemia, and hypertension.[42,43]
Like steroids, progesterone antagonists are effective in improving appetite and weight in patients with AIDS-related cachexia and CAS.[44,45] They may also improve muscle catabolism. In a study of tumor-bearing rats, use of megestrol acetate resulted in a reversal of muscle wasting and improved physical performance.[46,47] However, as with steroids, in clinical trials the improvement was shown to be temporary increases in fat and water mass without concomitant improvements in lean body mass or quality of life.[48,49]
A Cochrane review of 35 trials involving 3,963 patients reported the use of megestrol at doses of 160 to 800 mg/d for treatment of CAS. The only consistent benefits seen were weight gain and improved appetite. No definitive conclusions about other outcomes related to lean body mass, quality of life, or fatigue could be drawn. No improvement in survival was found.
A placebo-controlled study looked at megestrol acetate at a dose of 7.5 mg/kg per day in 26 children with weight loss exceeding 5%. The megestrol group had a mean weight gain of 19.7% compared with weight loss of 1.2% (P = .003) in the placebo group. Megestrol has also been studied in prophylaxis of weight loss, but again there was no demonstrated improvement in quality of life, lean muscle mass, or survival.[46,52,53] Concerns have also been raised about a possible increase in thromboembolic phenomena, sex hormone dysregulation, and suppression of the hypothalamic-pituitary axis, resulting in symptomatic adrenal insufficiency.
Interest in the use of cannabinoids in CAS is ongoing because of their effects on appetite and potential benefit in HIV-related cachexia. However, in a study of 469 patients comparing dronabinol alone versus megestrol acetate alone versus dronabinol plus megestrol acetate, dronabinol was inferior to megestrol acetate, and there was no additive effect when the drugs were used together. A similar European trial of 243 patients comparing dronabinol with placebo also found no benefit. Refer to the PDQ summary on Cannabis and Cannabinoids for more information about cannabis and cannabinoids.
Cyproheptadine is a serotonin and histamine antagonist developed as an antihistamine. Side effects include increased appetite and weight gain. Studied mostly in children with a wide range of disorders associated with anorexia and weight loss, cyproheptadine has been shown to result in significant improvements in weight in a number of studies.[59,60,61]
In a study of cyproheptadine use in children with CAS, one group of investigators evaluated 66 children with weight loss exceeding 5%. The children received cyproheptadine at a daily dosage of 0.25 mg/kg. Seventy-six percent of the patients were classified as responders, experiencing either weight gain or no further weight loss. Patients also showed a significant increase in serum leptin levels. Leptin is a protein hormone produced by adipocytes and is associated with body mass, particularly body fat. An increase in serum leptin has been correlated with an increase in body mass index.
CAS is a multifactorial disorder that occurs in more than 50% of patients with advanced cancer. Increases in cytokines associated with cancer—including tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-1—have been shown to be important in the etiology of this disorder. Pharmaceutical agents that inhibit the cytokine increases seen with cancer have been studied in patients with CAS.[63,64,65] EPA, an omega-3 fatty acid found in fish oil, has been used in a number of trials. However, a meta-analysis has failed to show a consistent improvement in CAS. Similarly, several systemic literature reviews of studies using nonsteroidal anti-inflammatory agents have failed to show conclusive evidence of efficacy.[67,68]
Specific targeted agents have also been studied. These include agents targeting TNF-alpha, such as etanercept, infliximab, and pentoxifylline, which, in small trials, have not had a significant impact.
Several studies using thalidomide, a nonspecific antagonist to TNF, have been performed.[70,71,72,73,74] Thalidomide is of interest as a treatment for CAS because of its immunomodulatory properties. A single-center, double-blind trial randomly assigned 50 pancreatic cancer patients who had lost at least 10% of their body weight to receive thalidomide 200 mg or placebo for 24 weeks. Thalidomide patients had a statistically significant reduction in weight loss compared with placebo patients. A similarly sized trial of thalidomide 100 mg demonstrated no significant treatment effect. Additionally, a Cochrane review on this topic reported insufficient evidence to support the use of thalidomide in patients with advanced cancer.
Other agents of interest
There has been interest in several other agents for the management of CAS, including mirtazapine, metoclopramide, formoterol, melatonin, and olanzapine.[44,77,78,79] However, no completed clinical trials support their use.
Given the multifactorial etiology of, and multiple mechanisms involved in, the development of CAS, it is possible that combining multiple agents with different mechanisms of action might result in greater efficacy.[80,81] In one study, 332 patients diagnosed with CAS were randomly assigned to one of five treatment arms: medroxyprogesterone alone; oral supplementation with EPA; L-carnitine; thalidomide; or a combination of all four agents. Investigators looked at lean body mass, resting energy expenditure, and fatigue. In this study, the combination arm was found to be superior. Another trial used megestrol alone versus megestrol plus L-carnitine, celecoxib, and antioxidants to treat 104 women with gynecologic malignancies. Again, the combination arm was found to be superior.
Researchers also looked at the combination of formoterol, an anabolic beta-2 adrenergic agonist, and megestrol acetate in 13 patients. Six of seven evaluable patients achieved a major response, with increases in muscle mass. Conversely, another study looking at megestrol plus meloxicam versus meloxicam plus EPA versus megestrol plus meloxicam and EPA showed no advantage to the three-drug regimen. However, such combinations also may result in increased cumulative toxicity. For these reasons, there is no recommended combination at this time. In addition, combining drug therapy with nutrition support and increased physical activity may have even greater efficacy.
Summary of pharmaceutical treatment strategies
CAS is a complex, multifactorial complication of cancer and its therapy, resulting in weight loss and decreased lean body mass. As understanding of the mechanisms of CAS improves and new agents that selectively target these proposed pathways become available, more efficacious treatments are also expected to become available. Trials of new agents must be able to compare similar groups of patients. In addition, treating preventatively in high-risk patients, as opposed to treating patients already suffering from CAS, may be associated with better outcomes. Further clinical trials are essential to determine the best possible therapies.
|Drug||Dose||Comments||Reference/Level of Evidence|
|bid = twice a day; EPA = eicosapentaenoic acid; qid = 4 times a day; tid = 3 times a day; VTE = venous thromboembolism.|
|a Adapted from Lexicomp Onlineand other references.|
|Megestrol acetate||160–800 mg daily (most-common dose: 400 or 800 mg)||Doses >160 mg/d associated with better weight gain; 800 mg may be optimal. More benefit seen than with dronabinol in comparative study. Addition of thalidomide to megestrol increased benefit.||[Level of evidence: I];[Level of evidence: I]|
|Medroxyprogesterone||500 mg bid||Improved appetite and stimulated weight gain. Notable for a VTE-related death.||[Level of evidence: I]|
|Dexamethasone||0.75 mg qid||Benefit similar to that seen with megestrol.||[Level of evidence: I]|
|Methylprednisolone||16 mg bid||Small trial (N = 40); increased appetite, but negligible change in weight.||[Level of evidence: I]|
|Prednisolone||5 mg tid||Provided short-term appetite improvement over placebo, with no increase in weight.||[Level of evidence: I]|
|Dronabinol||2.5 mg bid, maximum 20 mg daily||Given in divided doses; twice daily most common. No benefit seen when added to megestrol. One study showed as equal to placebo.||[Level of evidence: I];[Level of evidence: I]|
|Cyproheptadine||2 mg qid, maximum 16 daily||Has been used up to 24 mg daily. Enhances appetite but may not decrease weight loss in adults. Improved both appetite and weight gain in children.||[Level of evidence: I];[Level of evidence: II];[Level of evidence: II]|
|Mirtazapine||15–30 mg daily||24% of patients gained ≥1 kg.||[Level of evidence: II]|
|Olanzapine||20 mg daily||Dose escalation trial; modest effect on reducing weight loss.||[Level of evidence: II]|
|Melatonin||20 mg daily||Trial stopped for futility. Significantly fewer patients with >10% weight loss on melatonin vs. placebo.||[Level of evidence: I];[Level of evidence: I]|
|Omega-3 fatty acids||EPA, 1.09 g bid||No improvement in weight or appetite vs. megestrol vs. both.||[Level of evidence: I]|
|10 capsules daily (EPA, 1.8 g daily)||No improvement in appetite vs. placebo.||[Level of evidence: I]|
|EPA, 4.4 g daily||Poor compliance with treatment. Post-hoc dose-response analysis suggests improved lean body mass with EPA supplement.||[Level of evidence: I]|
|Pentoxifylline||400 mg tid||No effect on weight gain or arm circumference.||[Level of evidence: I]|
|No improvement in appetite.||[Level of evidence: I]|
|Thalidomide||100 mg daily||No significant difference vs. placebo.||[Level of evidence: I]|
|200 mg daily||At 8 wk, patients receiving thalidomide had lost significantly less weight than had patients receiving placebo.||[Level of evidence: I]|
|Oxandrolone||2.5–20 mg in divided doses, 2–4 times daily||Not studied in cancer patients.||[Level of evidence: IV]|
|Fluoxymesterone||10 mg bid||Inferior to dexamethasone and megestrol acetate.||[Level of evidence: I]|
Patients with advanced disease often develop new, or worsening, nutrition-related side effects associated with disease progression, treatment, or both. In a large systematic review of symptom prevalence in patients with incurable cancer, the most common nutrition impact symptoms were the following:
These symptoms were present in a large subset of patients receiving care in various settings and in a small subset of patients in their last 2 weeks of life. Other symptoms among advanced-cancer patients receiving care in inpatient palliative care units,[2,3] cancer cachexia specialty clinics, hospice, or non-hospice settings  included the following:[1,2,3,4]
In addition, advanced-cancer patients with pain and opioid-induced constipation (OIC) reported both physical and psychological distress related to the OIC.
Clinically refractory cachexia develops as a result of very advanced cancer or rapidly progressive disease that is unresponsive to antineoplastic therapy. It is associated with active catabolism and weight loss that is unresponsive to nutrition therapy. At the end of life, patients often have severely restricted oral intake of food and fluids as part of the normal dying process.[6,7]
The primary objective of nutrition intervention in patients with advanced cancer is to conserve or restore the best possible quality of life and control any nutrition-related symptoms that cause distress. However, issues related to nutrition and hydration for patients with advanced cancer may be a source of conflict among patients and their families and between patients and their health care teams. Providers may need to address the natural history of cachexia in end-stage cancer and help patients cope with the emotional implications of cancer cachexia-anorexia.
Goals of Nutrition Therapy in Advanced Cancer
Nutrition goals for a patient with advanced cancer may depend on the overall plan of care. These patients may be receiving anticancer therapy (with or without concurrent palliative care), may be receiving palliative care alone, or may be enrolled in hospice. Regardless of the care setting, patients are screened to determine the need for nutrition intervention. The Patient-Generated Subjective Global Assessment (PG-SGA) has been validated in cancer patients and addresses body weight history, food intake, symptoms, and functional status.[9,10] When palliative care is initiated early in the disease process, nutrition goals focus on supporting active treatment and aim to improve treatment outcomes, body composition, physical function, and symptom palliation.
As the focus of care shifts from cancer-modifying therapy to hospice or end-of-life care, nutrition goals may become less aggressive, with a shift in emphasis toward comfort. Continued assessment and adjustment of nutrition goals and interventions is required throughout this continuum to meet the changing needs of the patient receiving palliative or hospice care services.
Nutrition Intervention in Advanced Care
Ethical issues may arise when patients, families, or caregivers request artificial nutrition and hydration when there is no prospect of recovering from the underlying illness or accruing appreciable benefit from the intervention. When there is uncertainty about whether a patient will benefit from artificial nutrition, hydration, or both, a time-limited trial may be useful. Clear, measurable endpoints are outlined at the beginning of a time-limited trial. The caregiving team will explain that, as with other medical therapies, artificial nutrition and hydration can be stopped if the desired nutrition effects are not produced.
Randomized controlled trials of enteral or parenteral nutrition in cancer patients receiving formal palliative care are lacking. On the basis of available evidence and expert consensus, clinical guidelines recommend that the use of nutrition support therapy in advanced cancer be limited to patients who are very carefully selected.[13,14] Patients who have demonstrated a favorable response to parenteral nutrition include those with the following:[15,13,16]
If patients are to benefit from parenteral nutrition, they must be physically and emotionally capable of participating in their own care and have the following:
Patients with a life expectancy shorter than 40 days may be palliated with home intravenous (IV) fluid therapy, although this practice is controversial.
Nutrition Considerations for the End of Life
Patients and caregivers often consider the provision of food and fluids to be basic care. However, the use of artificial nutrition and hydration at the end of life is a complex and controversial intervention that is influenced by clinical, cultural, religious, ethical, and legal factors. Patients and families often believe the use of these interventions will improve quality and length of life, but evidence of clear benefit is lacking.[12,17] There are also potential burdens associated with this care, including the following:
In addition, agitated or confused patients receiving artificial nutrition and hydration may need to be physically restrained to prevent them from removing a gastrostomy tube, nasogastric tube, or central IV line.
Patients at the end of life who have increased difficulty with swallowing have less risk of aspiration with thick liquids than with thin liquids. Thirst can often be alleviated with sips of water, ice chips, and good mouth care. In the last few days of life, the incidence of swallowing problems can be as high as 79% and include frequent coughing, anorexia, and problems with oral secretions. Communication within the health care team and support of the family and caregivers is important in alleviating the distress concerning decreased food and fluid intake and in eliminating unrealistic expectations.
For patients at the end of life, the goals of nutrition therapy are directed at alleviating symptoms rather than reversing nutrition deficits. The pleasure of tasting food and the social benefits of participating in meals with family and friends can be emphasized over increasing caloric intake. A systematic review of practices and effects on cancer patients in the last week of life found no study supporting the use of artificial nutrition, and studies with artificial hydration had mixed results. Studies on hydration with positive effects reported less chronic nausea and physical signs of dehydration, while studies with negative effects found more ascites and intestinal drainage. Other studies found no effect on terminal delirium, thirst, chronic nausea, or fluid overload.
A well-designed randomized trial reported that hydration at 1 L/d for a week did not improve dehydration symptoms (fatigue, myoclonus, sedation, hallucinations) and provided no benefit in quality of life or survival. A prospective evaluation of Japanese national guidelines for parenteral hydration at the end of life suggests there is little harm or benefit; however, patients expressed a high level of satisfaction and felt it was beneficial. A subsequent study utilizing the Japanese guidelines reported that hydration-related symptoms (nausea, edema, dyspnea, abdominal pain/distention) were significantly improved, as were quality of life, global satisfaction, and feeling of benefit.
The American Academy of Hospice and Palliative Medicine suggests that providers facilitate respectful and informed discussions about the effects of artificial nutrition and hydration near the end of life among physicians, other health care professionals, patients, and families. It is incumbent on physicians and other health care providers to describe the options that exist when the implementation, continuation, or discontinuation of artificial nutrition and hydration is being considered, and to establish goals of care with the patient and/or surrogate decision-maker. Ideally, patients will make their own decisions on the basis of a careful assessment of potential benefits and burdens, consistent with legal and ethical norms that permit patients to accept or forgo specific medical interventions.
Ethical, Cultural, and Religious Issues in Medically Assisted Nutrition and Hydration in Advanced Cancer
Decisions about whether to provide artificial nutrition and hydration to patients in the late stages of life are complex and influenced by ethical, legal, cultural, and clinical considerations, and by patient and family preferences. The event of death itself, the manner in which it occurs, and the patient's quality of life are significant matters that have spiritual and psychological consequences for each person involved.
Guidelines on the ethical considerations about whether to forgo or discontinue hydration and nutrition support have been published by a number of organizations, including:
These guidelines reflect the judicial decisions that have supported the authority and liberty of the competent individual to refuse life-saving hydration and nutrition, the role of medical expertise, and respect for the dignity and values of the patient and family. (Refer to the Artificial Hydration and Artificial Nutrition sections in the PDQ summary on Last Days of Life for more information.)
Religion and religious traditions provide a set of core beliefs about life events and an ethical foundation for clinical decision-making. Although the fundamental principles of major religions provide perspectives on death and dying, decisions related to artificial nutrition and hydration remain complicated, varying even within the same major religion or faith tradition.
To provide an optimal and inclusive healing environment, all palliative team members need to be aware of their own spirituality and how it may differ from that of fellow team members and the spirituality of the patients and families they serve.[29,30] Clinical practice guidelines established by the National Consensus Project for Quality Palliative Care address spiritual, religious, and existential aspects of care. One group of researchers  has provided insight into the principles and perspectives held by Roman Catholic, Jewish, Buddhist, and Islamic faith traditions, and another group  has provided an extensive analysis of how world religions formulate ethical decisions related to withdrawing treatment and determining when death has occurred.
Religious beliefs are often closely related to cultural views. Individuals living in the midst of a particular tradition can continue to be influenced by it, even if they have stopped believing in or practicing it. In some cultures, individual autonomy is not the prevailing or predominant principle; some Asian, Native American, and Hispanic cultures favor family or community autonomy. Distinguishing between majority and minority cultures is important. Patients may rely on religion and spirituality as important means to interpret and cope with illness.
Religious and cultural preferences about artificial nutrition and hydration are expressions of a patient's autonomy and, in many cases, may outweigh clinical considerations. When these values conflict with clinical judgment, practitioners may work with the patient and/or surrogate in consulting with faith leaders and the ethnic community to which the patient belongs, as well as the institutional ethics committee, to facilitate resolution.[26,27]
The wide range of practices related to neutropenic diets reflects the lack of evidence regarding the efficacy of dietary restrictions in preventing infectious complications in cancer patients. Studies evaluating various approaches to diet restrictions have not shown clear benefit.
A meta-analysis and a systematic review of articles evaluating the effect of a neutropenic diet on infection and mortality rates in cancer patients found no superiority or advantage in using a neutropenic diet over a regular diet in neutropenic cancer patients.[1,2] Four studies were identified in the meta-analysis, one observational study and three randomized controlled trials, including 918 patients with cancer or stem cell transplant. Even after the observational study was omitted from the analysis, the results persisted. The systematic review identified only three randomized controlled trials,[3,4,5] which compared different diets in 192 children and adults. The review concluded that these individual studies provided no evidence showing that the use of a low-bacterial diet prevents infections.
Other studies have demonstrated potential adverse effects of neutropenic diets. One group of investigators  conducted a retrospective review of 726 patients who had undergone hematopoietic cell transplantation (HCT). The 363 patients who received the neutropenic diet experienced significantly more documented infections than did the 363 patients receiving the general hospital diet that permitted black pepper and well-washed fruits and vegetables and excluded raw tomatoes, seeds, and nuts. The difference in infection rates was especially evident after the resolution of neutropenia (P < .008). The neutropenic diet group had a significantly higher rate of infections that could be attributed to a gastrointestinal source, as well as a trend toward a higher rate of vancomycin-resistant enterococci infections.
Without clinical evidence to define the dietary restrictions required to prevent foodborne infection in immunocompromised cancer patients, recommendations for food safety are based on general food safety guidelines and the avoidance of foods most likely to contain pathogenic organisms. The effectiveness of these guidelines is dependent on patient and caregiver knowledge about, and adherence to, safe food handling practices and avoidance of higher-risk foods. Leading cancer centers provide guidelines for HCT patients and information about food safety practices related to food purchase, storage, and preparation (e.g., the University of Pittsburgh Medical Center's Stem Cell Transplant Diet and Memorial Sloan Kettering Cancer Center's Low-Microbial Diet). Comprehensive food safety information designed by the U.S. Department of Agriculture Food Safety and Inspection Service and the U.S. Food and Drug Administration for people with cancer and for transplant recipients is also available online.[7,8] Patients can be educated to regularly refer to FoodSafety.gov for up-to-date information about food recalls and alerts.
Recommendations support the use of safe food handling procedures and avoiding consumption of foods that pose a high risk of infection, as noted in Table 7.
|Food Group||May Eat||Do Not Eat|
|a Adapted from Tomblyn et al.and Lund.|
|b Although eating cooked soft cheese is not completely risk free, the risk of foodborne illness is low.|
|c Rinse under clean running water before use, including produce that is to be cooked or peeled, such as bananas, oranges, and melons.|
|d Shelf stable refers to unopened canned, bottled, or packaged food products that can be stored at room temperature before being opened; container may require refrigeration after being opened.|
|e Bring tap water to a rolling boil and boil for 15–20 minutes. Store boiled water in the refrigerator; discard unused water after 48 hours. Hematopoietic cell transplantation patients are advised not to use well water from private wells or from public wells in communities with limited populations because tests for bacterial contamination are performed too infrequently.|
|f Tap water from a city water service in a highly populated area that is tested >2 times/day for bacterial contamination. Listen for media alerts for a "boil water advisory," which means all tap water should be boiled >1 minute before being consumed. In addition, use a home water filter capable of removing particles >1 µm in diameter or filter by reverse osmosis to reduce risk of exposure toCryptosporidium.|
|g Bottled water can be used if it conforms to U.S. Food and Drug Administration standards and has been processed to removeCryptosporidium by reverse osmosis, distillation, or 1-μm-particulate absolute filtration. Contact the bottler directly to confirm which process is used. Contact information for water bottlers is available on the International Bottled Water Associationwebsite.|
|Dairy||All pasteurized grade "A" milk, milk products||Unpasteurized or raw milk|
|Dry, refrigerated, or frozen pasteurized whipped topping||Foods made from unpasteurized or raw milk|
|Commercially packaged hard and semisoft cheeses such as cheddar, mozzarella, Parmesan, Swiss, Monterey Jack||Cheeses from delicatessens|
|Cooked soft cheese such as brie, Camembert, feta, farmer'sb||Cheese containing chili peppers or other uncooked vegetables|
|Commercially sterile ready-to-feed and liquid-concentrate infant formulas||Cheeses with molds, such as blue, Stilton|
|Mexican-style soft cheeses such as queso fresco, queso blanco|
|Powdered infant formulas, if a ready-to-feed or liquid-concentrate alternative is available|
|Meat and meat substitutes||All meats, poultry, fish cooked to well-done (poultry >180°F; other meats >160°F)||Raw or undercooked meat, poultry, fish, game, tofu|
|Canned meats||Raw or undercooked (over easy, soft boiled, poached) eggs and unpasteurized egg substitutes|
|Eggs cooked until both white and yolk are firm||Meats & cold cuts from delicatessens|
|Pasteurized eggs and egg substitutes and powdered egg white (can be used undercooked)||Hard-cured salami in natural wrap|
|Commercially packaged salami, bologna, hot dogs, ham, other lunch meats (heated until steaming)||Refrigerated pâtés or meat spreads|
|Canned and shelf-stable smoked fish (refrigerate after opening)||Uncooked, refrigerated smoked seafood such as salmon or trout labeled nova-style, lox, kippered, smoked, or jerky|
|Pasteurized or cooked tofu||Pickled fish|
|Refrigerated smoked seafood such as salmon or trout if cooked to 160°F or contained in a cooked dish or casserole||Tempe (tempeh) products|
|Fruits and nuts||Well-washedc, raw, and frozen fruit, except berries||Unwashed raw fruits|
|Cooked, canned, and frozen fruit||Fresh or frozen berries|
|Pasteurized juices and frozen juice concentrates||Unpasteurized fruit and vegetable juices|
|Dried fruits||Fresh fruit salsa and unpasteurized raw-fruit–containing items found in grocery refrigerated case|
|Canned or bottled roasted nuts||Raw nuts|
|Shelled, roasted nuts and nuts in baked products||Roasted nuts in the shell|
|Commercially packaged nut butters (peanut, almond, soy nut)|
|Entrees and soups||All cooked entrees and soups||All miso products|
|Vegetables||Well-washedc raw and frozen vegetables||Unwashed raw vegetables or herbs|
|All cooked fresh, frozen, or canned vegetables, including potatoes||Fresh, unpasteurized vegetable salsa and unpasteurized raw-vegetable–containing items found in grocery refrigerated case|
|Shelf-stabled bottled salsa (refrigerate after opening)||All raw vegetable sprouts (alfalfa, clover, mung bean)|
|Cooked vegetable sprouts such as mung bean sprouts||Salads from delicatessens|
|Fresh, well-washedc herbs, dried herbs, and spices (added to raw or cooked foods)|
|Breads, grains, and cereal products||All breads, bagels, rolls, English muffins, muffins, pancakes, sweet rolls, waffles, French toast||Raw (not baked or cooked) grain products, such as raw oats|
|Potato chips, corn chips, tortilla chips, pretzels, popcorn|
|Cooked grains and grain products, including pasta and rice|
|All cereals, cooked and ready-to-eat|
|Beverages||Boiled well watere||Unboiled well water|
|Tap water and ice made from tap waterf||Cold-brewed tea made with warm or cold water|
|Commercially bottled distilled, spring, and natural watersg||Mate tea|
|All canned, bottled, and powdered beverages||Wine, unpasteurized beer (Note: all alcoholic beverages can be consumed if approved by physician.)|
|Instant and brewed coffee and tea; cold-brewed tea made with boiling water||Unpasteurized fruit and vegetable juices|
|Herbal teas brewed from commercially packaged tea bags||Powdered infant formulas, if a ready-to-feed or liquid-concentrate alternative is available|
|Commercial nutrition supplements, both liquid and powdered|
|Commercially sterile ready-to-feed and liquid-concentrate infant formulas|
|Desserts||Refrigerated commercial and homemade cakes, pies, pastries, and puddings||Unrefrigerated cream-filled pasty products (not shelf-stabled)|
|Refrigerated cream-filled pastries|
|Cookies, both homemade and commercially prepared|
|Shelf-stabled cream-filled cupcakes and fruit pies|
|Canned and refrigerated puddings|
|Ices, ice pops, and similar products|
|Fats||Vegetable oils and shortening||Fresh salad dressings (stored in grocery refrigerated case) containing raw eggs or cheeses listed as "Do Not Eat" under "Dairy"|
|Refrigerated lard, margarine, and butter|
|Commercial, shelf-stabled mayonnaise and salad dressings, including blue cheese and other cheese-based salad dressings (refrigerate after opening)|
|Cooked gravies and sauces|
|Other||Commercial pasteurized grade "A" honey||Raw honey, honey in the comb|
|Salt, granulated sugar, brown sugar||Herb and nutrient supplement preparations|
|Jams, jellies, syrups (refrigerate after opening)||Brewer's yeast, if uncooked|
|Catsup, mustard, barbecue sauce, soy sauce, other condiments (refrigerate after opening)|
|Pickles, pickle relish, olives (refrigerate after opening)|
Maintaining adequate nutrition while undergoing treatment for cancer is imperative because it can reduce treatment-related side effects, prevent delays in treatment, and help maintain quality of life. However, many patients view their diet as a way to enhance treatment effectiveness, minimize treatment-related toxicities, or target the cancer itself, often done by following a specific diet with supposed cancer-fighting benefits or by taking dietary supplements. Patients are likely to search the Internet and other lay sources of information for dietary approaches to manage cancer risk and to improve prognosis. Unfortunately, much of this information is not supported by a sufficient evidence base.
The sections below summarize the state of the science on some of the most popular diets and dietary supplements.
Vegetarian or vegan diet
A vegetarian diet is popular, is easy to implement and, if followed carefully, does not result in nutrition deficiencies. There is strong evidence that a vegetarian diet reduces the incidence of many types of cancer, especially cancers of the gastrointestinal (GI) tract. However, it is unknown how following a vegetarian or vegan diet can affect treatment-induced symptoms, cancer therapies, or outcomes for someone undergoing cancer therapy. There are no published clinical trials, pilot studies, or case reports on the effectiveness of a vegetarian diet for the management of cancer therapy and symptoms. There is no evidence suggesting a benefit of adopting a vegetarian or vegan diet upon diagnosis or while undergoing cancer therapy. On the other hand, there is no evidence that an individual who follows a vegetarian or vegan diet before cancer therapy should abandon it upon starting treatment.
One pilot study has suggested that following a plant-based diet can prevent tumor progression in men with localized prostate cancer. A randomized controlled trial based on this pilot study is under way to determine effectiveness. No other current clinical trials are studying the role of a vegetarian or vegan diet in cancer therapy.
A macrobiotic diet varies according to a person's sex, their level of activity, and the climate (and season) in which they live, among other variables. It is a high-carbohydrate, low-fat, plant-based diet stemming from philosophical principles promoting a healthy way of living. The diet consists of 35% to 50% (by weight) whole grains, 25% to 35% vegetables, 5% to 10% soup, 5% to 10% cooked vegetables and sea vegetables, and 5% to 10% fish.
Although there are anecdotal reports on the effectiveness of a macrobiotic diet as an alternative cancer therapy, none have been published in peer-reviewed, scientific journals. No clinical trials, observational studies, or pilot studies have examined the diet as a complementary or alternative therapy for cancer. In fact, two reviews of the diet and its evidence for effectiveness in cancer treatment concluded that there is no scientific evidence for the use of a macrobiotic diet in cancer treatment.[5,6] Because the current research is severely lacking, recommendations for or against the diet in conjunction with standard cancer treatment cannot be made. No current clinical trials are studying the role of the macrobiotic diet in cancer therapy.
A ketogenic diet has been well established as an effective alternative treatment for some cases of epilepsy and has gained popularity for use in conjunction with standard treatments for glioblastoma. The theory behind the diet as cancer treatment is that reducing glucose availability to a tumor can reduce tumor activity, and that this reduction can be achieved through entering a state of ketosis via the ketogenic diet's restriction of carbohydrates and increased fat intake.
The ketogenic diet can be difficult to follow and relies more on exact proportions of macronutrients (typically a 4 to 1 ratio of fat to carbohydrates and protein) than do other complementary and alternative medicine (CAM) diets. Therefore, most studies have focused on the diet's feasibility, tolerability, and safety, all of which have been shown for glioblastoma patients at various stages of the disease.[7,8,9]
Because safety and feasibility have been proven, several trials are recruiting patients to study the effectiveness of the ketogenic diet on glioblastoma. Therefore, if a patient diagnosed with glioblastoma wishes to start a ketogenic diet, it would be safe if implemented properly and under the guidance of a registered dietitian, but effectiveness for symptom and disease management remains unknown.
Refer to the PDQ summary on High-Dose Vitamin C for more information about the use of high-dose vitamin C as a treatment for people with cancer.
The use of probiotics has become prevalent within and outside of cancer therapy. Strong research has shown that probiotic supplementation during radiation therapy, chemotherapy, or both is well tolerated and can help prevent radiation- and chemotherapy-induced diarrhea, especially in those receiving radiation to the abdomen.[11,12,13] Therefore, if a patient is undergoing radiation to the abdomen or receiving a chemotherapy agent with diarrhea as a common side effect, starting a probiotic supplement upon initiation of therapy could be beneficial.
Melatonin is a hormone produced endogenously that has been used as a CAM supplement (along with chemotherapy or radiation therapy) for targeting tumor activity and for reducing treatment-related symptoms, primarily for solid tumors.
Several studies have shown tumor response to, or disease control with, chemotherapy alongside oral melatonin, as opposed to chemotherapy alone; one study has shown tumor response with melatonin in conjunction with radiation therapy.[14,15,16,17,18,19] The combination of melatonin with chemotherapy may, in fact, increase survival time compared with chemotherapy alone, for up to 5 years. However, another study did not demonstrate increased survival with melatonin, but did demonstrate improved quality of life.
Melatonin taken in conjunction with chemotherapy may help reduce or prevent some treatment-related side effects and toxicities that can delay treatment, reduce doses, and negatively affect quality of life. Melatonin supplementation has been associated with significant reductions in neuropathy and neurotoxicity, myelosuppression, thrombocytopenia, cardiotoxicity, stomatitis, asthenia, and malaise.[15,16,18,21] However, one study found no benefit in taking supplemental melatonin for reducing toxicities or improving quality of life.
Overall, several small studies show some evidence supporting melatonin supplementation alongside chemotherapy, radiation therapy, or both for solid tumor treatment, for aiding tumor response and reducing toxicities, while negative side effects for melatonin supplementation have not been found. Therefore, it may be appropriate to provide oral melatonin in conjunction with chemotherapy or radiation therapy to a patient with an advanced solid tumor.
Glutamine is an amino acid that is especially important for GI mucosal cells and their replication. These cells are often damaged by chemotherapy and radiation therapy, causing mucositis and diarrhea, which can lead to treatment delays and dose reductions and severely affect quality of life. Some evidence suggests that oral glutamine can reduce both of those toxicities by aiding in faster healing of the mucosal cells and entire GI tract.
For patients receiving chemotherapy who are at high risk of developing mucositis, either because of previous mucositis or having received known mucositis-causing chemotherapy, oral glutamine may reduce the severity and incidence of mucositis.[23,24,25]
For patients receiving radiation therapy to the abdomen, oral glutamine may reduce the severity of diarrhea and can lead to fewer treatment delays.[26,27] However, one study found no benefit to oral glutamine for preventing chemotherapy-related diarrhea.
In addition to reducing GI toxicities, oral glutamine may also reduce peripheral neuropathy in patients receiving the chemotherapy agent paclitaxel. Larger randomized controlled trials need to be conducted to further determine the effectiveness of oral glutamine in treating peripheral neuropathy.
Oral glutamine is a safe, simple, and relatively low-cost supplement that may reduce severe chemotherapy- and radiation-induced toxicities.
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Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about nutrition before, during, and after cancer treatment. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
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PDQ® Supportive and Palliative Care Editorial Board. PDQ Nutrition in Cancer Care. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/about-cancer/treatment/side-effects/appetite-loss/nutrition-hp-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389293]
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Last Revised: 2020-05-08
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