Review

Importance of nutritional screening in treatment of cancer-related weight loss

Lancet Oncol 2005; 6: 33443 Department of Primary Care, School of Health Related Professions (M B Huhmann MS) and Department of Family Medicine-Research Division (R S Cunningham PhD), University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, NJ, USA Correspondence to: Ms Maureen B Huhmann, Cancer Institute of New Jersey, 195 Little Albany St, New Brunswick, NJ 08903, USA huhmanma@umdnj.edu

Maureen B Huhmann, Regina S Cunningham

Weight loss is common in patients with cancer. Many factors, such as physiological abnormalities, response to the tumour, and treatment, contribute to this weight loss. Cancer-related weight loss affects a patients response to treatment, as well as survival and quality of life. Several nutritional screening and assessment tools have been developed for patients with cancer. This review describes the weight loss seen in patients with cancer as well as the methods of screening for nutritional deterioration and weight loss early in a cancer diagnosis. Nutritional approaches to the supportive care of patients with cancer are also discussed.

Introduction
Nutritional status is an important factor in prediction of the risks associated with cancer treatment and in affecting an individuals response to treatment.1 Evolving evidence continues to lend support to strong relations between nutritional status and various clinical outcomes, including quality of life, survival, and the ability to tolerate treatment.2 This review briey discusses the relation between weight loss and disease outcome in patients receiving treatment for cancer, and describes proactive strategies that can be used in clinical practice to identify and assess patients at nutritional risk, to provide early interventions, and potentially to improve the untoward outcomes associated with nutritional decits (gure 1).

Nutritional status and disease outcome

Weight loss is common in patients with cancer and can be a presenting sign of malignant disease; the type and location of tumours can be risk factors for weight loss. Many factors contribute to the weight loss in patients

with cancer.3,4 Loss of weight can be attributed to the physiological abnormalities associated with a tumour (such as malabsorption, obstruction, diarrhoea, and vomiting), the host response to the tumour (causing anorexia and altered metabolism), and the side-effects of anticancer treatment.3,4 Oral and gastrointestinal symptoms can cause changes in weight early in the course of a cancer.2,5 Fatigue, depression, anxiety, and pain can also result in weight loss.3 Reduction in weight is itself a constant reminder of disease, which further interferes with the patients quality of life.6 The frequency of weight loss and malnutrition in patients with cancer ranges from 31% to 87% depending on the tumour site and stage, with the highest frequencies seen in patients with cancers of the aerodigestive tract or in those with more advanced disease.7 Nutritional status has been empirically linked to clinical outcome.7 Malnutrition has been associated with reduced response to treatment,8 poorer survival,7 and diminished quality of life.9

Cancer cachexia-induced weight loss

Weight loss in patients with cancer can be profound and debilitating. Cancer cachexia is an extreme on the continuum of weight loss in cancer. Cachexia was dened by Costa and colleagues10 as a physical fading of wholeness. Cancer cachexia syndrome is a complex physiological process that is associated with progressive weight loss, anorexia, early satiety, fatigue, generalised weakness, decreased function, progressive wasting, and ultimately death.5 Risk factors for nutritional impairment and deterioration in cachexia include lung and gastrointestinal cancers, age (children11 and elderly people12), a history of pre-existing disorders that might affect nutritional status (such as metabolic diseases), disorders that affect digestion or absorption, and longterm nicotine use.13 Patients who are receiving therapeutic interventions that promote gastrointestinal dysfunction, those undergoing extensive surgical procedures, and those receiving stomatoxic chemotherapy are also at greater risk.14 Most anticancer treatments have the potential to affect dietary intake and nutritional status, depending on the treatment, administration schedule, and dose.4 The effects of these treatments vary according to regimen and individual response.
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Figure 1: Cancer-induced weight loss has striking effects on patient outcomes

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Cancer cachexia syndrome results from chronic and systemic inammatory responses.15 Many of the pathophysiological changes associated with cachexia are thought to be the result of cytokine and tumour products.16 Cytokines are implicated in the development of specic symptoms associated with cachexia, such as anorexia and early satiety, as well as derangements in protein, carbohydrate, and fat metabolism.16 Tumourspecic products, such as proteolysis-inducing factor, lipid-mobilising factor, and mitochondria-uncoupling proteins 1, 2, and 3, also play a part. Proteolysis-inducing factor seems to induce upregulation of the ubiquitinproteasome-proteolytic pathway, causing a rise in skeletal-muscle degradation and a depression in plasma concentrations of aminoacid.17 Lipid-mobilising factor causes an increase in the mitochondria-uncoupling proteins and subsequently induces lipolysis in adipocytes.17 Mitochondria-uncoupling proteins 1, 2, and 3 are involved in thermogenesis in brown adipose tissue and possibly in skeletal muscle, and could contribute to tissue wasting.15

Nutritional status and quality of life

Quality of life is an outcome that is especially important for patients with cancer. Nutritional status has an important effect on quality of life and sense of wellbeing in patients with cancer.18 Patients who report difculty eating, because of side-effects or their disease, often avoid social interactions with family and friends, resulting in further depression of appetite.19 Specic factors such as mouth pain, hoarseness, avoidance of eating in public, and unclear speech, have been associated with poorer overall quality of life in patients with cancer.19

Quality-of-life assessment
The most accurate assessment of quality of life is obtained from the patient rather than an observer. Physician-reported quality of life tends to emphasise physiological data, whereas patients and families place more emphasis on psychosocial features.20 Questionnaires that rely on an independent observer or physician are not as accurate as those completed by patients.21,22 Many questionnaires have been designed to assess quality of life and the effect that specic symptoms have.20 Assessment methods commonly used in patients with cancer include the Functional Assessment of Cancer Therapy series, the European Organisation for Research and Treatment of Cancer Quality of Life questionnaires, the Eastern Cooperative Group Performance Status, and the Symptom Distress Scale. The European Organisation for Research and Treatment of Cancer Quality of Life Tool was developed by the European Organisation for Research and Treatment of Cancer Data Centre and has been used widely in trials in Europe.23 This 30-item questionnaire is used to assess physical, cognitive, emotional, and social domains of quality of life. There are optional modules specic to
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different tumour types that can be used with the core 30-item questionnaire. This tool was developed mainly for clinical trials but it is now being used in surveys and in management and monitoring of patients.24 The Medical Outcomes Study Short Form Health Survey is a 36-item questionnaire designed to measure quality of life.25 The domains explored include physical, social, emotional, and cognitive function. This questionnaire is versatile and can be completed over the telephone, be self-administered, or done by interview, needing about 15 min to complete.25 The Short-Form Health Survey has been widely used in US studies of quality of life in patients with cancer. The Functional Assessment of Cancer Therapy was introduced by Cella and colleagues26 in 1993. It has a core questionnaire, with additional questions related to specic cancers or symptoms. The Functional Assessment of Cancer Therapy-General is a 27-item self-report questionnaire with four subscales each of which assesses a domain of health-related quality of life: physical wellbeing; social and family wellbeing; emotional wellbeing; and functional wellbeing. It has been validated in patients with all tumour types, and normative data are available; the questionnaire has been translated into more than 50 languages. Patients respond to each item on a ve-point Likert scale. As with the European Organisation for Research and Treatment of Cancer Quality of Life questionnaire, additional modules are available for specic tumour types.27,28 Eastern Cooperative Group Performance Status is used widely in clinical trails and in daily practice. It consists of a scale from zero (healthy activity) to four (bedridden), and is used as an independent prognostic predictor for patients with cancer.29 The Symptom Distress Scale developed by McCorkle and Young30 is a 13-item self-report scale that captures the degree of discomfort that patients have with regard to symptoms commonly encountered in cancer. The symptoms specically assessed by the scale include nausea, mood, appetite, insomnia, pain, mobility, fatigue, bowel pattern, concentration, and appearance.30 Each symptom is evaluated on a ve-point Likert-type scale. For most items, a score of one represents least distress and ve represents extreme distress. Total symptom distress is obtained by addition of unweighted scores for a total range from 13 (indicating little distress) to 65 (indicating severe symptom distress).30

Effect of symptoms on nutritional status

The assessment of quality-of-life outcomes and the relation between many of the variables that comprise quality of life (such as symptoms and functional status) have been included in nutritional studies.6,18,31 In early studies of the effect of nutritional counselling on quality of life, a rise in calorie and protein intake seen with bimonthly counselling with a registered dietician led to improved anthropometric measures, which corres335

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Tool Patient Generated Subjective Global Assessment Mini Nutritional Assessment Malnutrition Screening Tool Malnutrition Universal Screening Tool Nutrition Risk Assessment

Length (items) 17

Data included Weight history, food intake, symptoms, activity; metabolic demand, physical assessment;completed by patient and practitioner Weight history, food intake, activity, psychological stress, anthropometric measurement;completed by practitioner Weight history, effect of appetite; completed by patient Weight history, effect of disease; completed by practitioner Weight history, food/uid intake, activity, metabolic demand, laboratory values, skin condition; completed by practitioner

Validated in population with cancer Yes

Ref 35

18

Yes

36

measures alone are not specic enough to indicate nutritional risk.33 Therefore, screening questionnaires include several objective and subjective measures. A screening questionnaire should be easy to use, cost effective, valid, reliable, and sensitive. The American Society of Parenteral and Enteral Nutrition recommends that all patients undergo nutritional screening as a component of their initial assessment.34

3 3

Yes No

37 38

Nutritional screening
Various screening questionnaires have been used in cancer settings to identify patients who are at the greatest risk of developing nutritional problems, including substantial weight loss (table 1). The Patient-Generated Subjective Global Assessment,35 for example, was adapted by Ottery specically for the patients with cancer from the Subjective Global Assessment questionnaire.40 The questionnaire consists of two sections. The patient completes the rst section and the second section is completed by the health-care professional. The patient-completed section elicits information about weight history, the symptom experience, recent and past food intake, and activity. The health-care professional-completed section includes an assessment of metabolic demand, disease in relation to nutritional requirements, and ndings of a physical examination. Numerical and Subjective Global Assessment scores are assigned on the basis of these assessments and patients are categorised according to their nutritional status. The Subjective Global Assessment categories include mild, moderate, or severe malnutrition, and an algorithm is suggested for intervention. The numerical scores can be used as a triage system to initiate intervention.41 For example, a numerical score of 4 or higher requires intervention by a dietician in conjunction with the nurse or physician. Guidelines for follow-up are also based on score.41,42 If repeated at subsequent time points, the PatientGenerated Subjective Global Assessment numerical score is useful to show small improvements or deteriorations in nutritional status, which might not be reected in the Subjective Global Assessment score alone.43 One factor that can impede the routine use of the Patient-Generated Subjective Global Assessment in clinical practice is the training needed for accurate physical assessment and scoring of the questionnaire. The Oncology Practice Group of the American Dietetic Association has created an instructional video to assist practitioners when using the Patient-Generated Subjective Global Assessment.42 The Nestle Mini Nutritional Assessment36 is another example of a nutritional screening questionnaire. The Mini Nutritional Assessment, developed by Guigoz and colleagues with the Nestle Nutritional Corporation,36 is an 18-item questionnaire validated for use in an elderly population. Questions are divided into two main componentsscreening and assessment. Screening
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No

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Table 1: Selected tools for nutritional screening

ponded with better quality of life. However, this rise did not differ signicantly from that in controls.6 The quality-of-life questionnaire used in this study was based on the Spitzer quality-of-life index, which includes ve questions that assess involvement in occupation, activities of daily living, perception of health, outlook on life, and pleasure associated with eating. The questionnaire might not have been adequate to detect changes associated with improved calorie and protein intake. Recent data have more denitively indicated that nutritional counselling does lead to increases in the quality of life of patients with cancer. Ravasco and colleagues31 found that patients with head, neck, and gastrointestinal tumoursgroups deemed to be at high risk of malnutritioncould increase their energy intake substantially during radiotherapy after receiving nutritional counselling, despite severe symptoms. Quality-oflife scores, with the exception of pain scores, rose signicantly in these patients. Similarly, Isenring and coworkers18 found that patients with head and neck cancer receiving early intensive-nutritional counselling had less weight loss, better nutritional status, and quality of life than did those who did not receive such counselling. These patients were also more satised with their care.

Early interventions need early recognition

Early intervention is the key in effective management of nutritional issues in patients with cancer. Early recognition of malnutrition is possible through routine nutritional screening, dened as the process of identifying characteristics known to be associated with nutritional problems32 by the American Society of Parenteral and Enteral Nutrition. The purpose of the screening is to identify quickly individuals who are at nutritional risk.33 A nutritional screening questionnaire should incorporate objective and subjective data. Objective data commonly included are height, weight, weight change, primary diagnosis, disease stage, and the presence of comorbidities.34 However, individual objective
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includes questions related to changes in oral intake, weight loss, mobility, stress, and body-mass index; the questionnaire takes about 3 min to complete. A score of less than 11 on the screening component suggests malnutrition and that the remainder of the form needs to be completed.36 The assessment component includes measurement of arm and calf circumference, specic questions about eating habits, and questions about medical history. A total score is calculated (030 points) to provide a subjective judgment of proteinenergy malnutrition. A total score of less than 17 points denotes malnutrition; a score of 170235 indicates risk of malnutrition.36,44 Empirical evidence on the use of this questionnaire in the cancer population is limited, making it an area of focus for investigation. The Malnutrition Screening Tool37 is an example of a short screening tool. It contains three items, was developed by Ferguson and co-workers,37 has been validated both in patients undergoing acute care and in those with cancer who are receiving radiotherapy.45 This tool uses easily obtained data on weight history and appetite to predict nutrition risk. Another short tool, the Malnutrition Universal Screening Tool,38 also consists of a score derived from three items. However, attempts to validate the Malnutrition Universal Screening Tool in a population with cancer showed that it was unsuitable for use because of low sensitivity and specicity.38 The Nutrition Risk Assessment tool,39 developed in 1999 by the American Dietetic Association and the Consultant Dieticians in Health Care Facilities Practice Group, is widely used in US long-term care facilities. It uses data obtained for the Minimum Data Set, which must be submitted quarterly for patients in long-term care receiving Medicare benets.46 A randomised, prospective trial is under way to assess this tools validity.45 To be effective, the nutritional-screening process must be incorporated into routine clinical processes. All patients with cancer should be screened during their initial visit to establish a baseline and, subsequently, on the basis of clinical need. Early education of the patient and their family about nutritional issues is also crucial in the process of care. Teaching patients what to expect and report is essential to helping them to understand that nutritional care is a crucial component of cancer care.

examination, anthropometric measurements, and laboratory data.33 Nutritional assessment includes an assessment of body compartments and an analysis of the structure and function of organ systems and their effect on metabolism.34 A review of symptoms related to both the disease and treatment is also incorporated. Many patients develop symptoms that have the potential to interfere with appetite or nutritional intake; these symptoms must be managed aggressively to keep this effect to a minimum.47 The Patient Generated Subjective Global Assessment and the Mini Nutritional Assessment include these components and, therefore, can be used as screening or assessment tools.43,48 The nutritional care provided by a registered dietician, termed medical nutrition therapy, can effectively provide this assessment, intervention, and reassessment. Medical nutrition therapy is dened by the 2001 US Medicare benet legislation as nutritional diagnostic, treatment, and counselling services for the purpose of disease management, which are furnished by a registered dietician or nutrition professional.49 In 2003, the American Dietetic Association published the Nutrition Care Process and model. The Nutrition Care Process gives structure to the provision of nutrition care to all patients and provides a framework by which registered dieticians can think critically and make decisions about medical nutrition therapy. The process has four steps; assessment, diagnosis, intervention, and monitoring and evaluation.49

Multidisciplinary approach to care

The provision of nutritional care to patients with cancer is not restricted to the dietician alone. In fact, complete care requires the input of many disciplines.50 Most cancer centres do not have a dietician on staff to provide nutritional care.47,50 Multidisciplinary teams including a physician, nurse, pharmacist, dietician, psychologist, social worker, and physiotherapist help improve overall symptoms and sense of wellbeing.51 In the USA, the Joint Commission on Accreditation of Healthcare Organizations requires that outpatient-care facilities assess nutritional status when warranted by the patients condition and educate patients about nutritional interventions if necessary.52 There is no specication as to who should do these tasks, only that they be undertaken. Standard nutrition-assessment methods, such as the Patient-Generated Subjective Global Assessment and Mini Nutritional Assessment, can be used by any trained professional of any discipline to assess nutritional risk. Oncology nurses, advance-practice nurses, and oncologists could use these methods without the assistance of a trained nutritional professional to assess nutritional risk.47 Subsequent referral of patients who are at nutritional risk to a registered dietician or nutrition professional can assist with individualised nutritional intervention and follow-up.53
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Nutritional assessment
Nutritional screening is of little benet if it is not followed by systematic assessment and a clearly outlined plan for intervention and reassessment. Once patients have been identied as being at risk, they should undergo a more thorough assessment of their nutritional status. Nutritional assessment differs from nutritional screening. Commonly done by a registered dietician or nutrition professional, it incorporates medical history, a detailed dietary history, physical
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Symptom Taste changes Xerostomia Stomatitis or mucositis

Intervention Tart foods; highly avoured seasonings; plastic utensils and dishes; marinated foods Fluids with meals; moistened or pureed foods; moistening mouthwash or gel; papaya juice; avoidance of caffeine, alcohol, and commercial mouthwashes Avoidance of acidic, spicy, rough , or salty foods; consumption of bland, soft foods that are easy to swallow, cooked (especially vegetables) until soft and tender, cut into small pieces; or puree food in a blender; addition of broth, gravies, or sauces to ease swallowing; capsaicin candy Avoidance of high-fat foods, caffeine, alcohol, tobacco, strong spices; consumption of banana, rice, apple sauce, toast diet; initially low bre slowly increasing soluble bre; temporary avoidance of milk products (except yoghurt); increased uid intake (include juice and broth in this recommendation) Small, frequent meals (every 2 h); higher protein and fat content of meals; uids between meals; limitation of simple carbohydrates Gradual increase in bre intake; eight to ten glasses of uid daily; 48 ounces of prune juice once or twice daily; increased physical activity; bre supplement then stool softener, then laxative Avoidance of foods with strong odours, high-fat foods, and strong spices; uids between meals; cold foods that might be better tolerated Progress from no oral intake to clear liquid, full liquid, and then soft foods; maintenance of uid intake (include juice and broth in this recommendation) Avoidance of excessive intake of fat and bre; small, frequent meals (every 2 h); increased protein and carbohydrate content of meals; uids between meals

Diarrhoea

Dumping syndrome Constipation

Nausea Vomiting Early satiety

Table 2: Symptom-related nutritional interventions58

tailored to the individual patient. It should address symptom control, patient comfort, and the prevention or reversal of weight loss.57 Table 2 shows nutritional interventions for some of the symptoms reported by patients with cancer.58 The care plan might include changes in diet, liquid nutritional supplements, or enteral or parenteral nutrition. Resourceful thinking might be necessary, especially when working with uninsured and underinsured populations. The patient should remain at the centre of the plan, and his or her preferences should be incorporated. Regular follow-up, revision of interventions, and re-assessment of goals make a nutrition-care plan effective.49 Issues surrounding food and eating problems during chemotherapy are perceived by patients as highly stressful,19 and such issues should be addressed immediately. Once a care plan has been designed, it should be implemented in a timely manner. The American Dietetic Association published standard guidelines for the nutritional care of patients with cancer, called medical nutrition therapy protocols, in 1998.41 The goal of these guidelines was to dene the detailed care provided by dieticians and the expected outcomes.59

Medical nutritional treatment

Energy expenditure is difcult to predict in patients with cancer.54 There is a wide range of energy expenditure. Variability is caused by the inherent heterogeneity of cancer and of the host response to tumours.54,55 Weight loss in patients with cancer cannot be accounted for by diminished intake alone. Increased resting energy expenditure associated with cancer is not always reversed with increased oral intake or food and nutritional supplements.56 Planning of nutritional interventions in patients with cancer needs assimilation of information related to all parts of patient care. Concerns to be taken into account when planning nutritional interventions for patients include physiological abnormalities associated with the tumour (such as malabsorption, obstruction, loss of anatomy), host response to the tumour (such as anorexia and altered metabolism), symptoms associated with the cancer that have the potential to affect nutritional intake (such as pain, fatigue, or depression), and side-effects of anticancer treatment (such as mucositis, nausea and vomiting, or diarrhoea).41 In addition, the presence of a functional gastrointestinal tract, type of anticancer treatment, quality of life, performance status, prognosis, and cost-effectiveness must also be considered. The goals of medical nutrition therapy are to maintain adequate calorie and protein intake, to limit treatmentrelated symptoms, To maintain weight or reverse weight loss, to preserve lean body mass, and to achieve the best possible quality of life and functional status.41

Benets of nutritional intervention

Research did not always support the role of dietary counselling in treatment of weight loss.60 A systematic review by Baldwin and colleagues60 showed lack of evidence in support of the use of dietary advice to manage malnutrition. The review indicated a larger benet from oral nutritional supplements. Baldwin and colleagues review was compiled before the implementation of the American Dietetic Associations medical nutrition therapy protocols. Reported data describing outcomes in patients with cancer who receive nutritional intervention based on the medical nutrition therapy protocols illustrated less loss of weight and lean body mass,61 and less deterioration in nutritional status, quality of life, and physical functioning in patients who received nutritional counselling compared with those who do not.18,31 A common intervention used by health-care professionals in the treatment of cancer-induced weight loss is the initiation of liquid nutritional supplements.60,62 The use of these supplements seems to provide a demonstrable benet in patients who are malnourished, especially those with a body-mass index of less than 20 kg/m2.60,63 A Cochrane review of nutritional supplementation with energy and protein showed that these supplements produce a small but consistent weight gain, improvement in mortality, and shorter hospital stays.62

Specialised nutritional support in cancer

Specialised nutritional support refers to use of enteral or parenteral nutrition. The use of these approaches in patients with cancer is a commonly debated topic. Enteral nutrition has been associated with improvehttp://oncology.thelancet.com Vol 6 May 2005

Nutritional care plan

The nutritional care plan refers to the medical nutrition therapy interventions and goals. The care plan should be
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ments in nitrogen balance and is sometimes associated with weight gain.64 Parenteral nutrition has been associated with improvements in nitrogen balance and seems to cause weight gain more consistently than enteral nutrition.64 However, this weight gain is mainly body fat and not the desired lean body mass. Neither enteral nor parenteral nutrition has benecial effects on serum proteins in patients with cancer when administered for 749 days. These effects are not consistent with those seen in other diseases. Specialised nutritional support appears to have less of a benecial effect in cancer than in other disorders.34 The American Gastroenterological Association65 and American Society of Parenteral and Enteral Nutrition34 hold similar positions on the use of parenteral nutrition in patients with cancer. The panel shows the general contraindications to specialised nutrition support. Parenteral nutrition should not be given routinely to patients undergoing chemotherapy or radiotherapy for cancer. American Society of Parenteral and Enteral Nutrition guidelines further indicate that parenteral nutrition is appropriate only in malnourished patients who are expected to be unable to ingest or absorb adequate nutrients for a long period, dened as longer than 710 days.34 They further recommend that parenteral nutrition be avoided if the life expectancy of the patient is less than 4060 days.34 If intravenous intervention is desired in an individual with a life expectancy of less than 40 days, intravenous uids only are recommended.34 A frequently cited concern related to use of parenteral nutrition is the theoretical potential for tumour growth stimulation by glucose-based total parenteral nutrition. However, Bozzetti and colleagues comparative study66 of glucose-based and lipid-based total parenteral nutrition in adults with liver metastases has shown that this concern is misplaced. Although glucose uptake was higher in metastatic cells than in healthy cells, uptake was not increased by the provision of glucose-based parenteral nutrition, and lipid-based parenteral nutrition did not suppress glucose uptake by metastatic cells. Research is inconclusive as to the benets and risks of parenteral nutrition in patients with cancer.6769 Parenteral nutrition seems to provide more of a benet in relation to surgery than as an adjunct to chemotherapy.55

nutrition, with no improvement in survival. Risks associated with postoperative parenteral nutrition include greater intestinal permeability, increased infection rate, and increased complication rate, as well as higher costs.68,7173 Tolerance of the feeding method is an issue often raised in oncology care. Studies indicate that the frequency of diarrhoea, distention, vomiting, and other side-effects is decreased with the use of parenteral nutrition compared with enteral nutrition postoperatively;68,72 however, some reports contradict this nding.71,73,74 Papapietro and colleagues71 found similar rates of diarrhoea in patients with cancer undergoing total gastrectomy that received either enteral nutrition or parenteral nutrition. This similarity in frequency of diarrhoea for enteral and parenteral nutrition was also noted in patients with postoperative oesophagectomy who received enteral nutrition on postoperative day 1.73

Parenteral nutrition and chemotherapy

The use of parenteral nutrition during chemotherapy does not seem to improve outcome.75,76 Bone-marrow suppression, tumour response, and survival are not improved in patients receiving adjuvant parenteral nutrition during chemotherapy.77,78 The exception is the use of parenteral nutrition in stem-cell transplantation. Parenteral nutrition seems to shorten the hospital stay in patients receiving stem-cell transplantation, but with no effect on toxic effects.79,80 Parenteral nutrition might also prevent weight loss in patients undergoing stem-cell transplantation.81 Many of the trials that assessed the effects of parenteral nutrition have had weaknesses in study design, poorly matched treatment groups, differences in the amounts of nutrients received, and inadequate
Panel: Contraindications to specialised nutritional support34 Enteral nutrition Malfunctioning gastrointestinal tract Malabsorptive disorders Mechanical obstructions Severe bleeding Severe diarrhoea Intractable vomiting Gastrointestinal stula Prognosis not consistent with aggressive nutritional support Parenteral nutrition Functional gastrointestinal tract Need for nutritional support less than 5 days Poor prognosis Lack of adequate vascular access Request by patient or caregiver Haemodynamic instability Anuria without dialysis Profound metabolic or electrolyte disturbances

Perioperative parenteral nutrition

Early studies70 indicated lower morbidity and mortality with perioperative parenteral nutrition supplementation in patients with cancer, especially in those with gastrointestinal cancers. However, these studies have been strongly criticised because they used heterogeneous populations, inconsistent macronutrient provision, and had insufcient sample sizes. More recent studies6769 of perioperative parenteral nutrition indicate a heightened frequency of infection in patients receiving parenteral
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power, which preclude denitive conclusions. An important issue to be considered is that patients with cancer seem to prefer parenteral nutrition to enteral nutrition. Perceived comfort of intravenous feeding over tube feeding seemed to affect patients choice to the greatest extent.82

Enteral nutritional supplementation

The use of total enteral nutrition is much less controversial. Cited benets of the use of perioperative enteral nutrition include reduced complication rate, earlier return of bowel function,68,72 shorter postoperative stay,68 and lower relative risk of infection.83 Metabolic benets of enteral nutrition include improved peripheral protein kinetics,84 and lower frequencies of hypoglycaemia and electrolyte abnormalities.72 Enteral nutrition is also much less expensive than parenteral nutrition,72 an important consideration in todays health-care context. The use of specialised nutritional support in patients with cancer has been reviewed in-depth elsewhere.64,77,78,85 This brief overview barely touches on the controversy. Many factors including tumour type, stage of disease, anticancer treatment, and clinical status, as well as patients preference must be considered before use of specialised nutritional support in patients with cancer.

Immunonutrition
Immunonutrition refers to the use of specic nutrients enterally or parenterally to stimulate an immune response.86 Several individual nutrients such as glutamine,87 arginine,88,89 and -3 fatty acids,9092 as well as combinations of nutrients such as arginine, -3 fatty acids, and RNA93 have been investigated in the oncology population. Glutamine, an aminoacid abundant in the human body, has been supplemented in both enteral and parenteral nutrition.9496 A meta-analysis97 of human and animal studies suggested that glutamine is effective in decreasing the frequency and severity of chemotherapy-induced mucositis, irinotecan-induced diarrhoea, paclitaxel-induced neuropathy, and hepatic veno-occlusive disease. Standard parenteral nutrition does not contain glutamine because the aminoacid is unstable. Dipeptides, such as alanylglutamine and glycylglutamine, are more stable in aqueous solution.98 Perioperative parenteral glutamine has been associated with improved nitrogen balance in patients with colorectal cancer.94 In patients with acute myeloid leukaemia receiving high-dose chemotherapy without stem-cell transplantation, the neutrophil count improved more quickly in those given glutaminesupplemented parenteral nutrition than in those who did not receive such supplementation.98 Enteral glutamine has been associated with decreased length of hospital stay and decreased need for parenteral
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nutrition in patients receiving stem-cell transplants.95 Glutamine is postulated to provide an additional gutprotective effect when it is given enterally, although parenteral glutamine is metabolised similarly.97 Arginine has been investigated alone and in combination with other immunonutrients. Studies88 of enteral nutrition supplemented with arginine alone in patients with head and neck cancer indicate improvement in morbidity and length of stay with longer periods of supplementation. This improvement was not seen with a shorter duration of supplementation.89 Studies of arginine in combination with other immunonutrients indicate improved immune indices and decreased frequency of infection.34,9093 Perioperative parenteral arginine supplementation in patients with colorectal cancer improved immune responsiveness with compared controls.99 -3 fatty acids are involved in prostaglandin synthesis and inhibition of cyclo-oxygenase, and they might be effective in reducing proinammatory cytokines in cancer cachexia syndrome.100 Randomised controlled trials91,92 of -3 fatty acid-supplemented enteral nutrition are restricted mainly to patients with pancreatic cancer. One reported randomised controlled trial90 has explored the use of -3 fatty acidsupplemented enteral nutrition in a heterogeneous cancer population. These studies indicate that enteral nutrition supplemented with -3 fatty acids might help to stabilise the weight of patients who have cancerinduced weight loss.9092 Parenteral supplementation with -3 fatty acids in patients with colorectal cancer has been associated with improved concentrations of leukotriene 5 and decreased values of tumour necrosis factor.101 The most highly researched immunonutrition formula (Impact, Novartis Nutrition, Basel, Switzerland) contains arginine, RNA, and -3 fatty acids. This research has focused on non-specic indices of immunocompetence such as immunoglobulin concentrations, cytokine proles, T-cell proles, and macrophage function.93,102 These studies have indicated improvement in nutritional measures,102 immune concentrations, and frequency of infections.93,102 Metaanalysis103 shows a lower frequency of infectious complications with the use of this combination, especially with those formulas that were high in arginine. This benet was more substantial in patients undergoing surgery than in those who were critically ill. This formula seems especially benecial to patients with cancer who are malnourished and undergoing major thoracic or abdominal procedures.3,104,105 The relatively new specialty of immunonutrition seems to provide a real benet to particular categories of patients with cancer. More information is needed about optimum dose and administration schedule.
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Search strategy and selection criteria The references in this article were identied from the contributors personal knowledge of cancer-induced weight loss, reference lists in previously published work, and detailed searches of PubMed, MEDLINE, and CINAHL with the search terms cancer cachexia, PG-SGA, quality of life, supportive care, and nutrition interventions. Documents not published in English were excluded. Manual crossreferencing was done based on the bibliography of papers identied in the original searches.
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Conclusion
Patients with cancer are at high risk of weight loss and malnutrition. Early identication and assessment of weight loss is crucial. This review presents several easyto-use, concise, validated nutrition screening tools. All cancer patients should receive a nutritional screening at presentation and at subsequent time points determined by type of cancer and planned anticancer treatment regimen. Nutritional assessment provides the data necessary to plan intervention. Interventions should be individualised and revised frequently.
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