REVIEW URRENT C OPINION
Nutritional counseling and nutritional supplements: a cornerstone of multidisciplinary cancer care for cachectic patients Elizabeth A. Isenring a,b,c and Laisa Teleni a
Purpose of review The challenge with cancer cachexia is that it is not fully reversed by nutrition support. The purpose of this review is to provide an opinion on the nutritional management of cancer cachexia based on the most recent available evidence. Recent findings There continues to be a paucity of nutrition intervention studies in patients with cancer cachexia. In patients with cancer undergoing radiotherapy, there is strong evidence that nutrition counseling increases dietary intake, body weight, nutritional status and quality of life with some suggestion that dietary counseling may improve nutrition impact symptoms, treatment response and survival. In patients with cancer undergoing chemotherapy, the evidence is less clear. The use of n-3 polyunsaturated fatty acids may have some positive effects in patients with cancer; however, clinical judgment and care need to be taken in its application. Preliminary results of studies in the use of L-carnitine in improving fatigue are promising; however, the largest trial in ‘healthy’ cancer patients showed no benefit. Summary Further research into the most appropriate methods for identifying and treating cancer cachexia is required. Regardless of whether patients are experiencing reduced dietary intake resulting in malnutrition or due to cachexia, nutrition remains a cornerstone of multimodal treatment. Keywords cancer cachexia, malnutrition, nutrition
INTRODUCTION In 2006, the Dietitians Association of Australia endorsed the evidence-based practice guidelines for the nutritional management of cancer cachexia [1]. This guide for adult patients was framed by clinical questions pertaining to the identification, assessment, nutritional interventions and evaluation for the treatment of cancer cachexia. The guideline evaluated the available evidence using the National Health and Medical Research Council additional levels of evidence and grades for recommendations [2], reporting that although the evidence provides some support for nutrition intervention in improving outcomes in patients with cancer cachexia, care should be taken in its application (Level C; moderate evidence). Following on from these guidelines, this article will review the recent publications in the field and highlight the trends in clinical research surrounding the nutritional management of cancer cachexia with www.supportiveandpalliativecare.com
particular emphasis on gastrointestinal and head and neck cancer.
MALNUTRITION AND CANCER CACHEXIA Most cancer patients experience weight loss at some time as their disease progresses. [3–7] The resulting malnutrition increases risk of treatment complications and may lead to poor treatment response and/or tolerance, reduced quality of life and poor a
Department of Nutrition and Dietetics, Princess Alexandra Hospital, School of Human Movement Studies, University of Queensland, Brisbane and cFaculty of Medicine and Health Sciences, Bond University, Gold Coast, Australia b
Correspondence to Dr Elizabeth Isenring, Department of Nutrition and Dietetics, Princess Alexandra Hospital, Brisbane, Australia. Tel: þ61 7 31767132; fax: +61 7 5595 3524; e-mail: [email protected] Curr Opin Support Palliat Care 2013, 7:390–395 DOI:10.1097/SPC.0000000000000016 Volume 7 Number 4 December 2013
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Cancer cachexia and nutrition Isenring and Teleni
KEY POINTS There continues to be a paucity of nutrition intervention studies in patients with cancer cachexia. There is strong evidence that nutrition counseling increases dietary intake, body weight, nutritional status and quality of life in patients receiving radiotherapy with some suggestion that dietary counseling may improve nutrition impact symptoms, treatment response and survival. In patients with cancer undergoing chemotherapy, the evidence is less clear. The use of n-3 PUFAs may have some positive effects in patients with cancer; however, clinical judgment and care need to be taken in its application. Preliminary results of studies in the use of L-carnitine in improving fatigue are promising; however, the largest trial in ‘healthy’ cancer patients showed no benefit. Regardless of whether patients are experiencing reduced dietary intake resulting in malnutrition or due to cachexia, nutrition remains a cornerstone of multimodal treatment.
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survival [8,9 ,10,11,12]. The prevalence of malnutrition in cancer patients is thought to be as high as 80%, but reports vary with cancer location and stage, treatment history, clinical setting and assessment criteria [7,11]. Malnutrition (undernutrition) is a state of nutrition in which a deficiency of energy, protein and other nutrients adversely affects body composition, function and clinical outcome. The primary cause of malnutrition is, per definition, reduced food intake. A poor dietary intake in patients with cancer may be a consequence of treatment-related symptoms such as nausea and vomiting, [7] mucositis, malabsorption as well as other factors such as anorexia, fatigue, early satiety, mechanical obstructions (e.g. esophageal cancer) and pain. [1,13] There is strong evidence to support the use of nutrition intervention to help cancer patients maintain their weight through high-energy/protein diets, texture modification, supplementation and/or enteral feeding. [14 ] Conversely, progressive weight loss in cancer cachexia, as per definition, is in excess of that explained solely by reduced food intake and therefore is unlikely to be effectively treated by satisfying any deficit in intake alone. In cachexia, a multimodal approach should be implemented to address all aspects of cancer cachexia. However, a major hurdle in implementing an appropriate treatment for the weight-losing patient is differentiating between simple malnutrition and cancer cachexia. &&
There are significant differences between cachexia and malnutrition. Firstly, the ratio of tissue loss varies. In malnutrition due to starvation, three quarters of the weight is lost from adipose tissue with minimal losses from lean muscle mass. In cachexia, weight is lost equally from muscle and fat stores as a result of proinflammatory cytokines and a prolonged acute-phase response contributing to an increased energy expenditure, early satiety, weakness, fatigue and anemia [1] with adipose tissue losses detectable earlier in cancer cachexia than lean losses. [15] This altered carbohydrate, protein and lipid metabolism in cancer cachexia limits the efficacy of nutrition intervention in weight stabilization. Despite the metabolic derangements, the complexity of cachexia means that there are a number of definitions for cancer cachexia all with similar, but different diagnostic, criteria. The American Society of Enteral and Parenteral Nutrition states that cancer cachexia is characterized by progressive weight loss with clinical features of tissue wasting, anorexia, skeletal muscle atrophy, fatigue, anemia and hypoalbuminemia. [16] Most recently, Fearon et al. [17] developed a consensus document classifying the syndrome into: precachexia, clinical and metabolic signs precede 5% or more weight loss; cachexia, 5% or more weight loss in 6 months, which cannot be fully explained by starvation or weight loss more than 2% and sarcopenia or a body mass index (BMI) of less than 20 kg/m2; and refractory cachexia, associated with active catabolism or the presence of factors that render active management of weight loss no longer possible or appropriate. At this late stage, the burden of nutritional support outweighs any potential benefit and the nutritional goals shift from those of weight maintenance to comfort feeding. It is imperative to use clinical judgment when evaluating weight loss, as there are no precise biochemical cutoffs in cachexia and the definitions vary. Using three definitions of cachexia, Wallengren et al. [9 ] evaluated the diagnostic criteria for cancer cachexia in relation to adverse patient-centered outcomes such as weight and quality of life. The resultant prevalence of cancer cachexia varied widely with the differing definitions. In the absence of clear diagnostic criteria or biochemical parameters, malnutrition is easily misclassified as cachexia. However, irrespective of malnutrition or cancer cachexia, nutrition intervention should play a pivotal role in any multimodal management plan. Yet in clinical practice, a diagnosis of cachexia (correct or otherwise) can prematurely shift the care away from nutrition support, as the efficacy for nutrition intervention to improve
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outcomes in cachexia is less clear than in malnutrition.
NUTRITION SCREENING The 2006 cachexia guidelines recommend that nutrition screening be implemented to measure the contribution of anorexia to any weight loss. [1] Nutrition screening tools enable triage, prioritizing resources to those patients in need of nutrition support. Tools such as these usually incorporate data available on admission and can be implemented by those with minimal nutrition expertise. Although no screening tools have been validated specifically in patients with cancer cachexia, the Malnutrition Screening Tool (MST) has been validated in a number of cancer populations and settings [18,19] and is effective in the rapid identification of patients at risk of malnutrition. More recently, Bole´o-Tome´ et al. validated the Malnutrition Universal Screening Tool (MUST) in adults with cancer undergoing radiation treatment in the outpatient setting. [20 ] Using a prospective design, they found that the MUST identifies patients at risk for malnutrition with sensitivity and specificity of over 80% (comparable with the MST). Interestingly, the authors also found that more than 5% weight loss (comparing current measured weight with presymptom reported weight) was also highly specific and sensitive for nutrition screening. Assuming the screening tool has been validated in patients with cancer, for example NRS-2002 [21]; the use of any screening tool or method is probably more important than the use of a particular screening tool. The timing for nutrition screening is less clear. The updated evidence-based practice guidelines for the nutritional management of patients receiving radiation therapy and chemotherapy show that there is strong evidence for cancer patients at high nutritional risk (e.g. gastrointestinal and head and neck cancers receiving radiation therapy) to be automatically referred to a dietitian. [14 ] Other patients at nutrition risk such as those receiving chemotherapy should be routinely screened for nutrition risk. &
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NUTRITION ASSESSMENT It is important that patients identified as being at high nutritional risk be referred to a dietitian or equivalent trained in nutrition assessment and intervention. Nutritional status should be comprehensively evaluated using a validated nutrition assessment tool for identifying malnutrition in this population. [1,21] Completing a nutrition assessment should highlight symptoms impacting on dietary intake such as vomiting, anorexia, 392
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malabsorption or obstruction: assess diet and weight history and complete a physical assessment of body composition and relevant biochemical parameters. Dietary intake can be assessed via a diet history (specialist asks about usual oral intake using household measures and a checklist) or food and fluid diary (completed by the patient or carer including a mixture of week and weekend days and treatment and nontreatment days). Computerized software is used to generate macro and micronutrient intake. Estimated energy intake can then be compared with requirements using indirect calorimetry or energy calculations (e.g. Harris-Benedict or Schofield). Body composition can be assessed broadly via a physical examination of subcutaneous fat and muscle stores or more specifically via techniques such as bioelectrical impedance analysis, CT or dual-energy X-ray absorptiometry scan. In patients with malnutrition, it is expected that weight will stabilize or increase once these issues are resolved. In these cases, a patient should not be diagnosed as cachectic. The Subjective Global Assessment (SGA) identifies nutritional status based on medical history (changes in weight, dietary intake, presence of gastrointestinal symptoms for more than 2 weeks, functional capacity) and physical assessment (loss of subcutaneous fat, muscle wasting, edema or ascites) The scored Patient-Generated SGA Tool [22 ] builds on the SGA with additional questions pertaining to shorter-term weight loss, a comprehensive list of symptoms that impact on dietary intake, functional status as relating to changes in nutrition and a more detailed dietary intake history. This latter tool can be used to predict the direction and magnitude of changes in quality of life of patients with cancer [1,3]. &&
NUTRITION INTERVENTION Weight stabilization may be the most optimistic outcome to be expected in patients with cachexia and is still beneficial, as weight-losing patients with cancer cachexia who stabilize their weight have a greater quality of life and survival than those who continue to lose weight. [1] The head and neck cancer guidelines state that there is strong evidence to support the goal of minimizing weight loss and decline in nutritional status to maintain quality of life. [21] This recommendation remains unchanged in the updated radiation and chemotherapy guidelines. [14 ] Few nutrition intervention studies target cancer cachexia. However, nutrition studies have demonstrated improvements in patient outcomes. [14 ] Kiss et al. [23] reported that a dietitian-led head and &&
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neck radiation clinic reduced nutrition-related admissions and unplanned nasogastric tube insertions, improved oral diet transitions posttreatment and reduced need for medical follow-up during the immediate posttreatment period. Ravasco et al. [24 ] reported that early, individualized nutritional counseling and education during radiotherapy improve outcomes for colorectal cancer patients as part of a randomized trial. Compared with those who maintained their usual diet, over 90% of those who received nutrition counseling maintained their weight. In those undergoing chemotherapy, there is strong evidence for the use of nutrition intervention (dietary counseling supplements) in increasing dietary intake and weight. However, such interventions have been shown to have no impact on improving quality of life or survival in chemotherapy patients. [14 ] Optimization of patient protein and energy intake is the first step, as weight-stable cachectic patients receiving supporting care or chemotherapy have been shown to have higher intakes of protein and energy than those who were losing weight. [1] Nutrition counseling should incorporate symptom management, meal planning, texture modification or food fortification and self-monitoring to meet higher energy and protein needs. However, Wallengren et al. [9 ] reported that energy intake was not predictive of survival and was not consistently associated with adverse outcomes. Instead, symptom scales capturing the underlying causes of reduced food intake, such as that in the PG-SGA, are of better prognostic value. In the absence of indirect calorimetry to quantify energy requirements, dietary intake should at least meet 120 kJ/kg/day and a protein intake of 1.4 g/kg/day. Where an energy and/or protein deficit cannot be satisfied through diet with or without oral nutrition support supplements, tube feeding may be required [1,25 ]. Patients with a gastrostomy tube had significantly less weight loss, fewer complications and higher patient acceptance and duration of nutrition support. Prophylactic tube feeding has been shown to reduce hospital admissions and/or length of stay, [26] reduced treatment interruptions, and improved nutritional status. &&
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EICOSAPENTAENOIC ACID – THE EVIDENCE A Cochrane review in 2007 concluded that insufficient data to establish whether oral eicosapentaenoic acid was better than placebo [27]. In order to report the latest evidence for n-3 polyunsaturated fatty acids (PUFAs) in cancer cachexia, a recent systematic literature review of randomized controlled trials (RCTs) comparing effects on clinical
outcome parameters of oral or enteral supplementation of n-3 PUFAs in cancer patients receiving chemotherapy, radiotherapy, surgery or palliative care was conducted [28]. Nine (out of a total of 15) RCTs were of positive quality, five of neutral quality and one of negative quality, and performed in patients with various types of cancer. Fair evidence showed supplementation of n-3 PUFAs appeared to be well tolerated and may improve quality of life and physical activity in patients with cancer. The evidence for the effect on body weight, fat-free mass and performance status remains inconclusive. In summary, supplementation of n-3 PUFAs may have some positive effects in patients with cancer however clinical judgment and care needs to be taken in its application. Cochrane and systematic reviews have found conflicting results depending on the criteria used to critique individual studies. Therefore, although more work is being done in the precachexia phase and is one of the areas of research promise, this recommendation remains similar to that of the 2006 guidelines. [1] Despite calls for more well designed studies in the area, it is unclear whether the level of evidence will ever increase, n-3 PUFAs are now so widely available and relatively inexpensive that investigating different doses of n-3 FAs may be more appropriate than an RCT against a placebo.
CARNITINE Recently, L-carnitine has been evaluated for its potential role in improving clinical outcomes in patients with advanced cancer. Carnitine is a cofactor required for transforming free fatty acids to acyl carnitine and transporting them into the mitochondrial matrix for the production of acetyl coenzyme A via the b-oxidation pathway playing a pivotal role in energy metabolism. In addition, carnitine is required for the metabolism of several amino acids and pyruvate dehydrogenase, thus triggering the tricarboxylic acid cycle. There have been eight studies into carnitine supplementation with only four in patients with cancer cachexia. [29 ,30 ] Preliminary results show carnitine to be a promising treatment for fatigue, particularly in cachectic patients. However, the largest trial in this area failed to detect significant differences; [30 ] therefore, it is premature to make recommendations regarding carnitine in improving cancer-related fatigue. &
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DOES NUTRITION INTERVENTION IMPROVE OUTCOMES IN PATIENTS WITH CANCER CACHEXIA? It is difficult to make statements pertaining to the efficacy of nutrition intervention improving
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outcomes with cancer cachexia, as there is no universal agreement on cachexia criteria many nutrition trials do not specifically measure cachexia. In patients receiving radiotherapy, there is still strong evidence for nutritional issues to be identified early and for those at high risk to be automatically referred to a dietitian [14 ]. Early and appropriate intervention leads to improved dietary intake (energy and protein), weight, body composition and quality of life. [14 ] There is emerging evidence that dietary counseling leads to improved oncologic as well as quality of life outcomes. Longterm follow-up of a three-arm nutrition study conducted in patients receiving treatment for colorectal cancer by Ravasco et al. [24 ] reported benefits not only in nutritional outcomes but also in survival. Adequate nutritional status was maintained in 91% of those who received individualized nutrition counseling but not in any of the control group who maintained their usual diet. In these patients, worse radiotherapy toxicity, quality of life and mortality were associated with deteriorated nutritional status and intake. Likewise, depleted intake, nutritional status, and quality of life predicted shorter survival and late toxicity. Therefore early, individualized nutritional counseling and education during radiotherapy was valuable for this group of colorectal cancer patients. &&
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REFRACTORY CACHEXIA At the later stage of cachexia, the burden of nutritional support often outweighs any potential benefit and therefore the nutritional goals shift from those of weight maintenance to quality of life issues and comfort feeding as desired. A recent systematic review highlighted that patients and carers would like weight loss to be acknowledged by health professionals but unfortunately found there was often a lack of attention to nutritional issues and weight loss [31 ]. Psychosocial effects such as anger, anxiety and depression can result if there are unrealistic expectations about nutrition at this late stage by the patient, carer and/or staff [31 ]. Therefore, an understanding of the relevant psychosocial issues, education and support are required so that it is appreciated that at this stage, weight gain or even stabilization is unrealistic and should focus on quality of life, managing pain and symptoms and supporting whatever the patient desires to eat (or not eat). &&
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CONCLUSION The challenge with cancer cachexia is that it is not fully reversed by nutrition support. However, 394
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regardless of whether patients are experiencing reduced dietary intake resulting in malnutrition or due to cachexia, nutrition remains a cornerstone of multimodal treatment. There is strong evidence that nutrition counseling (with or without the provision of oral nutrition supplements) increases dietary intake, body weight, nutritional status and quality of life. There is some suggestion that in patients with colorectal cancer, dietary counseling may improve nutrition impact symptoms, treatment response and survival. However, there is less evidence for nutrition support during chemotherapy and further well designed studies with appropriate nutrition interventions are required. Further research into the most appropriate methods for identifying and treating cancer cachexia is required. Acknowledgements Funding: None to disclose Conflicts of interest There are no conflicts of interest.
REFERENCES AND RECOMMENDED READING Papers of particular interest, published within the annual period of review, have been highlighted as: & of special interest && of outstanding interest 1. Bauer J, Ash S, Davidson WL, et al. Evidence based practice guidelines for the nutritional management of cancer cachexia. Nutr Diet 2006; 63:S3–S32. 2. National Health Medical Research Council. NHMRC additional levels of evidence and grades for recommendation for developers of guidelines. Pilot Program 2005; Available from: http://www.nhmrc.gov.au/advice/consult.htm. 3. Bauer J, Capra S, Ferguson M. Use of the scored Patient-Generated Subjective Global Assessment (PG-SGA) as a nutrition assessment tool in patients with cancer. Eur J Clin Nutr 2002; 56:779–785. 4. Creaser N. Nutritional status of oncology patients admitted to a rural day chemotherapy unit as measured by the Patient Generated-Subjective Global Assessment. Nutr Diet 2010; 67:231–236. 5. Laviano A, Meguid MM, Rossi-Fanelli F. Cancer anorexia: clinical implications, pathogenesis, and therapeutic strategies. Lancet Oncol 2003; 4:686– 694. 6. Read JA, Choy STB, Beale P, Clarke SJ. An evaluation of the prevalence of malnutrition in cancer patients attending the outpatient oncology clinic. AsiaPac J Clin Onco 2006; 2:80–86. 7. Davidson W, Teleni L, Muller J, et al. Malnutrition and chemotherapy-induced nausea and vomiting: implications for practice. Oncol Nurs Forum 2012; 39:E340–E345. 8. Ravasco P, Grillo IB, Camilo M. Cancer wasting and quality of life react to early individualized nutritional counselling! Clin Nutr 2007; 26:7–15. 9. Wallengren O, Lundholm K, Bosaeus I. Diagnostic criteria of cancer cachexia: && relation to quality of life, exercise capacity and survival in unselected palliative care patients. Support Care Cancer 2013; 21:1569–1577. This article highlights the importance of not having a consensus on the definition of cancer cachexia by reporting the wide variation in the prevalence of this syndrome. This article also highlights the prognostic value of weight loss in this population. 10. Vandebroek AJV, Schrijvers D. Nutritional issues in anticancer treatment. Ann Oncol 2008; 19 (Suppl 5):v52–v55. 11. Bozzetti F, Arends J, Lundholm K, et al. ESPEN Guidelines on Parenteral Nutrition: nonsurgical oncology. Clin Nutr 2009; 28:445–454. 12. Brown T, Findlay M, von Dincklage J, et al. Using a wiki platform to promote guidelines internationally and maintain their currency: evidence-based guidelines for the nutritional management of adult patients with head and neck cancer. J Hum Nutr Diet 2013; 26:182–190. 13. Omlin A, Blum D, Wierecky J, et al. Nutrition impact symptoms in advanced cancer patients: frequency and specific interventions, a case-control study. J Cachexia Sarcopenia Muscle March 2013; 4:55–61.
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Cancer cachexia and nutrition Isenring and Teleni 14. Isenring E, Zabel R, Bannister M, et al. Updated evidence-based practice guidelines for the nutritional management of patients receiving radiation therapy and/or chemotherapy. Nutr Diet 2013; http://onlinelibrary.wiley. com/doi/10.1111/1747-0080.12013/abstract. This article provides clinical practice recommendations for the nutritional management of cancer patients undergoing radiotherapy or chemotherapy. This article provides a systematic review of the evidence. Recommendations are objectively graded according to the strength of the supporting evidence. 15. Das SK, Hoefler G. The role of triglyceride lipases in cancer associated cachexia. Trend Mol Med 2013; 19:292–301. 16. August DA, Huhmann MB. A.S.P.E.N. clinical guidelines: nutrition support therapy during adult anticancer treatment and in hematopoietic cell transplantation. JPEN J Parenter Enteral Nutr 2009; 33:472–500. 17. Fearon K, Strasser F, Anker SD, et al. Definition and classification of cancer cachexia: an international consensus. Lancet Oncol 2011; 12:489– 495. 18. Isenring E, Cross G, Daniels L, et al. Validity of the malnutrition screening tool as an effective predictor of nutritional risk in oncology outpatients receiving chemotherapy. Support Care Cancer 2006; 14:1152–1156. 19. Ferguson ML, Bauer J, Gallagher B, et al. Validation of a malnutrition screening tool for patients receiving radiotherapy. Radiation Oncol 1999; 43:325– 327. 20. Bole´o-Tome´ C, Monteiro-Grillo I, Camilo M, Ravasco P. Validation of the & Malnutrition Universal Screening Tool (MUST) in cancer. Brit J Nutr 2012; 108:343–348. This article is the first study to validate the use of the Malnutrition Universal screening tool in cancer patients. 21. Kondrup J, Rasmussen HH, Hamberg O, Stanga Z. Nutritional risk screening (NRS 2002): a new method. Clin Nutr 2003; 22:321–336. 22. Findlay M, Bauer J, Brown T, et al. Evidence based practice guidelines for the && nutritional management of adult patients with head and neck cancer. Online wiki guidelines 2013. [updated 26 February cited 2013 1 July, 2013]; Available from: http://wiki.cancer.org.au/australia/COSA:Head_and_neck_ cancer_nutrition_guidelines. This wiki provides clinical practice recommendations for the nutritional management of head and neck cancer. This article provides a systematic review of the evidence. Recommendations objectively graded according to the strength of the supporting evidence. This wiki is updated on a rolling 6 monthly basis. 23. Ottery FD. The clinical guide to oncology nutrition. In: McCallum P, Polisena C, editors. Patient generated subjective global assessment. Chicago, IL, USA: The American Dietetic Association; 2000. pp. 11–23. &&
24. Kiss NK, Krishnasamy M, Loeliger J, et al. A dietitian-led clinic for patients receiving (chemo)radiotherapy for head and neck cancer. Support Care Cancer 2012; 20:2111–2120. This article highlights the benefits of including a dietitian-led clinic for patients receiving radiotherapy with or without chemotherapy. This intervention study has important consequences for improving outcomes in a patient group inclusive of cancer cachexia. 25. Ravasco P, Monteiro-Grillo I, Camilo M. Individualized nutrition intervention is of && major benefit to colorectal cancer patients: long-term follow-up of a randomized controlled trial of nutritional therapy. Am J Clin Nutr 2012; 96:1346–1353. This article provides information on the long-term prognosis of patients who received individualized nutrition intervention. This study highlights the value of early individualized nutrition counseling and education for radiotherapy patients. 26. Sobani ZU, Ghaffar S, Ahmed BN. Comparison of outcomes of enteral feeding via nasogastric versus gastrostomy tubes in post operative patients with a principle diagnosis of squamous cell carcinoma of the oral cavity. J Pak Med Assoc 2011; 61:1042–1045. 27. Dewey A, Baughan C, Dean T, et al. Eicosapentaenoic acid (EPA, an omega-3 fatty acid from fish oils) for the treatment of cancer cachexia. Cochrane Database Syst Rev 2007; 1:CD004597. 28. Dewey A, Baughan C, Dean T, et al. ‘Should n-3 polyunsaturated fatty acids be prescribed in patients with cancer cachexia?’. OA Epidemiology 2013; 1:2. 29. Maccio A, Madeddu C, Gramignano G, et al. A randomized phase III clinical & trial of a combined treatment for cachexia in patients with gynecological cancers: evaluating the impact on metabolic and inflammatory profiles and quality of life. Gynecol Oncol 2012; 124:417–425. This article highlights the benefit of supplementing L-carnitine in treating fatigue in patients with cancer cachexia. 30. Cruciani RA, Zhang JJ, Manola J, et al. L-carnitine supplementation for the && management of fatigue in patients with cancer: an eastern cooperative oncology group phase III, randomized, double-blind, placebo-controlled trial. J Clin Oncol 2012; 30:3864–3869. This article reports results of the largest randomized, double-blind placebo-controlled trial supplementing L-Carnitine. This study was in ‘healthy’ cancer patients and demonstrated no benefit. 31. Oberholzer R, Hopkinson JB, Baumann K, et al. This interesting review && discusses the psychosocial effects of cancer cachexia and provides a model and suggestions for clinicians. J Pain Symptom Manage 2013; 46:77–95. doi: 10.1016/j.jpainsymman.2012.06.020. Epub 2012 Nov 15. Psychosocial effects of cancer cachexia: a systematic literature search and qualitative analysis. &&
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Nutritional counseling and nutritional supplements: a cornerstone of multidisciplinary cancer care for cachectic patients Elizabeth A. Isenring a,b,c and Laisa Teleni a
Purpose of review The challenge with cancer cachexia is that it is not fully reversed by nutrition support. The purpose of this review is to provide an opinion on the nutritional management of cancer cachexia based on the most recent available evidence. Recent findings There continues to be a paucity of nutrition intervention studies in patients with cancer cachexia. In patients with cancer undergoing radiotherapy, there is strong evidence that nutrition counseling increases dietary intake, body weight, nutritional status and quality of life with some suggestion that dietary counseling may improve nutrition impact symptoms, treatment response and survival. In patients with cancer undergoing chemotherapy, the evidence is less clear. The use of n-3 polyunsaturated fatty acids may have some positive effects in patients with cancer; however, clinical judgment and care need to be taken in its application. Preliminary results of studies in the use of L-carnitine in improving fatigue are promising; however, the largest trial in ‘healthy’ cancer patients showed no benefit. Summary Further research into the most appropriate methods for identifying and treating cancer cachexia is required. Regardless of whether patients are experiencing reduced dietary intake resulting in malnutrition or due to cachexia, nutrition remains a cornerstone of multimodal treatment. Keywords cancer cachexia, malnutrition, nutrition
INTRODUCTION In 2006, the Dietitians Association of Australia endorsed the evidence-based practice guidelines for the nutritional management of cancer cachexia [1]. This guide for adult patients was framed by clinical questions pertaining to the identification, assessment, nutritional interventions and evaluation for the treatment of cancer cachexia. The guideline evaluated the available evidence using the National Health and Medical Research Council additional levels of evidence and grades for recommendations [2], reporting that although the evidence provides some support for nutrition intervention in improving outcomes in patients with cancer cachexia, care should be taken in its application (Level C; moderate evidence). Following on from these guidelines, this article will review the recent publications in the field and highlight the trends in clinical research surrounding the nutritional management of cancer cachexia with www.supportiveandpalliativecare.com
particular emphasis on gastrointestinal and head and neck cancer.
MALNUTRITION AND CANCER CACHEXIA Most cancer patients experience weight loss at some time as their disease progresses. [3–7] The resulting malnutrition increases risk of treatment complications and may lead to poor treatment response and/or tolerance, reduced quality of life and poor a
Department of Nutrition and Dietetics, Princess Alexandra Hospital, School of Human Movement Studies, University of Queensland, Brisbane and cFaculty of Medicine and Health Sciences, Bond University, Gold Coast, Australia b
Correspondence to Dr Elizabeth Isenring, Department of Nutrition and Dietetics, Princess Alexandra Hospital, Brisbane, Australia. Tel: þ61 7 31767132; fax: +61 7 5595 3524; e-mail: [email protected] Curr Opin Support Palliat Care 2013, 7:390–395 DOI:10.1097/SPC.0000000000000016 Volume 7 Number 4 December 2013
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Cancer cachexia and nutrition Isenring and Teleni
KEY POINTS There continues to be a paucity of nutrition intervention studies in patients with cancer cachexia. There is strong evidence that nutrition counseling increases dietary intake, body weight, nutritional status and quality of life in patients receiving radiotherapy with some suggestion that dietary counseling may improve nutrition impact symptoms, treatment response and survival. In patients with cancer undergoing chemotherapy, the evidence is less clear. The use of n-3 PUFAs may have some positive effects in patients with cancer; however, clinical judgment and care need to be taken in its application. Preliminary results of studies in the use of L-carnitine in improving fatigue are promising; however, the largest trial in ‘healthy’ cancer patients showed no benefit. Regardless of whether patients are experiencing reduced dietary intake resulting in malnutrition or due to cachexia, nutrition remains a cornerstone of multimodal treatment.
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survival [8,9 ,10,11,12]. The prevalence of malnutrition in cancer patients is thought to be as high as 80%, but reports vary with cancer location and stage, treatment history, clinical setting and assessment criteria [7,11]. Malnutrition (undernutrition) is a state of nutrition in which a deficiency of energy, protein and other nutrients adversely affects body composition, function and clinical outcome. The primary cause of malnutrition is, per definition, reduced food intake. A poor dietary intake in patients with cancer may be a consequence of treatment-related symptoms such as nausea and vomiting, [7] mucositis, malabsorption as well as other factors such as anorexia, fatigue, early satiety, mechanical obstructions (e.g. esophageal cancer) and pain. [1,13] There is strong evidence to support the use of nutrition intervention to help cancer patients maintain their weight through high-energy/protein diets, texture modification, supplementation and/or enteral feeding. [14 ] Conversely, progressive weight loss in cancer cachexia, as per definition, is in excess of that explained solely by reduced food intake and therefore is unlikely to be effectively treated by satisfying any deficit in intake alone. In cachexia, a multimodal approach should be implemented to address all aspects of cancer cachexia. However, a major hurdle in implementing an appropriate treatment for the weight-losing patient is differentiating between simple malnutrition and cancer cachexia. &&
There are significant differences between cachexia and malnutrition. Firstly, the ratio of tissue loss varies. In malnutrition due to starvation, three quarters of the weight is lost from adipose tissue with minimal losses from lean muscle mass. In cachexia, weight is lost equally from muscle and fat stores as a result of proinflammatory cytokines and a prolonged acute-phase response contributing to an increased energy expenditure, early satiety, weakness, fatigue and anemia [1] with adipose tissue losses detectable earlier in cancer cachexia than lean losses. [15] This altered carbohydrate, protein and lipid metabolism in cancer cachexia limits the efficacy of nutrition intervention in weight stabilization. Despite the metabolic derangements, the complexity of cachexia means that there are a number of definitions for cancer cachexia all with similar, but different diagnostic, criteria. The American Society of Enteral and Parenteral Nutrition states that cancer cachexia is characterized by progressive weight loss with clinical features of tissue wasting, anorexia, skeletal muscle atrophy, fatigue, anemia and hypoalbuminemia. [16] Most recently, Fearon et al. [17] developed a consensus document classifying the syndrome into: precachexia, clinical and metabolic signs precede 5% or more weight loss; cachexia, 5% or more weight loss in 6 months, which cannot be fully explained by starvation or weight loss more than 2% and sarcopenia or a body mass index (BMI) of less than 20 kg/m2; and refractory cachexia, associated with active catabolism or the presence of factors that render active management of weight loss no longer possible or appropriate. At this late stage, the burden of nutritional support outweighs any potential benefit and the nutritional goals shift from those of weight maintenance to comfort feeding. It is imperative to use clinical judgment when evaluating weight loss, as there are no precise biochemical cutoffs in cachexia and the definitions vary. Using three definitions of cachexia, Wallengren et al. [9 ] evaluated the diagnostic criteria for cancer cachexia in relation to adverse patient-centered outcomes such as weight and quality of life. The resultant prevalence of cancer cachexia varied widely with the differing definitions. In the absence of clear diagnostic criteria or biochemical parameters, malnutrition is easily misclassified as cachexia. However, irrespective of malnutrition or cancer cachexia, nutrition intervention should play a pivotal role in any multimodal management plan. Yet in clinical practice, a diagnosis of cachexia (correct or otherwise) can prematurely shift the care away from nutrition support, as the efficacy for nutrition intervention to improve
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outcomes in cachexia is less clear than in malnutrition.
NUTRITION SCREENING The 2006 cachexia guidelines recommend that nutrition screening be implemented to measure the contribution of anorexia to any weight loss. [1] Nutrition screening tools enable triage, prioritizing resources to those patients in need of nutrition support. Tools such as these usually incorporate data available on admission and can be implemented by those with minimal nutrition expertise. Although no screening tools have been validated specifically in patients with cancer cachexia, the Malnutrition Screening Tool (MST) has been validated in a number of cancer populations and settings [18,19] and is effective in the rapid identification of patients at risk of malnutrition. More recently, Bole´o-Tome´ et al. validated the Malnutrition Universal Screening Tool (MUST) in adults with cancer undergoing radiation treatment in the outpatient setting. [20 ] Using a prospective design, they found that the MUST identifies patients at risk for malnutrition with sensitivity and specificity of over 80% (comparable with the MST). Interestingly, the authors also found that more than 5% weight loss (comparing current measured weight with presymptom reported weight) was also highly specific and sensitive for nutrition screening. Assuming the screening tool has been validated in patients with cancer, for example NRS-2002 [21]; the use of any screening tool or method is probably more important than the use of a particular screening tool. The timing for nutrition screening is less clear. The updated evidence-based practice guidelines for the nutritional management of patients receiving radiation therapy and chemotherapy show that there is strong evidence for cancer patients at high nutritional risk (e.g. gastrointestinal and head and neck cancers receiving radiation therapy) to be automatically referred to a dietitian. [14 ] Other patients at nutrition risk such as those receiving chemotherapy should be routinely screened for nutrition risk. &
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NUTRITION ASSESSMENT It is important that patients identified as being at high nutritional risk be referred to a dietitian or equivalent trained in nutrition assessment and intervention. Nutritional status should be comprehensively evaluated using a validated nutrition assessment tool for identifying malnutrition in this population. [1,21] Completing a nutrition assessment should highlight symptoms impacting on dietary intake such as vomiting, anorexia, 392
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malabsorption or obstruction: assess diet and weight history and complete a physical assessment of body composition and relevant biochemical parameters. Dietary intake can be assessed via a diet history (specialist asks about usual oral intake using household measures and a checklist) or food and fluid diary (completed by the patient or carer including a mixture of week and weekend days and treatment and nontreatment days). Computerized software is used to generate macro and micronutrient intake. Estimated energy intake can then be compared with requirements using indirect calorimetry or energy calculations (e.g. Harris-Benedict or Schofield). Body composition can be assessed broadly via a physical examination of subcutaneous fat and muscle stores or more specifically via techniques such as bioelectrical impedance analysis, CT or dual-energy X-ray absorptiometry scan. In patients with malnutrition, it is expected that weight will stabilize or increase once these issues are resolved. In these cases, a patient should not be diagnosed as cachectic. The Subjective Global Assessment (SGA) identifies nutritional status based on medical history (changes in weight, dietary intake, presence of gastrointestinal symptoms for more than 2 weeks, functional capacity) and physical assessment (loss of subcutaneous fat, muscle wasting, edema or ascites) The scored Patient-Generated SGA Tool [22 ] builds on the SGA with additional questions pertaining to shorter-term weight loss, a comprehensive list of symptoms that impact on dietary intake, functional status as relating to changes in nutrition and a more detailed dietary intake history. This latter tool can be used to predict the direction and magnitude of changes in quality of life of patients with cancer [1,3]. &&
NUTRITION INTERVENTION Weight stabilization may be the most optimistic outcome to be expected in patients with cachexia and is still beneficial, as weight-losing patients with cancer cachexia who stabilize their weight have a greater quality of life and survival than those who continue to lose weight. [1] The head and neck cancer guidelines state that there is strong evidence to support the goal of minimizing weight loss and decline in nutritional status to maintain quality of life. [21] This recommendation remains unchanged in the updated radiation and chemotherapy guidelines. [14 ] Few nutrition intervention studies target cancer cachexia. However, nutrition studies have demonstrated improvements in patient outcomes. [14 ] Kiss et al. [23] reported that a dietitian-led head and &&
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neck radiation clinic reduced nutrition-related admissions and unplanned nasogastric tube insertions, improved oral diet transitions posttreatment and reduced need for medical follow-up during the immediate posttreatment period. Ravasco et al. [24 ] reported that early, individualized nutritional counseling and education during radiotherapy improve outcomes for colorectal cancer patients as part of a randomized trial. Compared with those who maintained their usual diet, over 90% of those who received nutrition counseling maintained their weight. In those undergoing chemotherapy, there is strong evidence for the use of nutrition intervention (dietary counseling supplements) in increasing dietary intake and weight. However, such interventions have been shown to have no impact on improving quality of life or survival in chemotherapy patients. [14 ] Optimization of patient protein and energy intake is the first step, as weight-stable cachectic patients receiving supporting care or chemotherapy have been shown to have higher intakes of protein and energy than those who were losing weight. [1] Nutrition counseling should incorporate symptom management, meal planning, texture modification or food fortification and self-monitoring to meet higher energy and protein needs. However, Wallengren et al. [9 ] reported that energy intake was not predictive of survival and was not consistently associated with adverse outcomes. Instead, symptom scales capturing the underlying causes of reduced food intake, such as that in the PG-SGA, are of better prognostic value. In the absence of indirect calorimetry to quantify energy requirements, dietary intake should at least meet 120 kJ/kg/day and a protein intake of 1.4 g/kg/day. Where an energy and/or protein deficit cannot be satisfied through diet with or without oral nutrition support supplements, tube feeding may be required [1,25 ]. Patients with a gastrostomy tube had significantly less weight loss, fewer complications and higher patient acceptance and duration of nutrition support. Prophylactic tube feeding has been shown to reduce hospital admissions and/or length of stay, [26] reduced treatment interruptions, and improved nutritional status. &&
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EICOSAPENTAENOIC ACID – THE EVIDENCE A Cochrane review in 2007 concluded that insufficient data to establish whether oral eicosapentaenoic acid was better than placebo [27]. In order to report the latest evidence for n-3 polyunsaturated fatty acids (PUFAs) in cancer cachexia, a recent systematic literature review of randomized controlled trials (RCTs) comparing effects on clinical
outcome parameters of oral or enteral supplementation of n-3 PUFAs in cancer patients receiving chemotherapy, radiotherapy, surgery or palliative care was conducted [28]. Nine (out of a total of 15) RCTs were of positive quality, five of neutral quality and one of negative quality, and performed in patients with various types of cancer. Fair evidence showed supplementation of n-3 PUFAs appeared to be well tolerated and may improve quality of life and physical activity in patients with cancer. The evidence for the effect on body weight, fat-free mass and performance status remains inconclusive. In summary, supplementation of n-3 PUFAs may have some positive effects in patients with cancer however clinical judgment and care needs to be taken in its application. Cochrane and systematic reviews have found conflicting results depending on the criteria used to critique individual studies. Therefore, although more work is being done in the precachexia phase and is one of the areas of research promise, this recommendation remains similar to that of the 2006 guidelines. [1] Despite calls for more well designed studies in the area, it is unclear whether the level of evidence will ever increase, n-3 PUFAs are now so widely available and relatively inexpensive that investigating different doses of n-3 FAs may be more appropriate than an RCT against a placebo.
CARNITINE Recently, L-carnitine has been evaluated for its potential role in improving clinical outcomes in patients with advanced cancer. Carnitine is a cofactor required for transforming free fatty acids to acyl carnitine and transporting them into the mitochondrial matrix for the production of acetyl coenzyme A via the b-oxidation pathway playing a pivotal role in energy metabolism. In addition, carnitine is required for the metabolism of several amino acids and pyruvate dehydrogenase, thus triggering the tricarboxylic acid cycle. There have been eight studies into carnitine supplementation with only four in patients with cancer cachexia. [29 ,30 ] Preliminary results show carnitine to be a promising treatment for fatigue, particularly in cachectic patients. However, the largest trial in this area failed to detect significant differences; [30 ] therefore, it is premature to make recommendations regarding carnitine in improving cancer-related fatigue. &
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DOES NUTRITION INTERVENTION IMPROVE OUTCOMES IN PATIENTS WITH CANCER CACHEXIA? It is difficult to make statements pertaining to the efficacy of nutrition intervention improving
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outcomes with cancer cachexia, as there is no universal agreement on cachexia criteria many nutrition trials do not specifically measure cachexia. In patients receiving radiotherapy, there is still strong evidence for nutritional issues to be identified early and for those at high risk to be automatically referred to a dietitian [14 ]. Early and appropriate intervention leads to improved dietary intake (energy and protein), weight, body composition and quality of life. [14 ] There is emerging evidence that dietary counseling leads to improved oncologic as well as quality of life outcomes. Longterm follow-up of a three-arm nutrition study conducted in patients receiving treatment for colorectal cancer by Ravasco et al. [24 ] reported benefits not only in nutritional outcomes but also in survival. Adequate nutritional status was maintained in 91% of those who received individualized nutrition counseling but not in any of the control group who maintained their usual diet. In these patients, worse radiotherapy toxicity, quality of life and mortality were associated with deteriorated nutritional status and intake. Likewise, depleted intake, nutritional status, and quality of life predicted shorter survival and late toxicity. Therefore early, individualized nutritional counseling and education during radiotherapy was valuable for this group of colorectal cancer patients. &&
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REFRACTORY CACHEXIA At the later stage of cachexia, the burden of nutritional support often outweighs any potential benefit and therefore the nutritional goals shift from those of weight maintenance to quality of life issues and comfort feeding as desired. A recent systematic review highlighted that patients and carers would like weight loss to be acknowledged by health professionals but unfortunately found there was often a lack of attention to nutritional issues and weight loss [31 ]. Psychosocial effects such as anger, anxiety and depression can result if there are unrealistic expectations about nutrition at this late stage by the patient, carer and/or staff [31 ]. Therefore, an understanding of the relevant psychosocial issues, education and support are required so that it is appreciated that at this stage, weight gain or even stabilization is unrealistic and should focus on quality of life, managing pain and symptoms and supporting whatever the patient desires to eat (or not eat). &&
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CONCLUSION The challenge with cancer cachexia is that it is not fully reversed by nutrition support. However, 394
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regardless of whether patients are experiencing reduced dietary intake resulting in malnutrition or due to cachexia, nutrition remains a cornerstone of multimodal treatment. There is strong evidence that nutrition counseling (with or without the provision of oral nutrition supplements) increases dietary intake, body weight, nutritional status and quality of life. There is some suggestion that in patients with colorectal cancer, dietary counseling may improve nutrition impact symptoms, treatment response and survival. However, there is less evidence for nutrition support during chemotherapy and further well designed studies with appropriate nutrition interventions are required. Further research into the most appropriate methods for identifying and treating cancer cachexia is required. Acknowledgements Funding: None to disclose Conflicts of interest There are no conflicts of interest.
REFERENCES AND RECOMMENDED READING Papers of particular interest, published within the annual period of review, have been highlighted as: & of special interest && of outstanding interest 1. Bauer J, Ash S, Davidson WL, et al. Evidence based practice guidelines for the nutritional management of cancer cachexia. Nutr Diet 2006; 63:S3–S32. 2. National Health Medical Research Council. NHMRC additional levels of evidence and grades for recommendation for developers of guidelines. Pilot Program 2005; Available from: http://www.nhmrc.gov.au/advice/consult.htm. 3. Bauer J, Capra S, Ferguson M. Use of the scored Patient-Generated Subjective Global Assessment (PG-SGA) as a nutrition assessment tool in patients with cancer. Eur J Clin Nutr 2002; 56:779–785. 4. Creaser N. Nutritional status of oncology patients admitted to a rural day chemotherapy unit as measured by the Patient Generated-Subjective Global Assessment. Nutr Diet 2010; 67:231–236. 5. Laviano A, Meguid MM, Rossi-Fanelli F. Cancer anorexia: clinical implications, pathogenesis, and therapeutic strategies. Lancet Oncol 2003; 4:686– 694. 6. Read JA, Choy STB, Beale P, Clarke SJ. An evaluation of the prevalence of malnutrition in cancer patients attending the outpatient oncology clinic. AsiaPac J Clin Onco 2006; 2:80–86. 7. Davidson W, Teleni L, Muller J, et al. Malnutrition and chemotherapy-induced nausea and vomiting: implications for practice. Oncol Nurs Forum 2012; 39:E340–E345. 8. Ravasco P, Grillo IB, Camilo M. Cancer wasting and quality of life react to early individualized nutritional counselling! Clin Nutr 2007; 26:7–15. 9. Wallengren O, Lundholm K, Bosaeus I. Diagnostic criteria of cancer cachexia: && relation to quality of life, exercise capacity and survival in unselected palliative care patients. Support Care Cancer 2013; 21:1569–1577. This article highlights the importance of not having a consensus on the definition of cancer cachexia by reporting the wide variation in the prevalence of this syndrome. This article also highlights the prognostic value of weight loss in this population. 10. Vandebroek AJV, Schrijvers D. Nutritional issues in anticancer treatment. Ann Oncol 2008; 19 (Suppl 5):v52–v55. 11. Bozzetti F, Arends J, Lundholm K, et al. ESPEN Guidelines on Parenteral Nutrition: nonsurgical oncology. Clin Nutr 2009; 28:445–454. 12. Brown T, Findlay M, von Dincklage J, et al. Using a wiki platform to promote guidelines internationally and maintain their currency: evidence-based guidelines for the nutritional management of adult patients with head and neck cancer. J Hum Nutr Diet 2013; 26:182–190. 13. Omlin A, Blum D, Wierecky J, et al. Nutrition impact symptoms in advanced cancer patients: frequency and specific interventions, a case-control study. J Cachexia Sarcopenia Muscle March 2013; 4:55–61.
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Cancer cachexia and nutrition Isenring and Teleni 14. Isenring E, Zabel R, Bannister M, et al. Updated evidence-based practice guidelines for the nutritional management of patients receiving radiation therapy and/or chemotherapy. Nutr Diet 2013; http://onlinelibrary.wiley. com/doi/10.1111/1747-0080.12013/abstract. This article provides clinical practice recommendations for the nutritional management of cancer patients undergoing radiotherapy or chemotherapy. This article provides a systematic review of the evidence. Recommendations are objectively graded according to the strength of the supporting evidence. 15. Das SK, Hoefler G. The role of triglyceride lipases in cancer associated cachexia. Trend Mol Med 2013; 19:292–301. 16. August DA, Huhmann MB. A.S.P.E.N. clinical guidelines: nutrition support therapy during adult anticancer treatment and in hematopoietic cell transplantation. JPEN J Parenter Enteral Nutr 2009; 33:472–500. 17. Fearon K, Strasser F, Anker SD, et al. Definition and classification of cancer cachexia: an international consensus. Lancet Oncol 2011; 12:489– 495. 18. Isenring E, Cross G, Daniels L, et al. Validity of the malnutrition screening tool as an effective predictor of nutritional risk in oncology outpatients receiving chemotherapy. Support Care Cancer 2006; 14:1152–1156. 19. Ferguson ML, Bauer J, Gallagher B, et al. Validation of a malnutrition screening tool for patients receiving radiotherapy. Radiation Oncol 1999; 43:325– 327. 20. Bole´o-Tome´ C, Monteiro-Grillo I, Camilo M, Ravasco P. Validation of the & Malnutrition Universal Screening Tool (MUST) in cancer. Brit J Nutr 2012; 108:343–348. This article is the first study to validate the use of the Malnutrition Universal screening tool in cancer patients. 21. Kondrup J, Rasmussen HH, Hamberg O, Stanga Z. Nutritional risk screening (NRS 2002): a new method. Clin Nutr 2003; 22:321–336. 22. Findlay M, Bauer J, Brown T, et al. Evidence based practice guidelines for the && nutritional management of adult patients with head and neck cancer. Online wiki guidelines 2013. [updated 26 February cited 2013 1 July, 2013]; Available from: http://wiki.cancer.org.au/australia/COSA:Head_and_neck_ cancer_nutrition_guidelines. This wiki provides clinical practice recommendations for the nutritional management of head and neck cancer. This article provides a systematic review of the evidence. Recommendations objectively graded according to the strength of the supporting evidence. This wiki is updated on a rolling 6 monthly basis. 23. Ottery FD. The clinical guide to oncology nutrition. In: McCallum P, Polisena C, editors. Patient generated subjective global assessment. Chicago, IL, USA: The American Dietetic Association; 2000. pp. 11–23. &&
24. Kiss NK, Krishnasamy M, Loeliger J, et al. A dietitian-led clinic for patients receiving (chemo)radiotherapy for head and neck cancer. Support Care Cancer 2012; 20:2111–2120. This article highlights the benefits of including a dietitian-led clinic for patients receiving radiotherapy with or without chemotherapy. This intervention study has important consequences for improving outcomes in a patient group inclusive of cancer cachexia. 25. Ravasco P, Monteiro-Grillo I, Camilo M. Individualized nutrition intervention is of && major benefit to colorectal cancer patients: long-term follow-up of a randomized controlled trial of nutritional therapy. Am J Clin Nutr 2012; 96:1346–1353. This article provides information on the long-term prognosis of patients who received individualized nutrition intervention. This study highlights the value of early individualized nutrition counseling and education for radiotherapy patients. 26. Sobani ZU, Ghaffar S, Ahmed BN. Comparison of outcomes of enteral feeding via nasogastric versus gastrostomy tubes in post operative patients with a principle diagnosis of squamous cell carcinoma of the oral cavity. J Pak Med Assoc 2011; 61:1042–1045. 27. Dewey A, Baughan C, Dean T, et al. Eicosapentaenoic acid (EPA, an omega-3 fatty acid from fish oils) for the treatment of cancer cachexia. Cochrane Database Syst Rev 2007; 1:CD004597. 28. Dewey A, Baughan C, Dean T, et al. ‘Should n-3 polyunsaturated fatty acids be prescribed in patients with cancer cachexia?’. OA Epidemiology 2013; 1:2. 29. Maccio A, Madeddu C, Gramignano G, et al. A randomized phase III clinical & trial of a combined treatment for cachexia in patients with gynecological cancers: evaluating the impact on metabolic and inflammatory profiles and quality of life. Gynecol Oncol 2012; 124:417–425. This article highlights the benefit of supplementing L-carnitine in treating fatigue in patients with cancer cachexia. 30. Cruciani RA, Zhang JJ, Manola J, et al. L-carnitine supplementation for the && management of fatigue in patients with cancer: an eastern cooperative oncology group phase III, randomized, double-blind, placebo-controlled trial. J Clin Oncol 2012; 30:3864–3869. This article reports results of the largest randomized, double-blind placebo-controlled trial supplementing L-Carnitine. This study was in ‘healthy’ cancer patients and demonstrated no benefit. 31. Oberholzer R, Hopkinson JB, Baumann K, et al. This interesting review && discusses the psychosocial effects of cancer cachexia and provides a model and suggestions for clinicians. J Pain Symptom Manage 2013; 46:77–95. doi: 10.1016/j.jpainsymman.2012.06.020. Epub 2012 Nov 15. Psychosocial effects of cancer cachexia: a systematic literature search and qualitative analysis. &&
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