Weight-losing Cancer Patients Research Articles

The role of the nutrition in malnourished cancer patients: Revisiting an old dilemma

Background & aimsGLIM definition of malnutrition is recognised all over the world and, when is referring to cancer, it specifies that weight or muscle loss are associated with an inflammatory status. However, the real-world practice shows that GLIM definition cannot encompass all the wide and heterogenous clinical presentations of cancer patients with malnutrition, which involves many other drivers beyond inflammation. Moreover, placing an excessive emphasis on the inflammation can overshadow, in the clinical practice, the role of the nutritional support in malnourished cancer patients. The aim of this paper is not to criticize the rationale of the GLIM definition of cancer cachexia, but to show the complexity and heterogeneity of malnutrition of cancer patients and reasons why nutritional support should deserve such a better consideration among the oncologists. MethodsLiterature pertinent to pathophysiology of malnutrition of cancer patients is scrutinised and reasons for the frequent underuse of nutritional support are critically analysed. ResultsThe appraisal of the literature shows that there are various pathophysiological patterns of malnutrition among cancer patients and inflammatory markers are not universally present in weight-losing cancer patients. Inflammation alone does not account for weight loss in all cancer patients and factors other than inflammation can drive hypophagia and weight loss, and hypophagia appears to be a primary catalyst for weight loss. Furthermore, malnutrition may be the consequence of the presence of several Nutrition Impact Symptoms or of the oncologic therapy.The nutritional support may fail to show benefits in malnourished cancer patients because the golden standard to validate a therapy relies on RCT, but it is ethically impossible to have an unfed control group of malnourished patients. Furthermore, nutritional interventions often fell short of the optimal standards, adherence to treatment plans was often poor, nutritional support was mainly reserved for very advanced patients and the primary endpoints of the studies on nutritional support were sometimes unrealistic. ConclusionThere is a gap between the suggestion of the guidelines which advocate the use of nutritional support to improve the compliance of patients facing intensive oncologic treatments or to prevent an early demise when patients enter a chronic phase of slow nutritional deterioration, and the poor use of nutrition in the real-world practice. This requires a higher level of awareness of the oncologists concerning the reasons for the lacking evidence of efficacy of the nutritional support and an understanding of its potential contribute to improve the outcome of the patients. Finally, this paper calls for a change of the oncologist’s approach to the cancer patient, from only focusing on the cure of the tumour to taking care of the patient as a whole.

THU512 Elevated Insulin Like Growth Factor Binding Protein 2 Levels Are Associated With Muscle Wasting And Increased Insulin Sensitivity In Cancer Patients

Abstract Disclosure: L. Caeiro: None. L.J. Anderson: None. H. Liu: None. K. Krumm: None. J.M. Garcia: None. Cancer-associated weight loss is a complex metabolic syndrome characterized by a loss of skeletal muscle mass and function. Insulin resistance is present in cancer but its role in cancer-related muscle wasting is poorly understood. Recent data from in vitro and animal models show that tumor-derived insulin-like growth factor binding protein (IGFBP)-2 can lead to skeletal muscle wasting and insulin resistance in cancer. We hypothesized that muscle mass and function would be inversely associated with IGFBP-2 levels and insulin resistance in circulation. IGFBP-2, physical function, body composition, insulin and glucose (to calculate HOMA-IR), quality of life (QOL), and cytokines were assessed in male cancer patients with (CWL, n=25) or without (CWS, n=47) weight loss. Physical Function was assessed by hand grip strength (HGS), stair climb power (SCP), and one repetition maximum (1RM) tests of the major muscle groups. Body composition was measured by bioimpedance (BIA) and CT scans and QOL by Karnofsky and ECOG scores. Blood samples were obtained after an overnight fast to measure IGFBP-2, insulin, glucose, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in plasma. CWL had higher plasma IGFBP2 levels (p = 0.01) and lower skeletal muscle index (SMI) (p = 0.03) and body mass index (BMI) (p = 0.007) when compared to CWS, but no differences were found with SCP, HGS, 1RM tests, or with HOMA-IR. IGFBP2 was negatively correlated with SMI (N = 65, R² = -.58, P = <0.001), BMI (N=73, R² = -.54, P = <0.001), CT-derived muscle mass (N = 48, R² = -.56, P = <0.001), BIA fat percent, (N = 25, R² = -.56, P = 0.005), 6 month weight change (N = 73, R² = -.27, P = 0.020), 12 month weight change (N = 73, R² = -.24, P = 0.044), insulin (N = 53, R² = -.48, P = <0.001) ,and HOMA IR (N = 53, R² = -.51, P = <0.001) and positively correlated with IL-6 (N = 72, R² = .33, P = 0.005) and TNF-α (N = 72, R² = .27, P = 0.021) in cancer patients. HOMA-IR was positively correlated with SMI (N = 31, R² = .39, P = 0.029), CT-derived muscle mass (N = 31, R² = .38, P = 0.036), and BIA fat percent (N = 21, R² = .62, P = 0.003). No association was found with IGFBP2 and QOL, SCP, HGS or the other functional parameters with exception of Knee Extension (N = 26, R² = .39, P = 0.049). In conclusion, cancer weight losing patients have increased IGFBP2 levels that were associated with muscle wasting, decreased fat mass, weight loss, and elevated IL-6 and TNF-α. HOMA-IR was negatively correlated with IGFBP2 and positively correlated with muscle mass. We postulate that a decrease in fat mass seen in weight-losing cancer patients leads to an increase in insulin sensitivity. More studies are needed to test this hypothesis and establish the role of IGFBP-2 as a mediator of muscle wasting in cancer. Presentation: Thursday, June 15, 2023

SUN-P082: Comparison of the “ESPEN Guidelines on Nutrition in Cancer Patients 2016” with the Recommendations of the Dutch Dietitians in Oncology Group

Rationale: In 2016, a completely revised second version of the ‘Handbook Nutrition in Cancer’ (HNC, in Dutch) by the Dutch Dietitians Oncology Group (DDOG) was published. In this project, the DDOG evaluated similarities and potential discrepancies between DDOG recommendations and the ESPEN guidelines for the identification, prevention and treatment of reversible elements of malnutrition during and after cancer treatment. Methods: The recommendations of the DDOG, as published in the HCN, were systematically compared with the ESPEN guidelines on nutrition in cancer patients. guidelines. However, DDOG recommendations are more detailed, comprehensive, and practical. The DDOG and the ESPEN guidelines differ in that the DDOG 1) recommends the comprehensive PG-SGA and PG-SGA Short Form for screening and nutritional assessment; 2) recommends to start artificial nutrition at an earlier stage; 3) does not recommend increasing the ratio of energy from fat/energy from carbohydrates in weight-losing cancer patients with insulin resistance; 4) includes a less conservative recommendation on increasing energy intake for prevention of refeeding syndrome; and 5) supports a longer period of corticosteroid use to increase appetite (4-8 weeks vs ESPEN 1-3 weeks). Additionally Results: Overall, the DDOG recommendations are in line with the ESPEN , the DDOG does not include a specific advice for parenteral nutrition composition during intensive chemotherapy, and includes the advice to avoid fatty fish/fish oil 24 hours before and after specific chemotherapy treatment. Both guidelines recommend nutritional care to be accompanied by exercise training. Conclusion: The DDOG and ESPEN recommendations are generally in line with each other, but the DDOG recommendations are more specific and practical. DDOG and ESPEN are complementary to each other.

Adipose tissue fibrosis in human cancer cachexia: the role of TGF\u03b2 pathway

BackgroundCancer cachexia is a multifactorial syndrome that dramatically decreases survival. Loss of white adipose tissue (WAT) is one of the key characteristics of cachexia. WAT wasting is paralleled by microarchitectural remodeling in cachectic cancer patients. Fibrosis results from uncontrolled ECM synthesis, a process in which, transforming growth factor-beta (TGFβ) plays a pivotal role. So far, the mechanisms involved in adipose tissue (AT) re-arrangement, and the role of TGFβ in inducing AT remodeling in weight-losing cancer patients are poorly understood. This study examined the modulation of ECM components mediated by TGFβ pathway in fibrotic AT obtained from cachectic gastrointestinal cancer patients.MethodsAfter signing the informed consent form, patients were enrolled into the following groups: cancer cachexia (CC, n = 21), weight-stable cancer (WSC, n = 17), and control (n = 21). The total amount of collagen and elastic fibers in the subcutaneous AT was assessed by histological analysis and by immunohistochemistry. TGFβ isoforms expression was analyzed by Multiplex assay and by immunohistochemistry. Alpha-smooth muscle actin (αSMA), fibroblast-specific protein (FSP1), Smad3 and 4 were quantified by qPCR and/or by immunohistochemistry. Interleukin (IL) 2, IL5, IL8, IL13 and IL17 content, cytokines known to be associated with fibrosis, was measured by Multiplex assay.ResultsThere was an accumulation of collagen and elastic fibers in the AT of CC, as compared with WSC and controls. Collagens type I, III, VI, and fibronectin expression was enhanced in the tissue of CC, compared with both WSC and control. The pronounced expression of αSMA in the surrounding of adipocytes, and the increased mRNA content for FSP1 (20-fold) indicate the presence of activated myofibroblasts; particularly in CC. TGFβ1 and TGFβ3 levels were up-regulated by cachexia in AT, as well in the isolated adipocytes. Smad3 and Smad4 labeling was found to be more evident in the fibrotic areas of CC adipose tissue.ConclusionsCancer cachexia promotes the development of AT fibrosis, in association with altered TGFβ signaling, compromising AT organization and function.

A systematic review of health-related quality of life instruments in patients with cancer cachexia

Assessing the health-related quality of life (HRQOL) of cancer patients with cachexia is particularly important because treatments for cachexia are currently aimed at palliation and treatment efficacy must be measured in ways other than survival. The aim of this systematic review was to evaluate HRQOL assessment in cancer patients with cachexia. Using guidance from the Centre for Reviews and Dissemination, relevant databases were searched from January 1980 to January 2012 with terms relating to cancer, cachexia and HRQOL for papers including adult cancer patients with cachexia or documented weight loss at baseline. We found one cachexia-specific instrument, the Functional Assessment of Anorexia/Cachexia Therapy, but the tool has not been fully validated, does not cover all the relevant domains and the consensus-based standards for the selection of health status measurement instruments checklist highlighted a number of weaknesses in the methodological quality of the validation study. Sixty-seven studies assessed HRQOL in cachectic or weight-losing cancer patients. Most used generic cancer HRQOL instruments, limiting the amount of useful information they provide. A modified version of the Efficace minimum data checklist demonstrated that the quality of reporting on HRQOL tool use was inadequate in many of the studies. A negative relationship between HRQOL and weight loss was found in 23 of the 27 studies which directly examined this. There is a pressing need for a well-designed HRQOL tool for use with this patient group in both clinical trials and clinical practice.

Adipokines and Systemic Inflammation in Weight-Losing Lung Cancer Patients

Cancer cachexia is a devastating condition leading to loss of function and independence, decreased performance status, decreased quality of life, and poor prognosis. Adipokines play a role in a wide variety of physiological or pathological processes, including immunity and inflammation, in addition to having significant effects on metabolism and lipogenesis. The objective of the present study was to investigate the relationship of adipokines and systemic inflammation in weight-losing advanced-stage non-small-cell lung cancer (NSCLC) patients. Sixty-three male NSCLC patients (stages III and IV) and 25 age- and sex-matched controls were included. NSCLC patients were further divided into subgroups as those with a>5% weight loss in last 6 months and those who did not. Serum leptin, adiponectin, and TNF-α concentrations were measured by ELISA using commercially available kits. The positive acute-phase reactants (APR) CRP, leukocyte, ferritin, thrombocyte, and fibrinogen were higher in the NSCLC group. Serum albumin level (which is a negative APR) was lower in the cancer group, whereas there was no difference in transferrin level between the groups. TNF-α and leptin concentrations were similar in the cancer group and the control group, whereas adiponectin was lower in the cancer group. There was a difference in thrombocyte and transferrin levels between patients with and without weight loss, whereas CRP, TNF-α, and adiponectin levels were similar. Leptin was lower in weight-losing cancer patients. However, there was no correlation between adipokines and markers of systemic inflammation. These results revealed a lack of association between adipokine levels and systemic inflammation with cancer cachexia.

Lipid mobilization in cachexia

Extensive loss of body fat is considered as a hallmark of cancer cachexia which affects the quality of life and shortens survival. Evidence suggests that increased lipid mobilization has a central role in adipose tissue wasting. This review summarizes recent progress, with a particular focus on the mechanisms and the potential mediators of lipid mobilization in cachexia. Accelerated fat loss begins at around 7 months before death and predicts survival in advance cancer patients. Adipose tissue remodelling with reduced lipid storage is evident in cancer patients with cachexia. Enhanced lipolysis regulated by adipose triglyceride lipase and hormone-sensitive lipase could be essential for triacylglycerol degradation. In addition to cytokines, other factors such as zinc-α2-glycoprotein (ZAG) are implicated in adipose atrophy. ZAG expression and release by adipose tissue is upregulated in weight-losing cancer patients, and serum ZAG has been shown as a marker for pancreatic cancer-associated cachexia, suggesting that ZAG may function locally and systemically to stimulate lipid mobilization. Recent progress in clinical and mechanistic studies provides some new insights into the pathogenesis of adipose atrophy in cachexia. Further studies to unravel the mechanisms and mediators may lead to novel pharmacological targets to ameliorate cachexia syndrome.

Hormonal, hypothalamic and striatal responses to reduced body weight gain are attenuated in anorectic rats bearing small tumors

Lack of compensatory or even reduced food intake is frequently observed in weight-losing cancer patients and contributes to increased morbidity and mortality. Our previous work has shown increased transcription factor expression in the hypothalamus and ventral striatum of anorectic rats bearing small tumors. mRNA expression of molecules known to be involved in pathways regulating appetite in these structures was therefore assessed in this study. Given that pain, pro-inflammatory cytokines and metabolic hormones can modify food intake, spinal cord cellular activation patterns and plasma concentrations of cytokines and hormones were also studied. Morris hepatoma 7777 cells injected subcutaneously in Buffalo rats provoked a 10% lower body weight and 15% reduction in food intake compared to free-feeding tumor-free animals 4weeks later when the tumor represented 1–2% of body mass. No differences in spinal cord activation patterns or plasma concentration of pro-inflammatory cytokines were observed between groups. However, the changes in plasma ghrelin and leptin concentrations found in food-restricted weight-matched rats in comparison to ad libitum-fed animals did not occur in anorectic tumor-bearing animals. Real-time PCR showed that tumor-bearing rats did not display the increase in hypothalamic agouti-related peptide mRNA observed in food-restricted weight-matched animals. In addition, microarray analysis and real-time PCR revealed increased ventral striatal prostaglandin D synthase expression in food-restricted animals compared to anorectic tumor-bearing rats. These findings indicate that blunted hypothalamic AgRP mRNA expression, probably as a consequence of relatively high leptin and low ghrelin concentrations, and reduced ventral striatal prostaglandin D synthesis play a role in maintaining cancer-associated anorexia.

What to eat when off treatment and living with involuntary weight loss and cancer: a systematic search and narrative review

The aim of this study was to report a systematic search and narrative review of the evidence base that can inform dietary advice for patients off treatment living with cancer cachexia syndrome (CCS). Searches were conducted in MEDLINE, EMBASE, PsycINFO and CINAHL databases for publications about diet and cancer patients off treatment with symptoms of CCS. The following limits were applied: English language, from September 1998 to September 2008 and adults. In addition, a hand search included the reference lists of papers identified. Seven hundred and eighteen abstracts were assessed against inclusion/exclusion criteria and 88 were selected for full text independent examination by two researchers. Information from 48 papers was extracted, quality assessed, thematically analyzed and presented as a narrative synthesis. Two dominant perspectives emerged on what should be eaten by weight-losing cancer patients. The majority of authors advocated a nutrient-dense diet, facilitated by nutritional counselling. The alternative approach was to advise the patient to 'eat what they want'. There is little robust evidence to justify either approach as able to deliver on the range of physical and psychosocial objectives that they aim to achieve. A new model for the delivery of nutritional care may benefit cancer patients (off treatment) living with weight loss. The proposed model integrates the two identified perspectives to facilitate optimal food intake taking into account the patient's (1) disease symptoms and treatment side effects (2) emotional adaptation to illness and (3) social circumstances. Research is needed to establish which of these obstacles to eating can be changed for which patient groups to improve patient outcomes.

Effects by daily long term provision of ghrelin to unselected weight‐losing cancer patients

The short-term provision of ghrelin to patients with cancer indicates that there may be benefits from long-term provision of ghrelin for the palliative treatment of weight-losing cancer patients. This hypothesis was evaluated in a randomized, double-blind, phase 2 study. Weight-losing cancer patients with solid gastrointestinal tumors were randomized to receive either high-dose ghrelin treatment (13 microg/kg daily; n = 17 patients) or low-dose ghrelin treatment (0.7 microg/kg daily; n = 14 patients) for 8 weeks as a once-daily, subcutaneous injections. Appetite was scored on a visual analog scale; and food intake, resting energy expenditure, and body composition (dual x-ray absorpitometry) were measured before the start of treatment and during follow-up. Serum levels of ghrelin, insulin, insulin-like growth factor 1, growth hormone (GH), triglycerides, free fatty acids, and glucose were measured. Health-related quality of life, anxiety, and depression were assessed by using standardized methods (the 36-item Short Form Health Survey and the Hospital Anxiety and Depression Scale). Physical activity, rest, and sleep were measured by using a multisensor body monitor. Treatment groups were comparable at inclusion. Appetite scores were increased significantly by high-dose ghrelin analyzed both on an intent-to-treat basis and according to the protocol. High-dose ghrelin reduced the loss of whole body fat (P < .04) and serum GH (P < .05). There was a trend for high-dose ghrelin to improve energy balance (P < .07; per protocol). Otherwise, no statistically significant differences in outcome variables were observed between the high-dose and low-dose groups. Adverse effects were not observed by high-dose ghrelin, such as serum levels of tumor markers (cancer antigen 125 [CA 125], carcinoembryonic antigen, and CA 19-9). The current results suggested that daily, long-term provision of ghrelin to weight-losing cancer patients with solid tumors supports host metabolism, improves appetite, and attenuates catabolism.

Abstracts

Background: Up to 80% of people with cancer experience involuntary weight loss (1,2). This symptom of cancer cachexia syndrome (CCS) is associated with morbidity and mortality. However, feeding has little effect on weight and survival. There is no current consensus on appropriate diet for people living with CCS. Purpose: To report a systematic review of the evidence base that can inform dietary advice for patients living with CCS. Methods: Searches were conducted of MEDLINE, EMBASE, PsycINFO and CINAHL databases and reference lists, for publications about diet and cancer patients off treatment with symptoms of CCS. Limits were English language; 1998 to 9/2008; adults. 718 abstracts were assessed against nclusion/exclusion criteria and 90 were selected for full-text independent examination by two researchers. Information relevant to the review question was extracted, quality assessed, thematically analyzed and presented as a narrative description. Results: Sixty publications were included in the review. Two dominant perspectives emerged on what should be eaten by cancer patients living with involuntary weight loss. The majority of authors advocated a nutrition dense diet, achieved by nutritional counselling to i) educate on fortification of foods and ii) to advise frequent feeding. The alternative approach was to advise the patient to ‘eat what they want’. There is little robust evidence to justify either approach as able to deliver on the objectives they aim to achieve. Research is needed to establish which sub-groups of weight losing cancer patients can benefit from nutritional support. Conclusion: Feeding may not be futile if combined with other interventions and if evaluated against outcomes such as distress. A new model for the assessment and delivery of nutritional care may help patients living with CCS to optimize nutritional intake within the confines of their i/ disease process and treatment ii/ beliefs about food iii/ social resources iv/ coping approach.

Characterization of human skeletal muscle in weight-losing pancreatic cancer patients

9571 Background: Decreased body mass (cachexia) is a common cause of functional decline in pancreas carcinoma (PC) and other malignancies. The etiology is unknown. Characterization of human PC skeletal muscle, in regard to proteolysis and gene expression, compared to control muscle may reveal information about pathophysiology. Methods: Biopsies of rectus abdominus muscle were performed in weight-losing PC patients all stages (A) during cancer-related surgery and in cancer-free controls undergoing ventral hernia repair (B). Caspase-3, pAkt, and urinary 3-methylhistidine (u3-MH) were assessed by Western blot and high-performance liquid chromatography. Fat-free mass (FFM), body mass index (BMI), and time to progression were recorded. Muscle from five patients (median weight loss 21%) and five controls were analyzed for gene expression patterns using Affymetrix Human Genome U133 A 2.0 array chip. Two hundred differentially over- and under-expressed genes were examined in group A for potential association with cachexia. RT-PCR confirmation of six candidate genes was performed. Results: Thirty-eight patients were enrolled. Median weight loss in group A (N=27) was 14.5% (5% - 34%). No differences were noted between groups in caspase-3 and pAkt expression. Baseline u3-MH (p=0.86) and FFM (p= 0.28) did not differ; baseline BMI was lower in group A (p=0.04). BMI follow-up measurements (N=17) were significantly decreased (p=0.0005). In 65% patients, progressive disease was noted within median time of 3 months. RT-PCR established up-regulation of CHRNA1 and LMO7, but not GDF8. mRNA down-regulation for TRIM63, IGF-BP6, and MYH-1 was confirmed. Conclusions: Muscle proteolysis in human PC skeletal muscle was not demonstrated, perhaps due to unmeasurable proteolysis or use of non-informative endpoints. BMI decreased in group A with PD; further studies need tight control of BMI variables. New hypotheses about cachexia include neuromuscular junction dysfunction, as CHRNA1 has specific role in ion channel gating; this is disrupted in the paraneoplastic Eaton-Lambert syndrome. This is first study analyzing human muscle in weight-losing PC and proves symptom management multidisciplinary research is feasible in academic setting. Supported by American Cancer Society pilot grant. No significant financial relationships to disclose.

Increased expression of phosphorylated forms of RNA-dependent protein kinase and eukaryotic initiation factor 2α may signal skeletal muscle atrophy in weight-losing cancer patients

Previous studies suggest that the activation (autophosphorylation) of dsRNA-dependent protein kinase (PKR) can stimulate protein degradation, and depress protein synthesis in skeletal muscle through phosphorylation of the translation initiation factor 2 (eIF2) on the α-subunit. To understand whether these mediators are important in muscle wasting in cancer patients, levels of the phospho forms of PKR and eIF2α have been determined in rectus abdominus muscle of weight losing patients with oesophago-gastric cancer, in comparison with healthy controls. Levels of both phospho PKR and phospho eIF2α were significantly enhanced in muscle of cancer patients with weight loss irrespective of the amount and there was a linear relationship between phosphorylation of PKR and phosphorylation of eIF2α (correlation coefficient 0.76, P=0.005). This suggests that phosphorylation of PKR led to phosphorylation of eIF2α. Myosin levels decreased as the weight loss increased, and there was a linear relationship between myosin expression and the extent of phosphorylation of eIF2α (correlation coefficient 0.77, P=0.004). These results suggest that phosphorylation of PKR may be an important initiator of muscle wasting in cancer patients.

Insulin Treatment in Cancer Cachexia: Effects on Survival, Metabolism, and Physical Functioning

The present study was designed to evaluate whether daily insulin treatment for weight-losing cancer patients attenuates the progression of cancer cachexia and improves metabolism and physical functioning in palliative care. One hundred and thirty-eight unselected patients with mainly advanced gastrointestinal malignancy were randomized to receive insulin (0.11 +/- 0.05 units/kg/d) plus best available palliative support [anti-inflammatory treatment (indomethacin), prevention of anemia (recombinant erythropoietin), and specialized nutritional care (oral supplements + home parenteral nutrition)] according to individual needs. Control patients received the best available palliative support according to the same principles. Health-related quality of life, food intake, resting energy expenditure, body composition, exercise capacity, metabolic efficiency during exercise, and spontaneous daily physical activity as well as blood tests were evaluated during follow-up (30-824 days) according to intention to treat. Patient characteristics at randomizations were almost identical in study and control groups. Insulin treatment for 193 +/- 139 days (mean +/- SD) significantly stimulated carbohydrate intake, decreased serum-free fatty acids, increased whole body fat, particularly in trunk and leg compartments, whereas fat-free lean tissue mass was unaffected. Insulin treatment improved metabolic efficiency during exercise, but did not increase maximum exercise capacity and spontaneous physical activity. Tumor markers in blood (CEA, CA-125, CA 19-9) did not indicate the stimulation of tumor growth by insulin; a conclusion also supported by improved survival of insulin-treated patients (P<0.03). Insulin is a significant metabolic treatment in multimodal palliation of weight-losing cancer patients.

Evidence based practice guidelines for the nutritional management of cancer cachexia

The purpose of these guidelines is to provide dietitians in Australia with a user-friendly summary of the evidence to support the nutritional management of adult patients with cancer cachexia. This best available evidence is presented and used as a basis for providing recommendations about clinical practice. The clinical questions were as follows: How should patients be identified for referral to the dietitian in order to maximise nutritional intervention opportunities? How should nutritional status be assessed? What are the goals of nutrition intervention for patients with cancer cachexia? What is the nutrition prescription to achieve these goals? Should eicosapentaenoic acid be included in the prescription? What are effective methods of implementation to ensure positive outcomes? Does nutrition intervention improve outcomes in patients with cancer cachexia? This document is a general guide to appropriate practice to be followed only subject to the dietitian's judgement in each individual case. The guidelines are designed to provide information to assist decision-making and are based on the best information available at the date of compilation. The guidelines recommend intensive nutrition therapy. This has potential resource implications that may include additional staff, change to staff roles and increased use of high/protein energy supplements if they are considered. Therefore, in applying the guidelines these potential organisational and cost barriers need to be considered. These guidelines for practice are provided with the express understanding that they do not establish or specify particular standards of care, whether legal, medical or other.

ESPEN Guidelines on Enteral Nutrition: Non-surgical oncology

Enteral nutrition (EN) by means of oral nutritional supplements (ONS) and tube feeding (TF) offers the possibility of increasing or ensuring nutrient intake in cases where normal food intake is inadequate. These guidelines are intended to give evidence-based recommendations for the use of ONS and TF in cancer patients. They were developed by an interdisciplinary expert group in accordance with officially accepted standards, are based on all relevant publications since 1985 and were discussed and accepted in a consensus conference. Undernutrition and cachexia occur frequently in cancer patients and are indicators of poor prognosis. EN should be started if undernutrition already exists or if food intake is markedly reduced for more than 7-10 days. Standard formulae are recommended for EN. Nutritional needs generally are comparable to non-cancer subjects. In cachectic patients metabolic modulators such as progestins, steroids and possibly eicosapentaenoic acid may help to improve nutritional status. EN is indicated preoperatively for 5-7 days in cancer patients undergoing major abdominal surgery. During radiotherapy of head/neck and gastrointestinal regions dietary counselling and ONS prevent weight loss and interruption of radiotherapy. Routine EN is not indicated during (high-dose) chemotherapy.

Cardiotoxicity of Epirubicin Versus Doxorubicin: Cost and Clinical Results

drome by commenting on the importance of clinically relevant end points, the need for compliance assessment, and the potential of early intervention. These are important points, and we acknowledge that each of these three “negative” trials may have limitations. However, any such limitations in their own right do not justify the use of EPA. After three large “negative” studies, the onus of demonstrating benefit now rests in the hands of proponents of EPA. These proponents must put forth critical new evidence to convince cancer patients, their families, and oncologists that this agent continues to be worthy of clinical investigation. For others of us who continue to observe the devastating decline of weight-losing cancer patients on a daily basis—despite their ingestion of EPA-containing supplements—we think it time to move on and study other agents.

Body composition and time course changes in regional distribution of fat and lean tissue in unselected cancer patients on palliative care—Correlations with food intake, metabolism, exercise capacity, and hormones

Several investigations that yielded different results in terms of net changes in body composition of weight-losing cancer patients have been reported that employed a variety of methods based on fundamentally different technology. Most of those reports were cross-sectional, whereas to the authors' knowledge there is sparse information available on longitudinal follow-up measurements in relation to other independent methods for the assessment of metabolism and performance. For the current report, the authors evaluated time course changes in body composition (dual-energy X-ray absorptiometry) with measurements of whole body and regional distribution of fat and lean tissue in relation to food and dietary intake, host metabolism (indirect calorimetry), maximum exercise capacity (walking test), and circulating hormones in cancer patients who were receiving palliative care during 4-62 months of follow-up. The entire cohort comprised 311 patients, ages 68 years +/- 3 years who were diagnosed with solid gastrointestinal tumors (84 colorectal tumors, 74 pancreatic tumors, 73 upper gastrointestinal tumors, 51 liver-biliary tumors, 3 breast tumors, 5 melanomas, and 21 other tumor types). Decreased body weight was explained by loss of body fat, preferentially from the trunk, followed by leg tissue and arm tissue, respectively. Lean tissue (fat-free mass) was lost from arm tissue, whereas trunk and leg tissue compartments increased, all concomitant with declines in serum albumin, increased systemic inflammation (C-reactive protein, erythrocyte sedimentation rate), increased serum insulin, and elevated daily caloric intake; whereas serum insulin-like growth factor 1 (IGF-1), resting energy expenditure, and maximum exercise capacity remained unchanged in the same patients. Serum albumin levels (P < 0.001), whole body fat (P < 0.02), and caloric intake (P < 0.001) predicted survival, whereas lean tissue mass did not. Daily intake of fat and carbohydrate was more important for predicting survival than protein intake. Survival also was predicted by serum IGF-1, insulin, leptin, and ghrelin levels (P < 0.02 - P < 0.001). Serum insulin, leptin, and ghrelin (total) levels predicted body fat (P < 0.001), whereas IGF-1 and thyroid hormone levels (T3, free T3) predicted lean tissue mass (P < 0.01). Systemic inflammation primarily explained variation in lean tissue and secondarily explained loss in body fat. Depletion of lean arm tissue was related most to short survival compared with the depletion of lean leg and trunk tissue. The current results demonstrated that body fat was lost more rapidly than lean tissue in progressive cancer cachexia, a phenomenon that was related highly to alterations in the levels of circulating classic hormones and food intake, including both caloric amount and diet composition. The results showed importance in the planning of efficient palliative treatment for cancer patients.

Adiponectin and the systemic inflammatory response in weight-losing patients with non-small cell lung cancer

The aim of the present study was to examine the relationship between adiponectin and the systemic inflammatory response in weight-losing patients with non-small cell lung cancer (NSCLC). Measurement of anthropometry, acute phase proteins, interleukin-6, leptin (total and free) and adiponectin were carried out on healthy subjects ( n=13) and non-small cell lung cancer patients with weight loss ( n=20). The groups were age and sex matched. Compared with the controls the cancer group had a lower BMI ( p<0.01), mid-upper arm circumference ( p<0.001), triceps skinfold thickness ( p<0.05) and circulating concentrations of albumin ( p<0.001), haemoglobin ( p<0.05), free and total leptin ( p<0.05) and adiponectin ( p<0.01). In contrast, the cancer group had elevated circulating concentrations of interleukin-6 and C-reactive protein concentrations ( p<0.001). In the cancer group circulating adiponectin concentrations were significantly inversely correlated with both free ( r s =−0.675, p=0.001) and total leptin concentrations ( r s =−0.690, p=0.001). However, neither weight loss, interleukin-6 or C-reactive protein concentrations were correlated with either adiponectin, free or total leptin concentrations in the cancer group. These results suggest that adipokine production is normal and is unlikely to play a major role in the abnormal fat metabolism in weight-losing cancer patients.

Evidence that long-term COX-treatment improves energy homeostasis and body composition in cancer patients with progressive cachexia

Cancer patients lose weight due to negative energy balance because of insufficient appetite and inappropriately high energy expenditure. Host and tumor derived cytokines and more recently eicosanoids have been held responsible as mediators. Accordingly, observations in animal experiments and short-term clinical trials in selected groups of cancer patients, have implied that cyclo-oxygenase (COX) blockade can improve host metabolism and well-being, and long-term COX-treatment of unselected groups have implied improved survival. The aim of this study was to search for evidence that long-term COX-treatment improves energy and cardiovascular homeostasis in unselected weight-losing cancer patients. A retrospective case control analysis was performed on a data-base material collected consecutively. Weight-losing untreated cancer patients had elevated resting energy expenditure compared to undernourished non-cancer patients (23.3+/-0.1, n=702 vs 20.9+/-0.3 kcal/kg/day, n=132, p<0.001). This difference became significantly reduced by long-term indomethacin treatment (p<0.003). Heart rate was correspondingly decreased, while systolic blood pressure increased following indomethacin treatment of cancer patients (p<0.006-0.008). Total body fat was more preserved (p<0.005), while lean body mass was uninfluenced by long-term indomethacin to cancer patients. All these beneficial effects were parallel to a decrease in systemic inflammation (C-reactive protein, erythrocyte sedimentation rate) in cancer patients on indomethacin (p<0.0004). Systemic inflammation and resting energy metabolism predicted weight loss in progressive cancer (p<0.0001). Our data support the concept that COX-treatment may offer beneficial metabolic effects to weight-losing cancer patients by attenuation of resting metabolism and improved appetite due to decreased systemic inflammation.