The effect of nutritional counseling on muscle mass and treatment outcome in patients with metastatic colorectal cancer undergoing chemotherapy: A randomized controlled trial.

BACKGROUND & AIMS: A low muscle mass before start of treatment and loss of muscle mass during chemotherapy is related to adverse outcomes in patients with cancer. In this randomized controlled trial, the effect of nutritional counseling on change in muscle mass and treatment outcome in patients with metastatic colorectal cancer during first-line chemotherapy was studied. METHODS: Patients scheduled for first-line chemotherapy (n = 107) were randomly assigned to individualized nutritional counseling by a dietitian (NC) or usual care (UC). NC was aimed at sufficient protein- and energy intake, supported by oral supplements or enteral feeding if indicated. Furthermore, physical activity was encouraged. Outcomes were assessed at baseline (T0) and the time of the first (T1) and second (T2) regular follow-up computed tomography scans. The proportion of patients with a clinically relevant decrease in skeletal muscle area of ≥6.0 cm2, measured by computed tomography, was the primary outcome. Secondary outcomes included body weight, quality of life, treatment toxicity and progression free and overall survival. RESULTS: A total of 107 patients were enrolled (mean age, 65 years (SD, 11 years), 63% male). Mean change in skeletal muscle area from T0 till T1 was -2.5 (SD, 9.5) cm2, with no difference between NC versus UC (p = 0.891). The proportion of patients with a clinically relevant decrease in skeletal muscle area of ≥6.0 cm2 did not differ (NC 30% versus UC 31%, p = 0.467). NC compared with UC had a significant positive effect on body weight (B coefficient 1.7, p = 0.045), progression free survival (p = 0.039) and overall survival (p = 0.046). CONCLUSIONS: NC of patients undergoing chemotherapy for metastatic colorectal cancer had no effect on muscle mass. However, we found that NC may increase body weight and improve progression free survival and overall survival compared to UC in this group of patients. These findings need further evaluation in future clinical trials. CLINICAL TRIAL INFORMATION: ClinicalTrials.gov NCT01998152; Netherlands Trial Register NTR4223.

The new ESPEN diagnostic criteria for malnutrition predict overall survival in hospitalised patients.

BACKGROUND: In 2015 the European Society for Clinical Nutrition and Metabolism (ESPEN) presented new consensus criteria for the diagnosis of malnutrition. Whereas most previous definitions were based on involuntary weight loss and/or a low BMI, the ESPEN definition added Fat Free Mass Index (FFMI) to the set of criteria. AIM: To study the predictive value of the new ESPEN diagnostic criteria for malnutrition on survival, with specific focus on the additional value of FFMI. METHODS: Included were 335 hospitalized adult patients of the VU University Medical Center Amsterdam (60% female, age 58 ± 18 y). Three sets of criteria for malnutrition were used to study the predictive value for survival: Dutch definition for malnutrition, ESPEN diagnostic criteria for malnutrition and ESPEN diagnostic criteria for malnutrition without FFMI criterion. The association between malnutrition and three-months and one-year overall survival was analyzed by log rank tests and Cox regression. In multivariate analyses, adjustments were made for gender, age, care complexity and length of stay. RESULTS: Ninety patients (27%) were classified as malnourished by any of the sets of criteria; malnourished patients had significant lower survival rates than non-malnourished patients at three months (84% vs 94%; p = 0.01) and one year (76% vs 87%; p = 0.02). After adjustments, malnutrition remained significantly associated with three-months survival for the Dutch definition for malnutrition (HR:2.25, p = 0.04) and the ESPEN diagnostic criteria for malnutrition (HR:2.76, p = 0.02). Malnutrition remained significantly associated with one-year survival for the ESPEN diagnostic criteria for malnutrition (HR:2.17, p < 0.02) and the ESPEN diagnostic criteria for malnutrition without FFMI (HR:2.66, p < 0.01). CONCLUSION: The new ESPEN definition for malnutrition is predictive for both three-months and one-year survival in a general hospital population, whereas definitions without FFMI are predictive for either three-months or one year survival.

Percentiles for skeletal muscle index, area and radiation attenuation based on computed tomography imaging in a healthy Caucasian population.

BACKGROUND/OBJECTIVES: Muscle mass is a key determinant of nutritional status and associated with outcomes in several patient groups. Computed tomography (CT) analysis is increasingly used to assess skeletal muscle area (SMA), skeletal muscle index (SMI) and muscle radiation attenuation (MRA). However, interpretation of these muscle parameters is difficult since values in a healthy population are lacking. The aim of this study was to provide sex specific percentiles for SMA, SMA and MRA in a healthy Caucasian population and to examine the association with age and BMI in order to define age- and BMI specific percentiles. SUBJECTS/METHODS: In this retrospective cross-sectional study CT scans of potential kidney donors were used to assess SMA, SMI and MRA at the level of the third lumbar vertebra. Sex specific distributions were described and, based on the association between age/BMI and muscle parameters, age, and BMI specific predicted percentiles were computed. The 5th percentile was considered as cut-off. RESULTS: CT scans of 420 Individuals were included (age range 20-82 years and BMI range 17.5-40.7 kg/m2). Sex specific cut-offs of SMA, SMI and MRA were 134.0 cm2, 41.6 cm2/m2 and 29.3 HU in men and 89.2 cm2, 32.0 cm2/m2 and 22.0 HU in women, respectively. Correlations were negative between age and all three muscle parameters, positive between BMI and SMA/SMI and negative between BMI and MRA, resulting in age- and BMI specific percentiles. CONCLUSIONS: This study provides sex specific percentiles for SMA, SMI, and MRA. In addition, age- and BMI specific percentiles have been established.

Survival in Malnourished Older Patients Receiving Post-Discharge Nutritional Support; Long-Term Results of a Randomized Controlled Trial.

BACKGROUND: Previous analyses have shown that a post-discharge individualized nutritional intervention had positive effects on body weight, lean body mass, functional limitations and fall incidents in malnourished older patients. However, the impact of this intervention on survival has not yet been studied. OBJECTIVE: The objective of this randomized controlled study was to examine the effect of a post-discharge individualized nutritional intervention on survival in malnourished older patients. METHODS: Malnourished older patients, aged ≥ 60 years, were randomized during hospitalization to a three-months post-discharge nutritional intervention group (protein and energy enriched diet, oral nutritional supplements, vitamin D3/calcium supplement and telephone counseling by a dietitian) or to a usual care regimen (control group). Survival data were collected 4 years after enrollment. Survival analyses were performed using intention-to-treat analysis by Log-rank tests and Cox regression adjusted for confounders. RESULTS: The study population consisted of 94 men (45%) and 116 women with a mean age of 74.5 (SD 9.5) years. There were no statistically significant differences in baseline characteristics. Survival data was available in 208 out of 210 patients. After 1 and 4 years of follow-up, survival rates were respectively 66% and 29% in the intervention group (n=104) and 73% and 30% in the control group (n=104). There were no statistically significant differences in survival between the two groups 1 year (HR= 0.933, 95% CI=0.675-1.289) and 4 years after enrollment (HR=0.928, 95% CI=0.671-1.283). CONCLUSION: The current study failed to show an effect of a three-months post-discharge multi-component nutritional intervention in malnourished older patients on long-term survival, despite the positive effects on short-term outcome such as functional limitations and falls.

Insight in taste alterations during treatment with protein kinase inhibitors.

The role of Protein Kinase Inhibitors (PKI) in the treatment of various types of cancer is increasingly prominent. Their clinical application is accompanied by the development of side effects, among which patient-reported taste alterations. These alterations are missed frequently, but impair nutritional intake, are associated with weight loss and often result in significant morbidity, especially in the context of chronic administration. Accurate reporting of taste alterations is hampered by lack of modules for symptom objectification and inadequate understanding on the underlying mechanisms. In this review we initially describe the physiology of taste and smell and the mechanism of action of PKIs. We proceed to summarize taste related side effects as reported in major clinical trials and describe possible causal factors. Lastly, an in-depth analysis is given on potential molecular pathways responsible for the PKI-induced taste alterations. Objectification of patient-reported symptoms and universal reporting, along with a better understanding of the underlying mechanisms, will lead to early recognition and optimized treatment, ultimately improving patient adherence and quality of life.

The assessment of anorexia in patients with cancer: cut-off values for the FAACT-A/CS and the VAS for appetite.

PURPOSE: Anorexia is a frequently observed symptom in patients with cancer and is associated with limited food intake and decreased quality of life. Diagnostic instruments such as the Anorexia/Cachexia Subscale (A/CS) of the Functional Assessment of Anorexia/Cachexia Therapy (FAACT) questionnaire and the visual analog scale (VAS) for appetite have been recommended in the assessment of anorexia, but validated cut-off values are lacking. This study aimed to obtain cut-off values of these instruments for the assessment of anorexia in patients with cancer. METHODS: The FAACT-A/CS and the VAS for appetite were administered to patients with cancer before start of chemotherapy. As reference standard for anorexia, two external criteria were used: (1) a cut-off value of ≥2 on the anorexia symptom scale of the EORTC QLQ C-30 and (2) the question "Do you experience a decreased appetite?" (yes/no). ROC curves were used to examine the optimal cut-off values for the FAACT-A/CS and VAS. RESULTS: A total of 273 patients (58 % male; 64.0 ± 10.6 years) were included. The median score on the FAACT-A/CS was 38 (IQR 32-42) points and 77 (IQR 47-93) points on the VAS. Considering both external criteria, the optimal cut-off value for the FAACT-A/CS was ≤37 (sensitivity (se) 80 %, specificity (sp) 81 %, positive predictive value (PV(+)) 79 %, negative predictive value (PV(-)) 82 %) and for the VAS was ≤70 (se 76 %, sp 83 %, PV(+) 80 %, PV(-) 79 %). CONCLUSIONS: For the assessment of anorexia in patients with cancer, our study suggests cut-off values of ≤37 for the FAACT-A/CS and ≤70 for the VAS. Future studies should confirm our findings in other patient samples.

Critical weight loss is a major prognostic indicator for disease-specific survival in patients with head and neck cancer receiving radiotherapy.

BACKGROUND: Pre-treatment weight loss (WL) is a prognostic indicator for overall survival (OS) in head and neck cancer (HNC) patients. This study investigates the association between WL before or during radiotherapy and disease-specific survival (DSS) in HNC patients. METHODS: In 1340 newly diagnosed HNC patients, weight change was collected before and during (adjuvant) radiotherapy with curative intent. Critical WL during radiotherapy was defined as >5% WL during radiotherapy or >7.5% WL until week 12. Differences in 5-year OS and DSS between WL groups were analysed by Cox's regression with adjustments for important socio-demographic and tumour-related confounders. RESULTS: Before radiotherapy, 70% of patients had no WL, 16% had ≤5% WL, 9% had >5-10% WL, and 5% had >10% WL. Five-year OS and DSS rates for these groups were 71%, 59%, 47%, and 42% (P<0.001), and 86%, 86%, 81%, and 71%, respectively (P<0.001). After adjustment for potential confounders, >10% WL before radiotherapy remained significantly associated with a worse OS (HR 1.7; 95% CI 1.2-2.5; P=0.002) and DSS (HR 2.1; 95% CI 1.2-3.5; P=0.007).The 5-year OS and DSS rates for patients with critical WL during radiotherapy were 62% and 82%, compared with 70% and 89% for patients without critical WL (P=0.01; P=0.001). After adjustment, critical WL during radiotherapy remained significantly associated with a worse DSS (HR 1.7; 95% CI 1.2-2.4; P=0.004). CONCLUSION: Weight loss both before and during radiotherapy are important prognostic indicators for 5-year DSS in HNC patients. Randomised studies into the prognostic effect of nutritional intervention are needed.

Validity of nutritional screening with MUST and SNAQ in hospital outpatients.

BACKGROUND/OBJECTIVES: The majority of hospital outpatients with undernutrition is unrecognized, and therefore untreated. There is a need for an easy and valid screening tool to detect undernutrition in this setting. The aim of this study was to determine the diagnostic accuracy of the MUST (Malnutrition Universal Screening Tool) and SNAQ (Short Nutritional Assessment Questionnaire) tools for undernutrition screening in hospital outpatients. METHODS: In a large multicenter-hospital-outpatient population, patients were classified as: severely undernourished (body mass index (BMI) <18.5 (<65 years) or <20 ( ≥ 65 years) and/or unintentional weight loss >5% in the last month or >10% in the last 6 months), moderately undernourished (BMI 18.5-20 (<65 years) or 20-22 ( ≥ 65 years) and/or 5-10% unintentional weight loss in the last 6 months) or not undernourished. Diagnostic accuracy of the screening tools versus the reference method was expressed as sensitivity (Se), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV). RESULTS: Out of the 2236 outpatients, 6% were severely and 7% were moderately undernourished according to the reference method. MUST and SNAQ identified 9% and 3% as severely undernourished, respectively. MUST had a low PPV (Se=75, Sp=95, PPV=43, NPV=98), whereas SNAQ had a low Se (Se=43, Sp=99, PPV=78, NPV=96). CONCLUSIONS: The validity of MUST and SNAQ is insufficient for hospital outpatients. While SNAQ identifies too few patients as undernourished, MUST identifies too many patients as undernourished. We advise to measure body weight, height and weight loss, in order to define undernutrition in hospital outpatients.

Nutritional support in patients with GVHD of the digestive tract: state of the art.

An important complication of allo-SCT is GVHD, which commonly affects the skin, liver and digestive tract. Clinical symptoms of GVHD of the digestive tract (GVHD-DT) include excessive diarrhoea, abdominal pain and cramps, nausea and vomiting, gastrointestinal bleeding, dysphagia, and weight loss. Treatment is complicated and regarding nutritional support, only a few guidelines are available. Our aim was to critically appraise the literature on nutritional assessment, nutritional status and nutritional support for patients with GVHD-DT. Evidence shows that GVHD-DT is often associated with malnutrition, protein losing enteropathy, magnesium derangements, and deficiencies of zinc, vitamin B12 and vitamin D. Limited evidence exists on derangements of magnesium, resting energy expenditure, bone mineral density and pancreatic function, and some beneficial effects of n-3 polyunsaturated fatty acids and pancreatic enzyme replacement therapy. Expert opinions recommend adequate amounts of energy, at least 1.5 g protein/kg body weight, supplied by total parenteral nutrition in cases of severe diarrhoea. When diarrhoea is <500 mL a day, a stepwise oral upgrade diet can be followed. No studies exist on probiotics, prebiotics, dietary fibre and immunonutrition in GVHD-DT patients. Future research should focus on absorption capacity, vitamin and mineral status, and nutritional support strategies.

Oral nutritional supplements containing n-3 polyunsaturated fatty acids affect quality of life and functional status in lung cancer patients during multimodality treatment: an RCT.

BACKGROUND/OBJECTIVES: Our objective was to investigate effects of an oral nutritional supplement containing n-3 polyunsaturated fatty acids (FAs) on quality of life, performance status, handgrip strength and physical activity in patients with non-small cell lung cancer (NSCLC) undergoing multimodality treatment. SUBJECTS/METHODS: In a double-blind experiment, 40 patients with stage III NSCLC were randomised to receive 2 cans/day of a protein- and energy-dense oral nutritional supplement containing n-3 polyunsaturated FAs (2.02 g eicosapentaenoic acid+0.92 g docosahexaenoic acid/day) or an isocaloric control supplement, during multimodality treatment. Quality of life, Karnofsky Performance Status, handgrip strength and physical activity (by wearing an accelerometer) were assessed. Effects of intervention were analysed by generalised estimating equations. P-values <0.05 were regarded as statistically significant. RESULTS: The intervention group reported significantly higher on the quality of life parameters, physical and cognitive function (B=11.6 and B=20.7, P<0.01), global health status (B=12.2, P=0.04) and social function (B=22.1, P=0.04) than the control group after 5 weeks. The intervention group showed a higher Karnofsky Performance Status (B=5.3, P=0.04) than the control group after 3 weeks. Handgrip strength did not significantly differ between groups over time. The intervention group tended to have a higher physical activity than the control group after 3 and 5 weeks (B=6.6, P=0.04 and B=2.5, P=0.05). CONCLUSION: n-3 Polyunsaturated FAs may beneficially affect quality of life, performance status and physical activity in patients with NSCLC undergoing multimodality treatment.

No effect of consumption of green and black tea on plasma lipid and antioxidant levels and on LDL oxidation in smokers.

Intake of flavonoids is associated with a reduced cardiovascular risk. Oxidation of LDL is a major step in atherogenesis, and antioxidants may protect LDL from oxidation. Because tea is an important source of flavonoids, which are strong antioxidants, we have assessed in a randomized, placebo-controlled study the effect of consumption of black and green tea and of intake of isolated green tea polyphenols on LDL oxidation ex vivo and on plasma levels of antioxidants and lipids. Healthy male and female smokers (aged 34+/-12 years, 13 to 16 per group) consumed during a 4-week period 6 cups (900 mL) of black or green tea or water per day, or they received as a supplement 3.6 grams of green tea polyphenols per day (equivalent to the consumption of 18 cups of green tea per day). Consumption of black or green tea had no effect on plasma cholesterol and triglycerides, HDL and LDL cholesterol, plasma vitamins C and E, beta-carotene, and uric acid. No differences were found in parameters of LDL oxidation. Intake of green tea polyphenols decreased plasma vitamin E significantly in that group compared with the control group (-11% P=.016) but had no effect on LDL oxidation ex vivo. We conclude that consumption of black or green tea (6 cups per day) has no effect on plasma lipids and no sparing effect on plasma antioxidant vitamins and that intake of a high dose of isolated green tea polyphenols decreases plasma vitamin E. Although tea polyphenols had a potent antioxidant activity on LDL oxidation in vitro, no effect was found on LDL oxidation ex vivo after consumption of green or black tea or intake of a green tea polyphenol isolate.