Plasma Ghrelin Levels Are Associated with Anorexia but Not Cachexia in Patients with NSCLC

Background and Aims: The ghrelin receptor is one of the new therapeutic targets in the cancer anorexia-cachexia syndrome. Previous studies revealed that plasma ghrelin levels were high in patients with anorexia nervosa and low in obese subjects. We studied to what extent ghrelin levels are related with anorexia and cachexia in patients with cancer. Materials and Methods: Fasted ghrelin levels were determined as well as anorexia and cachexia in patients with stage III/IV non-small cell lung cancer before chemotherapy. Total plasma ghrelin was measured by radioimmunoassay. Anorexia was measured with the FAACT-A/CS questionnaire (cut-off value ≤ 37). Cachexia was determined as > 5% weight loss (WL) in 6 months or > 2% WL in 6 months in combination with low BMI or low muscle mass. The Kruskal-Wallis test was performed to assess differences in plasma ghrelin levels between four groups: patients with (+) or without (-) anorexia (A) or cachexia (C). Multiple regression analyses were performed to assess differences in plasma ghrelin levels between patients C+ and C- and patients with A+ and A- (adjusted for age and sex). Results: Forty patients with stage III (33%) or stage IV (68%) were recruited, of which 50% was male. Mean age was 59.6 ± 10.3 years. Sixteen patients had no anorexia or cachexia (A-C-), seven patients had both anorexia and cachexia (A+C+), ten patients had anorexia without cachexia (A+C-) and seven patients had cachexia without anorexia (A-C+). The levels of total plasma ghrelin were significantly different between the four groups of patients with or without anorexia or cachexia (p = 0.032): the A+C- patients had significantly higher ghrelin levels [median (IQR): 1,754 (1,404-2,142) compared to the A-C+ patients 1,026 (952-1,357), p = 0.003]. A+ patients had significantly higher ghrelin levels compared A- patients (C+ and C- combined, β: 304, p = 0.020). Plasma ghrelin levels were not significantly different in C+ patients compared to C- patients (A+ and A- combined, β: -99, p = 0.450). Conclusions: Patients with anorexia had significantly higher ghrelin levels compared to patients without anorexia. We therefore hypothesize that patients with cancer anorexia might benefit from treatment with a ghrelin receptor agonist to prevent WL and deterioration in physical functioning

Effect of nutritional interventions on nutritional status, quality of life and mortality in patients with head and neck cancer receiving (chemo)radiotherapy: a systematic review q

Head and neck cancer Radiotherapy s u m m a r y Background and aims: We performed a systematic review to examine the effect of nutritional interventions on nutritional status, quality of life (QoL) and mortality in patients with head and neck squamous cell cancer (HNSCC) receiving radiotherapy or chemoradiotherapy. Methods: We searched Pubmed, EMBASE, CENTRAL and Cinahl from inception through January 3rd, 2012 to identify randomized controlled trials (RCTs) from a broad range of nutritional interventions in patients with HNSCC during (chemo)radiotherapy. Two reviewers independently assessed study eligibility and risk of bias, and extracted data. Results: Of 1141 titles identified, 12 study reports were finally included, describing 10 different studies with 11 interventions. Four out of 10 studies examined the effects of individualized dietary counseling, and showed significant benefits on nutritional status and QOL compared to no counseling or general nutritional advice by a nurse (p < 0.05). Three studies on oral nutritional supplements (ONS) were inconsistent about the effect on nutritional status compared with no supplementation. One study showed that nasogastric tube feeding had beneficial effects on nutritional status compared to ONS, but not in all patient groups (p < 0.04). One study showed benefits of percutaneous endoscopic gastronomy (PEG) feeding on nutritional status shortly after RT compared with nasogastric feeding (p ¼ 0.001). Two studies showed that prophylactic PEG feeding was not superior over tube feeding if required. Conclusions: This review shows beneficial effects of individualized dietary counseling on nutritional status and QoL, compared to no counseling or standard nutritional advice. Effects of ONS and tube feeding were inconsistent

Cancer Cachexia: Identification by Clinical Assessment versus International Consensus Criteria in Patients with Metastatic Colorectal Cancer

Background: Cancer cachexia is associated with poorer outcomes and is often diagnosed by the Fearon criteria. Oncologists clinically identify cachexia based on a patient’s presentation. In this study agreement between these identification methods was evaluated and associations with outcomes were studied in patients with metastatic colorectal cancer. Methods: Fearon criteria comprised weight loss >5% OR weight loss >2% with either BMI <20 kg/m2 or sarcopenia (determined by CT-imaging). Clinical assessment by the oncologist was based on the patient’s clinical presentation. Agreement was tested with Kappa. Associations with treatment tolerance and progression free survival (PFS) were tested with logistic regressions and Cox proportional hazards, respectively. Results: Of 69 patients, 52% was identified as cachectic according to Fearon criteria and 9% according to clinical assessment. Agreement between both methods was slight (Kappa 0.049, P = 0.457). Clinically cachectic patients had a shorter PFS than clinically non-cachectic patients (HR 3.310, P = 0.016). No other differences in outcomes were found between cachectic vs. non-cachectic patients using both methods. Conclusions: The agreement between cancer cachexia identification by clinical assessment vs. Fearon criteria was slight. Further improvement of cachexia criteria is necessary to identify cachectic patients at risk of poorer outcomes, who may benefit from targeted cachexia interventions

Systematic screening for undernutrition in hospitals: Predictive factors for success.

BACKGROUND & AIMS: Since 2007, systematic screening for undernutrition has become a performance indicator (PI) for hospitals within the National Benchmarks on Quality of Care of the Dutch Health Care Inspectorate (HCI). Its introduction was guided by a national implementation program. The aim of this study was to evaluate the screening results from 2007 to 2010 and to identify predictive factors for achieved screening results. METHODS: All 97 Dutch hospitals were obliged to report screening results to the HCI. An additional questionnaire was developed to determine hospital characteristics, including hospital type, size, participation in implementation program, screening tool used, use of electronic records, presence of hospital-wide or ward task forces, and protocol-defined referral. Multivariate linear regression analysis was used to identify predictive factors for the obtained screening results in 2010. RESULTS: The mean screening percentage increased from 51 ± 28% in 2007 (n = 75 hospitals, n = 340,000 patients) to 72 ± 17% in 2010 (n = 97; n = 1,050,000) (p < 0.01). Eighty-one hospitals returned the questionnaire. A higher screening percentage was associated with more clinical admissions (highest vs. lowest tertile: β = 14.0, 95% CI 3.9-20.5; p < 0.01; middle vs. lowest: β = 7.3, -0.8 to 15.6; p = 0.05), presence of protocol-defined referral to a dietician (β = 10.5, 2.9-18.0; p < 0.01), and use of the SNAQ screening tool (vs. MUST: β = 9.1, 1.7-16.6; p = 0.02). CONCLUSION: Screening percentages have increased significantly since the introduction of the PI. Screening was more frequent in hospitals which have more patient admissions, protocol-defined referral to a dietician, and who use the SNAQ screening tool. This information may assist in improving Dutch screening rates and in implementation in other countries

Skeletal muscle analyses: Agreement between non-contrast and contrast CT scan measurements of skeletal muscle area and mean muscle attenuation

Low skeletal muscle area (SMA) and muscle radiation attenuation (MRA) have been associated with poor prognosis in various patient populations. Both non-contrast and contrast CT scans are used to determine SMA and MRA. The effect of the use of a contrast agent on SMA and MRA is unknown. Therefore, we investigated agreement between these two scan options. SMA and MRA of 41 healthy individuals were analysed on a paired non-contrast and contrast single CT scan, and agreement between paired scan results was assessed with use of Bland-Altman plots, intraclass correlation coefficients (ICCs), standard error of measurements (SEM) and smallest detectable differences at a 95% confidence level (SDD95). Analyses were stratified by tube voltage. Difference in SMA between non-contrast and contrast scans made with a different tube voltage was 7·0 ± 7·5 cm2; for scans made with the same tube voltage this was 2·3 ± 1·7 cm2. Agreement was excellent for both methods: ICC: 0·952, SEM: 7·2 cm2, SDD95: 19·9 cm2 and ICC: 0·997, SEM: 2·0 cm2, SDD95: 5·6 cm2, respectively. MRA of scans made with a different tube voltage differed 1·3 ± 11·3 HU, and agreement was poor (ICC: 0·207, SEM: 7·9 HU, SDD95: 21·8 HU). For scans made with the same tube voltage the difference was 6·7 ± 3·2 HU, and agreement was good (ICC: 0·682, SEM: 5·3 HU, SDD95: 14·6 HU). In conclusion, SMA and MRA can be slightly influenced by the use of contrast agent. To minimise measurement error, image acquisition parameters of the scans should be similar

Pre-cachexia and cachexia at diagnosis of stage III non-small-cell lung carcinoma: an exploratory study comparing two consensus-based frameworks

Despite the development of consensus-based frameworks to define cancer cachexia, the validity and usefulness of these frameworks are relatively unknown. The aim of the present study was to study the presence of pre-cachexia and cachexia in patients with stage III non-small-cell lung carcinoma (NSCLC) by using a cancer-specific framework and a general framework for cachexia, and to explore the prognostic value of pre-cachexia and cachexia. In forty patients at diagnosis of stage III NSCLC, weight loss, fat-free mass, handgrip strength, anorexia and serum biochemistry, assessed before the first chemotherapy, were used to define 'cancer cachexia' or 'cachexia'. The cancer-specific framework also classified for pre-cachexia and refractory cachexia. Additionally, quality of life was assessed by the European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire C30. Groups were compared using independent t tests, ANOVA, Kaplan-Meier and Cox survival analyses. Based on the cancer-specific framework, pre-cachexia was present in nine patients (23 %) and cancer cachexia was present in seven patients (18 %). Cancer cachexia was associated with a reduced quality of life (P= 0·03) and shorter survival (hazard ratio (HR) = 2·9; P= 0·04). When using the general framework, cachexia was present in eleven patients (28 %), and was associated with a reduced quality of life (P= 0·08) and shorter survival (HR = 4·4; P= 0·001). In conclusion, pre-cachexia and cachexia are prevalent in this small population of patients at diagnosis of stage III NSCLC. For both frameworks, cachexia appears to be associated with a reduced quality of life and shorter survival. Further studies are warranted to more extensively explore the validity and prognostic value of these new frameworks in cancer patients. © 2012 The Authors

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) 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

Methodology of Clinical Nutrition Guidelines for Adult Cancer Patients: How Good Are They According to AGREE Criteria?

Background: Malnutrition delays recovery from cancer treatment and can lead to additional serious complications. Clinical guidelines for the management of malnutrition in cancer patients are essential tools for optimizing nutritional care; therefore, their methodological quality is of great importance. This review assesses the methodological quality of international clinical guidelines for the management of malnutrition in adult cancer patients. Methods: Guidelines were identified through searches in multiple electronic databases; afterward, they were systematically reviewed with the AGREE instrument, which is one method of evaluating the methodological quality of guidelines. Results: The methodological quality of the guidelines reviewed varied greatly. The highest scores were observed in the domains "scope and purpose" and "clarity and presentation," while the lowest scores were awarded in the domains "editorial independence," "stakeholder involvement," and "applicability." Furthermore, there was consensus on the indication for parenteral nutrition and nutrition screening. However, there was a lack of consensus on how nutritional therapy should be provided. No improvement was observed in methodological quality of the more recent guidelines compared to the older ones. Conclusions: The methodological quality of clinical guidelines on malnutrition for cancer patients and the way they are reported need to be improved. To achieve this, developers should utilize available guideline assessment tools, such as the AGREE instrument, when writing or updating guidelines on this topic. © 2012 American Society for Parenteral and Enteral Nutrition