A systematic review examining nutrition support interventions in patients with incurable cancer.

PURPOSE: Recent guidelines by the European Society for Clinical Nutrition and Metabolism (ESPEN) have advocated increased attention to nutritional support in all patients with cancer; however, little is known about the optimal type of nutritional intervention. The aim of this review was to assess the current evidence for nutrition support in patients with incurable cancer. METHODS: This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Embase, MEDLINE and CINAHL were searched from 1990 to 2018. Evidence was appraised using a modified risk of bias table, based on guidance from the Cochrane Handbook for Systematic Reviews of Interventions. RESULTS: Sixty studies were assessed of which twelve met the eligibility criteria. Eleven studies examined body composition, with six studies reporting improvements in weight. Six studies examined nutritional status with three studies reporting an improvement. Nine studies examined nutritional intake with six showing improvements including significant improvements in dietary and protein intake. Ten studies examined quality of life, with six studies reporting improvements following intervention. The most common nutritional interventions examined were nutrition counselling and dietary supplementation. CONCLUSIONS: There is moderate quality evidence to support the need for increased attention to nutrition support in patients with incurable cancer; however, despite some statistically significant results being reported, the clinical effects of them were small. Key questions remain as to the optimal timing for these interventions to be implemented (e.g. cachexia stage, illness stage and timing with anticancer therapy) and the most appropriate endpoint measures.

Validity of dietary intake methods in cancer cachexia.

PURPOSE OF REVIEW: Accurate assessment of dietary intake, especially energy and protein intake, is crucial for optimizing nutritional care and outcomes in patients with cancer. Validation of dietary assessment methods is necessary to ensure accuracy, but the validity of these methods in patients with cancer, and especially in those with cancer cachexia, is uncertain. Validating nutritional intake is complex because of the variety of dietary methods, lack of a gold standard method, and diverse validation measures. Here, we review the literature on validations of dietary intake methods in patients with cancer, including those with cachexia, and highlight the gap between current validation efforts and the need for accurate dietary assessment methods in this population. RECENT FINDINGS: We analyzed eight studies involving 1479 patients with cancer to evaluate the accuracy and reliability of 24-hour recalls, food records, and food frequency questionnaires in estimating energy and protein intake. We discuss validation methods, including comparison with biomarkers, indirect calorimetry, and relative validation of dietary intake methods. SUMMARY: Few have validated dietary intake methods against objective markers in patients with cancer. While food records and 24-hour recalls show potential accuracy for energy and protein intake, this may be compromised in hypermetabolic patients. Additionally, under- and overreporting of intake may be less frequent, and the reliability of urinary nitrogen as a protein intake marker in patients with cachexia needs further investigation. Accurate dietary assessment is important for enhancing nutritional care outcomes in cachexia trials, requiring validation at multiple time points throughout the cancer trajectory.

Biomarker endpoints in cancer cachexia clinical trials: Systematic Review 5 of the cachexia endpoint series.

Regulatory agencies require evidence that endpoints correlate with clinical benefit before they can be used to approve drugs. Biomarkers are often considered surrogate endpoints. In cancer cachexia trials, the measurement of biomarkers features frequently. The aim of this systematic review was to assess the frequency and diversity of biomarker endpoints in cancer cachexia trials. A comprehensive electronic literature search of MEDLINE, Embase and Cochrane (1990-2023) was completed. Eligible trials met the following criteria: adults (≥18 years), prospective design, more than 40 participants, use of a cachexia intervention for more than 14 days and use of a biomarker(s) as an endpoint. Biomarkers were defined as any objective measure that was assayed from a body fluid, including scoring systems based on these assays. Routine haematology and biochemistry to monitor intervention toxicity were not considered. Data extraction was performed using Covidence, and reporting followed PRISMA guidance (PROSPERO: CRD42022276710). A total of 5975 studies were assessed, of which 52 trials (total participants = 6522) included biomarkers as endpoints. Most studies (n = 29, 55.7%) included a variety of cancer types. Pharmacological interventions (n = 27, 51.9%) were most evaluated, followed by nutritional interventions (n = 20, 38.4%). Ninety-nine different biomarkers were used across the trials, and of these, 96 were assayed from blood. Albumin (n = 29, 55.8%) was assessed most often, followed by C-reactive protein (n = 22, 42.3%), interleukin-6 (n = 16, 30.8%) and tumour necrosis factor-α (n = 14, 26.9%), the latter being the only biomarker that was used to guide sample size calculations. Biomarkers were explicitly listed as a primary outcome in six trials. In total, 12 biomarkers (12.1% of 99) were used in six trials or more. Insulin-like growth factor binding protein 3 (IGFBP-3) and insulin-like growth factor 1 (IGF-1) levels both increased significantly in all three trials in which they were both used. This corresponded with a primary outcome, lean body mass, and was related to the pharmacological mechanism. Biomarkers were predominately used as exploratory rather than primary endpoints. The most commonly used biomarker, albumin, was limited by its lack of responsiveness to nutritional intervention. For a biomarker to be responsive to change, it must be related to the mechanism of action of the intervention and/or the underlying cachexia process that is modified by the intervention, as seen with IGFBP-3, IGF-1 and anamorelin. To reach regulatory approval as an endpoint, the relationship between the biomarker and clinical benefit must be clarified.

Appetite and dietary intake endpoints in cancer cachexia clinical trials: Systematic Review 2 of the cachexia endpoints series.

There is no consensus on the optimal endpoint(s) in cancer cachexia trials. Endpoint variation is an obstacle when comparing interventions and their clinical value. The aim of this systematic review was to summarize and evaluate endpoints used to assess appetite and dietary intake in cancer cachexia clinical trials. A search for studies published from 1 January 1990 until 2 June 2021 was conducted using MEDLINE, Embase and Cochrane Central Register of Controlled Trials. Eligible studies examined cancer cachexia treatment versus a comparator in adults with assessments of appetite and/or dietary intake as study endpoints, a sample size ≥40 and an intervention lasting ≥14 days. Reporting was in line with PRISMA guidance, and a protocol was published in PROSPERO (2022 CRD42022276710). This review is part of a series of systematic reviews examining cachexia endpoints. Of the 5975 articles identified, 116 were eligible for the wider review series and 80 specifically examined endpoints of appetite (65 studies) and/or dietary intake (21 studies). Six trials assessed both appetite and dietary intake. Appetite was the primary outcome in 15 trials and dietary intake in 7 trials. Median sample size was 101 patients (range 40-628). Forty-nine studies included multiple primary tumour sites, while 31 studies involved single primary tumour sites (15 gastrointestinal, 7 lung, 7 head and neck and 2 female reproductive organs). The most frequently reported appetite endpoints were visual analogue scale (VAS) and numerical rating scale (NRS) (40%). The appetite item from the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) C30/C15 PAL (38%) and the appetite question from North Central Cancer Treatment Group anorexia questionnaire (17%) were also frequently applied. Of the studies that assessed dietary intake, 13 (62%) used food records (prospective registrations) and 10 (48%) used retrospective methods (24-h recall or dietary history). For VAS/NRS, a mean change of 1.3 corresponded to Hedge's g of 0.5 and can be considered a moderate change. For food records, a mean change of 231 kcal/day or 11 g of protein/day corresponded to a moderate change. Choice of endpoint in cachexia trials will depend on factors pertinent to the trial to be conducted. Nevertheless, from trials assessed and available literature, NRS or EORTC QLQ C30/C15 PAL seems suitable for appetite assessments. Appetite and dietary intake endpoints are rarely used as primary outcomes in cancer cachexia. Dietary intake assessments were used mainly to monitor compliance and are not validated in cachexia populations. Given the importance to cachexia studies, dietary intake endpoints must be validated before they are used as endpoints in clinical trials.

Body weight and composition endpoints in cancer cachexia clinical trials: Systematic Review 4 of the cachexia endpoints series.

Significant variation exists in the outcomes used in cancer cachexia trials, including measures of body composition, which are often selected as primary or secondary endpoints. To date, there has been no review of the most commonly selected measures or their potential sensitivity to detect changes resulting from the interventions being examined. The aim of this systematic review is to assess the frequency and diversity of body composition measures that have been used in cancer cachexia trials. MEDLINE, Embase and Cochrane Library databases were systematically searched between January 1990 and June 2021. Eligible trials examined adults (≥18 years) who had received an intervention aiming to treat or attenuate the effects of cancer cachexia for >14 days. Trials were also of a prospective controlled design and included body weight or at least one anthropometric, bioelectrical or radiological endpoint pertaining to body composition, irrespective of the modality of intervention (e.g., pharmacological, nutritional, physical exercise and behavioural) or comparator. Trials with a sample size of <40 patients were excluded. Data extraction used Covidence software, and reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance. This review was prospectively registered (PROSPERO: CRD42022276710). A total of 84 clinical trials, comprising 13 016 patients, were eligible for inclusion. Non-small-cell lung cancer and pancreatic cancer were studied most frequently. The majority of trial interventions were pharmacological (52%) or nutritional (34%) in nature. The most frequently reported endpoints were assessments of body weight (68 trials, n = 11 561) followed by bioimpedance analysis (BIA)-based estimates (23 trials, n = 3140). Sixteen trials (n = 3052) included dual-energy X-ray absorptiometry (DEXA)-based endpoints, and computed tomography (CT) body composition was included in eight trials (n = 841). Discrepancies were evident when comparing the efficacy of interventions using BIA-based estimates of lean tissue mass against radiological assessment modalities. Body weight, BIA and DEXA-based endpoints have been most frequently used in cancer cachexia trials. Although the optimal endpoints cannot be determined from this review, body weight, alongside measurements from radiological body composition analysis, would seem appropriate. The choice of radiological modality is likely to be dependent on the trial setting, population and intervention in question. CT and magnetic resonance imaging, which have the ability to accurately discriminate tissue types, are likely to be more sensitive and provide greater detail. Endpoints are of particular importance when aligned with the intervention's mechanism of action and/or intended patient benefit.

Quality of life endpoints in cancer cachexia clinical trials: Systematic review 3 of the cachexia endpoints series.

The use of patient-reported outcomes (PROMs) of quality of life (QOL) is common in cachexia trials. Patients' self-report on health, functioning, wellbeing, and perceptions of care, represent important measures of efficacy. This review describes the frequency, variety, and reporting of QOL endpoints used in cancer cachexia clinical trials. Electronic literature searches were performed in Medline, Embase, and Cochrane (1990-2023). Seven thousand four hundred thirty-five papers were retained for evaluation. Eligibility criteria included QOL as a study endpoint using validated measures, controlled design, adults (>18 years), ≥40 participants randomized, and intervention exceeding 2 weeks. The Covidence software was used for review procedures and data extractions. Four independent authors screened all records for consensus. Papers were screened by titles and abstracts, prior to full-text reading. PRISMA guidance for systematic reviews was followed. The protocol was prospectively registered via PROSPERO (CRD42022276710). Fifty papers focused on QOL. Twenty-four (48%) were double-blind randomized controlled trials. Sample sizes varied considerably (n = 42 to 469). Thirty-nine trials (78%) included multiple cancer types. Twenty-seven trials (54%) featured multimodal interventions with various drugs and dietary supplements, 11 (22%) used nutritional interventions alone and 12 (24%) used a single pharmacological intervention only. The median duration of the interventions was 12 weeks (4-96). The most frequent QOL measure was the EORTC QLQ-C30 (60%), followed by different FACIT questionnaires (34%). QOL was a primary, secondary, or exploratory endpoint in 15, 31 and 4 trials respectively, being the single primary in six. Statistically significant results on one or more QOL items favouring the intervention group were found in 18 trials. Eleven of these used a complete multidimensional measure. Adjustments for multiple testing when using multicomponent QOL measures were not reported. Nine trials (18%) defined a statistically or clinically significant difference for QOL, five with QOL as a primary outcome, and four with QOL as a secondary outcome. Correlation statistics with other study outcomes were rarely performed. PROMs including QOL are important endpoints in cachexia trials. We recommend using well-validated QOL measures, including cachexia-specific items such as weight history, appetite loss, and nutritional intake. Appropriate statistical methods with definitions of clinical significance, adjustment for multiple testing and few co-primary endpoints are encouraged, as is an understanding of how interventions may relate to changes in QOL endpoints. A strategic and scientific-based approach to PROM research in cachexia trials is warranted, to improve the research base in this field and avoid the use of QOL as supplementary measures.

Parenteral Nutrition in Advanced Cancer: The Healthcare Providers' Perspective.

INTRODUCTION: The evidence base for parenteral nutrition (PN) in advanced cancer patients is limited. We studied healthcare providers' (HCPs') experiences with PN in cancer patients, focusing on perceived treatment benefits and challenges. METHODS: An 18-item online survey was emailed to HCPs attending one of three regional palliative care seminars held within a 6-month period. The survey included single-response items, multiple-response items, and free text boxes concerning PN. Descriptive statistics and qualitative thematic content analysis were applied. RESULTS: One hundred and two seminar participants completed the survey. Ninety-three percent were female, 86% were nurses/oncological nurses, and 80% worked in primary care. Respondents reported a well-functioning collaboration across levels of care. They perceived that PN may increase the patients' level of energy, improve the general condition, and reduce eating-related distress. On the downside, HCPs observed burdensome side effects, that the treatment was resource-demanding, and that decisions on PN withdrawal were difficult. CONCLUSION: The study results are based on the perspectives of more than 100 HCPs with comprehensive clinical experience with PN. Their knowledge represents an important experience base for improvement of healthcare services and advanced care planning.

Apple, cherry, and blackcurrant increases nuclear factor kappa B activation in liver of transgenic mice.

Nuclear factor kappa B (NF-kappaB) is essential in normal physiology, and several human disorders involve inappropriate regulation of NF-kappaB. Diets dominated by plant-based foods protect against chronic diseases, and several food derived compounds have been identified as promising NF-kappaB modulators. We investigated the effects of diets supplemented with apple, blackcurrant, or cherries on lipopolysaccharide (LPS)-induced NF-kappaB activation in transgenic NF-kappaB-luciferase mice. Whole body and organ specific NF-kappaB activities were determined. The mice had ad libitum access to the respective experimental diets for 7 days. On Day 7, all mice were given an LPS-injection (2.5 mg/kg), and NF-kappaB activation was monitored by in vivo imaging for 6 h. After imaging, blood samples were taken, the mice were euthanized, and ex vivo imaging of organs was performed. Compared to the control group, the apple and cherry groups had slightly higher whole-body NF-kappaB activation at 4 h, and all 3 experimental groups had higher NF-kappaB activation at 6 h. LPS-induced NF-kappaB activation in liver was increased with all 3 experimental diets, but no effects were observed in other organs. Our findings indicate that high intakes of lyophilized fruits modulate in vivo NF-kappaB signaling in the liver following LPS-induced stress; however, consequences of this NF-kappaB modulation in hepatic tissue needs further investigation.

Power Comparisons and Clinical Meaning of Outcome Measures in Assessing Treatment Effect in Cancer Cachexia: Secondary Analysis From a Randomized Pilot Multimodal Intervention Trial.

Background: New clinical trials in cancer cachexia are essential, and outcome measures with high responsiveness to detect meaningful changes are crucial. This secondary analysis from a multimodal intervention trial estimates sensitivity to change and between treatment effect sizes (ESs) of outcome measures associated with body composition, physical function, metabolism, and trial intervention. Methods: The study was a multicenter, open-label, randomized pilot study investigating the feasibility of a 6-week multimodal intervention [exercise, non-steroidal anti-inflammatory drugs, and oral nutritional supplements containing polyunsaturated fatty acids (n-3 PUFAs)] vs. standard cancer care in non-operable non-small-cell lung cancer and advanced pancreatic cancer. Body composition measures from computerized tomography scans and circulating biomarkers were analyzed. Results: Forty-six patients were randomized, and the analysis included 22 and 18 patients in the treatment and control groups, respectively. The between-group ESs were high for body weight (ES = 1.2, p < 0.001), small for body composition and physical function [handgrip strength (HGS)] measures (ES < 0.25), moderate to high for n-3 PUFAs and 25-hydroxyvitamin D (25-OH vitamin D) (ES range 0.64-1.37, p < 0.05 for all), and moderate for serum C-reactive protein (ES = 0.53, p = 0.12). Analysis within the multimodal treatment group showed high sensitivity to change for adiponectin (ES = 0.86, p = 0.001) and n-3 PUFAs (ES > 0.8, p < 0.05 for all) and moderate for 25-OH vitamin D (ES = 0.49, p = 0.03). In the control group, a moderate sensitivity to change for body weight (ES = -0.84, p = 0.002) and muscle mass (ES = -0.67, p = 0.016) and a high sensitivity to change for plasma levels of 25-OH vitamin D (ES = -0.88, p = 0.002) were found. Conclusion: Demonstrating high sensitivity to change and between treatment ES and body composition measures, body weight still stands out as a clinical and relevant outcome measure in cancer cachexia. Body composition and physical function measures clearly are important to address but demand large sample sizes to detect treatment group differences. Trial registration: ClinicalTrials.gov identifier: NCT01419145.

Exercise and Nutrition Interventions in Patients with Head and Neck Cancer during Curative Treatment: A Systematic Review and Meta-Analysis.

The aim of this meta-analysis was to examine the effects of nutritional and physical exercise interventions and interventions combining these interventions during radiotherapy treatment for patients with head and neck cancer on body composition, objectively measured physical function and nutritional status. Systematic electronic searches were conducted in MEDLINE (PubMed interface), EMBASE (Ovid interface), CINAHL (EBSCO interface) and Cochrane Library (Wiley interface). We identified 13 randomized controlled trials (RCTs) that included 858 patients. For body composition, using only nutrition as intervention, a significant difference between treatment and control group were observed (SMD 0.42 (95CI 0.23-0.62), p < 0.001). Only pilot RCTs investigated combination treatment and no significant difference between the treatment and control groups were found (SMD 0.21 (95CI -0.16-0.58), p = 0.259). For physical function, a significant difference between treatment and control group with a better outcome for the treatment group were observed (SMD 0.78 (95CI 0.51-1.04), p < 0.001). No effects on nutritional status were found. This meta-analysis found significantly positive effects of nutrition and physical exercise interventions alone in favor of the treatment groups. No effects in studies with combined interventions were observed. Future full-scaled RCTs combining nutrition and physical exercise is warranted.

Physical rehabilitation in patients with head and neck cancer: Impact on health-related quality of life and suitability of a post-treatment program.

OBJECTIVE: Physical rehabilitation programs hold the potential to mitigate deterioration in health-related quality of life (HRQoL) in patients with head and neck cancer. The objective was to assess development in relevant domains of HRQoL following a physical exercise and nutrition intervention administrated during or after treatment. METHODS: In a pilot study, 41 patients were randomized to resistance training and oral nutritional supplements during (EN-DUR, n = 20) or after (EN-AF, n = 21) radiotherapy. Global health status/QoL (GHS) and physical functioning (PF) were measured by the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire at baseline, week 6, and week 14. Differences between the groups were assessed by analysis of covariance. A difference of ≥10 points in GHS and PF was interpreted as clinically relevant. RESULTS: No statistically significant differences were detected between the groups; however, clinically relevant changes and differences in GHS and PF were observed. From baseline to week 6, GHS decreased 9 points in the EN-DUR group and 23 points in the EN-AF group and PF decreased 13 points and 21 points, respectively. From week 6 to week 14, GHS increased 14 points in the EN-DUR group and 26 points EN-AF group and PF did not change (0 points) in the EN-DUR group and increased 16 points in the EN-AF group. CONCLUSION: The findings from the present pilot study are promising and indicate that a physical rehabilitation program may have a positive impact on HRQoL during treatment and enhance recovery after treatment. A definitive randomized trial is warranted. LEVEL OF EVIDENCE: 1b-Individual randomized controlled trial.

Effects of current parenteral nutrition treatment on health-related quality of life, physical function, nutritional status, survival and adverse events exclusively in patients with advanced cancer: A systematic literature review.

BACKGROUND: The aim was to evaluate the effects of current parenteral nutrition (PN) treatment on clinical outcomes in patients with advanced cancer. METHODS: This review was conducted according to the PRISMA guidelines (PROSPERO ID: 4201707915). RESULTS: Two underpowered randomized controlled trials and six observational studies were retrieved (n = 894 patients). Health-related quality of life and physical function may improve during anti-neoplastic treatment in who PN treatment is the only feeding opportunity, but not necessarily in patients able to feed enterally. Nutritional status may improve in patients regardless of anti-neoplastic treatment and gastrointestinal function. PN treatment was neither superior to fluid in terminal patients nor to dietary counselling in patients able to feed enterally in regards to survival. The total incidence of adverse events was low. CONCLUSION: Current PN treatment in patients with advanced cancer is understudied and the level of evidence is weak.

Patient interpretation of the Patient-Generated Subjective Global Assessment (PG-SGA) Short Form.

BACKGROUND: The Patient-Generated Subjective Global Assessment (PG-SGA) is a patient-reported instrument for assessment of nutrition status in patients with cancer. Despite thorough validation of PG-SGA, little has been reported about the way patients perceive, interpret, and respond to PG-SGA. The aim of this study was to investigate how patients interpret the patient-generated part of the PG-SGA, called PG-SGA Short Form. METHODS: Purposive sampling was used to identify participants that had experienced weight loss and/or reduced dietary intake and/or had a low body mass index. Data were collected from 23 patients by combining observations of patients filling in the PG-SGA Short Form, think-aloud technique and structured interviews, and analyzed qualitatively using systematic text condensation. RESULTS: Most of the participants managed to complete the PG-SGA Short Form without problems. However, participant-related and questionnaire-related sources of misinterpretation were identified, possibly causing misinterpretations or wrong/missing answers. Participants either read too fast and skipped words, or they struggled to find response options that were suitable for covering their entire situation perfectly. The word "normal" was perceived ambiguous, and the word "only" limited the participants' possibility to accurately describe their food intake. Long recall periods in the questions and two-pieced response options made it difficult for patients to select only one option. CONCLUSION: The results of this study provide a unique patient perspective of using the PG-SGA Short Form and valuable input for future use and revisions of the form. The identified sources of misunderstanding could be used to develop a standardized instruction manual for patients and health care personnel using the PG-SGA Short Form.

Endpoints in clinical trials in cancer cachexia: where to start?

PURPOSE OF REVIEW: The lack of agreement and knowledge of optimal endpoints in cachexia trials have impeded progress in finding interventions counteracting the devastating effects cancer cachexia has on morbidity and mortality. An endpoint should both be sensitive enough to detect change and specific enough not to be influenced by other conditions or treatments. RECENT FINDINGS: There is a wealth of potential and applied endpoints in trials investigating cachexia. As of today, there is no generally acknowledged consensus, but assessments of key factors such as body composition should continue to be applied. However, the impact and effect size necessary to achieve clinical benefit using these endpoints are not clear. Further, the use of other endpoints assessing physical function, symptom evaluation and quality of life remains to be elucidated. SUMMARY: It is essential that endpoints are clinically relevant and further research is therefore needed to develop endpoints that are meaningful for patients with cachexia.

Cancer cachexia: rationale for the MENAC (Multimodal-Exercise, Nutrition and Anti-inflammatory medication for Cachexia) trial.

Cancer cachexia is a multifactorial syndrome characterised by an ongoing loss of skeletal muscle mass that cannot be fully reversed by conventional nutritional support alone. Cachexia has a high prevalence in cancer and a major impact on patient physical function, morbidity and mortality. Despite the consequences of cachexia, there is no licensed treatment for cachexia and no accepted standard of care. It has been argued that the multifactorial genesis of cachexia lends itself to therapeutic targeting through a multimodal treatment. Following a successful phase II trial, a phase III randomised controlled trial of a multimodal cachexia intervention is under way. Termed the MENAC trial (Multimodal-Exercise, Nutrition and Anti-inflammatory medication for Cachexia), this intervention is based on evidence to date and consists of non-steroidal anti-inflammatory drugs and eicosapentaenoic acid to reduce inflammation, a physical exercise programme using resistance and aerobic training to increase anabolism, as well as dietary counselling and oral nutritional supplements to promote energy and protein balance. Herein we describe the development of this trial. TRIAL REGISTRATION NUMBER: NCT02330926.

Development of the EORTC QLQ-CAX24, A Questionnaire for Cancer Patients With Cachexia.

CONTEXT: Cachexia is commonly found in cancer patients and has profound consequences; yet there is only one questionnaire that examines the patient's perspective. OBJECTIVE: To report a rigorously developed module for patient self-reported impact of cancer cachexia. METHODS: Module development followed published guidelines. Patients from across the cancer cachexia trajectory were included. In Phase 1, health-related quality of life (HRQOL) issues were generated from a literature review and interviews with patients in four countries. The issues were revised based on patient and health care professional (HCP) input. In Phase 2, questionnaire items were formulated and translated into the languages required for Phase 3, the pilot phase, in which patients from eight countries scored the relevance and importance of each item, and provided qualitative feedback. RESULTS: A total of 39 patients and 12 HCPs took part in Phase 1. The literature review produced 68 HRQOL issues, with 22 new issues arising from the patient interviews. After patient and HCP input, 44 issues were formulated into questionnaire items in Phase 2. One hundred ten patients took part in Phase 3. One item was reworded, and 20 items were deleted as a consequence of patient feedback. CONCLUSIONS: The QLQ-CAX24 is a cancer cachexia-specific questionnaire, comprising 24 items, for HRQOL assessment in clinical trials and practice. It contains five multi-item scales (food aversion, eating and weight-loss worry, eating difficulties, loss of control, and physical decline) and four single items.

Dietary treatment of weight loss in patients with advanced cancer and cachexia: a systematic literature review.

PURPOSE: A systematical literature review evaluating the effect of dietary counseling in treating weight loss and improving energy intake in patients with advanced cancer with different stages of cachexia. PRINCIPAL RESULTS: Five publications were retrieved, of which three were randomized. Two out of five studies showed less weight loss with dietary counseling (+1% weight gain vs. -1.5% weight loss, p=0.03, 1.4kg vs. -2kg, p<0.05), two presented positive effect on energy intake (92% of total caloric need vs. 73%, p<0.01, 1865±317kcal vs. 1556±497kcal, ns). CONCLUSION: Dietary counseling can effect energy intake and body weight, however, apparent heterogeneity between studies is present. Based on these results there is not enough proof of evidence that dietary counseling given to patients with cancer is beneficial for improving weight or energy balance in the different cachexia stages. Nutrition is an essential part of cachexia treatment as it is not considered possible to increase or stabilize weight if nutritional needs are not met.

Plant extracts of spices and coffee synergistically dampen nuclear factor-κB in U937 cells.

A large array of bioactive plant compounds (phytochemicals) has been identified and synergy among these compounds might contribute to the beneficial effects of plant foods. The transcription factor nuclear factor-κB (NF-κB) has been suggested as a target for many phytochemicals. Due to the complexity of mechanisms involved in NF-κB regulation, including numerous feedback loops, and the large number of phytochemicals which regulate NF-κB activity, we hypothesize that synergistic or antagonistic effects are involved. The objectives of our study were to develop a statistical methodology to evaluate the concept of synergy and antagonism and to use this methodology in a monocytic cell line (U937 expressing an NF-κB-luciferase reporter) treated with lipopolysaccharide and phytochemical-rich plant extracts. Both synergistic and antagonistic effects were clearly observed. Observed synergy was most pronounced for the combinations of oregano and coffee, and thyme and oregano. For oregano and coffee the synergistic effect was highest at 5 mg/mL with 13.9% (P < .001), and for thyme and oregano the highest synergistic effects was at 3 mg/mL with 13.7% (P < .001). Dose dependent synergistic and antagonistic effects were observed for all combinations tested. In conclusion, this work presents a methodological tool to define synergy in experimental studies. Our results support the hypothesis that phytochemical-rich plants may exert synergistic and antagonistic effects on NF-κB regulation. Such complex mechanistic interactions between phytochemicals are likely to underlie the protective effects of a plant-based diet on life-style related diseases.

Degree of roasting is the main determinant of the effects of coffee on NF-kappaB and EpRE.

Coffee, one of the most popular beverages worldwide, is a major contributor of phytochemicals in the diet and contributes more than 50% of dietary antioxidants in many countries. A moderate intake of coffee has been linked to reduced risk of chronic diseases. Furthermore, experimental studies demonstrate bioactivity of coffee or coffee compounds in inflammation and oxidative stress, two major, related biological processes. We show that the degree of roasting correlates with the efficiency of dampening inflammation-induced NF-kappaB activity and inducing antioxidant defense through Nrf2/EpRE activity. Extracts of dark-roasted coffee inhibit NF-kappaB activity by more than 80% and induce EpRE activity more than 25-fold in vitro. In transgenic NF-kappaB-luciferase mice, a single dose of dark-roasted coffee extract per os inhibits NF-kappaB activation by 63% in the whole mouse, with the liver being the main target, with a 68% reduction in activity. In transgenic EpRE-luciferase mice, the extract of coffee increased overall EpRE activity by 30%, again with the liver as the main contributor, with a 2.7-fold increase. Our results demonstrate that dark-roasted coffee dampens a crucial mechanism in inflammation and induces a pivotal mechanism in oxidative stress defense.

Extract of oregano, coffee, thyme, clove, and walnuts inhibits NF-kappaB in monocytes and in transgenic reporter mice.

The transcription factor NF-kappaB is a promising target for chemoprevention. Several dietary plants are efficient inhibitors of NF-kappaB activation in vitro and could act synergistically on the NF-kappaB signaling pathway. In this study, we tested whether dietary plant extracts could inhibit NF-kappaB activation in a synergistic manner in vitro. Second, we investigated the potency of the same dietary plant extracts in the inhibition of NF-kappaB activation in vivo. A combined extract of clove, oregano, thyme, walnuts, and coffee synergistically inhibited lipopolysaccaride (LPS)-induced NF-kappaB activation in a monocytic cell line, compared with the sum of effects from the single extracts. Transgenic NF-kappaB luciferase reporter mice were given a single dose of the combined extract and subsequently challenged with LPS. NF-kappaB activation was monitored by in vivo imaging for 6 hours. In addition, NF-kappaB activity in organs and the expression of immune-related genes in liver were investigated. Based on the area under the curve, the extract decreased whole body LPS-induced NF-kappaB activity the first 6 hours by 35% compared with control mice. Organ-specific NF-kappaB activation was inhibited in intestine, liver, testis, and epididymis of the mice receiving the combination extract. In addition, dietary plants reduced the expression of genes related to inflammation, cell migration, and proliferation in liver. This study shows that dietary plants may be potent modulators of NF-kappaB signaling both in vitro and in vivo, and thus support further investigation of consumption of these plant foods as part of a healthy diet or as a mode of chemoprevention.