Parenteral Nutrition in Palliative Cancer Care: Detrimental, Futile, or Beneficial?

Palliative cancer care patients may live for a long time, but malnutrition worsens the prognosis. Parenteral nutrition (PN) is suitable for replenishing a calorie deficit, but its advantages and tolerance late in the cancer trajectory are debated. We examined symptom development in hospitalized patients with and without PN. A total of 21 palliative cancer care patients receiving PN and 155 palliative cancer care patients not receiving PN during hospitalization in a specialized unit were retrospectively compared. We studied symptom intensity at admission, symptom relief during the hospital stay, and survival. The patients had locally advanced or metastatic cancer, a mean age of 70 years, and their median ECOG performance status was III. Symptom burden at admission was similar in the compared groups. Symptom relief during hospitalization was also similar. However, patients already on PN at admission reported more nausea and patients receiving PN during hospitalization reported better nausea relief compared to patients not receiving this intervention. Overall median survival was less than two months and similar in the compared groups. Based on a limited number of observations and a suboptimal study design, we were not able to demonstrate an increased symptom burden for palliative cancer care patients receiving PN late in the disease 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.

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.

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.

Physical function endpoints in cancer cachexia clinical trials: Systematic Review 1 of the cachexia endpoints series.

In cancer cachexia trials, measures of physical function are commonly used as endpoints. For drug trials to obtain regulatory approval, efficacy in physical function endpoints may be needed alongside other measures. However, it is not clear which physical function endpoints should be used. The aim of this systematic review was to assess the frequency and diversity of physical function endpoints in cancer cachexia trials. Following a comprehensive electronic literature search of MEDLINE, Embase and Cochrane (1990-2021), records were retrieved. Eligible trials met the following criteria: adults (≥18 years), controlled design, more than 40 participants, use of a cachexia intervention for more than 14 days and use of a physical function endpoint. Physical function measures were classified as an objective measure (hand grip strength [HGS], stair climb power [SCP], timed up and go [TUG] test, 6-min walking test [6MWT] and short physical performance battery [SPPB]), clinician assessment of function (Karnofsky Performance Status [KPS] or Eastern Cooperative Oncology Group-Performance Status [ECOG-PS]) or patient-reported outcomes (physical function subscale of the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaires [EORTC QLQ-C30 or C15]). Data extraction was performed using Covidence and followed PRISMA guidance (PROSPERO registration: CRD42022276710). A total of 5975 potential studies were examined and 71 were eligible. Pharmacological interventions were assessed in 38 trials (54%). Of these, 11 (29%, n = 1184) examined megestrol and 5 (13%, n = 1928) examined anamorelin; nutritional interventions were assessed in 21 trials (30%); and exercise-based interventions were assessed in 6 trials (8%). The remaining six trials (8%) assessed multimodal interventions. Among the objective measures of physical function (assessed as primary or secondary endpoints), HGS was most commonly examined (33 trials, n = 5081) and demonstrated a statistically significant finding in 12 (36%) trials (n = 2091). The 6MWT was assessed in 12 trials (n = 1074) and was statistically significant in 4 (33%) trials (n = 403), whereas SCP, TUG and SPPB were each assessed in 3 trials. KPS was more commonly assessed than the newer ECOG-PS (16 vs. 9 trials), and patient-reported EORTC QLQ-C30 physical function was reported in 25 trials. HGS is the most commonly used physical function endpoint in cancer cachexia clinical trials. However, heterogeneity in study design, populations, intervention and endpoint selection make it difficult to comment on the optimal endpoint and how to measure this. We offer several recommendations/considerations to improve the design of future clinical trials in cancer cachexia.

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.

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.

Linguistic and content validation of the translated and culturally adapted PG-SGA, as perceived by Norwegian cancer patients and healthcare professionals.

BACKGROUND & AIMS: The Scored Patient-Generated Subjective Global Assessment (PG-SGA©) is a validated nutritional screening, assessment, monitoring, and triage tool. When translated to other languages, the questions and answering items need to be conceptually, semantically, and operationally equivalent to the original tool. In this study, we aimed to assess linguistic and content validity of the PG-SGA translated and culturally adapted for the Norwegian setting, as perceived by Norwegian cancer patients and healthcare professionals (HCPs). METHODS: We have translated and culturally adapted the original PG-SGA for the Norwegian setting, in concordance with the International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Cancer patients and HCPs, including nurses, dietitians and physicians, were invited to participate. Comprehensibility and difficulty were assessed by patients for the patient component (PG-SGA Short Form), and by HCPs for the professional component. Content validity was assessed for the full PG-SGA by HCPs only. The data were collected by a questionnaire and evaluations were operationalized by a 4-point scale. Item and scale indices were calculated for comprehensibility (Item CI, Scale CI), difficulty (Item DI, Scale DI) and content validity (Item CVI, Scale CVI). RESULTS: Fifty-one cancer patients and 92 HCPs participated in the study. The patients perceived comprehensibility and difficulty of the Norwegian PG-SGA Short Form as excellent (Scale CI = 0.99 and DI = 0.97). However, HCPs perceived comprehensibility and difficulty of the professional component as below acceptable (Scale CI = 0.78 and DI = 0.66), and the physical exam was being rated as the most difficult part (Item DI 0.26 to 0.65). Content validity for the full Norwegian PG-SGA was considered excellent (Scale CVI = 0.99) by the HCPs. CONCLUSION: The patient component of PG-SGA was considered clear and easy to complete, and the full Norwegian PG-SGA was considered as relevant by HCPs. In the final Norwegian PG-SGA, changes have been made to improve comprehensibility of the professional component. To improve perceived difficulty of completing the professional component, training of professionals is indicated.

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.

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.

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.

Pain management index (PMI)-does it reflect cancer patients' wish for focus on pain?

BACKGROUND: The pain management index (PMI) was developed to combine information about the prescribed analgesics and the self-reported pain intensity in order to assess physicians' response to patients' pain. However, PMI has been used to explore undertreatment of cancer pain. The present study explores prevalence of negative PMI and its associations to clinical variables, including the patient-perceived wish for more attention to pain. METHODS: A single-center, cross-sectional, observational study of cancer patients was conducted. Data on demographics and clinical variables, as well as patient-perceived wish for more attention to pain, were registered. PMI was calculated. Negative PMI indicates that the analgesics prescribed might not be appropriate to the pain intensity reported by the patient, and associations to negative PMI were explored by logistic regression models. RESULTS: One hundred eighty-seven patients were included, 53% had a negative PMI score. Negative PMI scores were more frequent among patients with breast cancer (OR 4.2, 95% CI 1.3, 13.5), in a follow-up setting (OR 12.1, 95% CI 1.4, 101.4), and were inversely associated to low performance status (OR 0.14, 95% CI 0.03, 0.65). Twenty-two percent of patients with negative PMI scores reported that they wanted more focus on pain management, versus 13% among patients with a non-negative PMI score; the difference was not statistically significant. CONCLUSION: A high prevalence of negative PMI was observed, but only 1/5 of patients with a negative PMI wanted more attention to pain by their physician. Our findings challenge the use of PMI as a measure of undertreatment of cancer pain.

Deterioration in Muscle Mass and Physical Function Differs According to Weight Loss History in Cancer Cachexia.

BACKGROUND: Muscle mass and physical function (PF) are common co-primary endpoints in cancer cachexia trials, but there is a lack of data on how these outcomes interact over time. The aim of this secondary analysis of data from a trial investigating multimodal intervention for cancer cachexia (ClinicalTrials.gov: NCT01419145) is to explore whether changes in muscle mass and PF are associated with weight loss and cachexia status at baseline. METHODS: Secondary analysis was conducted using data from a phase II randomized controlled trial including 46 patients with stage III-IV non-small cell lung cancer (n = 26) or inoperable pancreatic cancer (n = 20) due to commence chemotherapy. Cachexia status at baseline was classified according to international consensus. Muscle mass (assessed using computed tomography (CT)) and PF outcomes, i.e., Karnofsky performance status (KPS), self-reported PF (self-PF), handgrip strength (HGS), 6-minute walk test (6MWT), and physical activity (PA), were measured at baseline and after six weeks. RESULTS: When compared according to cachexia status at baseline, patients with no/pre-cachexia had a mean loss of muscle mass (-5.3 cm2, p = 0.020) but no statistically significant change in PF outcomes. Patients with cachexia also lost muscle mass but to a lesser extent (-2.8 cm2, p = 0.146), but demonstrated a statistically significant decline in PF; KPS (-3.8 points, p = 0.030), self-PF (-8.8 points, p = 0.027), and HGS (-2.7 kg, p = 0.026). CONCLUSIONS: Weight loss history and cachexia status at baseline are of importance if one aims to detect changes in PF outcomes in cancer cachexia trials. To improve the use of co-primary endpoints that include PF in future trials, outcomes that have the potential to detect change relative to weight loss should be investigated further.

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.

Combining optimal nutrition and exercise in a multimodal approach for patients with active cancer and risk for losing weight: Rationale and practical approach.

Weight loss and functional decline is a common and detrimental consequence of cancer. The interventions that are offered to patients with weight loss and functional decline often seem haphazard and varying from center to center. The lack of stringent management is probably based both on lack of knowledge of existing treatment guidelines and the current weak level of evidence of clinical effects of different nutritional and exercise interventions. Some studies evaluated multimodal interventions with various treatment combinations, including nutrition and exercise, that report clinically significant effects on cachexia outcomes. As of today, however, there is a paucity of large randomized controlled trials that incorporate both a fully structured exercise program and a well-described nutritional intervention. Studies investigating combinations of several interventions in patients with active cancer and risk for losing weight are too few and too heterogeneous to enable firm conclusions about effect, optimal dose, or timing of interventions. However, data presented in this review suggest an overall benefit, especially if interventions are started before weight loss and loss of function become too severe. Thus, the aim of this review was to examine the evidence for combined treatments targeting weight loss in cancer patients.

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.

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.

A cross-sectional study examining the prevalence of cachexia and areas of unmet need in patients with cancer.

PURPOSE: The semantics of defining cancer cachexia over the last decade has resulted in uncertainty as to the prevalence. This has further hindered the recognition and subsequent treatment of this condition. Following the consensus definition for cancer cachexia in 2011, there is now a need to establish estimates of prevalence. Therefore, the primary aim of the present study was to assess the prevalence of cachexia in an unselected cancer population. A secondary aim was to assess patient-perceived need of attention to cachexia. METHODS: A cross-sectional study in hospital patients was undertaken. Key inclusion criteria were the following: age > 18 years, cancer diagnosis, and no surgery the preceding 24 h. Data on demographics, disease, performance status, symptoms, cachexia, and patients' perceived need of attention to weight loss and nutrition were registered. RESULTS: Data were available on 386 of 426 eligible patients. Median age (IQR) was 65 years (56-72), 214 (55%) were male and 302 (78%) had a performance status of 0-1 (Eastern Cooperative Oncology Group). Prevalence of cachexia (inpatients/outpatients) was 51/22%. Prevalence was highest in patients with gastrointestinal cancer (62/42%) and lung cancer (83/36%). There was no major difference in prevalence between patients with metastatic (55/24%) and localized disease (47/19%). Twenty percent of inpatients and 15% of outpatients wanted more attention to weight loss and nutrition. Cachexia (p < 0.001), symptoms of mood disorder (p < 0.001), and male gender (p < 0.01) were independently associated with increased need of attention. CONCLUSION: Cachexia is a prevalent condition, affecting both patients with localized and metastatic cancer. Clinical attention to the condition is a sizeable unmet need.