Background
Cancer cachexia is a syndrome of weight loss (including muscle and fat), anorexia, and decreased physical function. It has been suggested that the optimal treatment for cachexia should be ...a multimodal intervention. The primary aim of this study was to examine the feasibility and safety of a multimodal intervention (n‐3 polyunsaturated fatty acid nutritional supplements, exercise, and anti‐inflammatory medication: celecoxib) for cancer cachexia in patients with incurable lung or pancreatic cancer, undergoing chemotherapy.
Methods
Patients receiving two cycles of standard chemotherapy were randomized to either the multimodal cachexia intervention or standard care. Primary outcome measures were feasibility assessed by recruitment, attrition, and compliance with intervention (>50% of components in >50% of patients). Key secondary outcomes were change in weight, muscle mass, physical activity, safety, and survival.
Results
Three hundred and ninety‐nine were screened resulting in 46 patients recruited (11.5%). Twenty five patients were randomized to the treatment and 21 as controls. Forty‐one completed the study (attrition rate 11%). Compliance to the individual components of the intervention was 76% for celecoxib, 60% for exercise, and 48% for nutritional supplements. As expected from the sample size, there was no statistically significant effect on physical activity or muscle mass. There were no intervention‐related Serious Adverse Events and survival was similar between the groups.
Conclusions
A multimodal cachexia intervention is feasible and safe in patients with incurable lung or pancreatic cancer; however, compliance to nutritional supplements was suboptimal. A phase III study is now underway to assess fully the effect of the intervention.
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.
NCT02330926.
Abstract
Background. Sarcopenia is a defining feature of cancer cachexia associated with physical decline, poor quality of life and poor prognosis. Thus, maintaining muscle mass is an important aim ...of cachexia treatment. Many patients at risk for developing cachexia or with cachexia experience side effects of chemotherapy that might aggravate the development of cachexia. However, achieving tumor control might reverse the catabolic processes causing cachexia. There is limited knowledge about muscle mass changes during chemotherapy or whether changes in muscle mass are associated with response to chemotherapy.
Patients and methods. In this pilot study, patients with advanced non-small cell lung cancer (NSCLC) receiving three courses of palliative chemotherapy were analyzed. Muscle mass was measured as skeletal muscle cross sectional area (SMCA) at the level of the third lumbar vertebrae using CT images taken before and after chemotherapy.
Results. In total 35 patients, 48% women, mean age 67 years (range 56-86), participated; 83% had stage IV disease and 71% were sarcopenic at baseline. Mean reduction in SMCA from pre- to post-chemotherapy was 4.6 cm2 (CI 95% −7.3-−1.9; p < 0.002), corresponding to a 1.4 kg loss of whole body muscle mass. Sixteen patients remained stable or gained SMCA. Of these, 14 (56%) responded to chemotherapy, while two progressed (p = 0.071). Maintaining or gaining SMCA resulted in longer median overall survival (loss: 5.8 months, stable/gain: 10.7 months; p = 0.073). Stage of disease (p = 0.003), treatment regimen (p = 0.023), response to chemotherapy (p = 0.007) and SMCA change (p = 0.040), but not sarcopenia at baseline, were significant prognostic factors in the multivariate survival analyses.
Conclusion. Almost half of the patients had stable or increased muscle mass during chemotherapy without receiving any cachexia treatment. Nearly all of these patients responded to the chemotherapy. Increase in muscle mass, but not sarcopenia at baseline, was a significant prognostic factor.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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),
< 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),
= 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),
< 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.
Abstract
Background. How to assess cachexia is a barrier both in research and in clinical practice. This study examines the need for assessing both reduced food intake and loss of appetite, to see if ...these variables can be used interchangeably. A secondary aim is to assess the variance explained by food intake, appetite and weight loss by using tumor-related factors, symptoms and biological markers as explanatory variables. Material and methods. One thousand and seventy patients with incurable cancer were registered in an observational, cross sectional multicenter study. A total of 885 patients that had complete data on food intake (PG-SGA), appetite (EORTC QLQ-C30) and weight loss were included in the present analysis. The association between reduced food intake and appetite loss was assessed using Spearman's correlation. To find the explained variance of the three symptoms a multivariate analysis was performed. Results. The mean age was 62 years with a mean survival of 247 days and a mean Karnofsky performance status of 72. Thirteen percent of the patients who reported eating less than normal had good appetite and 25% who had unchanged or increased food intake had reduced appetite. Correlation between appetite loss and food intake was 0.50. Explained variance for the regression models was 44% for appetite loss, 27% for food intake and only 13% for weight loss. Conclusion. Both appetite loss and food intake should be assessed in cachectic patients since conscious control of eating may sometimes overcome appetite loss. The low explained variance for weight loss is probably caused by the need for more knowledge about metabolism and inflammation, and is consistent with the cancer cachexia definition that claims that in cachexia weight loss is not caused by reduced food intake alone. The questions concerning appetite loss from EORTC-QLQ C30 and food intake from PG-SGA seem practical and informative when dealing with advanced cancer patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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.
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 (
-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.
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,
< 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,
< 0.05 for all), and moderate for serum C-reactive protein (ES = 0.53,
= 0.12). Analysis within the multimodal treatment group showed high sensitivity to change for adiponectin (ES = 0.86,
= 0.001) and n-3 PUFAs (ES > 0.8,
< 0.05 for all) and moderate for 25-OH vitamin D (ES = 0.49,
= 0.03). In the control group, a moderate sensitivity to change for body weight (ES = -0.84,
= 0.002) and muscle mass (ES = -0.67,
= 0.016) and a high sensitivity to change for plasma levels of 25-OH vitamin D (ES = -0.88,
= 0.002) were found.
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.
ClinicalTrials.gov identifier: NCT01419145.
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.
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.
When compared according to cachexia status at baseline, patients with no/pre-cachexia had a mean loss of muscle mass (-5.3 cm
,
= 0.020) but no statistically significant change in PF outcomes. Patients with cachexia also lost muscle mass but to a lesser extent (-2.8 cm
,
= 0.146), but demonstrated a statistically significant decline in PF; KPS (-3.8 points,
= 0.030), self-PF (-8.8 points,
= 0.027), and HGS (-2.7 kg,
= 0.026).
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.
Background
Many cancer survivors experience late effects of cancer treatment and therefore struggle to return to work. Norway provides rehabilitation programs to increase labor force participation ...for cancer survivors after treatment. However, the extent to which such programs affect labor force participation has not been appropriately assessed. This study aims to investigate i) labor force participation, sick leave and disability rates among cancer survivors up to 10 years after being diagnosed with cancer and identify comorbidities contributing to long-term sick leave or disability pensioning; ii) how type of cancer, treatment modalities, employment sectors and financial- and sociodemographic factors may influence labor force participation; iii) how participation in rehabilitation programs among cancer survivor affect the longterm labor force participation, the number of rehospitalizations and incidence of comorbidities.
Design and methods
Information from four medical, welfare and occupational registries in Norway will be linked to information from 163,279 cancer cases (15.68 years old) registered in the Norwegian Cancer Registry from 2004 to 2016. The registries provide detailed information on disease characteristics, comorbidities, medical and surgical treatments, occupation, national insurance benefits and demographics over a 10-year period following a diagnosis of cancer.
Expected impact of the study for Public Health
The study will provide important information on how treatment, rehabilitation and sociodemographic factors influence labor force participation among cancer survivors. Greater understanding of work-related risk factors and the influence of rehabilitation on work-participation may encourage informed decisions among cancer patients, healthcare and work professionals and service planners.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Background:
Disability related to incurable cancer affects over a million Europeans each year and people with cancer rank loss of function among the most common unmet supportive care needs.
...Objectives:
To test the clinical and cost-effectiveness of an integrated short-term palliative rehabilitation intervention, to optimise function and quality of life in people affected by incurable cancer.
Design:
This is a multinational, parallel group, randomised, controlled, assessor blind, superiority trial.
Methods:
The INSPIRE consortium brings together leaders in palliative care, oncology and rehabilitation from partner organisations across Europe, with complementary expertise in health service research, trials of complex interventions, mixed-method evaluations, statistics and economics. Partnership with leading European civil society organisations ensures citizen engagement and dissemination at the highest level. We will conduct a multinational randomised controlled trial across five European countries, recruiting participants to assess the effectiveness of palliative rehabilitation for people with incurable cancer on the primary outcome – quality of life – and secondary outcomes including disability, symptom burden and goal attainment. To support trial conduct and enhance analysis of trial data, we will also conduct: comparative analysis of current integration of rehabilitation across oncology and palliative care services; mixed-method evaluations of equity and inclusivity, processes and implementation for the intervention, at patient, health service and health system levels. Finally, we will conduct an evidence synthesis, incorporating INSPIRE findings, and a Delphi consensus to develop an international framework for palliative rehabilitation practice and policy, incorporating indicators, core interventions, outcomes and integration methods.
Scientific contribution:
If positive, the trial could produce a scalable and equitable intervention to improve function and quality of life in people with incurable cancer and reduce the burden of care for their families. It could also upskill the practitioners involved and motivate future research questions. The intervention could be adapted and integrated into different health systems using existing staff and services, with little or no additional cost.
Summary Background & aims Objective assessment of daily physical activity (PA) by body-worn accelerometers offers potential as a novel endpoint in the clinical management of advanced cancer patients. ...This study aimed to assess criterion-based validity of an accelerometer-based activity monitoring system (AM-system), ActivPAL™, using two different methods. Methods Advanced cancer in patients and outpatients (Karnofsky Performance Status (KPS) 40–100). ActivPAL™ measurements were validated against (i) observations and (ii) energy expenditure (EE) measured by 2-week doubly-labelled water (DLW) protocol. Results Absolute errors for mean time spent in different body positions (<0.1%) and number of transfers (0%) were low. Step count error was significantly higher in patients with KPS 40–60 (non-self caring) compared to KPS 70–100 (self-caring) (33 vs. 24%, p = 0.006). Post-hoc mathematical analysis demonstrated that absolute errors for the mean energy expenditure of activity (EEA) (1.4%) and mean total EE (0.4%) were low, but agreement was also low. Conclusions AM-systems provide valid estimates of body positions and transfers, but not step count, especially in non-self caring patients. ActivPAL™ can derive estimates of EE but there is considerable variability in results, which is consistent, in part, with the inaccuracy in step count. Further studies are required to assess the validity of different endpoints derived from AM-systems in advanced cancer patients.
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