Spiritual quality of life in family carers of patients with advanced cancer-a cross-sectional study.

PURPOSE: Caring affects carers' psychological and physical health, mortality, and quality of life (QoL) negatively. Lower spiritual QoL is associated with anxiety and depression, but the spiritual dimension is rarely investigated in carers. The present study aimed to explore which patient- and carer-related characteristics were associated with spiritual QoL in carers of patients with advanced cancer. METHODS: Secondary analyses were conducted using data from a prospective study investigating integration between oncology and palliative care. Adult patients with advanced cancer and their carers were included, and baseline data considering demographics, clinical characteristics, symptoms, social support, and religious meaning-making were registered. Spiritual QoL was measured using the Functional Assessment of Chronic Illness Therapy - Spiritual well-being (FACIT-Sp-12) questionnaire. Associations to spiritual QoL were explored by bivariate and multivariate regression models. RESULTS: In total, 84 carers were included, median age was 62.5 years, 52 (62%) were female, and the average spiritual QoL score was 23.3. In bivariate analyses, higher education, social support, and lower patients' symptom burden were significantly associated with higher spiritual QoL. The multivariate regression model (n=77) had an explained variance (R2) = 0.34 and showed a significant association for social support, higher education, having children < 18 years living at home, and patient's age. CONCLUSION: The study indicates that spiritual QoL in carers were low and were negatively affected by several factors related to both carers and patients. However, there could be other important factors not yet described. Health care professionals should be aware of the known associated factors, as carers who hold these may need extra support.

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.

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.

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.

Nutritional experiences in head and neck cancer patients.

OBJECTIVE: Extensive research has documented the negative nutritional impact of head neck cancer (HNC) treatment, but few studies have addressed the patients' experiences. The purpose of this study was to describe how patients with HNC experience the nutritional situation and perceive nutritional support from diagnosis to the post-treatment phase. METHODS: Patients with HNC were recruited from a randomised pilot study. Individual interviews were conducted after radiotherapy with 10 participants aged 49 - 70 years and analysed by qualitative content analysis. RESULTS: Undergoing surgery was experienced as a poor nutritional starting point for the upcoming radiotherapy. During radiotherapy, increasing side effects made the participants customise their meals to improve food intake. About halfway through radiotherapy, virtually no food intake was experienced and hospital admissions and initiations of tube-feeding occurred in this period. Oral nutritional supplements were recommended for all, but eventually became unbearable to ingest. When radiotherapy was finally completed, the participants felt discouraged about the persistent side effects preventing them from resume eating. The participants missed tailored information about development of side effects and involvement of a dietitian when reflecting on the treatment-period. CONCLUSION: The comprehensive nutritional problems experienced by patients with HNC require early nutritional assessments and improved individually tailored nutritional support.

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.

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.

Disulfiram repurposing combined with nutritional copper supplement as add-on to chemotherapy in recurrent glioblastoma (DIRECT): Study protocol for a randomized controlled trial.

Background: Disulfiram (DSF) is a well-tolerated, inexpensive, generic drug that has been in use to treat alcoholism since the 1950s. There is now independent preclinical data that supports DSF as an anticancer agent, and experimental data suggest that copper may increase its anti-neoplastic properties. There is also some clinical evidence that DSF is a promising anticancer agent in extracranial cancers. In glioblastoma, DSF induced O 6-methylguanine methyltransferase (MGMT) inhibition may increase response to alkylating chemotherapy. A recent phase I study demonstrated the safety of DSF in glioblastoma patients when DSF was administered at doses below 500 mg/day together with chemotherapy. We plan to assess the effects of DSF combined with nutritional copper supplement (DSF-Cu) as an adjuvant to alkylating chemotherapy in glioblastoma treatment. Methods: In an academic, industry independent, multicenter, open label randomized controlled phase II/III trial with parallel group design (1:1) we will assess the efficacy and safety of DSF-Cu in glioblastoma treatment. The study will include 142 patients at the time of first recurrence of glioblastoma where salvage therapy with alkylating chemotherapy is planned. Patients will be randomized to treatment with or without DSF-Cu. Primary end-point is survival at 6 months. Secondary end-points are overall survival, progression free survival, quality of life, contrast enhancing tumor volume and safety. Discussion: There is a need to improve the treatment of recurrent glioblastoma. Results from this randomized controlled trial with DSF-Cu in glioblastoma will serve as preliminary evidence of the future role of DSF-Cu in glioblastoma treatment and a basis for design and power estimations of future studies. In this publication we provide rationale for our choices and discuss methodological issues. Trial registration: The study underwent registration in EudraCT 2016-000167-16 (Date: 30.03.2016,) and Clinicaltrials.gov NCT02678975 (Date: 31.01.2016) before initiating the study.

Feasibility and preliminary effects of resistance training and nutritional supplements during versus after radiotherapy in patients with head and neck cancer: A pilot randomized trial.

BACKGROUND: Patients with head and neck cancer (HNC) experience involuntary weight loss that has a negative impact on physical function, morbidity, and survival. The objective of the current study was to evaluate the feasibility of an exercise and nutrition intervention during radiotherapy (RT) compared with after RT, and to examine preliminary effects on skeletal muscle mass. METHODS: Patients with HNC were randomized to an exercise and nutrition intervention during RT (EN-DUR) or after RT (EN-AF). The EN-DUR intervention was conducted at a hospital and the EN-AF intervention took place at a rehabilitation center. The interventions consisted of progressive resistance training (PRT) and oral nutritional supplements (ONS). Feasibility outcomes were tracked weekly and muscle mass was measured by computed tomography scans before and after RT and at 2 months follow-up. RESULTS: Of the 50 eligible patients, 41 (82%) agreed to participate. 90% of patients completed the EN-DUR intervention and the adherence to PRT and ONS was 81% and 57%, respectively. 52% of patients attended the EN-AF intervention and adherence to PRT and ONS was 94% and 76%, respectively. The EN-DUR demonstrated a trend toward mitigating loss of muscle mass during RT and the EN-AF demonstrated a similar trend after RT. No difference in muscle mass was detected between the groups from baseline to week 14. CONCLUSIONS: An exercise and nutrition intervention is feasible for patients with HNC during RT, and the intervention is potentially effective in mitigating loss of muscle mass both during and after RT. Future trials should assess the feasibility and effects of extended interventions during and after treatment. Cancer 2017;123:4440-8. © 2017 American Cancer Society.

A randomized phase II feasibility trial of a multimodal intervention for the management of cachexia in lung and pancreatic cancer.

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.

Multimodal nutrition/anabolic therapy for wasting conditions.

PURPOSE OF REVIEW: Significant progress has been made in the field of defining and describing the pathophysiology of wasting conditions such as cachexia. The number of new promising drugs, nutritional therapy alternatives, and exercise/rehabilitation programs is increasing. The purpose of this review is to give an overview of recent clinical findings from intervention studies investigating multimodal anabolic therapies utilizing drug, nutritional, and/or exercise interventions in order to counteract wasting. RECENT FINDINGS: Anabolic agents such as ghrelin and selective androgen receptor modulators are under late-phase clinical testing and hold promise as new therapies, and their ability to mitigate weight loss and improve muscle mass and physical function is evaluated. In the past 2 years, eight new studies investigating interventions with anabolic potential in wasting have been published, among which three of these studies were multimodal. SUMMARY: Targeted anabolic therapies aiming to prevent or reverse wasting might involve a combination of anabolic pharmacologic drugs, nutrition, and physical exercise working concurrently to enhance muscle protein synthesis and reduce breakdown. Some anabolic pharmacological interventions demonstrate the potential to improve muscle mass, but the multimodal interventions seem in greater extent to also demonstrate improvement in physical function.

Evidence base for multimodal therapy in cachexia.

PURPOSE OF REVIEW: The lack of success of unimodal treatment studies in cachexia and the growing awareness that multiple components are responsible for the development of cachexia have led to the view that cachexia intervention should include multimodal treatment. The aim of this article is to examine the evidence for multimodal treatment in the management of cancer cachexia. RECENT FINDINGS: There are some studies involving multimodal treatment that indicate significant effects on cachexia outcomes. There are, however, no randomized controlled trials to date that incorporate fully a structured exercise program, nutrition, good symptom treatment as well as drug treatment, to counteract the effects of altered metabolism. SUMMARY: The effectiveness of any drug intervention for cancer cachexia probably will only be maximized if incorporated into multimodal treatment. Further, cachexia treatment trials should also aim to include patients at an early phase in their cachexia trajectory and use validated outcome measures.