Patrick Stone

A study to investigate the prevalence, severity and correlates of fatigue among patients with cancer in comparison with a control group of volunteers without cancer

BACKGROUND Determining the prevalence of fatigue among cancer patients is complicated by the high prevalence of fatigue symptoms in the general population. The aim of this study was to determine the prevalence, severity and correlates of fatigue among both cancer patients and control subjects without cancer. PATIENTS AND METHODS A total of 227 cancer patients and 98 control subjects were recruited to the study. They completed a number of questionnaires about fatigue, quality of life and psychological symptoms. The majority of subjects also underwent assessment of voluntary muscle function and nutritional status. Severe fatigue in the patients was defined as a score on the Fatigue Severity Scale in excess of the 95th percentile of the control group. RESULTS The prevalence of severe fatigue was 15% among patients with recently diagnosed breast cancer, 16% among patients with recently diagnosed prostate cancer, 50% among patients with inoperable non small cell lung cancer and 78% among patients receiving specialist inpatient palliative care. In the patients a combination of dyspnoea, psychological distress, pain, and a measure of overall disease burden accounted for 56% of the variance in fatigue scores. CONCLUSIONS Severe fatigue is a common problem among cancer patients, particularly those with advanced disease. Fatigue is significantly associated with the severity of psychological symptoms (anxiety and depression) and with the severity of pain and dyspnoea.

Fatigue in patients with cancer

This paper reviews current knowledge regarding cancer-related fatigue assessment, prevalence, mechanisms and management. Most quality of life questionnaires contain at least some items pertaining to fatigue and a number of more specific self-assessment tools have now also been developed. As a results, there is a growing body of literature which documents the extent and severity of fatigue in cancer populations. Unfortunately most of these studies are uncontrolled and do not, therefore, provide an accurate estimate of the prevalence or severity of cancer fatigue relative to that found in the general population. Data from controlled studies are limited and the results are conflicting. Cross-sectional studies suggest that fatigue is the result of a combination of physical and psychological causes. Although no one treatment is proven to alleviate cancer-related fatigue a number of strategies show therapeutic promise.

Fatigue in advanced cancer: a prospective controlled cross-sectional study.

SummaryUncontrolled studies have reported that fatigue is a common symptom among patients with advanced cancer. It is also a frequent complaint among the general population. Simply asking cancer patients whether or not they feel fatigued does not distinguish between the ‘background’ level of this symptom in the community and any ‘excess’ arising as a result of illness. The aim of this study was to determine the prevalence of fatigue among palliative care inpatients in comparison with a control group of age and sex-matched volunteers without cancer. In addition, the correlates of fatigue were investigated. The prevalence of ‘severe subjective fatigue’ (defined as fatigue greater than that experienced by 95% of the control group) was found to be 75%. Patients were malnourished, had diminished muscle function and were suffering from a number of physical and mental symptoms. The severity of fatigue was unrelated to age, sex, diagnosis, presence or site of metastases, anaemia, dose of opioid or steroid, any of the haematological or biochemical indices (except urea), nutritional status, voluntary muscle function, or mood. A multivariate analysis found that fatigue severity was significantly associated with pain and dypnoea scores in the patients, and with the symptoms of anxiety and depression in the controls. The authors conclude that subjective fatigue is both prevalent and severe among patients with advanced cancer. The causes of this symptom remain obscure. Further work is required in order to determine if the associations reported between fatigue and pain and between fatigue and dyspnoea are causal or coincidental.

A Systematic Review and Meta-Analysis of the Pharmacological Treatment of Cancer-Related Fatigue

BACKGROUND Cancer-related fatigue is an important clinical problem. It is common, distressing, and often difficult to treat. There is a role for drug treatment of cancer-related fatigue, but no consensus has been reached on which drugs are useful. This systematic review and meta-analysis aims to review the available evidence and make recommendations for practice and research. METHODS We searched the Cochrane register of controlled trials (through the second quarter 2007), Medline (January 1, 1966, through August 1, 2007), and EMBASE (January 1, 1980, through August 1, 2007) by use of a predetermined list of search terms. Cochrane Collaboration meta-analysis review methodology was used for this study. The change in fatigue score on the instrument used in each study and other outcomes of interest (adverse events and withdrawal rates) were compared between treatment and control arms by use of the standardized mean difference (SMD) with 95% confidence intervals (CIs). All statistical tests were two-sided. RESULTS We identified 27 eligible trials of drug treatments for cancer-related fatigue (with a total of 6746 participants). The overall effect size for all drug classes was small. A meta-analysis of two studies (n = 264 patients) indicated that methylphenidate (a psychostimulant) was superior to placebo (standardized mean difference [SMD] in change in fatigue score = -0.30, 95% confidence interval [CI] = -0.54 to -0.05; P = .02) for treating cancer-related fatigue. A meta-analysis of 10 studies (n = 2226 patients) evaluating erythropoietin in anemic cancer patients who were undergoing chemotherapy indicated that erythropoietin was superior to placebo (SMD = -0.30, 95% CI = -0.46 to -0.29; P = .008). Among anemic patients (four studies with n = 964 patients), improvement in fatigue was associated with darbepoetin treatment compared with placebo treatment (SMD = -0.13, 95% CI = -0.27 to 0.00; P = .05). Progestational steroids and paroxetine were no better than placebo in the treatment of cancer-related fatigue. CONCLUSIONS There is some evidence that treatment of cancer-related fatigue with methylphenidate appears to be effective. More robust evidence indicates that treatment with hematopoietic agents appears to relieve cancer-related fatigue caused by chemotherapy-induced anemia. Further confirmatory trials are required for both observations.

A systematic review of the scales used for the measurement of cancer-related fatigue (CRF)

BACKGROUND Fatigue in cancer is very common and can be experienced at all stages of disease and in survivors. There is no accepted definition of cancer-related fatigue (CRF) and no agreement on how it should be measured. A number of scales have been developed to quantify the phenomenon of CRF. These vary in the quality of psychometric properties, ease of administration, dimensions of CRF covered and extent of use in studies of cancer patients. This review seeks to identify the available tools for measuring CRF and to make recommendations for ongoing research into CRF. METHODS A systematic review methodology was used to identify scales that have been validated to measure CRF. The inclusion criteria required the scale to have been validated for use in cancer patients and/or widely used in this population. Scales also had to meet a minimum quality score for inclusion. RESULTS The reviewers identified 14 scales that met the inclusion criteria. The most commonly used scales and best validated were the Functional Assessment of Cancer Therapy Fatigue (FACT F), the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ C30) (fatigue subscale) and the Fatigue Questionnaire (FQ). CONCLUSIONS Unidimensional scales are the easiest to administer and have been most widely used. The authors recommend the use of the EORTC QLQ C30 fatigue subscale or the FACT F. The FQ gives a multidimensional assessment and has also been widely used. A substantial minority of the scales identified have not been used extensively or sufficiently validated in cancer patients and cannot be recommended for routine use without further validation.

Fatigue in palliative care patients — an EAPC approach:

Fatigue is one of the most frequent symptoms in palliative care patients, reported in .80% of cancer patients and in up to 99% of patients following radio- or chemotherapy. Fatigue also plays a major role in palliative care for noncancer patients, with large percentages of patients with HIV, multiple sclerosis, chronic obstructive pulmonary disease or heart failure reporting fatigue.This paper presents the position of an expert working group of the European Association for Palliative Care (EAPC), evaluating the available evidence on diagnosis and treatment of fatigue in palliative care patients and providing the basis for future discussions. As the expert group feels that culture and language influence the approach to fatigue in different European countries, a focus was on cultural issues in the assessment and treatment of fatigue in palliative care. As a working definition, fatigue was defined as a subjective feeling of tiredness, weakness or lack of energy. Qualitative differences between fatigue in cancer patients and in healthy controls have been proposed, but these differences seem to be only an expression of the overwhelming intensity of cancer-related fatigue. The pathophysiology of fatigue in palliative care patients is not fully understood. For a systematic approach, primary fatigue, most probably related to high load of proinflammatory cytokines and secondary fatigue from concurrent syndromes and comorbidities may be differentiated. Fatigue is generally recognized as a multidimensional construct, with a physical and cognitive dimension acknowledged by all authors. As fatigue is an inherent word only in the English and French language, but not in other European languages, screening for fatigue should include questions on weakness as a paraphrase for the physical dimension and on tiredness as a paraphrase for the cognitive dimension. Treatment of fatigue should include causal interventions for secondary fatigue and symptomatic treatment with pharmacological and nonpharmacological interventions. Strong evidence has been accumulated that aerobic exercise will reduce fatigue levels in cancer survivors and patients receiving cancer treatment. In the final stage of life, fatigue may provide protection and shielding from suffering for the patient and thus treatment may be detrimental. Identification of the time point, where treatment of fatigue is no longer indicated is important to alleviate distress at the end of life. Palliative Medicine 2008; 22: 13—22.

A comparison of the use of sedatives in a hospital support team and in a hospice

This study examines how frequently and for what indications sedatives are prescribed in a hospital support team and in a hospice. We also looked at the survival of sedated patients from the date of admission and from the start of sedation. Overall 26% of patients were prescribed sedatives in order to sedate them (31 % at the hospice and 21 % at the hospital) and 43% of patients were given sedatives for symptom control (67% at the hospice and 21 % at the hospital). Sedated patients survived for a mean of 1.3 days after the start of sedation, and there was no detectable difference in survival from the date of admission between sedated and nonsedated patients.

Cancer-related fatigue

Fatigue is a common symptom in patients with cancer and in disease-free survivors. It has a significant impact on the quality of life. Although subjective fatigue is often related to objective changes in physical functioning or impaired performance status, the two phenomena are not synonymous and need to be distinguished. A number of robust and reliable assessment instruments to measure fatigue severity are now available and criteria for cancer-related fatigue syndrome have been proposed. The underlying mechanisms and pathophysiology of cancer-related fatigue are unclear. Management strategies include the use of psycho-educational interventions, exercise programmes and pharmacological treatments. The best evidence for the effectiveness of drug treatments is for the haematopoietic agents in anaemic patients undergoing chemotherapy and for methylphenidate in an on-treatment population.

Cancer cachexia: A systematic literature review of items and domains associated with involuntary weight loss in cancer

BACKGROUND The concept of cancer-related anorexia/cachexia is evolving as its mechanisms are better understood. To support consensus processes towards an updated definition and classification system, we systematically reviewed the literature for items and domains associated with involuntary weight loss in cancer. METHODS Two search strings (cachexia, cancer) explored five databases from 1976 to 2007. Citations, abstracts and papers were included if they were original work, in English/German language, and explored an item to distinguish advanced cancer patients with variable degrees of involuntary weight loss. The items were grouped into the 5 domains proposed by formal expert meetings. RESULTS Of 14,344 citations, 1275 abstracts and 585 papers reviewed, 71 papers were included (6325 patients; 40-50% gastrointestinal, 10-20% lung cancer). No single domain or item could consistently distinguish cancer patients with or without weight loss or having various degrees of weight loss. Anorexia and decreased nutritional intake were unexpectedly weakly related with weight loss. Explanations for this could be the imprecise measurement methods for nutritional intake, symptom interactions, and the importance of systemic inflammation as a catabolic drive. Data on muscle mass and strength is scarce and the impact of cachexia on physical and psychosocial function has not been widely assessed. CONCLUSIONS Current data support a modular concept of cancer cachexia with a variable combination of reduced nutritional intake and catabolic/hyper-metabolic changes. The heterogeneity in the literature revealed by this review underlines the importance of an agreed definition and classification of cancer cachexia.

A comparison of the characteristics of disease-free breast cancer survivors with or without cancer-related fatigue syndrome.

Purpose To determine the prevalence of cancer-related fatigue syndrome (CRFS) in a population of disease-free breast cancer survivors and to investigate the relationship between CRFS and clinical variables. Patients and methods Women (200) were recruited. All participants were between 3 months and 2 years after completion of primary therapy for breast cancer and were disease free. Subjects completed a diagnostic interview for CRFS and structured psychiatric interview. Participants also completed quality of life, mood and fatigue questionnaires, and provided a blood sample for haematological and biochemical analysis and a 24-h urine specimen for cortisol estimation. Subjects wore a wrist actigraph for 7 days to measure activity and sleep. Results Sixty women (30% of participants) were found to fulfil the criteria for CRFS. There were statistically significant differences between fatigued and non-fatigued women with respect to fatigue severity (p < 0.01), mood (p < 0.01) and quality of life scores (p < 0.05). There were significant differences in blood variables including raised total white cell count and lower sodium (all p < 0.02). There was no difference in the 24 h urinary free cortisol levels. Actigraphic data demonstrated significant differences in sleep quality and disturbance, but not in overall levels of daytime activity or circadian rhythm. Conclusion CRFS affects 30% of women after breast cancer treatment and has significant effects on quality of life and mood. There is some evidence that CRFS is related to sleep disturbance or to a persistent inflammatory or immune response.