Prevalence and risk factors of cancer-related fatigue in childhood cancer survivors: A DCCSS LATER study.

BACKGROUND: Cancer-related fatigue is a debilitating late effect after treatment for childhood cancer. The prevalence of fatigue in childhood cancer survivors (CCSs) and associated factors for fatigue has varied widely in previous studies. Two important aspects of cancer-related fatigue, its severity and chronicity, are often not assessed. This study investigated the prevalence of, and risk factors for, severe chronic fatigue (CF) in a national cohort of Dutch CCSs. METHODS: In this study, 2810 CCSs (5-year survivors of all childhood malignancies diagnosed between 1963 and 2001 with a current age of 12-65 years) and 1040 sibling controls were included. CF was assessed with the Short Fatigue Questionnaire and was defined as a score ≥ 18 and persistence of fatigue for ≥6 months. Cancer- and treatment-related characteristics, current health problems, and demographic and lifestyle variables were assessed as potential risk factors for CF via multivariable logistic regression analyses. RESULTS: In adult CCSs and sibling controls (≥18 years old), the prevalence of CF was 26.1% and 14.1%, respectively (P < .001). In adolescent CCSs and sibling controls (<18 years old), the prevalence of CF was 10.9% and 3.2%, respectively. Female gender (odds ratio [OR], 2.13; 95% confidence interval [CI], 1.73-2.62), unemployment (OR, 2.18; 95% CI, 1.67-2.85), having 1 or more health problems (OR for 1-2, 1.48; 95% CI, 1.18-1.87; OR for >2, 2.20; 95% CI, 1.50-3.21), and a central nervous system diagnosis (OR, 1.74; 95% CI, 1.17-2.60) were significantly associated with CF in adult CCSs. CONCLUSIONS: This study shows that CCSs, regardless of their cancer diagnosis, report CF more often than sibling controls. This study provides new evidence for the prevalence of fatigue in CCSs.

Methodology of the DCCSS later fatigue study: a model to investigate chronic fatigue in long-term survivors of childhood cancer.

BACKGROUND: A debilitating late effect for childhood cancer survivors (CCS) is cancer-related fatigue (CRF). Little is known about the prevalence and risk factors of fatigue in this population. Here we describe the methodology of the Dutch Childhood Cancer Survivor Late Effect Study on fatigue (DCCSS LATER fatigue study). The aim of the DCCSS LATER fatigue study is to examine the prevalence of and factors associated with CRF, proposing a model which discerns predisposing, triggering, maintaining and moderating factors. Triggering factors are related to the cancer diagnosis and treatment during childhood and are thought to trigger fatigue symptoms. Maintaining factors are daily life- and psychosocial factors which may perpetuate fatigue once triggered. Moderating factors might influence the way fatigue symptoms express in individuals. Predisposing factors already existed before the diagnosis, such as genetic factors, and are thought to increase the vulnerability to develop fatigue. Methodology of the participant inclusion, data collection and planned analyses of the DCCSS LATER fatigue study are presented. RESULTS: Data of 1955 CCS and 455 siblings was collected. Analysis of the data is planned and we aim to start reporting the first results in 2022. CONCLUSION: The DCCSS LATER fatigue study will provide information on the epidemiology of CRF and investigate the role of a broad range of associated factors in CCS. Insight in associated factors for fatigue in survivors experiencing severe and persistent fatigue may help identify individuals at risk for developing CRF and may aid in the development of interventions.

Fatigue-Related Cognitive-Behavioral Factors in Survivors of Childhood Cancer: Comparison with Chronic Fatigue Syndrome and Survivors of Adult-Onset Cancer.

Purpose: Cancer-related fatigue is a burdensome late effect of cancer treatment. A pilot study showed the effectiveness of cognitive-behavioral therapy (CBT) in fatigued survivors of childhood cancer (CCS). The aim of this study is to investigate whether the six cognitive-behavioral factors that are addressed during CBT differ in CCS compared with patients with chronic fatigue syndrome (CFS) and survivors of adult-onset cancer (ACS). Levels of self-esteem, optimism, and depressive symptoms, variables that are also related to fatigue, were also compared between groups. Methods: Retrospective analyses were performed on 34 CCS (ages 11-42 years), 102 patients with CFS, and 95 ACS who were referred for evaluation of severe fatigue. Fatigue severity, possible cognitive-behavioral fatigue maintaining factors, depressive symptoms, self-esteem, and optimism were assessed using questionnaires and actigraphy. Results: No significant differences were found in the factors coping with the experience of having had cancer, fear of cancer recurrence, physical activity, and in levels of self-esteem and optimism. CCS attributed their fatigue significantly more often to psychosocial causes and reported fewer problems in sleep/rest compared with patients with CFS. Compared with ACS, CCS reported significantly more social support, more problems in sleep/rest, and more depressive symptoms. Conclusions: There is substantial overlap in cognitive-behavioral factors that can maintain fatigue between CCS and CFS patients or ACS. Also differences were found regarding attribution of fatigue, the sleep/rest pattern, social support, and depressive symptoms that might have clinical implications when CBT for fatigue is provided to CCS.

Short fatigue questionnaire: Screening for severe fatigue.

OBJECTIVE: To determine psychometric properties, a cut-off score for severe fatigue and normative data for the 4-item Short Fatigue Questionnaire (SFQ) derived from the multi-dimensional fatigue questionnaire Checklist Individual Strength (CIS). METHODS: Data of previous studies investigating the prevalence of fatigue in ten chronic conditions (n = 2985) and the general population (n = 2288) was used to determine the internal consistency (Cronbach's alpha) of the SFQ, its relation with other fatigue measures (EORTC QLQ-30 fatigue subscale and digital fatigue diary), a cut-off score for severe fatigue (ROC analysis) and to examine whether the four SFQ items truly measure the same construct. Norms were calculated for ten patient groups and the Dutch general population. RESULTS: Cronbach's alpha of the SFQ were excellent in almost all groups. Pearson's correlations between the SFQ and the EORTC-QLQ-C30 fatigue subscale and a fatigue diary were respectively 0.76 and 0.68. ROC analysis showed an area under the curve of 0.982 (95% CI: 0.979-0.985) and cut-off score of 18 was suggested which showed a good sensitivity (0.984) and specificity (0.826) as well as excellent values for the positive and negative prediction values within all groups using the CIS as golden standard. Factor analysis showed a one factor solution (Eigenvalue: 3.095) with factor loadings of all items on the factor being greater than 0.87. CONCLUSION: The SFQ is an easy to use, reliable and valid instrument to screen for severe fatigue in clinical routine and research.

Severe fatigue after treatment for childhood cancer.

BACKGROUND: Treatment strategies for childhood cancer are improving, resulting in higher survival rates. However, the consequences of childhood cancer do not end with the successful completion of cancer treatment. Most patients will develop late effects after cessation of treatment. Severe fatigue is seen as a common and debilitating late effect in cancer survivors. Although most research on fatigue has been performed in patients after adult-onset cancer, our review focuses on fatigue after childhood cancer. OBJECTIVES: To estimate the prevalence of severe fatigue after treatment for childhood cancer. Secondary objectives are to describe the course of severe fatigue following cancer treatment and to examine risk factors for fatigue, or factors associated with it. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (the Cochrane Library 2019; issue 8 March 2019), MEDLINE/PubMed (from 1945 to 8 March 2019), Embase/Ovid (from 1947 to 8 March 2019), reference lists of included articles and several conference proceedings from 2011 to 2018. SELECTION CRITERIA: Observational studies, randomised controlled trials and controlled clinical trials reporting on fatigue in participants after treatment for childhood cancer. Case series and case reports were not eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed risks of bias. If the publication did not present the prevalence of severe fatigue, we contacted study authors for additional information. MAIN RESULTS: We included 30 studies (18,682 participants in total). Eighteen studies contributed to the main objective and 22 studies contributed to the secondary objectives. We found substantial differences between studies in cancer diagnosis, cancer treatment, age of participants, questionnaires used to assess fatigue, and sample size. All included studies scored at least one 'Risk of bias' item as unclear or high risk. We identified both clinical and statistical heterogeneity and therefore could not pool results, so we present them descriptively. Eighteen studies (describing 14,573 survivors) reported the prevalence of severe fatigue, which ranged from 0% to 61.7%. In a subgroup of three studies including children aged up to 18 years at fatigue assessment (268 survivors), prevalence rates ranged from 6.7% to 12.5%. In comparison, in a subgroup of 12 studies including participants aged 16 and over (13,952 survivors), prevalence rates ranged from 4.4% to 61.7%. The prevalence of severe fatigue in a subgroup of survivors of haematological cancer was presented in seven studies and ranged from 1.8% to 35.9% (1907 survivors). Prevalence of severe fatigue in brain cancer survivors was presented in two studies (252 survivors) and was 14.6% and 21.1% respectively. One study presented a prevalence for bone cancer survivors of 0.0% (17 survivors). Four studies provided prevalence rates of severe fatigue in control groups of siblings or population-based controls, which ranged from 3.1% to 10.3%. In these four studies, survivors were more often fatigued than controls, but this difference was statistically significant in only two studies. Studies assessing risk and associated factors for fatigue were heterogeneous, and definitions of the factors under study were often inconsistent, with results therefore presented descriptively. They found that depression might be associated with fatigue. In contrast, age at diagnosis and education level did not seem to be associated with fatigue. We were unable to calculate any overall risk estimate for any of the reported risks and associated factors, because we could not conduct meta-analysis. One study provided information about the course of fatigue over time, and found that over the course of 2.7 years, 32 of the 102 participants (31.4%) reported persistent severe fatigue. AUTHORS' CONCLUSIONS: It is unclear how many childhood cancer survivors suffer from severe fatigue. This review encountered several difficulties. We found statistical and clinical heterogeneity and great variation in the reporting of possible risk and associated factors. The evidence in this review is therefore weak, and the exact prevalence of severe fatigue after treatment for childhood cancer remains to be determined. This is also the case for the course of severe fatigue following treatment and the strength of the relationship between fatigue and associated and risk factors. Despite these limitations, our review does provide a comprehensive overview of the existing literature about severe fatigue after treatment for childhood cancer.