Severe fatigue after treatment for childhood cancer

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.

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.

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.

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.

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.

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.

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.