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

Abstract

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.

Keywords: Associated factors; Cancer related fatigue; Childhood Cancer survivors; Chronic fatigue; Methodology; Multivariable fatigue model.

Fig. 1

Hypothesized multivariable CRF model in CCS. Model showing associated factors of CRF divided into predisposing- (genetic factors and blood biomarkers which are thought to impact the vulnerability to fatigue), triggering- (factors related to the cancer diagnosis and treatment during childhood and are thought to trigger fatigue symptoms), maintaining- (daily life- and psychosocial factors which may perpetuate fatigue once triggered) and moderating factors (factors which might influence the way fatigue symptoms express in individuals). Continuous lines: factors that are hypothesized to be directly related to CRF. Dashed lines: factors that are hypothesized to possibly act as moderator or confounder for other factors, but might also directly be related to CRF. BMI: Body Mass Index. * Included comorbidities are categorized into the following main organ systems: Neoplasms, Cardiac-, vascular-, respiratory-, gastro-intestinal-, hepatobiliary-, renal and urinary tract-, endocrine-, musculoskeletal-, ear-, eye-, nervous system-, and other conditions

Fig. 2

Flowcharts. a: Flowchart of the CCS participants. b: Flowchart of the sibling participants. IC – no participation: Gave consent, however did not participate. No/missing fat. Data: Did not complete the Checklist Individual Strength subscale fatigue (CIS-fatigue), or duration fatigue symptoms was unknown. When only one item of the CIS-fatigue was missing, the missing value was imputed with the mean score of the other seven items (n = 5 survivors and n = 3 siblings). Participants with two or more missing values on the CIS-fatigue were excluded