Longitudinal development of fatigue after treatment for childhood cancer: a national cohort study

Abstract

Background

Fatigue is a distressing and prevalent long-term sequela of treatment for childhood cancer, and there is a need for longitudinal studies to investigate the development of fatigue over time. The objective of this study was to calculate growth-curves for the longitudinal development of fatigue after treatment for childhood cancer, and to investigate the effects of biopsychosocial predictors.

Materials and methods

Participants were recruited from a patient monitoring program and data extracted from medical records. Parent-proxy and self-report versions of PedsQL^TM Multidimensional Fatigue Scale were used to repeatedly assess fatigue up to 5 years after the end of treatment for childhood cancer. Fatigue was assessed 2440 times for 761 participants (median:3) with proxy-reports (age 2–8 years) and 2657 times for 990 participants with self-reports (above 8 years) (median:2). Mixed models were used to establish growth-curves and to analyze the effect of predictors separately for participants with solid tumors (ST), hemato-oncological malignancies and central nervous system-tumors (CNS).

Results

CNS-tumors were associated with more cognitive fatigue than ST at the end of treatment, for both proxy-reports (−11.30, p<.001) and self-reports (−6.78, p=.002), and for proxy-reports of general fatigue (−6.78, p=.002). The only significant difference in change over time was for self-reports of sleep-rest fatigue. The raw scores for the CNS-group decreased with −0.87 per year (95% CI −1.64; −0.81, p=.031) compared to the ST-group. Parental distress was overall the variable most associated with increased fatigue, while immunotherapy was the most frequent medical predictor. National centralization of childhood cancer care decreased fatigue for the CNS-group, but not for other diagnoses.

Discussion

Children and adolescents treated for CNS-tumors reported more fatigue than other participants after the end of treatment, and this difference remained over time. Results from this study may help to facilitate the early recognition of children with insufficient recovery of fatigue symptoms.

Keywords:

• Childhood cancer
• fatigue
• long-term effects
• longitudinal
• patient reported-outcomes

Acknowledgements

We acknowledge the efforts of the KLIK-team at the Princess Máxima Centrum for Childhood Oncology, for their dedicated work with implementing KLIK in clinical practice.

Ethical approval

Data was extracted from the patient-reported outcome monitoring program for all patients for whom informed consent was given. Using data collected in care for research questions was approved by the ethics committee of Rotterdam Center (decision number MEC-2016-739). Additionally, the scientific committee of the Princess Máxima Centrum approved of the project.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

Deidentified individual participant data (including data dictionaries) will be made available, in addition to the statistical analysis plan. The data will be made available after publication upon request to researchers who provide a methodologically sound proposal and after a signed data sharing agreement is reached. Proposals should be submitted to [email protected].

Additional information

Funding

Dr Elin Irestorm is the receiver of a grant from the Swedish Research Council [grant number 2021-00328]. The study was funded by the Children Cancer Free Foundation [grant number 416].