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Relationship between circadian activity rhythms and fatigue in hospitalized children with CNS cancers receiving high-dose chemotherapy

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Abstract

Purpose

Robust circadian rhythms are increasingly recognized as essential to good health. Adult cancer patients with dysregulated circadian activity rhythms (CAR) experience greater fatigue, lower responsiveness to chemotherapy, and shorter time to relapse. There is scant research describing circadian rhythms and associated outcomes in children with cancer. As part of a larger study examining whether a cognitive-behavioral intervention could preserve sleep in children and adolescents with central nervous system cancers hospitalized for high-dose chemotherapy (HDCT), this study aimed to compare CAR of these children to published values and to investigate the relationship between CAR and fatigue.

Methods

Participants aged 4–19 years wore an actigraph throughout their hospitalization (5 days). From activity counts recorded by actigraphy, six CAR variables were calculated: amplitude, 24-h autocorrelation (r24), dichotomy index (I < O), interdaily stability (IS), intradaily variability (IV), and acrophase. Parent-reported child fatigue and child/adolescent self-reported fatigue measures were collected daily.

Results

Thirty-three participants were included. Three CAR variables (amplitude, r24, and I < O) showed dysregulation compared to published values. Older age was significantly associated with later acrophase and greater dysregulation of all other CAR variables. Controlling for age, more dysregulated amplitude (p = 0.001), r24 (p = 0.003), IS (p = 0.017), and IV (p = 0.001) were associated with higher parent-reported fatigue; more dysregulated IV (p = 0.003) was associated with higher child-reported fatigue.

Conclusions

Participants demonstrated dysregulated CAR during hospitalization for HDCT. Greater dysregulation was associated with greater fatigue. Research on circadian dysregulation and its relationship to health-related outcomes in children with cancer, and interventions to support circadian rhythmicity, is urgently needed.

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Funding

This study was funded by an Alex’s Lemonade Stand Foundation grant and a Cancer Center Support grant (CA 21765) from the National Cancer Institute and American Lebanese Syrian Associated Charities. We received support of the University of Maryland, Baltimore, Institute for Clinical & Translational Research (ICTR).

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Authors and Affiliations

  1. University of Maryland, 655 W. Lombard Street, Baltimore, MD, 21201, USA

    Valerie E. Rogers & Shijun Zhu

  2. St. Jude Children’s Research Hospital, Memphis, TN, USA

    Belinda N. Mandrell

  3. University of California, San Diego, CA, USA

    Sonia Ancoli-Israel & Lianqi Liu

  4. Nursing, Children’s National Health System and George Washington University, Washington, DC, USA

    Pamela S. Hinds

Authors
  1. Valerie E. Rogers
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  2. Shijun Zhu
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  3. Belinda N. Mandrell
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  4. Sonia Ancoli-Israel
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  5. Lianqi Liu
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  6. Pamela S. Hinds
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Corresponding author

Correspondence to Valerie E. Rogers.

Ethics declarations

The sleep intervention was approved by the St. Jude Institutional Review Board, and the University of Maryland Institutional Review Board granted exempt status for this retrospective examination of CAR data.

Conflict of interest

Dr. Sonia Ancoli-Israel is a consultant for Eli Lilly and Co., Eisai Inc., Merck, Pfizer, and Purdue Pharma, although she has no conflict of interest related to this research. All other authors have no conflicts of interest to disclose.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Rogers, V.E., Zhu, S., Mandrell, B.N. et al. Relationship between circadian activity rhythms and fatigue in hospitalized children with CNS cancers receiving high-dose chemotherapy. Support Care Cancer 28, 1459–1467 (2020). https://doi.org/10.1007/s00520-019-04960-5

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