A pilot randomized controlled trial to improve sleep and fatigue in children with central nervous system tumors hospitalized for high‐dose chemotherapy

Abstract

Objectives To determine whether a sleep intervention compared with standard of care (SOC) was successful in preserving nighttime sleep in children with central nervous system cancers hospitalized for high‐dose chemotherapy (HDCT) and autologous stem cell rescue, and to explore associations between sleep and fatigue during treatment. Methods An unblinded, randomized, controlled, multicomponent intervention (NCT00666614) including evidence‐based cognitive and behavioral strategies to improve sleep was implemented in 33 children (age 4–12 years) and adolescents (age 13–19 years) during hospitalization. Children wore an actigraph to measure sleep and wake, and reported fatigue scores daily. Parents concurrently kept a sleep diary and reported fatigue scores for their children. Results The mean age was 9.5 ± 3.9 years, 81.8% were white, and 60.6% were male. Sleep in all children was seriously disturbed throughout the study. Children in the intervention group maintained their longest nighttime sleep across the study, while it declined in children receiving SOC (P = 0.009 for interaction). There were few other differences in sleep between groups. Controlling for age and baseline fatigue, higher nighttime activity score, and lower percent sleep were significantly associated with higher next‐day adolescent‐reported fatigue (P < 0.05); longest sleep was significantly positively associated with next‐day child‐reported fatigue (P = 0.018). Conclusion In this sample of children undergoing HDCT, a multicomponent sleep intervention modestly preserved nighttime sleep duration, although overall sleep was poor in both groups. Sleep is an integral component of health, and may influence outcomes of children receiving HDCT. Further investigation into methods of preserving sleep in children undergoing intensive cancer therapy is warranted.

Neurodevelopmental Consequences of Pediatric Cancer and Its Treatment: The Role of Sleep

“…The treatment of sleep disturbances can also ensure adequate production of endogenous melatonin, a hormone with anti-tumor and anti-inflammatory functions, which stimulates the proliferation of stem cells [15,54,55]; the regularization of circadian rhythms is important for a correct functioning of the hypothalamic-pituitary-adrenal axis, unfortunately often involved in pediatric neoplasms [37,41,42], with consequent improvement of the production of hormones synthesized by these metabolic pathways, also important for the processes of growth of the child.…”

“…A very recent study has evaluated the effects of the treatment of sleep disturbances in children with CNS tumors exposed to high doses of chemotherapy, hypothesizing that the treatment of sleep disturbances and the protection of endogenous melatonin production might be followed by a better outcome of autologous stem cell transplantation too [15]. The same investigation suggested the usefulness of chronopharmacology with chemotherapy agents, as also reported by other studies [65]; this chrono-chemotherapy approach is innovative and exploits the circadian biology of individual tumors and the specific circadian variations influencing the pharmacokinetics and pharmacodynamics of drugs, and consequently proving effective in reducing the doses of some drugs with the same efficacy, and, finally, ensuring a better toxicity profile.…”

“…Melatonin is a powerful free radical scavenger and has a chelating action, and therefore reduces oxidative stress and inflammatory reactions and stabilizes cell membranes. It has been hypothesized that melatonin can improve the survival of stem cells and facilitate their differentiation [55]; it was also shown that preserving endogenous melatonin production improves response to autologous stem cell transplantation [15].…”

“…Duplicates were also excluded, and the reference list of the retrieved articles was reviewed and pertinent articles published during the same time period specified above were added to the final list of papers. However, only four articles [13][14][15][16] dealt with cancer, neurodevelopmental disorders and sleep at the same time; for this reason, the following sections of this paper discuss the topic by using all pertinent articles that approached various aspects of the problem, even if not focusing on the very specific topic of our search.…”

A call to action for expanded sleep research in pediatric oncology: A position paper on behalf of the International Psycho‐Oncology Society Pediatrics Special Interest Group

“…Inpatient hospitalizations disrupt a child's sleep, due in part to the frequency of nocturnal awakenings for care provision, potentially resulting in delirium, which has not been studied in oncology. Even a comprehensive intervention intended to improve sleep in patients with CNS tumors receiving conditioning chemotherapy before hematopoietic stem cell transplantation could not increase total sleep time compared with controls because of the care required throughout the night . Past studies show that sleep disturbances (including difficulty initiating and maintaining sleep, daytime napping, and variable sleep patterns) are common in ALL patients and can substantially impact their QoL .…”