Valerie McLaughlin Crabtree and Chasity Brimeyer

Introduction

Each year more than 61,000 children and adolescents under the age of 20 are diagnosed with a malignancy.¹ Significant advances in treatment including surgery, intensive chemotherapy, and targeted radiation therapy have led to substantial increases in survival, with survival rates of 83% by 2009.¹ As survival rates have increased over the past several years, both researchers and clinicians have increased focus on quality of life, including sleep and fatigue, in pediatric oncology patients and survivors.

Fatigue and sleep disturbances have consistently been found to be among the most frequently reported symptoms experienced by both adult and pediatric oncology patients undergoing cancer-directed therapy.2–4 Both fatigue and sleep disturbance have been reported in these patients, and it is important to distinguish between these two complaints. Fatigue, which is reported to be one of the most distressing symptoms in pediatric oncology patients, is defined as the subjective feeling of physical, emotional, or cognitive tiredness that interferes with the ability to participate in physical or social activities.⁵ In pediatric oncology patients, this may be directly caused by treatments including chemotherapy and/or radiation therapy, a side effect of specific medications, such as corticosteroids, and/or secondary to treatment-related effects such as anemia. Sleep disturbances are also observed in oncology patients and can be the direct cause of the fatigue identified by these patients. Sleep disturbances and fatigue are of particular concern for children and adolescents with cancer because they may negatively impact immune functioning and healing, daily functioning, social activities, depressive symptoms, behavior problems, and overall quality of life.^2,6–9

Common Sleep Complaints

Sleep complaints are commonly associated with pediatric cancer, and include restless sleep, excessive daytime sleepiness (EDS), obstructive sleep apnea symptoms, and difficulty initiating and maintaining sleep.5,10 Zupanec and colleagues¹¹ observed a detrimental impact on sleep habits in children following a diagnosis of acute lymphocytic leukemia (ALL), the most common childhood cancer. Sixty-seven percent of parents reported sleep problems, increased restlessness, nighttime awakenings, bedtime resistance, frequency of nightmares, and more changes in sleep location during the night. Parents attributed their children’s poorer sleep habits and subsequent decreased sleep quality to medication schedules and side effects, among other psychological factors related to their diagnosis and treatment.¹¹ Hinds and colleagues¹² reported that children on ALL maintenance therapy slept longer while receiving dexamethasone treatment (a backbone of leukemia treatment) but demonstrated poorer sleep quality with more nighttime awakenings, more restless sleep, and more daytime napping as documented by actigraphic recording.

Sleep complaints are frequently reported not only when children are undergoing treatment for cancer, but also in the survivorship period. One study of childhood cancer survivors referred to a sleep center revealed that 60% of children presented with EDS, 40% with sleep-disordered breathing, 24% with insomnia, 4% with circadian rhythm dysfunction, and 9% demonstrated parasomnias.¹³ Furthermore, sleep disruptions in pediatric brain tumor survivors may be enduring. While sleep complaints have been found to resolve following treatment in child survivors of leukemias, brain tumor survivors continue to experience sleep disruptions even 1 year post treatment¹⁴ and report excessive daytime sleepiness more than 5 years post treatment.¹⁵ In addition to excessive daytime sleepiness, adolescents with cancer have continued to report significant fatigue up to 5 years after treament and even into adulthood.^16,17

Contributors to Sleep Disturbance

Many factors contribute to sleep disturbances in children and adolescents who are receiving cancer-directed therapy, including disease process, treatment modality,⁶ frequent nocturnal awakenings in hospitalized patients,³ nighttime caretaking needs, and poor sleep quality.²²

Disease-related variables are likely to account for the significant fatigue in pediatric oncology patients both during and after treatment. Several studies have investigated children’s sleep and fatigue while receiving treatment, typically for ALL, and have found that use of steroids, a backbone of leukemia treatment, may contribute to fatigue. Both actigraphic recording and parent report have indicated that children with ALL have poor sleep while receiving treatment. This poor sleep has been characterized by decreased total sleep time at night, increased daytime napping, increased nighttime awakenings, and more restless sleep, particularly while children are receiving steroid treatment in comparison to days when they are not receiving steroids.12,23

Excessive daytime sleepiness can result from the cumulative effect of insufficient sleep, fragmented sleep, irregular sleep–wake schedules, and circadian rhythm disruption.¹⁰ In pediatric patients with centrally located brain tumors, the mechanism of EDS is likely twofold because the hypothalamus regulates both neurological sleep control and weight. First, EDS may result from hypothalamic injury following tumor resection and/or from the tumor itself, resulting in the child’s inability to effectively maintain sleep and wakefulness. Second, increased risk for obesity due to hypothalamic dysfunction or injury may result in obstructive sleep apnea.^{10,13,18,24,25} In this way, tumor location, rather than type, is more of a determinant of EDS symptoms. One study of children referred to a sleep center who were currently receiving cancer treatment or had completed treatment found that children with brain tumors, particuarly tumors of the hypothalamus, thalamus, and brainstem, accounted for over two-thirds of all referrals.¹³ In pediatric brain tumor survivors evaluated during their survivorship clinic visits who had not been referred to a sleep clinic, however, tumor location was not as consistently related to levels of excessive daytime sleepiness.¹⁵ Thus, while survivors of CNS tumors have increased likelihood of sleep disturbances, the etiology of these sleep disruptions is complex and likely multifactorial.

Demographic Variables Related to Differences in Sleep Problems

Demographic variables that may relate to differences in sleep and fatigue in pediatric oncology patients have received limited attention; however, there is some evidence to suggest that gender and age may contribute to sleep disturbance and fatigue. For example, in a study examining sleep disruption in pediatric ALL patients in the maintenance phase of treatment, girls were found to nap more and had more consolidated nighttime sleep than did boys. This finding was consistent even after controlling for differences in age, treatment, and risk group.²⁶ Another study examining changes in fatigue over the course of cancer treatment also found that girls reported more fatigue than boys.²⁷ However, this is an equivocal finding, as other studies of pediatric oncology patients have found no gender differences.²⁸ Research related to age differences has also yielded mixed results. One study compared children with ALL to their healthy same-age peers and found that only younger children with ALL exhibited significantly longer sleep duration.⁸ Conversely, a study of children successfully treated for CNS tumors found that patients aged 8–12 exhibited significantly more sleep disturbances, while patients aged 4–8 and 12–18 did not exhibit greater sleep difficulties than their same-age peers.²⁹ On the other hand, children aged 6–12 have been reported to experience a decrease in fatigue over the course of treatment while adolescents aged 13–18 experienced no change.²⁸

Impact of Sleep Disturbance

Sleep disturbances have been associated with poorer health, mood, behavior regulation, academic performance, neurocognitive function, immune function, and overall quality of life.30–32 The consequences of sleep disturbances are of particular concern to pediatric oncology patients because sleep is critical for neural recovery and tissue renewal; disrupted sleep may hinder the child’s recovery.^17,30 Similarly, the consequences of sleep disruption on the child’s psychological well-being should be considered. More specifically, reduced adaptive functioning, limited engagement in social activities, behavioral and mood problems, and/or negative impact on treatment adherence have been associated with nocturia, fatigue, and disturbance of sleep–wake cycles.^2,6,7,27