It is critical that clinicians and healthcare systems adopt routine screening and affordable interventions to reduce chronic insomnia and improve the quality of life in cancer patients and survivors. We provide expert clinical advice on how to manage sleep-wake disturbances that occur comorbidly with cancer. Our discussion focuses on the etiology, screening, and assessment of sleep-wake disturbances, and on both nonpharmacologic and pharmacologic interventions to manage sleep disturbances, insomnia, and sleep-related breathing disorders. We share a simplified sleep management algorithm based on evidence-based guidelines and resources from the National Cancer Institute, National Comprehensive Cancer Network, and Oncology Nursing Society, as well as case studies that illustrate how oncology professionals can use the algorithm. Finally, we describe ways to strengthen the partnership between clinicians and patients in the management of sleep-wake disorders and related symptoms.
How Do We Treat Sleep-Wake Disturbances That Are Comorbid With Cancer?
Research investigating interventions to treat sleep-wake disturbances that are comorbid with cancer has advanced steadily in the last two decades. Step 4 of the algorithm (see Figure) outlines sleep hygiene (SH) education that is fundamental knowledge for all patients (ISI = 0 to 28). If a patient’s ISI score is ≤ 14, then Step 5 is skipped and a follow-up assessment is scheduled in 12 weeks (Step 6). If a patient’s ISI score is ≥ 15, then selection of nonpharmacologic and/or pharmacologic interventions is indicated (Step 5). The clinicians collaborates with the patient to select an intervention categorized as “recommended for practice” or “likely to be effective” by ONS PEP experts, in addition to SH education.[21-23] Step 6 is a follow-up assessment 12 weeks later or if a change occurs in the patient’s condition.
Tom is a 58-year-old African-American man with stage III colon cancer treated with a colon resection and chemotherapy. He has a history of poor sleep, excessive daytime sleepiness, and fatigue (6 on a scale of 0 to 10) that has interfered with his work at a manufacturing plant and with his social life. He has been overweight throughout adulthood. His wife notes his loud snoring and frequent gasps at night, which have worsened since he started treatment with a hypnotic drug after surgery.
APPLICATION OF THE ALGORITHM
Step 1: Screen – Yes.
Step 2: His STOP-Bang score is 6; yes. He is referred to a sleep specialist and diagnosed with obstructive sleep apnea; he is started on continuous positive airway pressure (CPAP) treatment and his hypnotic is tapered.
Step 3: His Insomnia Severity Index (ISI) score is 11, due largely to a history of poor sleep.
Step 4: Emphasis on regular sleep schedule, routine exercise, and healthy eating.
Step 5: Assessment at 12 weeks indicates CPAP is improving sleep at night, with better daytime function and fatigue. ISI = 8; fatigue is rated as mild (3 on a scale of 0 to 10). Continue to reassess the patient, especially when his schedule changes upon his return to work.
Patients with cancer who are experiencing sleep-wake disturbances may benefit from treatments that were originally developed for and tested in adults without cancer. Several meta-analyses and systematic reviews have examined the efficacy of nonpharmacologic[4,30,31] and pharmacologic interventions to improve sleep-wake disturbances occurring comorbidly with cancer. The ONS PEP program uses standardized criteria to conduct ongoing analyses of research evidence for a variety of sleep interventions. ONS PEP experts have concluded that cognitive-behavioral interventions or approaches (CBI/A) for insomnia have strong and consistent evidence to supports their recommendation for clinical use. CBI/A is a multicomponent therapy aimed at changing detrimental sleep-related thoughts and behaviors. Although more time consuming than administering medication, CBI/A is well received by patients and produces sustained improvements in both sleep quality and duration. Standard components of CBI/A include sleep restriction, stimulus control, SH education, and cognitive therapy, with or without relaxation.[33,34] These components reduce the hyperarousal and other factors that perpetuate sleep-wake disturbances—by modifying sleep schedules, habits, and dysfunctional misconceptions. Combining CBI/A with medications can optimize outcomes, although there is scant evidence to guide the integration of these approaches into clinical practice.
The ONS-PEP category of “likely to be effective” includes exercise and mindfulness-based stress reduction (MBSR). Exercise is characterized by “FITT,” or frequency, intensity, time, and type. Exercise interventions have improved sleep in patients both during and after cancer treatments. Guidelines for interventions to improve sleep in cancer patients with normal functional status are similar to those used in healthy populations. Aerobic exercise maintains and/or improves mental and emotional health in stressful times and strengthens 24-hour circadian activity rhythms, a factor associated with longer survival in patients with advanced cancer. MBSR is “likely to be effective” in improving cancer-related sleep-wake disturbances and may be particularly helpful in patients with anxiety, but more evidence is needed from large, well-designed studies.
Sedative/hypnotic medications may be beneficial as short-term strategies to treat sleep-wake disturbances and often are used in conjunction with SH and other nonpharmacologic strategies that take longer to show benefits. Table 2 synthesizes information from NCI and NCCN about sedative/hypnotic medications approved by the US Food and Drug Administration to treat sleep-wake disturbances. Selection of a sedative/hypnotic agent needs to be based on the type of sleep problem encountered. Short-acting agents are preferred for sleep initiation, and long-acting agents are used for sleep maintenance. Comorbid conditions such as anxiety and depression also should be considered. The clinician’s decision to prescribe sleep medication must be made carefully; both the patient and caregiver need to be aware of potential adverse effects, drug-drug interactions, long-term implications, and safety issues associated with a particular agent.
The preferred classes of prescription drugs for short-term use (< 7 days) by patients with sleep-wake disturbances are benzodiazepines and nonbenzodiazepine benzodiazepine receptor agonists. Hypnotics and sedatives can create a hang-over effect upon awakening and may result in reduced memory and performance, leading to impaired daytime functioning. This effect also occurs with over-the-counter sleep aids containing antihistamines. Other potentially serious adverse effects of sedative/hypnotic medications that should be discussed with patients and caregivers include complex sleep-related behaviors such as sleep-driving, worsening of depression, and psychological and/or physical dependence. Sleep experts recommend starting medications at low doses, monitoring patients closely for side effects, and tapering the drugs slowly to prevent withdrawal symptoms and rebound insomnia. The use of herbal sleep aids is strongly discouraged due to a lack of information about drug-drug interactions.
Two clinical scenarios (case studies) show how the algorithm (Figure) is applied in the management of patients with cancer and comorbid sleep-wake disturbances.
- One-third to one-half of adult patients with cancer self-report problems with sleep duration and quality.
- Screening and focused assessment for sleep-wake disturbances need to be integrated into oncology clinical care.
- Access to diagnosis and treatment of sleeping disorders is essential to reduce long-term negative outcomes.
- For cancer patients with insomnia and sleep-wake disturbances, pharmacologic interventions are for short-term use. Evidence-based practice guidelines recommend nonpharmacologic interventions for long-term use and best outcomes.
NCCN survivorship guidelines on sleep-wake disturbances were released in 2015; ONS PEP reviewers rated interventions as “effectiveness established” and “likely to be effective,” and disseminated this information online.[21,22] Patient, clinician, and system-level resources need to be developed for widespread implementation and adoption of guidelines for the management of sleep-wake disturbances in practice settings. There is tension in busy oncology clinics between delivery of cancer treatment and supportive care such as screening and management of sleep-wake disturbances. NCI PDQ is an example of a resource for patients.
In both primary care and oncology settings, screening patients for sleep-wake disturbances comorbid with cancer and their daytime consequences can reduce the economic burden of untreated sleep problems. Clinicians and systems need to value the electronic medical record and dedicate its use to tracking screening methods, treatments prescribed, and outcomes for patients with sleep-wake disturbances. Referrals, SH education, and evidence-based interventions need to be readily available to patients—and performed by qualified clinicians. Treatment is most likely to be successful when it is tailored to the individual and focuses on specific physiologic and behavioral factors. Survivorship care plans also need to address this issue. Like nutrition and exercise, resources to address difficulties with sleep need to be included in public health initiatives.
Financial Disclosure: The authors have no significant financial interest in or other relationship with the manufacturer of any product or provider of any service mentioned in this article.
Acknowledgment: We thank Dilorom Djalilova, BSN, BA for her assistance in preparing this manuscript.
1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66:7-30.
2. VanHoose L, Black LL, Doty K et al. An analysis of the distress thermometer problem list and distress in patients with cancer. Support Care Cancer. 2015;23:1225-32.
3. Albusoul RM, Berger AM, Gay CL, et al. Symptom clusters change over time in women receiving adjuvant chemotherapy for breast cancer. J Pain Symptom Manage. 2017; 53:880-6.
4. Bower JE, Ganz PA, Irwin MR, et al. Inflammation and behavioral symptoms after breast cancer treatment: do fatigue, depression, and sleep disturbance share a common underlying mechanism? J Clin Oncol. 2011;29:3517-22.
5. American Academy of Sleep Medicine. International classification of sleep disorders. 3rd Edition. American Academy of Sleep Medicine, Darien, IL; 2014.
6. Daley M, Morin C, LeBlanc M, et al. The economic burden of insomnia: direct and indirect costs for individuals with insomnia syndrome, insomnia symptoms, and good sleepers. Sleep. 2009;32:55-64.
7. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. American Psychatric Publishing, Arlington, VA; 2013.
8. Sateia MJ, Lang BJ. Sleep and cancer: recent developments. Curr Oncol Rep. 2008;10:309-18.
9. Berger AM, Desaulniers G, Matthews EE et al. Sleep wake disturbances. In: Irwin M, Johnson J (editors). Putting evidence into practice: a pocket guide to cancer symptom management. Oncology Nursing Society, Pittsburgh, PA; 2014; pp 255-267.
10. Savard J, Ivers H, Savard MH et al. Cancer treatments and their side effects are associated with aggravation of insomnia: results of a longitudinal study. Cancer. 2015;121:1703-11.
11. Savard J, Morin C. Insomnia in the context of cancer: a review of a neglected problem. J Clin Oncol. 2001;19:895-908.
12. Savard J, Simard S, Blanchet J, et al. Prevalence, clinical characteristics, and risk factors for insomnia in the context of breast cancer. Sleep. 2001;24:583-590.
13. Matthews EE, Tanner JM, Dumont NA. Sleep disturbances in acutely ill patients with cancer. Crit Care Nurs Clin North Am. 2016;28:253-68.
14. Galiano-Castillo N, Cantarero-Villanueva I, Fernandez-Lao C, et al. Telehealth system: a randomized controlled trial evaluating the impact of an internet-based exercise intervention on quality of life, pain, muscle strength, and fatigue in breast cancer survivors. Cancer. 2016;122:3166-74.
15. Mercadante S, Adile C, Ferrera P et al. Sleep disturbances in advanced cancer patients admitted to a supportive/palliative care unit. Support Care Cancer. 2017;25:1301-6.
16. Palesh O, Roscoe J, Mustian KM, et al. Prevalence, demographics, and psychological associations of sleep disruption in patients with cancer: University of Rochester Cancer Center-Community Clinical Oncology Program. J Clin Oncol. 2010;28:292-8.
17. Zhou J, Jolly S. Obstructive sleep apnea and fatigue in head and neck cancer patients. Am J Clin Oncol. 2015;38:411-4.
18. Garrett K, Dhruva A, Koetters T, et al. Differences in sleep disturbance and fatigue between patients with breast and prostate cancer at the initiation of radiation therapy. J Pain Symptom Manage. 2011;42:239-50.
19. Spielman AJ, Glovinsky PB. A conceptual framework of insomnia for primary care practitioners: predisposing, precipitating and perpetuating factors. Sleep Medicine Alert. 2004;9.1:1-6.
20. National Cancer Institute. Sleep disorders (PDQ®)- Health Professional Version. https://www.cancer.gov/about-cancer/treatment/side-effects/sleep-disorders-hp-pdq#cit/section_4.30. Accessed July 24, 2017.
21. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology Survivorship. Version 1.2017. https://www.nccn.org/professionals/physician_gls/pdf/survivorship.pdf. Accessed July 24, 2017. Accessed July 24, 2017.
22. Oncology Nursing Society Putting Evidence into Practice. Sleep-wake disturbances. https://www.ons.org/practice-resources/pep/sleep-wake-disturbances.
23. Howell D, Keller-Olaman S, Oliver TK, et al. A pan-Canadian practice guideline and algorithm: screening, assessment, and supportive care of adults with cancer-related fatigue. Curr Oncol. 2013;20:e233-e246.
24. Siefert ML, Hong F, Valcarce B, et al. Patient and clinician communication of self-reported insomnia during ambulatory cancer care clinic visits. Cancer Nurs. 2014;37:E51-E59.
25. Pachman DR, Barton DL, Swetz KM, et al. Troublesome symptoms in cancer survivors: fatigue, insomnia, neuropathy, and pain. J Clin Oncol. 2012;30:3687-96.
26. Morin CM. Cognitive behavioral therapy for chronic insomnia: state of the science versus current clinical practices. Ann Intern Med. 2015;163:236-7.
27. Sivertsen B, Vedaa Ø, Nordgreen T. The future of insomnia treatment—the challenge of implementation. Sleep. 2013;36:303-4.
28. Berger AM, Mitchell SA, Jacobsen PB, et al. Screening, evaluation, and management of cancer-related fatigue: ready for implementation to practice? CA Cancer J Clin. 2015;65:190-211.
29. Savard M, Savard J, Simard S, et al. Empirical validation of the Insomnia Severity Index in cancer patients. Psychooncology. 2005;14:429-41.
30. Garland SN, Johnson JA, Savard J, et al. Sleeping well with cancer: a systematic review of cognitive behavioral therapy for insomnia in cancer patients. Neuropsychiatr Dis Treat. 2014;10:1113-24.
31. Langford DJ, Lee K, Miaskowski C. Sleep disturbance interventions in oncology patients and family caregivers: a comprehensive review and meta-analysis. Sleep Med Rev. 2012;16:397-414.
32. Sateia MJ, Buysse D, Krystal AD, et al. Clinical practice guideline for the pharmacologic treatment of chronic insomnia in adults: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. 2016;12:307-9.
33. Morin CM, Benca R. Chronic insomnia. Lancet. 2012;379:1129-41.
34. Edinger JD, Carney CE. Overcoming insomnia: a cognitive-behavioral therapy approach, therapist guide. 2nd Ed. Oxford University Press, New York; 2014.
35. American Council on Exercise. ACE personal trainer manual. American Council on Exercise, San Diego, CA; 2003.
36. Berger AM, Matthews EE. Physical activity for promoting sleep. In: Bernardo LM, Becker BJ (editors). Integrating physical activity into cancer care: an evidence-based approach. Oncology Nursing Society, 2017.
37. Jankowski CM, Matthews EE. Exercise guidelines for adults with cancer: a vital role in survivorship. Clin J Oncol Nurs, 2011;15:683-6.
38. Mormont MC, Waterhouse J, Bleuzen P, et al. Marked 24-h rest/activity rhythms are associated with better quality of life, better response, and longer survival in patients with metastatic colorectal cancer and good performance status. Clin Cancer Res. 2000;6:3038-45.
39. Turner C, Handford ADF, Nicholson AN. Sedation and memory: studies with a histamine H-1 receptor antagonist. J Psychopharmacol. 2006;20:506-17.
40. National Cancer Institute. Sleep disorders (PDQ®)-Patient Version. https://www.cancer.gov/about-cancer/treatment/side-effects/sleep-disorders-pdq. Accessed July 24, 2017.
41. Carney CE, Buysse DJ, Ancoli-Israel S, et al. The consensus sleep diary: standardizing prospective sleep self-monitoring. Sleep. 2012;35:287-302.
42. Morin C. Insomnia. Guilford Press, New York; 1993.
43. Yu L, Buysse DJ, Germain A, et al. Development of short forms from the PROMIS sleep disturbance and Sleep-Related Impairment item banks. Behav Sleep Med. 2011;10:6-24.
44. Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep. 1991;14:540-5.
45. Chung F, Yegneswaran B, Liao P, et al. STOP questionnaire: a tool to screen patients for obstructive sleep apnea. Anesthesiology. 2008;108:812-21.
46. Buysse D, Reynolds CF 3rd, Monk TH, et al. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989.28:193-213.