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EDITORIALS
November 02, 2009

Recognition and Treatment of Sleep Disturbances in Cancer

Publication: Journal of Clinical Oncology
Fatigue is recognized by oncologists as one of the most frequent complaints of patients with cancer. More importantly, fatigue is among the symptoms about which patients express the most concern. What is less recognized is that there are many components of fatigue, including physiologic factors (such as pain, anemia or menopause), psychological factors (such as depression or anxiety), and chronobiologic factors (such as circadian rhythms disorders and sleep).1 In particular, the relationship between fatigue and sleep is becoming more clear, with data suggesting that sleep problems are significantly correlated with increased fatigue.2 Yet, patients with cancer are not always asked about their sleep nor treated appropriately for their sleep problems.
Insomnia is defined as difficulty falling asleep, difficulty staying asleep, and/or nonrestorative sleep, resulting in daytime dysfunction.3 The most common sleep-related complaints of patients with cancer are difficulty falling asleep, difficulty staying asleep, and frequent and prolonged nighttime awakenings.4,5 In other words, patients with cancer are complaining of insomnia.
The risk factors for insomnia in cancer include the cancer itself (eg, tumors that increase steroid production, symptoms of tumor invasion resulting in pain, dyspnea, nausea, pruritus), treatment factors (eg, corticosteroids, hormonal fluctuations), medications (eg, narcotics, chemotherapy, neuroleptics, sympathomimetics, steroids, sedative hypnotics), environmental factors (eg, temperature extremes or too much light or noise in the bedroom), psychosocial disturbances (eg, depression, anxiety, stress), and comorbid medical disorders (eg, headaches, other primary sleep disorders).6 In a study of cancer survivors, 52% reported sleeping difficulties, and although two thirds reported their insomnia began before their cancer diagnosis, 58% reported that having cancer aggravated their sleep problem.7 This suggests a negative feedback loop where the challenges faced by patients with cancer may contribute to insomnia, which in turn may feed back to exacerbate medical conditions comorbid with cancer.4 Treatment of the sleep problem at any time point might therefore break that cycle.
An important aspect of treatment is, of course, identifying the problem. Sleep needs to be thought of as part of the symptom cluster often associated with cancer. The concept of symptom clusters is not new in the field of cancer.8,9 In a study by Liu et al,10 which examined a symptom cluster of poor sleep, fatigue and depression, results suggested that the more symptoms within that symptom cluster the patients experienced before the start of chemotherapy, the worse the symptoms they experienced during chemotherapy. In addition, those patients with more frequent and more severe symptoms pretreatment experienced the most severe symptoms during treatment.
However, several studies have shown that many patients with cancer do not mention their sleep problems, with close to 80% assuming it is caused by the treatment, 60% wrongly assuming that the symptoms will not last, and almost half believing that their physicians cannot do anything to help them.11,12 What this means is that clinicians need to include sleep as part of the symptom cluster already recognized, and to ask all patients about their sleep. Without asking the question, “How are you sleeping?” this important problem might never be identified and addressed.
The importance of treatment rises from the knowledge that insomnia results in more severe fatigue, leads to mood disturbances, contributes to immunosuppression, affects quality of life, and potentially affects the course of the cancer.6,13 The question for every clinician then becomes, “How do I best treat insomnia in my patients with cancer?”
Insomnia in this patient population may be due to a variety of causes; therefore, treatment may need to be multimodal and include both pharmacologic treatment (eg, benzodiazepine receptor agonists or melatonin receptor agonists) and nonpharmacologic therapies.6,13 The 2005 National Institutes of Health State-of-the-Science Conference statement on insomnia concluded that behavioral therapies are the most effective treatments for insomnia,3 and there have now been several studies showing that cognitive behavioral therapy for insomnia is effective in treating this sleep problem in cancer survivors.1417 These studies all confirmed that cognitive behavioral therapy for insomnia improved sleep efficiency (the percent of time spent sleeping out of time in bed), increased total sleep time, improved fatigue and mood (ie, decreased depression and anxiety), and improved quality of life, with therapeutic effects maintained at 3-, 6- and 12-month follow-up.
One of the innovative features of the Berger et al study18 in this issue of Journal of Clinical Oncology is that intervention was initiated before the patients with cancer developed sleep disturbances and severe fatigue. Results suggested that although sleep improved at 90 days postchemotherapy in the group administered behavioral therapy for insomnia, unlike the studies that initiated treatment postchemotherapy to patients with insomnia, at 1 year there were no longer any differences between the groups. Whereas Berger et al18 concluded that clinicians need to identify and intervene with behavioral therapy at the point that patients with cancer report moderate/severe insomnia, the other take-home message should be that treatment initiated during chemotherapy may have short-term benefits, and additional treatment might be needed postchemotherapy. Berger et al18 are correct that clinicians need to ask their patients about their sleep and initiate treatment when the problem is identified.
In summary, sleep disorders, particularly insomnia, are common in patients with cancer. Sleep needs to be assessed carefully in patients with cancer to improve quality of life and possibly to help improve the course of the disease. There are a variety of effective pharmacologic and nonpharmacologic therapies available for the management of cancer-related insomnia. But for those therapies to work, the clinician must first identify the problem by communicating with the patient and then be willing to initiate the appropriate treatment. Only then will we be able to improve the quality of life for our patients with cancer during and after their cancer treatment.
See accompanying article on page 6033

Authors' Disclosures of Potential Conflicts of Interest

Although all authors completed the disclosure declaration, the following author(s) indicated a financial or other interest that is relevant to the subject matter under consideration in this article. Certain relationships marked with a “U” are those for which no compensation was received; those relationships marked with a “C” were compensated. For a detailed description of the disclosure categories, or for more information about ASCO's conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors.
Employment or Leadership Position: None Consultant or Advisory Role: Sonia Ancoli-Israel, sanofi-aventis (C), Sepracor (C), Ferring Pharmaceuticals (C), GlaxoSmithKline (C), Orphagen Pharmaceuticals (C), Pfizer (C), Respironics (C), Schering-Plough (C) Stock Ownership: None Honoraria: None Research Funding: Sonia Ancoli-Israel, Sepracor Expert Testimony: None Other Remuneration: None

References

1.
S Ancoli-Israel, P Moore, V Jones: The relationship between fatigue and sleep in cancer patients: A review Eur J Cancer Care 10: 245– 255,2001
2.
L Liu, S Ancoli-Israel: Sleep disturbances in cancer Psychiatric Annals 38: 627– 634,2009
3.
Sleep 28: 1049– 1057,2005 National Institutes of Health State of the Science Conference Statement on Manifestations and Management of Chronic Insomnia in Adults June 13–15, 2005
4.
L Fiorentino, S Ancoli-Israel: Insomnia and its treatment in women with breast cancer Sleep Med Rev 10: 419– 429,2006
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CA Engstrom, RA Strohl, L Rose, etal: Sleep alterations in cancer patients Cancer Nurs 22: 143– 148,1999
6.
JF O'Donnell: Insomnia in cancer patients Clin Cornerstone 6: S6– S14,2004 suppl 1D
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J Savard, S Simard, J Blanchet, etal: Prevalence, clinical characteristics, and risk factors for insomnia in the context of breast cancer Sleep 24: 583– 590,2001
8.
C Miaskowski, M Dodd, K Lee: Symptom clusters: The new frontier in symptom management research J Natl Cancer Inst Monogr 17– 21,2004
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AH Miller, S Ancoli-Israel, JE Bower, etal: Neuroendocrine-immune mechanisms of behavioral comorbidities in patients with cancer J Clin Oncol 26: 971– 982,2008
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L Liu, L Fiorentino, L Natarajan, etal: Pretreatment symptom cluster in breast cancer patients is associated with worse sleep, fatigue and depression during chemotherapy Psycho-oncology 18: 187– 194,2009
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P Stone, A Richardson, E Ream, etal: Cancer-related fatigue: Inevitable, unimportant and untreatable? Results of a multi-centre patient survey—Cancer Fatigue Forum Ann Oncol 11: 971– 975,2000
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GA Curt, W Breitbart, D Cella, etal: Impact of cancer-related fatigue on the lives of patients: New findings from the Fatigue Coalition Oncologist 5: 353– 360,2000
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C Quesnel, J Savard, S Simard, etal: Efficacy of cognitive-behavioral therapy for insomnia in women treated for nonmetastatic breast cancer J Consult Clin Psychol 71: 189– 200,2003
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J Savard, S Simard, H Ivers, etal: Randomized study on the efficacy of cognitive-behavioral therapy for insomnia secondary to breast cancer, part I: Sleep and psychological effects J Clin Oncol 23: 6083– 6096,2005
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CA Espie, L Fleming, J Cassidy, etal: Randomized controlled clinical effectiveness trial of cognitive behavior therapy compared with treatment as usual for persistent insomnia in patients with cancer J Clin Oncol 26: 4651– 4658,2008
17.
L Fiorentino, JR McQuaid, L Liu, etal: Cognitive behavioral therapy for insomnia in breast cancer survivors: A randomized controlled crossover study Sleep 31: A295,2008
18.
AM Berger, BR Kuhn, LA Farr, etal: One-year outcomes of a behavioral therapy intervention trial on sleep quality and cancer-related fatigue J Clin Oncol 27: 6033– 6041,2009

Information & Authors

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Published In

Journal of Clinical Oncology
Pages: 5864 - 5866
PubMed: 19884528

History

Published online: November 02, 2009
Published in print: December 10, 2009

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Sonia Ancoli-Israel
Department of Psychiatry, University of California San Diego, and Rebecca and John Moores University of California San Diego Cancer Center, San Diego, CA

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Sonia Ancoli-Israel
Journal of Clinical Oncology 2009 27:35, 5864-5866

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