High Rates of Sleep Deficiency and Cancer-Related Fatigue Across Diagnoses

Among patients with cancer, sleep deficiency and cancer-related fatigue rank highest in prevalence and severity during all treatment phases, regardless of cancer type or stage.

Sleep deficiency and cancer-related fatigue can severely affect day-to-day functioning in cancer survivors, even years after treatment. According to Ann M. Berger, PhD, MSN, APRN, AOCNS, FAAN, Professor and Dorothy Hodges Olson Endowed Chair in Nursing, College of Nursing, University of Nebraska Medical Center, Omaha, there is an urgent need for further research in this area to alleviate these symptoms and enhance quality of life among survivors of all types of cancer.

At the 2018 Multinational Association of Supportive Care in Cancer meeting, Dr Berger discussed the association between cancer-related fatigue and sleep deficiency symptoms and function, the strengths and weaknesses in the current literature, and the implications for clinical practice and future research.

Sleep Deficiency and Cancer-Related Fatigue

Sleep deficiency is defined by the National Institutes of Health as “deficit in the quantity or quality of sleep obtained versus the amount needed for optimal health, performance and well being.”¹

The National Comprehensive Cancer Network defines cancer-related fatigue as “a distressing, persistent, subjective sense of physical, emotional, and/or cognitive tiredness or exhaustion related to cancer or cancer treatment that is not proportional to recent activity and interferes with usual functioning.”²

Postoperative Symptom Burden

In one study of patients with breast cancer, the rate of postoperative cancer-related fatigue was 24%, and approximately 33% of those patients also had mood disturbance.³

In patients with early-stage lung cancer, the most severe postoperative symptoms were cancer-related fatigue, pain, shortness of breath, and disturbed sleep; poor performance status and the presence of comorbidities were associated with increased pain.⁴

Before and After Chemotherapy

In a study of 78 patients with gynecologic cancers, high cancer-­related fatigue before chemotherapy was also associated with increased rates of depression.⁵ At the start of chemotherapy, women with gynecologic cancers had increased rates of cancer-related fatigue, which is associated with minutes of wake after sleep onset.⁵ In patients with breast cancer and cancer-related fatigue, sleep disturbances and depression increased from baseline to the fourth treatment.⁶

In a study of patients with breast cancer, the rate of cancer-related fatigue rose to 31% when patients received adjuvant therapy, and approximately 33% of those patients had mood disturbances.³

In one large study, in patients with a mixed diagnosis, those who presented with insomnia had higher rates of fatigue and depression than good sleepers, and 43% of the patients met the criteria for “insomnia syndrome.”⁷

Another large study of patients with a mixed diagnosis showed that higher level of morning fatigue and worse attentional function were associated with sleep disturbances.⁸

Sleep Deficiency Still Prevalent in Survivors

One breast cancer survey revealed that survivors still had sleep disturbances and cancer-related fatigue up to 10 years after treatment.⁹ “These patients were many years into survivorship, but still had these symptoms,” Dr Berger noted.

In patients who had undergone autologous stem-cell transplant, 41% still reported sleep disruption at 6 to 18 months after the transplant, and wake after sleep onset was measured at 66 minutes¹⁰; this was surprising to researchers, because they expected the wake after sleep onset to be less than 30 minutes, Dr Berger said. Distress, fear, and cognitive dysfunction were also associated with the reported sleep disruption.¹⁰

In patients with colorectal cancer, worsening anxiety and cancer-related fatigue were associated with worse sleep approximately 10 months after diagnosis.¹¹ The most frequent symptoms in patients with rectal cancer were feeling “worn out” or “tired” and having disturbed sleep.¹² Approximately 40% of patients with mixed diagnoses still had insomnia 18 months after surgery.¹³

Another study on survivorship show­ed that cancer-related fatigue at baseline predicted cancer-related fatigue 1 year after the patient’s last treatment, and the severity of cancer-related fatigue was not influenced by cancer type or treatment type.¹⁴

“Based on self-reporting from patients starting chemotherapy, these symptoms get worse during treatment,” Dr Berger said. “And even in the survivorship phase, when they return closer to baseline, their functioning is still not the same as normal controls.”

Impact of Symptoms on Functioning

In a sample of patients with lung cancer who were evaluated from baseline to 48 weeks after treatment, poor sleep quality and symptoms of depression negatively affected quality of life, whereas a regular sleep-wake rhythm positively affected quality of life.¹⁵

Patients with breast cancer who had moderate attentional and physical cancer-related fatigue in addition to severe sleep disturbance, depression, and anxiety had significantly lower quality of life 2 years after surgery.¹⁶

“In this sample, the presurgery symptom profile predicted quality of life 2 full years after treatment,” Dr Berger said.

Fatigue Across the Cancer Continuum

According to Dr Berger, there is a strong, evidence-based need for baseline screening, assessment, and treatment for sleep deficiency, cancer-related fatigue, mood, and pain.

“We need to be sure that patients receive targeted and realistic interventions from baseline throughout their cancer journey,” she said, stressing the need for more objective measures in addition to patient-reported outcomes.

Furthermore, the current clinical practice is not helping to reduce the prevalence or severity of these often severely significant symptoms over time, which highlights the need for further research in this area. In future studies, distinct patient groups and trajectories of multiple co-­occurring symptoms will be most informative, Dr Berger added.

References

1. National Center on Sleep Disorders Research. National Institutes of Health Sleep Disorders Research Plan. November 2011. www.nhlbi.nih.gov/files/docs/ncsdr/201101011NationalSleepDisordersResearchPlanDHHSPublication11-7820.pdf. Accessed August 30, 2018.
2. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines): Cancer-Related Fatigue. Version 2.2018. February 20, 2018. www.nccn.org/professionals/physician_gls/PDF/fatigue.pdf. Accessed August 17, 2018.
3. Goldstein D, Bennett BK, Webber K, et al. Cancer-related fatigue in women with breast cancer: outcomes of a 5-year prospective cohort study. J Clin Oncol. 2012;30:1805-1812.
4. Fagundes CP, Shi Q, Vaporciyan AA, et al. Symptom recovery after thoracic surgery: measuring patient-reported outcomes with the MD Anderson Symptom Inventory. J Thorac Cardiovasc Surg. 2015;150:613.e2-619.e2.
5. Jim HSL, Small B, Faul LA, et al. Fatigue, depression, sleep, and activity during chemotherapy: daily and intraday variation and relationships among symptom changes. Ann Behav Med. 2011;42:321-333.
6. Liu L, Rissling M, Neikrug A, et al. Fatigue and circadian activity rhythms in breast cancer patients before and after chemotherapy: a controlled study. Fatigue. 2013;1:12-26.
7. Palesh OG, Roscoe JA, 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;28:292-298.
8. Mark S, Cataldo J, Dhruva A, et al. Modifiable and non-modifiable characteristics associated with sleep disturbance in oncology outpatients during chemotherapy. Support Care Cancer. 2017;25:2485-2494.
9. Berger AM, Visovsky C, Hertzog M, et al. Usual and worst symptom severity and interference with function in breast cancer survivors. J Support Oncol. 2012;10:112-118.
10. Nelson AM, Jim HSL, Small BJ, et al. Sleep disruption among cancer patients following autologous hematopoietic cell transplantation. Bone Marrow Transplant. 2018;53:307-314.
11. Coles T, Tan X, Bennett AV, et al. Sleep quality in individuals diagnosed with colorectal cancer: factors associated with sleep disturbance as patients transition off treatment. Psychooncology. 2018;27:1050-1056.
12. Gosselin TK, Beck S, Abbott DH, et al. The symptom experience in rectal cancer survivors. J Pain Symptom Manage. 2016;52:709-718.
13. Savard J, Ivers H, Villa J, et al. Natural course of insomnia comorbid with cancer: an 18-month longitudinal study. J Clin Oncol. 2011;29:3580-3586.
14. Goedendorp MM, Gielissen MF, Verhagen CA, Bleijenberg G. Development of fatigue in cancer survivors: a prospective follow-up study from diagnosis into the year after treatment. J Pain Symptom Manage. 2013;45:213-222.
15. Chang WP, Lin CC. Changes in the sleep–wake rhythm, sleep quality, mood, and quality of life of patients receiving treatment for lung cancer: a longitudinal study. Chronobiol Int. 2017;34:451-461.
16. Chen ML, Liu LN, Miaskowski C, et al. Presurgical symptom profiles predict quality of life 2 years after surgery in women with breast cancer. Support Care Cancer. 2016;24:243-251.