Cancer Patients Near End of Life Have Disrupted Sleep-Wake Cycles

NEW YORK (Reuters Health) - Cancer patients receiving palliative care have disturbed sleep-wake cycles, researchers from Canada have found.

Sleep problems plague nearly all patients with advanced cancer, and non-pharmacological interventions are needed to improve patients’ circadian rhythms, the team notes online November 16 in Chronobiology International.

"Sleep-wake cycles are markedly disrupted in palliative cancer patients, especially near the end of life. A less rhythmic sleep-wake cycle was associated with shorter time to death (from the first home visit related to the study) and with lower 24-hour light exposure," Marie Solange Bernatchez of Laval University in Quebec City told Reuters Health by email.

Bernatchez and her colleagues analyzed the sleep-wake cycles and rest-activity rhythms of 55 adult cancer patients (mean age, 66) who were receiving palliative care for advanced cancer while living at home. The patients had an Eastern Cooperative Oncology Group scale (ECOG) performance status of 2 or 3, indicating significant alteration in daytime functioning.

Forty-five patients had ECOG 2 status; 10 had ECOG 3 status.

The researchers visited the patients at home twice, one week apart. At these visits, the patients, with the help of their caregivers if needed, completed questionnaires, including the Mini-Mental State Examination; the Physical Symptoms Questionnaire; the Functional Assessment of Chronic Illness Therapy Fatigue Scale; the Hospital Anxiety and Depression Scale; the Missoula-VITAS Quality of Life Index; and the Sleep Behaviors Questionnaire.

For seven consecutive days, participants wore the Actiwatch-64 actigraphic recorder from Philips Respironics on their wrist to monitor orientation and movement in 30-second periods throughout the day. They also wore the Actilight light recorder from Cambridge Neurotechnology on their clothes when out of bed to monitor light intensity in lux in 30-second periods.

Patients completed daily sleep diaries to help score naps, periods of light and darkness, and times when the actigraph was removed. And they kept a pain diary to record on a scale from 0 to 10 their daily estimates of the worst pain they'd felt during the past 24 hours. At the end of the week, the researchers and patients completed any remaining questionnaires and scales.

The researchers found dampened circadian rhythm, low mean activity level, early mean daytime peak activity time, late-morning activity-starting time, and early evening activity decline. Also, less-rhythmic sleep-wake cycles were linked with shorter time to death from the first home visit and with lower 24-hour light exposure.

On average, participants had severely disrupted sleep-wake activity cycles. Peak activity rhythm (acrophase) averaged 13 hours and 35 minutes; activity level (mesor) averaged 45.4; and rhythm amplitude averaged 47.0.

On average, time from low to high activity (up-mesor) was 8 hours and 18 minutes, and time from high to low activity (down-mesor) was 19 hours and 23 minutes.

No significant differences were found on any circadian rest-activity rhythm variable between patients with ECOG 2 versus ECOG 3 status. Moderate effect sizes were seen for differences on mean activity level, rhythm amplitude, and morning-activity starting time.

Dr. Kimberly A. Curseen, a palliative-cancer expert at Emory University in Atlanta, Georgia, told Reuters Health by email, "We often recommend behavioral changes to improve sleep for patients, but these findings did not find a significant correlation between maladaptive sleep behaviors and sleep-wake cycles. So behavioral therapy may not be sufficient as the only intervention for suffering from disrupted sleep-wake cycles."

"Lower light exposure is associated with greater disruption in sleep-wake cycles. The role of bright-light therapy is not clear but may be useful," said Dr. Curseen, who was not involved in the study.

"The sample size was small and only a few patients had an ECOG of 3, which may affect generalizability in palliative-care practices. Lack of diversity may affect this as well," she noted.

Dr. Reena Mehra, a sleep-medicine specialist at Cleveland Clinic, in Ohio, who was not involved in the study, said the findings are consistent with those from prior literature.

"However, they shed light on indirect measures of the circadian rhythm collected by actigraphy, which is unique," she told Reuters Health by email.

"The major strength was the use of actigraphy monitoring to collect objective data. A limitation was that for truly accurate assessments of circadian biology, careful experiments in a research lab under standardized conditions should be performed; also, the core body temperature minimum, which is tied closely with our circadian rhythm, is not precisely measured by actigraphy. Another limitation is the lack of a control group," she pointed out.

"The study sets the stage for further studies to illuminate our understanding of the likely bi-directional relationships of sleep and pain, which is important in palliative care of cancer patients, e.g., does improving sleep improve ability to control pain?" she said.

Dr. Mehra added, "The research also sets the stage for further study of types of sleep interventions which could be used, such as hypnotic medications or non-pharmacologic strategies (e.g., phototherapy, relaxation techniques, etc.) to improve sleep and in turn improve outcomes that are important to patients and their families, such as daytime sleepiness, fatigue and pain control."


Chronobiol Int 2017.


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