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Precisely Timed Light May Reduce Chemotherapy-Related Sleep Disruption and Fatigue

Precisely Timed Light May Reduce ChemotherapyRelated Sleep Disruption and Fatigue

Results from a controlled pilot study

By Catherine Darley, ND

REFERENCE

Wu H-S, Davis JE, Chen L. Bright light shows promise in improving sleep, depression, and quality of life in women with breast cancer during chemotherapy: findings of a pilot study. Chronobiol Int. 2021;38(5):694-704.

STUDY OBJECTIVE

To learn if home-based bright-light treatment customized to participants’ circadian phase preference would impact their sleep, fatigue, daytime sleepiness, depression, and quality-of-life measures while undergoing chemotherapy

DESIGN

Controlled pilot study

PARTICIPANTS

A total of 18 women newly diagnosed with breast cancer stages I to III participated in this study, with 16 completing it in entirety. Their ages ranged from 29 to 68 years, with the majority being white/Caucasian and college-educated. Most were being treated for stage II breast cancer. People were excluded if they had a history of seasonal affective or psychiatric disorders, were on photosensitizing or sleep medications, or had other malignancies or cancer treatments, along with other exclusions.

INTERVENTION

Investigators assigned participants to the experimental condition (bright blue-green light of 12,000 lux) or the control condition (dim red light of 5 lux). Participants received the light therapy for 30 minutes via a light visor each day at customized times depending on their circadian chronotype. Evening types began the light within 30 minutes of waking, and morning types had the light exposure between 7 to 8 pm. The light therapy was delivered for 21 consecutive days after the second cycle of chemotherapy.

STUDY PARAMETERS ASSESSED

Investigators collected a variety of both subjective and objective measures. They collected baseline data prior to participants’ initiating their second cycle of chemotherapy, and they performed final data collection on the day of the third chemotherapy treatment. Subjective measures included the Patient-Reported Outcomes Measurement Information System (PROMIS), which measures fatigue. Subjective sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI), and daytime sleepiness was assessed using the Epworth Sleepiness Scale (ESS). The Patient Health Questionnaire (PHQ-9) measured depression. Quality of life was measured using the European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC QLQ-C30). Sleep was assessed objectively using ambulatory polysomnography (PSG).

PRIMARY OUTCOME MEASURES

Investigators computed the relative change from baseline data to post-test data for both groups. Also a between-group analysis was done using 2 sample t-tests.

KEY FINDINGS

The experimental group had meaningful improvements in their sleep, both subjectively and objectively. Subjectively, falling asleep took less time—only 10 minutes in the experimental group versus 20 minutes in controls (P=0.045). This was corroborated by the PSG data (14 vs 63 min) from the 7 participants who used the PSG at home. Polysomnography showed a longer sleep time of 467 minutes and greater sleep efficiency at 74% in those who received bright light, versus 315 minutes total sleep and only 58% sleep efficiency in the control group. While these differences did not reach statistical significance, the trends in the short time period of the study warrant mention here. There was a 30% relative decrease in depression for those in the bright light group, and a 24% relative increase in the controls, but again these did not reach statistical significance. Quality of life was less negatively impacted by chemotherapy for those in the intervention group, with symptom intensity (as reported in the EORTC questionnaire scores) increasing 33% versus 166% in the control group. Fatigue levels did not change with bright-light therapy, despite apparently better sleep.

PRACTICE IMPLICATIONS

Given that fatigue and sleep disruption affect a large proportion of breast cancer patients, if validated, this approach could have a significant impact on a large population of women. Light therapy is relatively low-cost and easy to implement and has few, if any, negative side effects. Light therapy is currently used to treat circadian rhythm sleep-wake disorders and seasonal affective disorder. Maybe we can add adjunct to chemotherapy to that list?

The sleep improvements seen with light therapy in this study were quite amazing, with greater than 2 hours more sleep each night and 16% greater sleep efficiency in the experimental group. For the individual cancer patient (and other patients), improved sleep can translate into better daytime function. Adults are recommended to get between 7 to 9 hours of sleep nightly.1 The light therapy group achieves this goal after 21 days of treatment.

Poor sleep quality or duration will translate into multiple impairments from performance to mood to health measures. Notably, sleep-stage percentages remained abnormal in both the control and experimental groups, with 78% Stage 2 sleep (increased from normal of about 50%) and reduced REM and Stage 3 sleep percentages. It may be that fatigue levels did not change in part because REM and Stage 3 sleep were reduced from normal.

This study was unique in using the participants’ chronotype to determine the time of day for the intervention. Our chronotype is an inherent characteristic, set by the suprachiasmatic nucleus in the hypothalamus, and reinforced by the clock genes within each cell.2 With light therapy (and slightly by melatonin supplementation), the circadian phase can be manipulated. However, once the light therapy is discontinued, the person will return to their natural phase preference. Therefore, a third evaluation of cancer patients after the treatment period would be useful to see if any changes recorded when doing active light therapy are maintained (and if so, for how long), or if light therapy needs to be ongoing. It is interesting that the treatment group was not separated into the 2 treatment conditions: light in the morning versus light at night. Light at these different times of day has significantly different impacts on our circadian system.3 Light in the evening will suppress evening melatonin production and shift the circadian rhythm later, while light in the morning will have the opposite effect, shifting the circadian rhythm earlier, and boosting the next night’s nocturnal melatonin peak. The researchers intentionally customized the light-therapy timing so as to shift participants to a more neutral circadian phase. This furthers the earlier work by Dr. Sonia Ancoli-Israel,4 which demonstrated that morning bright light worked to prevent both quality of life and fatigue from declining during chemotherapy.

Additionally, humans have historically been exposed to bright light in the morning, but not in the evening. Our circadian system evolved in accordance with this pattern in the color and brightness of light in the natural environment. It is known that artificial light at night can have negative effects on human health, including cancer risk. The International Agency for Research on Cancer came to the conclusion that night shift is a probable carcinogen (Group 2A carcinogen).5 Other research reviews have found that women who work night shift are at increased risk of breast cancer.6 For these reasons we are cautious in the clinic about giving light therapy during a patient’s circadian night.

In future studies with more participants, it would be interesting to see the morning and evening treatment groups

This study was unique in using the participants’ chronotype to determine the time of day for the intervention. “ ”

reported separately. Also, there was no mention of the ambient light conditions of the control group in their homes and lifestyles, so it is unknown how much light they were getting at the intervention times. The control group may have been in bright-light (or blue-light) conditions in their home environment.

This pilot study gives hope that light therapy, a relatively easy and low-cost treatment, can improve the sleep and quality of life of women receiving chemotherapy for breast cancer. Stay tuned as this approach develops.

REFERENCES

1 Watson NF, Badr MS, Belenky G, et al. Recommended amount of sleep for a healthy adult: consensus statement of the American Academy of Sleep and Sleep

Research Society. Sleep. 2015;38(6):843-844. 2 Scammell TE, Arrigoni E, Lipton JO. Neural circuitry of wakefulness and sleep.

Neuron. 2017;94(4);747-765. 3 Emens JS, Burgess HJ. Effect of light and melatonin and other melatonin receptor agonists on human circadian physiology. Sleep Med Clin. 2015;10(4):435-453. 4 Ancoli-Israel S, Rissling M, Neikrug A, et al. Light treatment prevents fatigue in women undergoing chemotherapy for breast cancer. Support Care Cancer. 2012;20(6):1211-1219. 5 Erren TC, Morfeld P, Groß JV, et al. IARC 2019: “Night shift work” is probably carcinogenic: what about disturbed chronobiology in all walks of life? J Occup Med

Toxicol. 2019;14:29. 6 Gehlert S, Clanton M. Shift work and breast cancer. Int J Environ Res Public Health. 2020;17(24):9544.

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