Advanced cancer patients in a randomized clinical trial of night-simulating eyeglasses observed to have a normal 24-h circadian rhythm during chemotherapy

Abstract

Objectives: Cancer patients routinely exhibit dysfunctional circadian organization. Indeed, a dysfunctional circadian organization is a hallmark of advanced cancer. A cohort of advanced cancer patients undergoing chemotherapy was recruited to investigate whether manipulating exposure to blue light could restore or ameliorate their circadian organization.

Methods: Thirty advanced metastatic cancer patients participated in a randomized crossover trial to evaluate whether blue light-blocking night-simulating eyeglasses could ameliorate a disrupted circadian organization better than sham eyeglasses. Circadian organization was evaluated by actigraphy and patients' self-reports of sleep, fatigue, and quality of life. Kruskal-Wallis tests compared patients' outcomes in circadian organization with a cohort of non-cancer, disease-free individuals with normal sleep as a negative control, and with advanced cancer patients with disrupted circadian organization as a positive control. Quality-of-life outcomes of the patients were compared with population-based controls (negative controls) and with cohorts of advanced cancer patients (positive controls).

Results: Actigraphy measurements, self-reported sleep, fatigue levels, and quality-of-life outcomes of trial participants were similar to those of negative controls with a normal circadian organization, in spite of the trial patients' concurrent chemotherapy. Night-simulating glasses did not improve circadian organization. The 24-h correlation of day-to-day rhythms of rest and activity was 0.455 for the experimental eyeglasses and 0.476 for the sham eyeglasses (p = 0.258). Actigraphic and patient-reported outcomes compared favorably to outcomes of positive controls.

Conclusion: The circadian organization of patients in this study unexpectedly resembled that of healthy controls and was better than comparison populations with disrupted circadian organization. The study clinic implements chronomodulated chemotherapy and a systematic, supportive integrative treatment protocol. Results suggest a need for further research on interventions for circadian rhythm. Although the study intervention did not benefit the participants, this work highlights the value of supporting circadian time structure in advanced cancer patients.

Keywords: Circadian organization; cancer; chronomodulated chemotherapy; circadian rhythms; fatigue; integrative therapies; quality of life; sleep.

Figure 1.

Comparison of trial participants with outside cohorts (ad hoc analysis). The figure describes the ad hoc analysis evaluating the underlying causes of why this trial failed. The chart identifies the cohorts used in the analysis. Participants’ results were compared to positive controls (cancer cohorts with a disrupted CO) and negative controls. Positive and negative controls were found for actigraphy, PSQI, EORTC QLQ-C30, and QLI. Piper Fatigue Scale had no positive control. Finally, a comparison was made with a hospital patient cohort of recurrent breast and colon cancer patients as a sound comparator cohort for a positive control using the EORTC QLQ-C30.

Figure 2.

Study flowchart describing the participant recruitment process and participant retention.

Figure 3.

The 24-h activity counts (mean accelerations/minute ± standard error) of Block advanced cancer patients, the advanced cancer patient comparison group, and controls without sleep problems. The three groups differ significantly (Wilcoxon, p = 0.0105). The Block and control patients do not differ significantly (p = 0.6016), while the Block and control groups do differ significantly from the comparison patients (p = 0.0159 and p = 0.0140, respectively).

Figure 4.

Kaplan–Meier survival curves: the trial participants (Block advanced cancer patients), omitting hormonally driven cancers (e.g. breast, prostate), and the advanced cancer comparison group.