The association of quality of life with potentially remediable disruptions of circadian sleep/activity rhythms in patients with advanced lung cancer

Abstract

Background: Cancer patients routinely develop symptoms consistent with profound circadian disruption, which causes circadian disruption diminished quality of life. This study was initiated to determine the relationship between the severity of potentially remediable cancer-associated circadian disruption and quality of life among patients with advanced lung cancer.

Methods: We concurrently investigated the relationship between the circadian rhythms of 84 advanced lung cancer patients and their quality of life outcomes as measured by the EORTC QLQ C30 and Ferrans and Powers QLI. The robustness and stability of activity/sleep circadian daily rhythms were measured by actigraphy. Fifty three of the patients in the study were starting their definitive therapy following diagnosis and thirty one patients were beginning second-line therapy. Among the patients who failed prior therapy, the median time between completing definitive therapy and baseline actigraphy was 4.3 months, (interquartile range 2.1 to 9.8 months).

Results: We found that circadian disruption is universal and severe among these patients compared to non-cancer-bearing individuals. We found that each of these patient's EORTC QLQ C30 domain scores revealed a compromised capacity to perform the routine activities of daily life. The severity of several, but not all, EORTC QLQ C30 symptom items correlate strongly with the degree of individual circadian disruption. In addition, the scores of all four Ferrans/Powers QLI domains correlate strongly with the degree of circadian disruption. Although Ferrans/Powers QLI domain scores show that cancer and its treatment spared these patients' emotional and psychological health, the QLI Health/Function domain score revealed high levels of patients' dissatisfaction with their health which is much worse when circadian disruption is severe. Circadian disruption selectively affects specific Quality of Life domains, such as the Ferrans/Powers Health/Function domain, and not others, such as EORTC QLQ C30 Physical Domain.

Conclusions: These data suggest the testable possibility that behavioral, hormonal and/or light-based strategies to improve circadian organization may help patients suffering from advanced lung cancer to feel and function better.

Figure 1

Comparison of the circadian activity rhythm of healthy controls and lung cancer patients. Healthy controls (A) show a more robust circadian activity rhythm compared to lung cancer inpatients and outpatients combined (B). Outpatients (C) have better circadian organization of sleep/activity compared to the hospitalized group (D). Concurrent plot of all groups (E) shows that peak daytime activity is compromised in all lung cancer patients and especially among hospitalized ones. Nightly sleep is, however, markedly and identically disturbed among lung cancer patients regardless of where it is measured.

Figure 2

Relationship between quality of life and circadian organization among inpatients and outpatients. Lung cancer patients who are most quiet in the nighttime and active during the day (highest circadian Rhythm Quotient) are the least fatigued, both in hospitalized and at home settings (A). The more stable the day-to-day pattern of daily activity and nighttime sleep (24-hour Autocorrelation), the better the overall ability to fulfill daily functions among outpatients (B), and the greater the patient's satisfaction with his/her health among inpatients and outpatients (C). The greater the peak activity, the greater the patient's overall satisfaction with life among outpatients (D, E).

Figure 3

The relationships among two measures of quality of life and circadian rhythm stability. The greater the circadian rhythm in activity/rest, the greater the PF Health and Functioning; the lower the EORTC Fatigue Score (A) and the greater the EORTC Global Health Score (C) in the group as a whole. These relationships are especially clear among outpatients (B, D). *Significant r, p < 0.05. ^†Marginal r, p=0.08.