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Background. The aims of this study were to examine the potential association between sleep problems, symptom burden, and survival in advanced cancer patients.

Methods. A prospective study of 294 patients with gastrointestinal cancer were administered questionnaires assessing sleep, depression, anxiety, stress, pain, fatigue, and health-related quality of life. Serum levels of cytokines including Interleukin (IL)-1α, IL-1β, Tumor Necrosis Factor-α, IL-10, IL-2, and IFNγ were measured to assess biological mediation between sleep and survival. Survival was measured as time from diagnosis to death.

Results. Fifty-nine percent of patients reported poor sleep quality, 53% reported poor sleep efficiency, 39% reported sleep latency greater than 30 minutes, and 45% reported sleeping <6 hours or >10 hours. We found a significant association between sleep duration and symptom burden. Shorter sleep duration was significantly associated with higher levels of fatigue (r=-0.169, p=0.01), pain (r=-0.302, p=0.01), anxiety (r=-0.182, p=0.01), depression (r=-0.172, p=0.003) and lower levels of quality of life (r=0.240, p=0.01). After adjustment for demographic, psychological, and disease-specific factors, short sleep duration was associated with reduced survival HR linear = 0.485, 95% CI=0.275-0.857] and there was also evidence for a quadratic pattern [HR quadratic =1.064, 95% CI=1.015-1.115] suggesting a curvilinear relationship between sleep duration and survival. Interleukin-2 was the only cytokine significantly related to survival [HR=1.01, p=0.003] and sleep duration [β=--30.11, p=-0.027]. When serum levels of IL-2 was added to the multivariable model, short and long sleep [β =-0.557, p=0.097; β=0.046, p=0.114] were no longer significantly related to survival, suggesting mediation by IL-2.

Conclusion. Sleep duration was associated with symptom burden and poorer survival and IL-2 was found to mediate the association between sleep and survival. Screening and treatment of sleep problems in patients diagnosed with cancer is warranted.