Purpose: Sleep is essential for life, as well as having a major impact on quality of life. Not much attention has been given to this important factor in the care of lung cancer patients.
Patients and Methods: We retrospectively analyzed a cohort of 404 lung cancer patients treated in our institute between 2010 and 2018. Data about sleep quality, distress and pain were self-reported by questionnaires administered to patients at their first clinic visit to the Institute of Oncology. Sex, age, histology, stage, smoking and marital status were extracted from the patients’ charts. Uni- and multi-variate analyses were carried out to evaluate the correlation of these factors with survival.
Results: Most patients reported some level of distress and pain. Sleep abnormalities were reported by 58.7% of patients. Distress, pain and bad sleep were correlated with shorter survival in univariate analyses; however, only sleep remained associated with survival in multivariate analysis. Patients reporting bad sleep had a median survival of 16 months, compared to 27 months for patients reporting good sleep (hazard ratio 1.83, 95% C.I. 1.27– 2.65). Frequent arousals at night were more tightly correlated with survival than difficulty falling asleep.
Conclusion: Sleep quality, as reported by lung cancer patients, is highly correlated with survival. Further studies are required to comprehend whether poor sleep quality is directly impacting survival or is a result of the cancer aggressiveness and patients’ conditions.


Keywords: lung cancer, sleep quality, survival, distress, pain, patient-reported outcomes


INTRODUCTION


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Sleep remains one of the great mysteries of biology, comprising a period of vulnerable apparent inactivity, observed basically in all animals with a nervous system.1,2 The overarching need for sleep across species substantiates its essentially for life. In humans, sleep quality and length are associated with mortality in a complex manner.3 Both short4 and long sleep periods were associated with increased mortality and morbidity including obesity, diabetes and cardiovascular diseases.5 Sleep disturbances are correlated with increased blood levels of inflammatory mediators.6 In a mice model, sleep disruption caused accelerated atherosclerosis and impacted hematopoiesis.7 Sleep is essential for memory consolidation and other cognitive functions.8 Protein phosphorylation and various molecular correlates of the need-for-sleep, and of sleep-wake cycles have been described.9 Recent reports of sleep impact on chromatin modulations and repair of double-strand DNA breaks in neurons might offer an explanation to the essentially of sleep.10

Complex interactions exist between sleep abnormalities and cancer. Sleeping disturbances clearly violate the circadian rhythm.11 Association of the circadian rhythm with various aspects of cancer biology,12 gene expression,13 and cancer metabolism14 has been identified and studied. Disturbed circadian rhythm in mice increased the risk of liver damage and hepatic cancer.15 Insomnia and disturbances in the circadian rhythm can lead to reduced melatonin secretion.16 Melatonin in turn impacts the immune system favorably, potentially opposing cancer through various mechanisms17 such as antioxidative activity and modulation of the immune response.18 Sleep disturbances have been reported to correlate with increased cancer risk.19,20

Cancer patients commonly report abnormal sleep.21,22 Short sleep duration and snoring prior to cancer diagnosis were correlated with shorter survival of breast cancer patients.23 Poor sleep quality was correlated with reduced survival among advanced breast cancer patients,24 with most deaths being breast cancer-related rather than other co-morbidities.25 This association was independent of potential confounders as depression, cancer treatment, and cortisol levels. In that study, survival was not associated with sleep duration but rather with sleep efficiency (total sleep time/time spent in bed). Sleep disturbances were correlated with more aggressive cancer features among breast cancer patients.26 Deciphering cause and effect here is difficult, as cancer may negatively impact sleep. A model of breast cancer in immune-competent mice demonstrated cancer-induced abnormal orexin signaling causing fragmented sleep as well as altered glucose metabolism.27 Several mechanisms may thus explain an association of reduced sleep quality with cancer aggressiveness.22,28–30 Importantly, although disturbed sleep, depression, fatigue and stress seem closely correlated, each of these symptoms may endow a separate pathogenesis.29

Lung cancer is the most common cause of cancer-related death worldwide.31 Night shift work, known to be associated with poor sleep quality, has been correlated with increased incidence of several cancers including lung cancer.32 Melatonin was demonstrated to induce apoptosis, reduce cell proliferation of lung cancer cell lines and reduced metastatic spread in mouse models of lung cancer.33 In a mouse model of lung cancer, circadian rhythm disruption accelerated lung cancer progression, with evidence of a direct tumor-suppressive role for circadian clock genes.34 Sleep disturbances are common in lung cancer patients.35 The psychological, physiological and molecular correlates of poor sleep may impact lung cancer progression and response to therapy. In this study, we aimed to examine whether sleep quality correlated with survival of lung cancer patients. We evaluated sleep based on the reply to a single question, and demonstrate a significant correlation of sleep quality assessed this way with patients’ survival. To the best of our knowledge, this is the first report of the association of sleep quality with survival in lung cancer patients, as well as a unique demonstration of the utility of a simple self-reported sleep quality in this context.

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