ABSTRACT
Introduction: Disrupted sleep and sleep-wake activity are frequently observed in cancer patients undergoing oncological treatment. These disruptions are often associated with aggravated symptom burden and diminished health-related quality of life that in turn may compromise treatment adherence and, thus, effectiveness. In addition, disrupted sleep has been linked to carcinogenic processes, which ultimately could result in worse prognostic outcomes. Aims: Our aim was to systematically review and conduct a meta-analysis of studies examining the associations between sleep and sleep-wake activity and prognostic outcomes in cancer patients undergoing oncological treatment. Methods: A comprehensive systematic search of English language papers was undertaken in June 2020 using PubMed, The Cochrane Library, and CINAHL. Two reviewers independently screened 4,879 abstracts. A total of 26 papers were included in the narrative review. Thirteen papers reporting hazard ratios reflecting associations between a dichotomized predictor variable (sleep) and prognostic outcomes were subjected to meta-analysis. Results: Nineteen of the 26 eligible studies on a total of 7,092 cancer patients reported associations between poorer sleep and poorer response to treatment, shorter time to progression, and/or reduced overall survival, but were highly heterogeneous with respect to the sleep and outcome parameters investigated. Meta-analysis revealed statistically significant associations between poor self-reported sleep and reduced overall survival (HR = 1.33 [95% CI 1.09-1.62], k = 11), and shorter time to progression (HR = 1.40 [95% CI 1.23-1.59], k = 3) and between poor objectively assessed sleep and reduced overall survival (HR = 1.74 [95% CI 1.05-2.88], k = 4). Conclusion: The current findings indicate that disturbed sleep during treatment may be a relevant behavioral marker of poor cancer prognosis. The limited number of studies, the common use of single item sleep measures, and potential publication bias highlight the need for further high quality and longitudinal studies.
ABSTRACT
Background: Tumors of the central nervous system (CNS) are the most common solid childhood malignancy. Over the last decades, treatment developments have strongly contributed to the improved overall 5-year survival rate, which is now approaching 75%. However, children now face significant long-term morbidity with late-effects including sleep disorders that may have detrimental impact on everyday functioning and quality of life. The aims of this study were to (1) describe the symptoms that lead to polysomnographic evaluation; (2) describe the nature of sleep disorders diagnosed in survivors of childhood CNS tumor using polysomnography (PSG); and (3) explore the association between tumor location and diagnosed sleep disorder. Methods: An extensive literature search following the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines (PRISMA) was conducted. Inclusion criteria were children and adolescents diagnosed with a CNS tumor age <20 years having a PSG performed after end of tumor treatment. The primary outcome was sleep disorder confirmed by PSG. Results: Of the 1,658 studies identified, 11 met the inclusion criteria. All the included articles were appraised for quality and included in the analysis. Analyses indicated that sleep disorders commonly occur among childhood CNS tumor survivors. Symptoms prior to referral for PSG were excessive daytime sleepiness (EDS), fatigue, irregular breathing during sleep and snoring. The most common sleep disorders diagnosed were sleep-related breathing disorders (i.e., obstructive sleep apnea) and central disorders of hypersomnolence (i.e., narcolepsy). Conclusion: Our findings point to the potential benefit of systematically registering sleep disorder symptoms among CNS tumor patients together with tumor type and treatment information, so that at-risk patients can be identified early. Moreover, future rigorous and larger scale controlled observational studies that include possible modifiable confounders of sleep disorders such as fatigue and obesity are warranted. Clinical Trial Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021243866, identifier [CRD42021243866].
ABSTRACT
BACKGROUND: Radiation therapy (RT) to the brain may result in cognitive impairment. The primary objective of the present study was to examine the relationship between RT dose to the hippocampus and learning and memory functions. Secondary objective was to examine relationships between doses to other brain structures and specific cognitive functions. METHODS: A cross-sectional analysis was undertaken in 78 primary brain tumour patients after RT. Cognitive function was assessed by neuropsychological tests. Test scores were standardized using normative data adjusted for age and level of education. Test-specific cognitive impairment was determined as a z-score ≤-1.5. Radiation dose to brain structures and test-specific cognitive impairment outcomes were fitted to a logistic regression model. RESULTS: High RT dose to the left hippocampus was associated with impaired verbal learning and memory (p = 0.04). RT dose to the left hippocampus, left temporal lobe, left frontal lobe and total frontal lobe were associated with verbal fluency impairment (p < 0.05) and doses to the thalamus and the left frontal lobe with impaired executive functioning (p ≤ 0.03). Finally, RT dose to the brain and thalamus were associated with impaired processing speed (p ≤ 0.05). CONCLUSION: The present study indicates that the hippocampus may be vulnerable to radiation and that high radiation doses to the left hippocampus may lead to significant verbal learning and memory impairment. High RT doses to the left hippocampus and other left side structures may result in impairments in verbal fluency, executive function, and processing speed. Validation of these findings are being undertaken in a prospective study.
