Sleep disturbances are prevalent in cancer patients and linked to levels of fatigue and depressive symptoms with a major impact on quality of life. A growing body of evidence links sleep disturbances with various health outcomes, including increased risk of depression, cancer, and overall mortality. Inflammation is suggested to be an underlying mechanism both driving and maintaining the symptom cluster of sleep disturbance, fatigue and depressive symptoms, as well as being bi-directionally linked to sleep. The main purpose of the present study is to investigate the prevalence of sleep disturbance and its association with psychological and physical symptoms as well as the clinical response to ICI in non-small-cell lung cancer patients (NSCLC), with a secondary aim of exploring the role of inflammation.
A total of 240 cancer patients diagnosed with advanced NSCLC, referred to treatment with ICI will be enrolled in this prospective observational study. Patients will be assessed prior to initiation of treatment (baseline) and every third subsequent week, corresponding to each treatment cycle over a period of 18 weeks. Assessments will include questionnaires, sleep diaries, actigraphy, and blood and saliva samples to examine sleep, fatigue, psychological and physical symptoms, the sleep-wake-cycle, inflammation, and cortisol. Additionally, the patients will be asked to complete a reduced questionnaire every week within the 18 weeks period, to address weekly fluctuations in sleep quality, fatigue, and mood. Treatment response is assessed after 9 and 18 weeks. Aims: 1. To explore possible associations between sleep and the clinical response to treatment with ICI. 2. To investigate the prevalence of sleep disturbance in patients with NSCLC during treatment with ICI. 3. To prospectively assess changes in sleep parameters over the course of treatment. 4. To examine associations between sleep parameters and fatigue, depression, anxiety, and inflammation. 5. To explore possible associations between sleep, fatigue, depression, inflammatory responses and the clinical response to treatment with ICIs. Hypotheses: Patients with high levels of sleep disturbance (insomnia severity) will experience 1) poorer clinical response to ICI, 2) more depressive symptoms, 3) higher levels of fatigue, 4) poorer overall health-related quality of life (HRQoL), 5) higher levels of inflammation.
Study Type
OBSERVATIONAL
Enrollment
49
Aarhus University Hospital
Aarhus, Central Jutland, Denmark
Clinical response to treatment
Radiological evaluation of the clinical response to treatment with ICI, according to RECIST criteria.
Time frame: Changes from baseline to 9 and 18 weeks after treatment initiation, respectively.
Insomnia Severity
Changes in insomnia severity as measured with The Insomnia Severity Index (ISI). Total score ranges from 0 to 28. Interpreted as follows: absence of insomnia (0-7); sub-threshold insomnia (8-14); moderate insomnia (15-21); and severe insomnia (22-28).
Time frame: Weekly from baseline to 18 weeks after treatment initiation, and follow-up 1, 2 and 3 years from baseline, respectively.
Sleep diary
Changes in Standard sleep metrics (nightly sleep onset latency (SOL), wakefulness after initial sleep onset (WASO), total sleep time (TST), total time spent in bed (TIB), sleep efficiency (SE).
Time frame: Baseline, and week 3, 6, 9, 12, 15 and 18, respectively.
Fatigue
Changes in subjective fatigue as measured with the Multidimensional Fatigue Symptom Inventory - Short Form (MFSI-SF). Subscales (general, physical, emotional, and mental fatigue) are summed and the vigor scale subtracted to create a fatigue total score, with higher scores indicating higher levels of fatigue.
Time frame: Baseline, and week 3, 6, 9, 12, 15 and 18, respectively, and follow-up 1, 2 and 3 years from baseline, respectively.
Depressive symptoms
Changes in depressive symptoms as measured with the Patient-Reported Outcomes Measurement Information System (PROMIS®) Depression - Short Form 8a. Total raw score ranges from 8 to 40, with higher scores indicating greater severity of depression.
Time frame: Baseline, and week 3, 6, 9, 12, 15 and 18, respectively, and follow-up 1, 2 and 3 years from baseline, respectively.
Health-related quality of life
Changes in health-related quality of life as measured with The European Organization for Research and Treatment of Cancer, Quality of Life questionnaire for cancer patients (EORTC QLQ-C30). The standardized raw score, ranges from 0 to 100; a higher score represents a higher ("better") level of functioning, or a higher ("worse") level of symptoms.
Time frame: Baseline, and week 3, 6, 9, 12, 15 and 18, respectively, and follow-up 1, 2 and 3 years from baseline, respectively.
Disease specific health-related quality of life
Changes in disease specific health-related quality of life as measured with The European Organization for Research and Treatment of Cancer, Quality of Life Lung Cancer Module (EORTC QLQ-LC29). The standardized raw score, ranges from 0 to 100; a high score for the symptom scales / single items represents a high level of symptomatology or problems.
Time frame: Baseline, and week 3, 6, 9, 12, 15 and 18, respectively, and follow-up 1, 2 and 3 years from baseline, respectively.
Perceived Stress
Changes in perceived stress as measured with The Perceived Stress Scale (PSS). Total score ranges from 0 to 40, with higher scores indicating higher perceived stress.
Time frame: Baseline, and week 3, 6, 9, 12, 15 and 18, respectively, and follow-up 1, 2 and 3 years from baseline, respectively.
Sickness behavior
Changes in subjective sickness behavior as measured with the Sickness Questionnaire (SicknessQ). Total score ranges from 0 to 30, with higher scores indicating more sickness behaviour.
Time frame: Baseline, and week 3, 6, 9, 12, 15 and 18, respectively, and follow-up 1, 2 and 3 years from baseline, respectively.
Cortisol
Cortisol awakening response (CAR), and the diurnal cortisol slope (DCS)
Time frame: Baseline, and week 3, 6, 9, 12, 15 and 18, respectively.
Inflammatory response 1
CRP
Time frame: Baseline, and week 3, 6, 9, 12, 15 and 18, respectively.
Inflammatory response 2
IL-6
Time frame: Baseline, and week 3, 6, 9, 12, 15 and 18, respectively.
Inflammatory response 3
TNF-a
Time frame: Baseline, and week 3, 6, 9, 12, 15 and 18, respectively.
Inflammatory response 4
Se-Cortisol
Time frame: Baseline, and week 3, 6, 9, 12, 15 and 18, respectively.
Inflammatory response 5
White blood cell count.
Time frame: Baseline, and week 3, 6, 9, 12, 15 and 18, respectively.
Actigraphy 1
Objective sleep outcome. Nightly sleep onset latency (SOL)
Time frame: Baseline to 18 weeks after initiation of treatment.
Actigraphy 2
Objective sleep outcome: Wakefulness after initial sleep onset (WASO)
Time frame: Baseline to 18 weeks after initiation of treatment.
Actigraphy 3
Objective sleep outcome: Total sleep time (TST)
Time frame: Baseline to 18 weeks after initiation of treatment.
Actigraphy 4
Objective sleep outcome: Total time spent in bed (TIB)
Time frame: Baseline to 18 weeks after initiation of treatment.
Actigraphy 5
Objective sleep outcome: Sleep efficiency (SE, i.e., the percent of the time asleep out of amount of time spent in bed)
Time frame: Baseline to 18 weeks after initiation of treatment.
Actigraphy 6
Objective sleep outcome: Circadian activity rhythms.
Time frame: Baseline to 18 weeks after initiation of treatment.
Disease status
Changes in disease status after treatment initiation with ICI. Changes are evaluated according to RECIST criteria.
Time frame: 1, 2 and 3 years from treatment initiation (baseline).
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