Abstract
Background: Patients with advanced non-small cell lung cancer (NSCLC) face poor prognosis. However, new therapies like immune checkpoint inhibitors (ICIs) have improved survival. Nevertheless, ICIs act through immune activation – a proposed underlying mechanism of frequently reported symptoms such as sleep and circadian disturbances. The objective of this study was to longitudinally investigate sleep and circadian rest-activity rhythms and associations with psychological symptoms in NSCLC during ICI treatment. Methods: Newly diagnosed NSCLC patients were included in this prospective study, assessing insomnia severity, total sleep time, circadian rest-activity rhythms, and psychological symptoms (fatigue, depression, and stress) during the first five months of ICI treatment, using validated questionnaires, sleep diaries and actigraphy. Results: Forty-nine patients were included. Prior to treatment, patients slept on average 5.8 hours/night and 49 % reported clinical levels of insomnia. Spontaneous improvements in insomnia severity and total sleep time were observed, along with marginal but non-significant improvements in circadian rest-activity rhythm robustness. Insomnia severity was significantly associated with higher levels of fatigue (p = .004), depression (p = .007), and perceived stress (p = .033). Moreover, lower circadian rest-activity robustness was associated with more fatigue (p = .021). At baseline, mean levels of fatigue, depression, and perceived stress were below clinical levels and declined further over time. Conclusion: Sleep disturbances, circadian disruption, and psychological symptom burden in NSCLC patients were greatest prior to and shortly after initiation of ICI treatment, with gradual improvement over the first five months. However, inter-individual differences in sleep and circadian disturbances were evident and linked to psychological symptoms.
| Original language | English (US) |
|---|---|
| Article number | 106740 |
| Journal | Sleep Medicine |
| Volume | 134 |
| DOIs | |
| State | Published - Oct 2025 |
Funding
Lisa Marie Wu's effort was supported by the European University of Brain and Technology (NeurotechEU grant 101004080) funded by the Erasmus + Programme of the European Union . With respect to circadian rest-activity rhythms, no established cut-off currently exists for CFI [44]. Furthermore, calculating cut-off values for clinical symptoms based on a small sample size is generally not recommended, as it can lead to biased, and non-generalizable thresholds [75,76]. However, to support comparisons in future studies, we report CFI medians from our data. No statistically significant main effect of time was found for CFI, so we report the baseline median CFI (M = .65), and the range of the 18 other time points (Mean range = .60–.69). Other studies have found the dichotomy index (I < O) a useful measure of clinical outcomes in cancer [77,78]. The dichotomy index is a different measure of rest-activity rhythms, yet also derived from actigraphy. This unidimensional measure that calculates the percentage of daytime activity counts that exceed nighttime counts [79], could be relevant to explore in future analyses.Lisa Marie Wu's effort was supported by the European University of Brain and Technology (NeurotechEU grant 101004080) funded by the Erasmus+ Programme of the European Union.The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Lisa Maria Wu reports financial support was provided by European Union. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Keywords
- Cancer patients
- Circadian rest-activity rhythms
- Depression
- Fatigue
- Immune check point inhibitors
- Sleep
- Stress
ASJC Scopus subject areas
- General Medicine
