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Circadian rest-activity rhythm as an objective biomarker of patient-reported outcomes in patients with advanced cancer
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Innominato, Pasquale F., Komarzynski, Sandra, Palesh, Oxana G., Dallmann, Robert, Bjarnason, Georg A., Giacchetti , Syvie, Ulusakarya , Ayhan, Bouchahda, Mohamed, Haydar, Mazen, Ballesta, Annabelle, Karaboué, Abdoulaye, Wreglesworth, Nicholas I., Spiegel, David and Lévi, Francis A. (2018) Circadian rest-activity rhythm as an objective biomarker of patient-reported outcomes in patients with advanced cancer. Cancer Medicine, 7 (9). pp. 4396-4405. doi:10.1002/cam4.1711
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Official URL: https://doi.org/10.1002/cam4.1711
Abstract
Background
Psychosocial symptoms often cluster together, are refractory to treatment, and impair health‐related quality of life (HR‐QoL) in cancer patients. The contribution of circadian rhythm alterations to systemic symptoms has been overlooked in cancer, despite a causal link shown under jet lag and shift work conditions. We investigated whether the circadian rest‐activity rhythm provides a reliable and objective estimate of the most frequent patient‐reported outcome measures (PROMs).
Methods
Two datasets were used, each involving concomitant 3‐day time series of wrist actigraphy and HR‐QoL questionnaires: EORTC QLQ‐C30 was completed once by 237 patients with metastatic colorectal cancer; MD Anderson Symptom Inventory (MDASI) was completed daily by 31 patients with advanced cancer on continuous actigraphy monitoring, providing 1015 paired data points. Circadian function was assessed using the clinically validated dichotomy index I < O. Nonparametric tests compared PROMs and I < O. Effect sizes were computed. Sensitivity subgroup and temporal dynamics analyses were also performed.
Results
I < O values were significantly lower with increasing symptom severity and worsening HR‐QoL domains. Fatigue and anorexia were worse in patients with circadian disruption. The differences were both statistically and clinically significant (P < 0.001; d ≥ 0.33). Physical and social functioning, and global quality/enjoyment of life were significantly better in patients with robust circadian rhythm (P < 0.001; d ≥ 0.26). Sensitivity analyses validated these findings.
Conclusion
Objectively determined circadian disruption was consistently and robustly associated with clinically meaningfully severe fatigue, anorexia, and interference with physical and social functioning. This supports an important role of the circadian system in the determination of cancer patients’ HR‐QoL and symptoms that deserves therapeutic exploitation.
| Item Type: | Journal Article | |||||||||||||||
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| Subjects: | Q Science > QP Physiology R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) |
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| Divisions: | Faculty of Medicine > Warwick Medical School > Biomedical Sciences Faculty of Science > Mathematics Faculty of Medicine > Warwick Medical School |
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| Library of Congress Subject Headings (LCSH): | Cancer -- Treatment, Circadian rhythms, Biochemical markers | |||||||||||||||
| Journal or Publication Title: | Cancer Medicine | |||||||||||||||
| Publisher: | Wiley | |||||||||||||||
| ISSN: | 2045-7634 | |||||||||||||||
| Official Date: | September 2018 | |||||||||||||||
| Dates: |
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| Date of first compliant deposit: | 4 July 2018 | |||||||||||||||
| Volume: | 7 | |||||||||||||||
| Number: | 9 | |||||||||||||||
| Page Range: | pp. 4396-4405 | |||||||||||||||
| DOI: | 10.1002/cam4.1711 | |||||||||||||||
| Status: | Peer Reviewed | |||||||||||||||
| Publication Status: | Published | |||||||||||||||
| Access rights to Published version: | Open Access | |||||||||||||||
| RIOXX Funder/Project Grant: |
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