Circadian rest‐activity rhythm as an objective biomarker of patient‐reported outcomes in patients with advanced cancer
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...
Saved in:
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2018-09-01
|
| Series: | Cancer Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cam4.1711 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849766635333746688 |
|---|---|
| author | Pasquale F. Innominato Sandra Komarzynski Oxana G. Palesh Robert Dallmann Georg A. Bjarnason Sylvie Giacchetti Ayhan Ulusakarya Mohamed Bouchahda Mazen Haydar Annabelle Ballesta Abdoulaye Karaboué Nicholas I. Wreglesworth David Spiegel Francis A. Lévi |
| author_facet | Pasquale F. Innominato Sandra Komarzynski Oxana G. Palesh Robert Dallmann Georg A. Bjarnason Sylvie Giacchetti Ayhan Ulusakarya Mohamed Bouchahda Mazen Haydar Annabelle Ballesta Abdoulaye Karaboué Nicholas I. Wreglesworth David Spiegel Francis A. Lévi |
| author_sort | Pasquale F. Innominato |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-e4e3a0683bbc487d80d05d53f77dea47 |
| institution | DOAJ |
| issn | 2045-7634 |
| language | English |
| publishDate | 2018-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj-art-e4e3a0683bbc487d80d05d53f77dea472025-08-20T03:04:30ZengWileyCancer Medicine2045-76342018-09-01794396440510.1002/cam4.1711Circadian rest‐activity rhythm as an objective biomarker of patient‐reported outcomes in patients with advanced cancerPasquale F. Innominato0Sandra Komarzynski1Oxana G. Palesh2Robert Dallmann3Georg A. Bjarnason4Sylvie Giacchetti5Ayhan Ulusakarya6Mohamed Bouchahda7Mazen Haydar8Annabelle Ballesta9Abdoulaye Karaboué10Nicholas I. Wreglesworth11David Spiegel12Francis A. Lévi13North Wales Cancer Centre Ysbyty Gwynedd Betsi Cadwaladr University Health Board Bangor UKCancer Chronotherapy Team Cancer Research Centre Warwick Medical School Coventry UKDepartment of Psychiatry and Behavioral Sciences Stanford University Stanford CaliforniaCancer Chronotherapy Team Cancer Research Centre Warwick Medical School Coventry UKSunnybrook Odette Cancer Centre University of Toronto Toronto ON CanadaUnit 935 French National Institute for Health and Medical Research (INSERM) Villejuif FranceUnit 935 French National Institute for Health and Medical Research (INSERM) Villejuif FranceUnit 935 French National Institute for Health and Medical Research (INSERM) Villejuif FranceChronotherapy Unit Department of Medical Oncology Paul Brousse Hospital Public Hospitals of Paris (AP‐HP) Villejuif FranceCancer Chronotherapy Team Cancer Research Centre Warwick Medical School Coventry UKAK‐SCIENCE, Research and Therapeutic Innovation Vitry‐sur‐Seine FranceNorth Wales Cancer Centre Ysbyty Gwynedd Betsi Cadwaladr University Health Board Bangor UKDepartment of Psychiatry and Behavioral Sciences Stanford University Stanford CaliforniaCancer Chronotherapy Team Cancer Research Centre Warwick Medical School Coventry UKAbstract 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.https://doi.org/10.1002/cam4.1711actigraphyCircadianpatient‐reported outcomequality of lifesymptom |
| spellingShingle | Pasquale F. Innominato Sandra Komarzynski Oxana G. Palesh Robert Dallmann Georg A. Bjarnason Sylvie Giacchetti Ayhan Ulusakarya Mohamed Bouchahda Mazen Haydar Annabelle Ballesta Abdoulaye Karaboué Nicholas I. Wreglesworth David Spiegel Francis A. Lévi Circadian rest‐activity rhythm as an objective biomarker of patient‐reported outcomes in patients with advanced cancer Cancer Medicine actigraphy Circadian patient‐reported outcome quality of life symptom |
| title | Circadian rest‐activity rhythm as an objective biomarker of patient‐reported outcomes in patients with advanced cancer |
| title_full | Circadian rest‐activity rhythm as an objective biomarker of patient‐reported outcomes in patients with advanced cancer |
| title_fullStr | Circadian rest‐activity rhythm as an objective biomarker of patient‐reported outcomes in patients with advanced cancer |
| title_full_unstemmed | Circadian rest‐activity rhythm as an objective biomarker of patient‐reported outcomes in patients with advanced cancer |
| title_short | Circadian rest‐activity rhythm as an objective biomarker of patient‐reported outcomes in patients with advanced cancer |
| title_sort | circadian rest activity rhythm as an objective biomarker of patient reported outcomes in patients with advanced cancer |
| topic | actigraphy Circadian patient‐reported outcome quality of life symptom |
| url | https://doi.org/10.1002/cam4.1711 |
| work_keys_str_mv | AT pasqualefinnominato circadianrestactivityrhythmasanobjectivebiomarkerofpatientreportedoutcomesinpatientswithadvancedcancer AT sandrakomarzynski circadianrestactivityrhythmasanobjectivebiomarkerofpatientreportedoutcomesinpatientswithadvancedcancer AT oxanagpalesh circadianrestactivityrhythmasanobjectivebiomarkerofpatientreportedoutcomesinpatientswithadvancedcancer AT robertdallmann circadianrestactivityrhythmasanobjectivebiomarkerofpatientreportedoutcomesinpatientswithadvancedcancer AT georgabjarnason circadianrestactivityrhythmasanobjectivebiomarkerofpatientreportedoutcomesinpatientswithadvancedcancer AT sylviegiacchetti circadianrestactivityrhythmasanobjectivebiomarkerofpatientreportedoutcomesinpatientswithadvancedcancer AT ayhanulusakarya circadianrestactivityrhythmasanobjectivebiomarkerofpatientreportedoutcomesinpatientswithadvancedcancer AT mohamedbouchahda circadianrestactivityrhythmasanobjectivebiomarkerofpatientreportedoutcomesinpatientswithadvancedcancer AT mazenhaydar circadianrestactivityrhythmasanobjectivebiomarkerofpatientreportedoutcomesinpatientswithadvancedcancer AT annabelleballesta circadianrestactivityrhythmasanobjectivebiomarkerofpatientreportedoutcomesinpatientswithadvancedcancer AT abdoulayekaraboue circadianrestactivityrhythmasanobjectivebiomarkerofpatientreportedoutcomesinpatientswithadvancedcancer AT nicholasiwreglesworth circadianrestactivityrhythmasanobjectivebiomarkerofpatientreportedoutcomesinpatientswithadvancedcancer AT davidspiegel circadianrestactivityrhythmasanobjectivebiomarkerofpatientreportedoutcomesinpatientswithadvancedcancer AT francisalevi circadianrestactivityrhythmasanobjectivebiomarkerofpatientreportedoutcomesinpatientswithadvancedcancer |