Abstract
The disruption of the circadian timing system (CTS), which rhythmically controls cellular metabolism and proliferation, accelerated experimental cancer progression. A measure of CTS function in cancer patients could thus provide novel prediction information for outcomes, and help to identify novel specific therapies. The rest-activity circadian rhythm is a reliable and non-invasive CTS biomarker, which was monitored using a wrist watch accelerometer for 2 days in 436 patients with metastatic colorectal cancer. The relative percentage of activity in-bed versus out-of-bed (I<O) constituted the tested CTS measure, whose prognostic value for overall survival (OS) and progression-free survival (PFS) was determined in a pooled analysis of three patient cohorts with different treatment exposures. Median OS was 21.6 months [17.8-25.5] for patients with I<O above the median value of 97.5% as compared to 11.9 months [10.4-13.3] for those with a lower I<O (Log-rank p<0.001). Multivariate analyses retained continuous I<O as a joint predictor of both OS and PFS, with respective hazard ratios (HR) of 0.954 (p<0.001) and 0.970 (p<0.001) for each 1% increase in I<O. HRs had similar values in all the patient subgroups tested. The circadian physiology biomarker I<O constitutes a robust and independent quantitative predictor of cancer patient outcomes, that can be easily and cost-effectively measured during daily living. Interventional studies involving 24-h schedules of clock-targeted drugs, light intensity, exercise and/or meals are needed for testing the relevance of circadian synchronization for the survival of patients with disrupted rhythms.
| Original language | English |
|---|---|
| Pages (from-to) | 891-900 |
| Number of pages | 10 |
| Journal | Chronobiology International |
| Volume | 31 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - 1 Jan 2014 |
| Externally published | Yes |
Keywords
- Biomarkers
- Cancer
- Circadian clock
- Rest-activity rhythm
- Survival
Cite this
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Wrist actimetry circadian rhythm as a robust predictor of colorectal cancer patients survival. / Lévi, Francis; Dugué, Pierre Antoine; Innominato, Pasquale; Karaboué, Abdoulaye; Dispersyn, Garance; Parganiha, Arti; Giacchetti, Sylvie; Moreau, Thierry; Focan, Christian; Waterhouse, Jim; Spiegel, David.
In: Chronobiology International, Vol. 31, No. 8, 01.01.2014, p. 891-900.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Wrist actimetry circadian rhythm as a robust predictor of colorectal cancer patients survival
AU - Lévi, Francis
AU - Dugué, Pierre Antoine
AU - Innominato, Pasquale
AU - Karaboué, Abdoulaye
AU - Dispersyn, Garance
AU - Parganiha, Arti
AU - Giacchetti, Sylvie
AU - Moreau, Thierry
AU - Focan, Christian
AU - Waterhouse, Jim
AU - Spiegel, David
PY - 2014/1/1
Y1 - 2014/1/1
N2 - The disruption of the circadian timing system (CTS), which rhythmically controls cellular metabolism and proliferation, accelerated experimental cancer progression. A measure of CTS function in cancer patients could thus provide novel prediction information for outcomes, and help to identify novel specific therapies. The rest-activity circadian rhythm is a reliable and non-invasive CTS biomarker, which was monitored using a wrist watch accelerometer for 2 days in 436 patients with metastatic colorectal cancer. The relative percentage of activity in-bed versus out-of-bed (I<O) constituted the tested CTS measure, whose prognostic value for overall survival (OS) and progression-free survival (PFS) was determined in a pooled analysis of three patient cohorts with different treatment exposures. Median OS was 21.6 months [17.8-25.5] for patients with I<O above the median value of 97.5% as compared to 11.9 months [10.4-13.3] for those with a lower I<O (Log-rank p<0.001). Multivariate analyses retained continuous I<O as a joint predictor of both OS and PFS, with respective hazard ratios (HR) of 0.954 (p<0.001) and 0.970 (p<0.001) for each 1% increase in I<O. HRs had similar values in all the patient subgroups tested. The circadian physiology biomarker I<O constitutes a robust and independent quantitative predictor of cancer patient outcomes, that can be easily and cost-effectively measured during daily living. Interventional studies involving 24-h schedules of clock-targeted drugs, light intensity, exercise and/or meals are needed for testing the relevance of circadian synchronization for the survival of patients with disrupted rhythms.
AB - The disruption of the circadian timing system (CTS), which rhythmically controls cellular metabolism and proliferation, accelerated experimental cancer progression. A measure of CTS function in cancer patients could thus provide novel prediction information for outcomes, and help to identify novel specific therapies. The rest-activity circadian rhythm is a reliable and non-invasive CTS biomarker, which was monitored using a wrist watch accelerometer for 2 days in 436 patients with metastatic colorectal cancer. The relative percentage of activity in-bed versus out-of-bed (I<O) constituted the tested CTS measure, whose prognostic value for overall survival (OS) and progression-free survival (PFS) was determined in a pooled analysis of three patient cohorts with different treatment exposures. Median OS was 21.6 months [17.8-25.5] for patients with I<O above the median value of 97.5% as compared to 11.9 months [10.4-13.3] for those with a lower I<O (Log-rank p<0.001). Multivariate analyses retained continuous I<O as a joint predictor of both OS and PFS, with respective hazard ratios (HR) of 0.954 (p<0.001) and 0.970 (p<0.001) for each 1% increase in I<O. HRs had similar values in all the patient subgroups tested. The circadian physiology biomarker I<O constitutes a robust and independent quantitative predictor of cancer patient outcomes, that can be easily and cost-effectively measured during daily living. Interventional studies involving 24-h schedules of clock-targeted drugs, light intensity, exercise and/or meals are needed for testing the relevance of circadian synchronization for the survival of patients with disrupted rhythms.
KW - Biomarkers
KW - Cancer
KW - Circadian clock
KW - Rest-activity rhythm
KW - Survival
UR - http://www.scopus.com/inward/record.url?scp=84907057890&partnerID=8YFLogxK
U2 - 10.3109/07420528.2014.924523
DO - 10.3109/07420528.2014.924523
M3 - Article
C2 - 24927369
AN - SCOPUS:84907057890
VL - 31
SP - 891
EP - 900
JO - Chronobiology International
JF - Chronobiology International
SN - 0742-0528
IS - 8
ER -