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 -