Wrist actimetry circadian rhythm as a robust predictor of colorectal cancer patients survival

Francis Lévi, Pierre Antoine Dugué, Pasquale Innominato, Abdoulaye Karaboué, Garance Dispersyn, Arti Parganiha, Sylvie Giacchetti, Thierry Moreau, Christian Focan, Jim Waterhouse, David Spiegel

Research output: Contribution to journalArticleResearchpeer-review

45 Citations (Scopus)

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 languageEnglish
Pages (from-to)891-900
Number of pages10
JournalChronobiology International
Volume31
Issue number8
DOIs
Publication statusPublished - 1 Jan 2014
Externally publishedYes

Keywords

  • Biomarkers
  • Cancer
  • Circadian clock
  • Rest-activity rhythm
  • Survival

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