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Relevance of internal time and circadian robustness for cancer patients

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Ortiz-Tudela, Elisabet, Innominato, Pasquale F., Rol, Maria Angeles, Lévi, Francis A. and Madrid, Juan Antonio (2016) Relevance of internal time and circadian robustness for cancer patients. BMC Cancer, 16 (1). 285. doi:10.1186/s12885-016-2319-9

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Official URL: http://dx.doi.org/10.1186/s12885-016-2319-9

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Abstract

Background:
Adequate circadian timing of cancer treatment schedules (chronotherapy) can enhance tolerance and efficacy several-fold in experimental and clinical situations. However, the optimal timing varies according to sex, genetic background and lifestyle. Here, we compute the individual phase of the Circadian Timing System to decipher the internal timing of each patient and find the optimal treatment timing.

Methods:
Twenty-four patients (11 male; 13 female), aged 36 to 77 years, with advanced or metastatic gastro-intestinal cancer were recruited. Inner wrist surface Temperature, arm Activity and Position (TAP) were recorded every 10 min for 12 days, divided into three 4-day spans before, during and after a course of a set chronotherapy schedule. Pertinent indexes, I < O and a new biomarker, DI (degree of temporal internal order maintenance), were computed for each patient and period.

Results:
Three circadian rhythms and the TAP rhythm grew less stable and more fragmented in response to treatment. Furthermore, large inter- and intra-individual changes were found for T, A, P and TAP patterns, with phase differences of up to 12 hours among patients. A moderate perturbation of temporal internal order was observed, but the administration of fixed chronomodulated chemotherapy partially resynchronized temperature and activity rhythms by the end of the study.

Conclusions:
The integrated variable TAP, together with the asynchrony among rhythms revealed by the new biomarker DI, would help in the personalization of cancer chronotherapy, taking into account individual circadian phase markers.

Item Type: Journal Article
Subjects: Q Science > QP Physiology
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Divisions: Faculty of Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Metabolic and Vascular Health (- until July 2016)
Faculty of Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine
Faculty of Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH): Cancer -- Patients -- Treatment, Circadian rhythms
Journal or Publication Title: BMC Cancer
Publisher: BioMed Central Ltd.
ISSN: 1471-2407
Official Date: 21 April 2016
Dates:
DateEvent
21 April 2016Published
15 April 2016Accepted
13 July 2015Submitted
Volume: 16
Number: 1
Article Number: 285
DOI: 10.1186/s12885-016-2319-9
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access
Funder: Instituto de Salud Carlos III, Spain. Ministerio de Economía y Competitividad [Ministry of Economy and Competitiveness] (MINECO), Spain. Ministerio de Ciencia e Innovación, Fonds Européen de Développement Économique et Régional (FEDER), Fundación Séneca, Association pour la Recherche sur le Temps Biologique et la Chronothérapie (ARTBC), European Union (EU)
Grant number: RETICEF RD12/0043/0011, SAF2013-49132-C2-1-R (Spain. Ministerio de Ciencia e Innovación), 19410/PI/14 (Fundación Séneca), Grant agreement No: 250505 (EU)

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