Relevance of internal time and circadian robustness for cancer patients

Apr 23, 2016BMC cancer

Importance of body clock and daily rhythm stability for cancer patients

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Abstract

Three circadian rhythms became less stable and more fragmented in 24 patients with advanced gastro-intestinal cancer during treatment.

Significant inter- and intra-individual variations were observed in temperature, activity, and position patterns, with phase differences of up to 12 hours.
A moderate disruption of the body's internal timing system was noted in response to treatment.
The administration of fixed chronomodulated chemotherapy partially resynchronized temperature and activity rhythms by the end of the study.
The new biomarker, degree of temporal internal order maintenance (DI), indicated asynchrony among rhythms, which may aid in personalizing cancer chronotherapy.

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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.

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Relevance of internal time and circadian robustness for cancer patients

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