Spatial Organization of Temperature-Related Circadian and Vasomotor Rhythms

National Institute Of Biomedical Imaging And Bioengineering, Bethesda

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Abstract

Chronotherapeutics involve the administration of treatments in specific relationships to circadian rhythms. Circadian timing of anti-cancer medications has been shown to improve treatment tolerability up to fivefold and to double efficacy in pre-clinical and clinical studies. However, the physiological and molecular components of the circadian timing system (CTS), as well as gender, critically affect the success of a standardized chronotherapeutic schedule. In addition, a wrongly timed therapy or an excessive drug dose disrupts the CTS. Therefore, a non-invasive approach to accurately detect and monitor circadian rhythms is needed for a dynamic assessment of the CTS in order to personalize chronomodulated drug delivery schedules in cancer patients. Since core body temperature is a robust circadian biomarker, we recorded temperature continuously at multiple locations on the skin of the upper chest and back of controls and cancer patients. Variability in the circadian phase existed among patch locations in individual subjects over the course of 2-6 days, demonstrating the need to monitor multiple skin temperature locations to determine the precise circadian phase. Additionally, we observed that locations identified by infrared imaging as relatively cool had the largest 24 h temperature variations. Disruptions in skin temperature rhythms during treatment were found, pointing to the need to continually assess circadian timing and personalize chronotherapeutic schedules.