Tracking Daily Variations in Rest-Wake to Guide Personalized Timing of Temozolomide for High-Grade Glioma Patients

Area of Science:

• Neuro-oncology
• Chronobiology
• Pharmacology

Background:

• High-grade gliomas (e.g., glioblastoma multiforme) are aggressive brain tumors treated with temozolomide (TMZ).
• Previous studies suggest morning TMZ dosing may improve patient survival.
• Circadian variations in O6-methylguanine-DNA methyltransferase (MGMT) may influence TMZ efficacy, but the impact of patient sleep patterns on drug timing is unknown.

Purpose of the Study:

• To investigate whether individual sleep patterns affect the biological timing of temozolomide (TMZ) administration in high-grade glioma patients.
• To assess the utility of wrist actigraphy in determining personal circadian time for optimized drug delivery.

Main Methods:

• 10 high-grade glioma patients undergoing post-surgical treatment used wrist actigraphy to monitor daily sleep-wake cycles.
• The timing of oral temozolomide (TMZ) delivery was recorded in both wall clock time and internal biological time.
• Data analysis focused on the variability of dosing times relative to individual circadian rhythms.

Main Results:

• Significant variability was observed in the internal biological timing of TMZ doses, both within and between patients.
• Some evening doses (20:00 h) were closer to a patient's internal biological morning than expected based on wall clock time.
• Wrist actigraphy proved to be a reliable method for estimating personal circadian time.

Conclusions:

• Individual circadian rhythms and sleep patterns cause substantial variation in the biological timing of temozolomide (TMZ) delivery.
• Wrist actigraphy can non-invasively estimate personal circadian time, potentially enabling more precise and effective TMZ administration.
• Findings support the development of personalized circadian medicine for optimizing chemotherapy delivery in neuro-oncology.