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

May 28, 2025Journal of biological rhythms

Daily Rest and Wake Patterns to Help Personalize Chemotherapy Timing for Aggressive Brain Tumor Patients

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Abstract

Wrist actigraphy from 10 glioma patients shows that dosing times of temozolomide (TMZ) may differ significantly from clock time due to individual biological rhythms.

Morning dosing of TMZ may improve overall survival compared to evening dosing.
Circadian variations in MGMT gene expression could increase tumor sensitivity to TMZ when taken in the morning.
Daily rhythms in sleep patterns may affect the timing of drug administration and overall survival.
Wrist actigraphy provides a reliable way to measure individual biological time for drug delivery.
These findings may support personalized approaches to optimizing TMZ treatment timing in patients.

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High-grade gliomas, like glioblastoma multiforme (GBM), are the most common malignant brain tumors in adults and are treated with the chemotherapy drug temozolomide (TMZ). In humans, a retrospective analysis of patients' overall survival suggests that morning dosing may confer a benefit over evening dosing. Circadian variation in O6-methylguanine-DNA methyltransferase (MGMT) gene expression and promoter methylation has been implicated in increased tumor cell sensitivity to TMZ in the morning. Although patient compliance with timed oral administration of TMZ was high in a prospective trial, it is not known whether differences in daily sleep patterns of patients impact the biological time of drug administration or overall survival. Using wrist actigraphy collected from 10 high-grade glioma patients, we quantified the moment of oral TMZ delivery in terms of wall clock time and internal biological time during the months after surgical tumor resection. We found that variation of daily rhythms within and between individuals caused dosing times to vary more in their internal biological time than wall clock time so that, for example, some doses taken by patients assigned for the evening (2000 h) were closer to the patient's internal biological morning. We conclude that wrist actigraphy provides a reliable and non-invasive estimate of personal circadian time that could improve efficacy and precision of TMZ delivery. These findings may inform personalized circadian medicine and optimized times for TMZ delivery in the clinic.

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

Abstract

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