Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Temporal Considerations in Brain Metastases Radiation Therapy: The Intersection of Chronobiology and Patient Profiles

Version 1 : Received: 23 January 2024 / Approved: 24 January 2024 / Online: 24 January 2024 (09:29:44 CET)

A peer-reviewed article of this Preprint also exists.

Nelson, N.G.; Burke, S.E.; Cappelli, L.; Matlack, L.E.; Smith, A.P.; Francois, N.; Lombardo, J.F.; Shah, Y.B.; Wen, K.-Y.; Shafi, A.A.; Simone, N.L. Temporal Considerations in Brain Metastases Radiation Therapy: The Intersection of Chronobiology and Patient Profiles. Clocks & Sleep 2024, 6, 200-210. Nelson, N.G.; Burke, S.E.; Cappelli, L.; Matlack, L.E.; Smith, A.P.; Francois, N.; Lombardo, J.F.; Shah, Y.B.; Wen, K.-Y.; Shafi, A.A.; Simone, N.L. Temporal Considerations in Brain Metastases Radiation Therapy: The Intersection of Chronobiology and Patient Profiles. Clocks & Sleep 2024, 6, 200-210.

Abstract

Background: The circadian system, a vital temporal regulator influencing physiological processes, has implications for cancer development and treatment response. Our study assesses circadian timing's impact on whole-brain radiotherapy outcomes in brain metastases for personalized cancer therapy insights. Aim: Evaluate circadian influence on radiation treatment timing and its correlation with clinical outcomes. Identify patient populations benefiting from interventions synchronizing circadian rhythms, considering subgroup differences and potential disparities related to social determinants of health (SDoH). Design: IRB-approved retrospective analysis of 237 patients undergoing whole-brain radiotherapy for brain metastases (2017–2021), receiving over 80% of treatments in the morning or afternoon. Survival analyses utilized Kaplan–Meier curves. Setting/Participants: Single-institution study involving patients receiving whole-brain radiotherapy. Collected demographic, disease, and socioeconomic parameters from electronic medical records. Results: Morning treatment (n=158) showed a trend towards improved overall survival vs. afternoon (n=79), median survival 158 vs. 79 days (p=0.20, HR=0.84, CI95% 0.84–0.91). Subgroup benefits for morning treatment in females (p=0.04) and trends in controlled primary disease (p=0.11) and breast cancer metastases (p=0.08). SDoH-based disparities observed, with Black and lower-income patients exhibiting diminished circadian influence. Conclusions: Emphasizes chronobiological factors' relevance in brain metastases radiation therapy. Morning treatment correlates with improved survival, particularly in specific subgroups. Identifies potential circadian influence disparities based on SDoH, laying a foundation for personalized cancer therapy and interventions synchronizing circadian rhythms for enhanced treatment efficacy.

Keywords

brain metastases; cancer; chronobiology; circadian clocks; radiation therapy; whole-brain radiotherapy; breast cancer; lung cancer; stress

Subject

Medicine and Pharmacology, Oncology and Oncogenics

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