Abstract P1-21-07: Implications for chronoradiobiology: Differential effect of radiation response for breast cancer patients with brain metastases depending on treatment time
Authors: Matlack Lauren , Lombardo Joseph , Nelson Nicolas , Smith Alexandria , Shi Wenyin , Simone Nicole 
Published: March 2022

Abstract
Purpose/Objectives: Circadian clock dysregulation has been implicated in cancer risk such that The World Health Organization classifies circadian disruption as a probable carcinogen following several reports of night shift workers with an increased risk of breast cancer. There are studies which outline a link between time of day a patient receives radiation therapy and toxicity from their radiation treatment. In order to ascertain if chronomodulation should be considered for radiation toxicity and survival outcome improvements, we sought to assess if time of day for radiation treatment delivery affected outcomes for breast cancer patients with brain metastases. Materials/Methods: Retrospective data was collected for patients with a primary diagnosis of breast cancer with brain metastases who were treated with whole brain radiotherapy between 2015 and 2021. Eligible patients were included if ≥80% of their total dose was delivered either before or after 12:00 noon as documented by treatment times in the electronic medical record and if outcome data was available. Information including sex, age, performance status, control of primary disease, extracranial metastases, radiation dose, race, height, weight, BMI, and zip code were collected. Whole brain radiation was delivered to a median dose of 3000 cGy. Patients were eligible to be included in the analysis since ≥80% of their total dose was delivered either before or after 12:00 noon. A survival analysis was performed using a log-rank test to compare Kaplan-Meier curves between groups. Results: Between 2015 and 2021, 46 breast cancer patients with brain metastases were treated with whole brain radiation with ≥80% of their total dose was delivered. either before or after 12:00 noon. Patient characteristics were evenly split between those treated predominantly in the morning or afternoon with regards to age, extracranial disease, race and BMI at time of brain metastases diagnosis however 97.83% were female. The overall breakdown of race was 65.5% white, with 34.8% identifying as black or African American, Hispanic, or unknown. The average survival time for patients treated in the morning was 293 days compared to the afternoon patients which averaged 168 days. Kaplan meier curve showed statistically significant improvement in survival for the group that received ≥80% of treatments in the morning (p=0.0048). Conclusions: Survival was significantly improved in patients with breast cancer and brain metastases who received whole brain radiation in the morning compared to the afternoon. Limitations of our study include a low sample size due to our stringent criteria for inclusion in analysis but further investigation using a multi-center approach is warranted. Circadian effects on tumors or their environment, potentially through melatonin related signaling should be further evaluated. Future investigation in methods to entrain the circadian clock to harness positive chronobiological impact on tumors including pharmacologic intervention in an attempt to improve radiation outcomes and or toxicity and continued research is warranted.
Citation Format: Lauren Matlack, Joseph Lombardo, Nicolas Nelson, Alexandria Smith, Wenyin Shi, Nicole Simone. Implications for chronoradiobiology: Differential effect of radiation response for breast cancer patients with brain metastases depending on treatment time [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-21-07.