International journal of radiation oncology, biology, physics | 2021
Circadian Factors Impact Survival From Brain Metastases for Patients Treated With Whole Brain Radiation.
Abstract
PURPOSE/OBJECTIVE(S)\nThere are established links between circadian clock dysregulation, and cancer risk. Numerous reports of increased risk for breast cancer in night shift workers led the World Health Organization to classify circadian disruption as a probable carcinogen. Additionally, the circadian clock has been known to influence the body s response to medications and most recently, a handful of studies demonstrate a link between radiation toxicity and time of day the patient received radiation. Prior studies investigating the temporal association of radiotherapy outcomes have yielded overall conflicting data and contemporary evaluations of this effect are sparse. To determine if chronotherapy should be considered to modulate radiation outcomes, we sought to evaluate if the time of day when radiation treatment was delivered affected outcomes for patients with brain metastases.\n\n\nMATERIALS/METHODS\nRetrospective data was collected for all consecutive patients between 2010 and 2020 with a diagnosis of brain metastases who were treated with whole brain radiotherapy. Patients were eligible to be 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. Data on sex, age, performance status, control of primary disease, extracranial metastases, radiation dose, race, BMI, and zip code were collected. Radiation was delivered as whole-brain radiation to a median dose of 3000 cGY. Analysis of survival was performed using Mantel-Haenszel hazard ratio and log-rank test to compare Kaplan-Meier curves between groups.\n\n\nRESULTS\nComplete data were available for 84 patients. The majority of patients had a primary diagnosis of breast or lung cancer (93%) and a small minority had a melanoma, thyroid, or unknown primary. 43 (51%) patients were excluded who did not receive ≥80% of their cumulative radiation either before or after noon, leaving n\u202f=\u202f41 patients included for analysis. Demographic data were comparable between groups and overall: 56% female, 44% male; 56% ≥65 years, 44% younger. Distributions for BMI, extracranial metastasis, control of primary disease, and performance status were also similar between groups. Results showed a strong trend toward improved survival in the group that received ≥80% treatment in the afternoon (P\u202f=\u202f0.057, HR 0.28-1.02).\n\n\nCONCLUSION\nTreatment time of day impacted survival from brain metastases in our patient population treated with whole brain radiation. Potential explanations for these results include the influence of multiple circadian pathways on tissue and tumor sensitivity through melatonin signaling and other mechanisms, warranting further exploration. Future investigations into entraining circadian rhythms via time of day treatments, light therapy or pharmaceutical interventions to alter radiation outcomes and toxicity should be considered.