Effects of circadian rhythms and treatment times on the response of radiotherapy for painful bone metastases

Stephanie Chan, Liying Zhang, Leigha Rowbottom, Rachel McDonald, Georg A. Bjarnason, May Tsao, Elizabeth Barnes, Cyril Danjoux, Marko Popovic, Henry Lam, Carlo DeAngelis, Edward Chow


Background: Previous studies have observed how the time of radiotherapy delivery can impact toxicities and outcomes. The goal of this study was to determine whether treatment time influenced radiotherapy response for bone metastases.
Methods: Patients who received radiation treatment to painful bone metastases from January 2000 to December 2010 were included in our analysis. Demographic and treatment information including performance status, primary site, treatment dose and fraction, and response were collected prospectively. Treatment times were extracted from patient medical records. Patients were allocated to 8:00 AM–11:00 AM, 11:01 AM–2:00 PM, or 2:01 PM–5:00 PM cohorts based on their treatment times. To compare treatment response between the three cohorts, the Fisher exact test was used. A two-sided P value of <0.05 was considered statistically significant. Analysis was repeated with males and females separately.
Results: A total of 194 patients were included. The median age was 68 years and 55.5% of patients responded to treatment. The dose and fraction of radiation received differed significantly between treatment cohorts using all allocation methods. Females in the 11:01 AM–2:00 PM cohort exhibited a significantly higher response rate (P=0.02) and differing proportions of response types (P=0.03) compared to the 8:00 AM–11:00 AM and 2:01 PM–5:00 PM cohorts when allocated using all treatment times. No significant differences in response were seen between cohorts when all patients were analysed together or analysed for males only.
Conclusions: Treatment time may affect response in female patients receiving radiotherapy for painful bone metastases. Subsequent chronotherapy studies in radiation should investigate these gender differences.