Could time of whole brain radiotherapy delivery impact overall survival in patients with multiple brain metastases?
OBJECTIVE
Whole brain radiotherapy (WBRT) is commonly used to treat brain metastases. Previous studies have explored how radiotherapy treatment time can affect response. The present study evaluated the influence of treatment time on overall survival (OS) for cancer patients receiving WBRT.


METHODS
Patients who received WBRT from 2004 to 2016 were included. Demographic information including age, performance status, primary site, dose, fraction, treatment time, and date of death were collected. Based on different percentages of treatment times falling into one time frame (i.e., 100%, ≥80%, ≥70%, or ≥60%), patients were allocated to three cohorts (8:00-11:00 AM, 11:01 AM-2:00 PM, 2:01-5:00 PM). Demographics were compared among cohorts using the Kruskal-Wallis nonparametric test and Fisher exact test. To control the multiple comparisons on select demographic variables a Bonferroni adjusted P value was considered statistically significant. Kaplan-Meier curves were created for OS. Univariate and multivariate Cox proportional hazard (PH) model were used to find predictive factors of OS in all patients, females and males.


RESULTS
A total of 755 patients were included with a median age of 66 years. The actuarial median OS was 2.37 months. Treatment time was not associated with OS for all patients or males only. In elderly female patients (>65 years), a significant difference in OS was found among treatment cohorts (P=0.02). Treatment time (when ≥80% or ≥70% of treatment times were in one time frame), age, and Karnofsky performance status (KPS) were significant predictive factors of OS in univariate analysis for females. Only age and KPS remained significant in multivariate analysis.


CONCLUSIONS
Time of WBRT delivery for brain metastases was significantly related to OS upon univariate analyses in females only. Future investigations should be conducted prospectively with homogenous patient groups to elucidate the effect of chronotherapy in palliative brain metastases patients as time of WBRT administration may affect OS in specific subsets of patients.
Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada.
Stephanie
S
Chan
Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada.
Leigha
L
Rowbottom
Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada.
Rachel
R
McDonald
Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada.
Liying
L
Zhang
Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada.
Georg A
GA
Bjarnason
Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada.
May
M
Tsao
Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada.
Cyril
C
Danjoux
Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada.
Elizabeth
E
Barnes
Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada.
Henry
H
Lam
Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada.
Marko
M
Popovic
Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada.
Carlo
C
DeAngelis
Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada. edward.chow@sunnybrook.ca.
Edward
E
Chow
D017677:Age Distribution; D000368:Aged; D001932:Brain Neoplasms / Q000401:mortality / Q000532:radiotherapy* / Q000556:secondary; D019454:Chronotherapy / Q000379:methods / Q000401:mortality; D016371:Cranial Irradiation / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D011446:Prospective Studies; D011788:Quality of Life; D012189:Retrospective Studies; D017678:Sex Distribution; D016896:Treatment Outcome
Radiotherapy; brain metastases; chronotherapy; circadian rhythm; overall survival (OS)