title: Differences in toxicity and outcome associated with circadian variations between patients undergoing daytime and evening radiotherapy for prostate adenocarcinoma.
abstract: This retrospective study tested the hypothesis that disease control and treatment-related toxicity in patients undergoing high-dose radiotherapy (HDRT) for prostate cancer varies in a circadian manner. Patients with localized prostate adenocarcinoma receiving HDRT (median 78 Gy) to the prostate and involved seminal vesicle(s) without elective pelvic irradiation were divided into a daytime treatment (before 5 PM) group (n = 267) and evening treatment (after 5 PM) group (n = 142). Biochemical failure (Phoenix definition), acute and late gastrointestinal (GI) and genitourinary toxicities (Common Terminology Criteria for Adverse Events version 4), biochemical failure-free survival (BFFS) and freedom from late toxicity were assessed. Analyses were performed by binary logistic regression and Cox proportional hazard regression. The median follow-up was 68 months, and 75% of patients were ≥70 years old. Evening HDRT was significantly associated with worse freedom from ≥grade 2 late GI complications (hazard ratio = 2.96; p < 0.001). The detrimental effect of evening HDRT was significant in patients older than 70 years old (p < 0.001) but not in younger patients (p = 0.63). In a subgroup of propensity score-matched cohort with T2b-T3 disease (n = 154), the 5-year BFFS was worse in the evening group than the daytime group (72% vs. 85%, hazard ratio = 1.95, p = 0.05). Our study indicates that evening HDRT may lead to more GI complications, especially in older patients, and worse BFFS in patients with T2b-T3 disease.
authors.affiliation: a Division of Radiation Oncology, Department of Oncology , National Taiwan University Hospital , Taipei , Taiwan.
authors.forename: Feng-Ming
authors.initials: FM
authors.lastname: Hsu
authors.affiliation: b Department of Radiation Oncology , City of Hope Cancer Center , Duarte , California , USA.
authors.forename: Wei-Hsien
authors.initials: WH
authors.lastname: Hou
authors.affiliation: c Department of Urology , National Taiwan University College of Medicine , Taipei , Taiwan.
authors.forename: Chao-Yuan
authors.initials: CY
authors.lastname: Huang
authors.affiliation: a Division of Radiation Oncology, Department of Oncology , National Taiwan University Hospital , Taipei , Taiwan.
authors.forename: Chia-Chun
authors.initials: CC
authors.lastname: Wang
authors.affiliation: a Division of Radiation Oncology, Department of Oncology , National Taiwan University Hospital , Taipei , Taiwan.
authors.forename: Chiao-Ling
authors.initials: CL
authors.lastname: Tsai
authors.affiliation: d Division of Medical Oncology, Department of Oncology , National Taiwan University Hospital , Taipei , Taiwan.
authors.forename: Yu-Chieh
authors.initials: YC
authors.lastname: Tsai
authors.affiliation: c Department of Urology , National Taiwan University College of Medicine , Taipei , Taiwan.
authors.forename: Hong-Jeng
authors.initials: HJ
authors.lastname: Yu
authors.affiliation: c Department of Urology , National Taiwan University College of Medicine , Taipei , Taiwan.
authors.forename: Yeong-Shiau
authors.initials: YS
authors.lastname: Pu
authors.affiliation: a Division of Radiation Oncology, Department of Oncology , National Taiwan University Hospital , Taipei , Taiwan.|e Graduate Institute of Oncology, National Taiwan University College of Medicine , Taipei , Taiwan.
authors.forename: Jason Chia-Hsien
authors.initials: JC
authors.lastname: Cheng
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000532:radiotherapy*; D000368:Aged; D000369:Aged, 80 and over; D002940:Circadian Rhythm / Q000502:physiology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011467:Prostate / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000532:radiotherapy*; D012189:Retrospective Studies; D016896:Treatment Outcome
keywords: Circadian rhythm; intensity modulated radiotherapy; prostate cancer; toxicity