Description: Publication date: Available online 29 December 2015 Source: Radiotherapy and Oncology Author(s): Emma B. Holliday, Nathan F. Dieckmann, Tasha L. McDonald, Arthur Y. Hung, Charles R. Thomas, Lisa J. Wood Background and purpose Mechanisms of fatigue reported during radiotherapy are poorly defined but may include inflammatory cytokines and/or sleep disturbances. This prospective, longitudinal, phase II study assessed fatigue, sleep, and serum cytokine levels during radiotherapy for early-stage prostate cancer (PCa). Material and methods Twenty-eight men undergoing radiotherapy for early-stage PCa wore an Actiwatch Score to record fatigue level, sleep time, onset latency, efficiency and wake after sleep onset. Serum levels of IL-1α, IL-1β, TNF-α, IL-6, IL-8, IL-10 and VEGF were measured weekly during radiotherapy. Patient reported quality of life (QOL) metrics were collected before and after treatment. Linear mixed effects models examined trajectories across treatment weeks. Results Fatigue increased across treatment weeks ( P 〈 .01), and fatigue was associated with decreased patient-reported QOL. Sleep efficiency increased across treatment weeks (rate of change over time = .29, P = .03), and sleep onset latency decreased (rate of change over time = .86, P = .06). IL-6 tended to increase during treatment ( P = 0.09), but none of the cytokine levels or sleep variables were significantly related to fatigue trajectories. Conclusions Despite increased sleep efficiency across treatment weeks, fatigue significantly increased. Although IL-6 increased during the course of radiotherapy, cytokines levels were not associated with fatigue scores or sleep disturbance. Further studies are needed to define the mechanisms for fatigue during radiotherapy.