Impact of circadian rhythm-based radiotherapy timing on toxicities in localised prostate cancer patients: a prospective cohort study protocol

Prostate cancer (PCa) remains a significant health concern worldwide, with radiotherapy (RT) being one of the main treatment modalities. While RT is effective, it may be accompanied by side effects that can affect patients’ functional capacity and quality of life (QoL). Clinical evidence suggests that individual chronotypes influence RT response and toxicity profiles, but prospective evidence is scarce. This prospective observational cohort study aims to evaluate the association between RT-related toxicities and individual chronotypes in patients with localised PCa, exploring whether aligning treatment schedules with circadian biology can minimise adverse effects. Participants will be characterised by their chronotype via the Munich ChronoType Questionnaire, and salivary melatonin levels will determine dim light melatonin onset. Primary endpoints include acute and late RT-related toxicities graded using the RTOG scoring schema. Secondary endpoints will be addressed by QoL and fatigue questionnaires. Statistical analyses will explore associations between circadian metrics, toxicity outcomes, QoL, and fatigue changes, adjusting for potential confounders. This study will provide evidence on implementing personalised chronotype-driven RT strategies to minimise toxicities and improve the QoL for PCa patients. The findings can support the feasibility of clinical protocols integrating circadian biology into RT, paving the way for more patient-centred and optimised cancer treatment approaches.