The predominant mode of radiation-induced cell death for solid tumours is mitotic catastrophe, which is in part dependent on sublethal damage repair being complete at around 6 h. Circadian variation appears to play a role in normal cellular division, and this could influence tumour response of radiation treatment depending on the time of treatment delivery. We tested the hypothesis that radiation treatment later in the day may improve tumour response and nodal downstaging in rectal cancer patients treated neoadjuvantly with radiation therapy. Recruitment was by retrospective review of 267 rectal cancer patients treated neoadjuvantly in the Department of Radiation Oncology at the Canberra Hospital between January 2010 and November 2015. One hundred and fifty-five patients met the inclusion criteria for which demographic, pathological and imaging data were collected, as well as the time of day patients received treatment with each fraction of radiotherapy. Data analysis was performed using the Statistical Package R with nonparametric methods of significance for all tests set at p < 0.05. Of the 45 female and 110 male patients, the median age was 64. Seventy-three percent had cT3 disease and there was a mean tumour distance from the anal verge of 7 cm. Time to surgical resection following radiotherapy ranged from 4 to 162 days with a median of 50 days, with a complete pathological response seen in 21% of patients. Patients exhibiting a favourable pathological response had smaller median pre- and postradiotherapy tumour size and had a greater change in tumour size following treatment (p < 0.01). Patients who received the majority of their radiotherapy fractions after 12:00 pm were more likely to show a complete or moderate pathological response (p = 0.035) and improved nodal downstaging. There were also more favourable responses amongst patients with longer time to surgical resection postradiotherapy (p < 0.004), although no relationship was seen between response and tumour distance from the anal verge. Females were less likely to exhibit several of the above responses. Neoadjuvant radiotherapy for locally advanced rectal cancer performed later in the day coupled with a longer time period to surgical resection may improve pathological tumour response rates and nodal downstaging. A prospective study in chronomodulated radiotherapy in this disease is warranted.

relatively lower radioprotection in cells with a weak clock during normothermia. We were also able to demonstrate that if torpor weakened the circadian clock, a protective effect could be partially restored by an external drive such as lighting schedules to aid entrainment i.e: Blue light exposure for periods of awake and no light for rest times For the propulsion simulation, estimated transit times from Earth to Mars were 258 days for chemical propulsion with 165.9mSv received, 209 days for nuclear propulsion with 134.4mSv received and 80 days for electrical propulsion with 51.4mSv received. Conclusion A state of torpor for astronauts on deep space missions may not only improve weight, fuel and storage requirements but also provide a potential biological radiation protection strategy. Moreover, maintaining a controlled circadian rhythm during torpor conditions may aid radioprotection. In the not too distant future, propulsion techniques will be improved to limit transit time and hence decrease radiation dose to astronauts. Limiting exposure time and enhancing physiological radioprotection during transit could provide superior radioprotection benefits compared with active and passive radiation shielding strategies alone.

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