Local Hypothermia as a Radioprotector of the Rectal Wall during Prostate Stereotactic Body Radiotherapy

Publication date: Available online 11 January 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Brian A. Hrycushko, Rajiv Chopra, James W. Sayre, James A. Richardson, Michael R. Folkert, Robert D. Timmerman, Paul M. Medin
IntroductionThe rectum is an important dose-limiting structure for patients receiving prostate stereotactic body radiation therapy (SBRT) and no radioprotective agent is currently widely accepted or implemented as standard of care treatment. There is evidence that hypothermia may provide a protective effect for large single-fraction doses of x-ray irradiation. This study was performed to compare the single-fraction dose-related incidence of rectal obstruction and/or bleeding in normothermic and hypothermic rectums of a rat model.Methods and MaterialsA 1.9cm length of rectum was irradiated with a single fraction in 57 Sprague-Dawley rats using a dedicated image-guided small animal irradiator and Monte Carlo-based treatment planning system. All rats had a rectal temperature control apparatus placed during irradiation and were stratified to achieve either a normothermic (37°C) or hypothermic (15°C) rectal wall temperature. Radiation was delivered to a 1cm diameter cylindrical volume about the cooling device and rectal wall. The radiation dose was escalated from 16 Gy up to 37 Gy to assess the dose response in each arm. The primary endpoint of this study was rectal obstruction and/or bleeding during a follow-up of 180-186 days. Histologic scoring was performed on all study rats.ResultsProbit analysis showed an ED50 for the primary endpoint of 24.6Gy and 40.8Gy for normothermic and hypothermic arms, respectively. The occurrence of obstruction and/or bleeding correlated with the post treatment histologic score for normothermic rats; however, there was no difference in histologic score between normothermic and hypothermic rats at the highest dose levels evaluated.ConclusionsA significant radioprotective effect was observed using local hypothermia during a single-large dose of radiation for the functional endpoint of rectal obstruction and/or bleeding. A confirmatory study in a large animal model with anatomical and physiological similarities to humans is suggested.

Teaser

SBRT for prostate cancer has shown high local control rates comparable to conventional fractionation. However, there is an increased risk of late rectal toxicity with dose escalation. This work shows locally applied cooling to be a radioprotector of the rectal wall during a large-single fraction dose in a rat model for the primary endpoint of rectal obstruction and/or bleeding. If translated to humans, local hypothermia will be attractive as a radioprotector due to its simplicity.


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