Optimal interfraction interval to minimize small bowel radiation injury in treatment regimens with two fractions per day: an experimental study in a rat model

Background: Normal tissue damage in fractionated radiotherapy is influenced by a number of factors including sublethal damage repair and cellular proliferation. The therapeutic benefit of regimens with multiple fractions per day may thus be offset by increased normal tissue injury if there is insufficient time between daily fractions. We examined the influence of interfraction interval on radiation injury of the intestine, an organ at significant risk during treatment of abdominal and pelvic tumors. Methods: A total of 150 male rats were orchiectomized, and a functionally intact loop of small bowel was sutured to the inside of the scrotum. The intestine within this 'artificial hernia' was irradiated twice daily for 9 days with 2.8 Gy fractions at intervals of 0, 2, 4, 6, or 8 h. Animals were observed for development of radiation-induced intestinal complications and euthanized at either 2 weeks and 26 weeks for subsequent histopathologic examination of irradiated and shielded intestine. Results: Increasing the interfraction interval from 0 to 6 h was associated with a statistically significant reduction in intestinal complications (from 53% to 0%, P<0.001), and in Radiation Injury Score (RIS) (from 10 to 6, P<0.01) in long-term observed animals. Extending the interfraction interval to 8 h did not confer additional benefit. Conclusion: An interfraction interval of 6 h minimizes the risk of chronic radiation enteropathy in this rat model