Timing of concomitant boost irradiation affects incidence and severity of intestinal complications

Abstract

Purpose: In an effort to increase the therapeutic ratio of radiation therapy, so-called "nonstandard" irradiation regimens are being used more frequently. One such regimen, concomitant boost, entails giving a second daily fraction during part of the treatment course, thus reducing the total treatment time and decreasing the opportunity for tumor cell proliferation during treatment. The probability of tumor control is, therefore, increased for a given total dose. Timing of the boost, i.e., whether it is given early or late during the treatment course, affects both normal tissue and tumor response. This study assessed the influence of timing of a second daily boost on the development of intestinal radiation injury in a rat model.

Methods and materials: A functionally intact segment of distal ileum was sutured to the inside of the scrotum in 52 orchiectomized, male Sprague-Dawley rats. After a 3-week postoperative recovery period, the intestine contained in the "scrotal hernia" was irradiated. All rats received a total dose of 50.4 Gy, given over a 12-day period as two different boost regimens, daily fractions of 2.8 Gy plus six concomitant boost doses of 2.8 Gy. The early boost group received the additional boost during the first 6 days and the late boost group received the additional boost during the last 6 days. The boost was given 6 h after the daily fraction. Groups of rats were sacrificed at 24 h (acute changes), 2 weeks (subacute changes), and 26 weeks (chronic changes) after the end of the irradiation schedule. Radiation injury was assessed by frequency of radiation-induced complications, histopathologic radiation injury score, collagen content, and epithelial cytokinetics.

Results: Radiation injury in the early boost group was significantly more severe than in the late boost group in terms of incidence of complication and histopathologic injury. Relative collagen content of irradiated intestine was significantly increased in the early boost group when compared to the late boost group at 2 weeks and at 26 weeks. Irradiated intestine in the early boost group exhibited decreased labeling index at 2 weeks, whereas irradiated intestine in the late boost group exhibited normal labeling index and increased total crypt cellularity at 2 weeks.

Conclusion: When small intestine has to be included in the treatment field during radiation therapy, concomitant boost should be given towards the end of the radiation schedule, after the onset of compensatory proliferation, to minimized the risk of subsequent complications.