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Subacute Effects of Pulsed Low Dose Rate Radiotherapy and Conventional Radiotherapy On Normal Mouse Tissues

D Cvetkovic

D Cvetkovic*, B Wang , L Chen , C Ma , Fox Chase Cancer Center, Philadelphia, PA


SU-E-T-715 (Sunday, July 12, 2015) 3:00 PM - 6:00 PM Room: Exhibit Hall

Purpose:Pulsed low-dose-rate radiotherapy (PLDR) can be used as a re-irradiation technique for recurrent cancers. We hypothesized that PLDR induces less toxicity to normal mouse tissues than conventional radiotherapy (CRT) for the same dose and regimen.

Methods:Experiment 1: 22 male BALB/c nude mice were randomly assigned into a non-irradiated control group (n=2), a CRT group (n=10), and a PLDR group (n=10). The mice received 8Gy total body irradiation (TBI) either continuously at a dose rate of 300MU/min (CRT) or in 0.2Gyx40 pulses separated by 3min intervals (PLDR). The mice were weighed daily, sacrificed when terminally ill or by day 12, and various organs were removed, formalin-fixed, paraffin-embedded and stained with H&E. Morphological changes were observed under a microscope. Experiment 2: 10 male nude mice were assigned into a control group, a 7Gy CRT, a 7Gy PLDR, an 8Gy CRT, and an 8Gy PLDR group; n=2 for each group. Body weight, urine/feces output, and food and water consumption were recorded daily, mice sacrificed on day 7, and organs collected for histology.

Results:Statistically significant differences were found in the weight and survival time (8 vs. 12 days) between the CRT and PLDR groups (Exp 1). The greatest body weight decline in Exp 2 was observed in the 8Gy CRT group. Histopathological analysis revealed atrophy in spleen, bone marrow and small intestine of all irradiated animals. The damage was mild to moderate in PLDR groups, and severe in CRT groups. Additionally, stomach atrophy was seen in all of the CRT cases, but only in 25% of PLDR cases. There was no apparent difference in the level of tissue radiation injury at 7Gy and 8Gy.

Conclusion:Our results verified the hypothesis that PLDR reduces the normal tissue toxicity from radiotherapy. Therefore, PLDR is an effective treatment for recurrent cancers.

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