Tolerance limit of external beam radiotherapy combined with low-dose rate brachytherapy in normal rabbit tissue

BACKGROUND: Dosage-optimized multimodal radiotherapies that are safe for head and neck cancer patients are desirable. In this study, we investigated tissue tolerance to varying doses of external beam radiotherapy (EBRT) combined with low-dose rate brachytherapy in the neck of a rabbit model. METHODS: Twenty rabbits were used in the four test groups (five each) with iodine-125 seeds implanted in the neck treated with EBRT in four doses at 50, 40, 30 and 20 Gy each. Twelve rabbits for three control groups (four each). Three months after implantation, all rabbits were euthanized, and target tissues were collected. Analyses included seed implantation assessment, histopathological evaluation, immunohistochemistry staining, terminal deoxynucleotidyl transferase dUTP nick end labeling assay, electron microscopy and statistics with the SPSS software. RESULTS: Five rabbits died in the four test groups, and three rabbits died in the three control groups (one per group), which showed no significant difference by survival analysis. The calculated minimum peripheral dose was 17.6 Gy, the maximum dose near the seed was 1812.5 Gy, the D90 was 34.5 Gy and the mean dose was 124.5 Gy. In all groups that received radiation, apoptosis occurred primarily in the esophageal mucosa and corresponded to the dose of radiation; a higher dose caused a greater apoptosis, with significant difference between groups (P < 0.05). Electron microscopy of carotid arteries revealed that endothelial cells were swollen and some were shed from basement membrane, but no other noticeable tissue damages. CONCLUSIONS: Limited EBRT at maximal dose (50 Gy) combined with the brachytherapy interstitially applied to the neck was tolerated well in the rabbit model.