Effect of implant dose/volume and surgical resection on survival in a rat glioma brachytherapy model: implications for brain tumor therapy.

Abstract

This study sought to investigate the effects of implant dose/volume and surgical resection on survival in a rat glioma brachytherapy model. Two doses were investigated to determine a suitable therapeutic range. We performed two experiments. Three treatment groups and one control group of male F-344 rats bearing 9L brain tumors 12 days after tumor inoculation were used in the first experiment. Day 12 tumors were an average of 4 to 6 mm in diameter. Animals treated with brachytherapy received a tumor dose of 80 Gy delivered to a 5.5-mm-radius volume. Total macroscopic tumor removal was achieved by microsurgical techniques. A subsequent experiment compared the survival of tumor-burdened rats treated with an implant dose of 60 Gy delivered to a 5.5-mm-radius volume with a control group. Surgery alone produced an increased life span of 28.6% over control animals treated with sham surgery and dummy seed implants, a statistically significant increase in survival (P = 0.0023, log-rank test). Brachytherapy alone produced the most significant increase in survival over control animals (P = 0.0001, log-rank test; median survival not attained with an implant dose of 80 Gy delivered to a 5.5-mm-radius volume; and P = 0.0001, increased life span 121% with an implant dose of 60 Gy delivered to a 5.5-mm-radius volume). This was not improved by the addition of surgical tumor removal. We have demonstrated a relationship between implant dose/volume and survival of tumor-burdened rats in this model that is not improved by the addition of tumor removal. Implications for brain tumor brachytherapy are discussed.