Low dose rate radiotherapy for transplantable gliosarcoma in the rat brain

Interstitial brachytherapy with low energy radionuclides is becoming widely used in conjunction with external beam radiotherapy in the treatment of primary malignant gliomas of the brain. Few radiobiological studies have been carried out with low dose rate brachytherapy for brain tumors. Since we have recently developed a non-invasive low dose rate radiotherapy model for the treatment of transplantable 9L gliosarcoma growing in the rat brain, we carried out a series of radiobiological studies to determine the dose rate effect on the tumor and normal brain tissue. Using TCD50 (the radiation dose to control 50% tumor control) as the endpoints, we obtained the results indicating that the tumor control rate was highly dependent on the dose rate and the total dose delivered to the tumor. The TCD50 of dose rates ranging from 100 cGy/min, 120 cGy/hr, and 40 cGy/hr were 25 Gy, 80 Gy, and 100 Gy, respectively. The normal tissue effects were most pronounced with high dose rate irradiation (100 cGy/min). The LD50 for high dose rate irradiation to the whole brain was 29 Gy. In contrast, the majority of animals treated with low dose rate radio-therapy behaved quite normal up to a year follow-up. The late histopathological changes of the irradiated brain usually consisted of vascular and white matter necrosis, although the extent of such changes showed a considerable individual variation within the long-term survivors.