Continuous irradiation of the Lewis lung carcinoma in vivo at clinically-used "ultra" low-dose-rates

Abstract

The in vivo response of the transplantable Lewis lung tumor to continuous irradiation (CI) at the clinical "ultra" low-dose-rates of 10-30 cGy/h was investigated. Tumor-bearing mice were housed in a dedicated 137Cs unit for up to three weeks while receiving CI. The horizontal 137Cs beam allowed secondary shielding of the lower body, but full irradiation of the dorsally-placed tumor and part of the upper body. Radiation survival curves were measured using an excision assay and tumor-cell colony formation in soft agar. The relative cell survival per tumor decreased exponentially with time and the irradiation periods required to reach a surviving fraction of 10(3) at the three dose-rates (10, 15 and 30 cGy/h) were 15.4, 10.2 and 4.3 days. As a function of dose, the survival curves were exponential and indistinguishable between the three dose-rates, the average DO value being 5.04 Gy. Neither the hypoxic fraction of the tumor nor the intrinsic cellular radiosensitivity were altered in the tumor cells surviving CI. The effects of the three dose-rates on the growth of Lewis lung tumors differed considerably, with clear volume regression at the highest dose rate (30 cGy/h) and exponential decreases in clonogenic cells per tumor with time at 15 and 30 cGy/h. Since the overall effect of CI is determined by the competition between cell killing and cell repopulation, the response of slowly-growing human tumors should be proportionately greater.