Discrimination of human tumor radioresponsiveness using low-dose rate irradiation

Abstract

Purpose: Evaluation of the theoretical and practical value of using low-dose rate (LDR) irradiation to increase the resolution of radiosensitivity testing of primary human tumors using clonogenic assays.Methods and Materials: Fourteen human tumor cell lines were assessed for surviving fraction at 2–8 Gy (SF2–SF8) using low-dose rate irradiation and a clonogenic assay. Further data were collected from the literature for 64 low-dose rate irradiation survival curves from human tumor cell lines. The data were grouped into five different radioresponsiveness categories (A–E). An analysis was made of the ability of the graded survival levels to discriminate between the different radioresponse groups and compared with previous analyses for high-dose rate SF2. Fifteen human cervical carcinoma specimens were analysed for SF2 and SF3.5 following high- and low-dose rate irradiation.Results: Low-dose rate irradiation increased the spread of tumor cell line radiosensitivity data and the ability to discriminate between radioresponse groups was greater at low than at high-dose rates. Using low-dose rate irradiation on primary tumor specimens and a soft agar clonogenic assay decreased the success rate in obtaining data. The latter dropped from 70% for high-dose rate SF2 to 51% for low-dose rate SF3.5.Conclusions: The work on cell lines illustrates that low-dose rate irradiation does improve the ability of clonogenic radiosensitivity measurements to discriminate between tumors of different radioresponsiveness groups. However, using low-dose rate irradiation on primary human tumors with a soft agar clonogenic assay was not practical because of reducing the success rate for obtaining data for radiosensitivity measurements.