Radiobiological Difference Between Flattening Filter Free (FFF) Vs. Flattening Filter (FF) X-Ray Beams in Lung Cancer Cells

Abstract

Stereotactic Body Radiotherapy (SBRT) is a well-established therapeutic option for early lung cancer, and many clinical trials indicate that SBRT can provide excellent local control and survival with limited toxicity. Compared with conventional flattening filter (FF) beams, flattening filter free (FFF) beams are characterized by higher average dose rate with higher dose per pulse and inhomogeneous dose distribution with reduced peripheral dose. These benefits make FFF beams an attractive alternative for SBRT. Therefore, it is crucially to determine whether there are any differences in biological effects of FFF beams compared with FF beams. However, there are still conflicts on them between two beams. Therefore, we investigated the radiobiological effect between FF and FFF beam in human lung cancer cell lines. Three human lung cancer cell lines with different genetic characteristics (A549, NCI-H1299, NCI-H1650) were used. Irradiation was performed with a 10 MV linear accelerator (Versa HD, Elekta AB). The dose rate and dose per pulse for FF and FFF beams were 5 and 22 Gy/min, and 0.042 cGy and 0.171 cGy, respectively. To investigate the effect by different dose rate, but with same dose per pulse, FFF beam of 22 Gy/ min was modified to 5 Gy/min by increasing pulse interval. The radiobiologic effect was studied with three different conditions: FF (5 Gy/min, 0.042 cGy/pulse), FFF (5 Gy/min, and 0.171 cGy/pulse) and FFF (22 Gy/min, 0.171 cGy/pulse). Cell survival was measured using clonogenic assay and protein expression was measured using Western blot analysis. No significant differences in cell survival were observed upon three kinds of irradiation for all the three cell lines. No significant differences were observed in the expression of γ-H2AX and repair proteins (DNA-PKcs, Rad 51) after irradiation in all the three cell lines. There is no radiobiological difference (cell survival, DNA damage and repair) between FF and FFF beams in lung cancer cells.