Improved Survival of Mice After Total Body Irradiation with 10 MV Photon, 2400 MU/min SRS Beam

Background/Aim: We evaluated the radiobiological effects of stereotactic radiosurgery (SRS) photon beams on survival of C57BL/6NTac mice following total body irradiation. Materials and Methods: Survival of Lewis lung carcinoma (3LL) cells was tested after irradiation using 6 MV: 300 MU/min or 1400 MU/min; or 10 MV: 300 MU/min or 2400 MU/min. Survival of C57BL/6NTac mice after a dose which is lethal to 50% of the mice in 30 days (LD50/30) (9.25 Gy) total body irradiation (TBI) and 21 Gy to orthotopic 3LL tumors was tested. We quantitated levels of organ-specific gene transcripts by Real Time Polymerase Chain Reaction (RT-PCR). Results: While 3LL cell survival and inhibition of orthotopic tumor growth was uniform, 10 MV photons at 2400 MU/min TBI led to significantly greater survival (p=0.0218), with higher levels of intestinal (Sod2), (Gpx1), (Nrf2), and (NFκB) RNA transcripts. Conclusion: Clinical 10 MV-2400 cGy/min SRS beams led to unexpected protection of mice on TBI and increased radioprotective gene transcripts. Clinical trials using stereotactic radiosurgery (SRS) have demonstrated effective tumor control with escalating doses (1). Ionizing irradiation therapy using accelerated dose delivery and higher beam energy has improved dosimetry, shortened treatment duration, and has the potential to enhance clinical efficiency, minimize patient discomfort and target motion (1). Stereotactic body radiotherapy (SBRT) using these principles reduces the toxicity of protocols involving concomitant chemotherapy (2-5). Because tumor target volumes in SRS are smaller and doses higher, it has been assumed that the normal tissue radiobiology of currently evaluable (SRS) photon energies and dose rates is uniform and should not require investigation. Increased irradiation dose rate may saturate the cellular damage response to ionizing radiation, while lower dose rates should better-allow repair of DNA damage (2-5); however, the known radiobiological effects of dose rate (2-5) should not be relevant to the dose rates used in these studies. We compared clinically-utilized 6 MV with 10 MV photons, and dose rates of 300 MU/min, 1400 MU/min, and 2400 MU/min in SRS with respect to in vitro and in vivo measurements of tumor control and normal tissue response in a mouse model.