Potential for Improved Effectiveness and Reduced Toxicity of Radiotherapy With Ultrahigh Dose-Rate FLASH Irradiation

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Studies in vitro have suggested that sub-millisecond pulses of radiation produce less genomic instability than continuous prolonged irradiation at the same total dose. In a study reported in Science Translational Medicine, Favaudon and colleagues assessed the effects of ultrahigh dose-rate irradiation (FLASH) in mouse models.

In C57BL/6J mice exposed to short pulses (≤ 500 ms) of radiation at ultrahigh dose rate (FLASH at ≥ 40 Gy/s) or to conventional dose-rate irradiation (≤ 0.03 Gy/s) in single doses, conventional treatment at 15 Gy resulted in lung fibrosis associated with activation of the transforming growth factor-β cascade, whereas no complications were observed after FLASH doses < 20 Gy for > 36 weeks after irradiation.

FLASH irradiation was also not associated with acute radiation-induced apoptosis in normal smooth muscle and epithelial cells; apoptosis could be reinduced by treatment with systemic tumor necrosis factor-α prior to irradiation. FLASH was as effective as conventional irradiation in suppressing growth of human HBCx-12A and HEp-2 tumor xenografts in nude mice and syngeneic TC-1 Luc–positive orthotopic lung tumors in C57BL/6J mice.

The authors concluded, “Together, these results suggest that FLASH radiotherapy might allow complete eradication of lung tumors and reduce the occurrence and severity of early and late complications affecting normal tissue.” ■

Favaudon V, et al: Sci Transl Med 6:245ra93, 2014.