Review of FLASH Radiotherapy_West China Medical Journal

Authors：

GAO Feng ¹ , YANG Yiwei ² , DAI Tangzhi ¹ , WU Dai ³ ,  DU Xiaobo ¹

1. Oncology Department, Mianyang Central Hospital, Mianyang, Sichuan 621000, P. R. China;
2. Institute of Nuclear Physics and Chemistry, China Academy of Engineering Physics, Mianyang, Sichuan 621900, P. R. China;
3. Institute of Applied Electronics, China Academy of Engineering Physics, Mianyang, Sichuan 621900, P. R. China;

Corresponding author：

DU Xiaobo, Email: duxiaobo2005@126.com

Keywords：

FLASH radiotherapy; Tumor; Review

DOI：

10.7507/1002-0179.201912078

Video：

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Abstract Full text Figures/Tables Video References Cited by

FLASH radiotherapy is a hotspot in the domain of tumor radiotherapy in recent years, which delivers at ultra-high dose rate (usually > 100 Gy/s) in an ultra-short time (1−50 ms) to the target volume. The FLASH effect will be generated after the organism is treated with FLASH radiotherapy, which makes the tumor more easy to be killed and the normal tissue is protected after radiotherapy. Because of the differences in sensitivity to FLASH radiotherapy between tumor tissues and normal tissues, FLASH radiotherapy has a subversive advantage in the treatment of tumors. In this paper, several studies since 1959 on the effects of ultra-high dose rate rays and FLASH radiation on cells and organisms are summarized. As the predecessor of FLASH radiotherapy, ultra-high dose rate radiotherapy has laid a very important foundation for the development of FLASH radiotherapy.

Citation： GAO Feng, YANG Yiwei, DAI Tangzhi, WU Dai, DU Xiaobo. Review of FLASH Radiotherapy. West China Medical Journal, 2020, 35(2): 225-229. doi: 10.7507/1002-0179.201912078 Copy

1.	Montay-Gruel P, Petersson K, Jaccard M, et al. Irradiation ina flash: unique sparing of memory in mice after whole brain irradiation with dose rates above 100 Gy/s. Radiother Oncol, 2017, 124(3): 365-369.
2.	Favaudon V, Caplier L, Monceau V, et al. Ultrahigh dose-rate FLASH irradiation increases the differential response between normal and tumor tissue in mice. Sci Transl Med, 2014, 6(245): 245ra93.
3.	Montay-Gruel P, Bouchet A, Jaccard M, et al. X-rays can trigger the FLASH effect: ultra-high dose-rate synchrotron light source prevents normal brain injury after whole brain irradiation in mice. Radiother Oncol, 2018, 129(3): 582-588.
4.	Dewey DL, Boag JW. Modification of the oxygen effect when bacteria are given large pulses of radiation. Nature, 1959, 183(4673): 1450-1451.
5.	Town CD. Radiobiology. Effect of high dose rates on survival of mammalian cells. Nature, 1967, 215(5103): 574-548.
6.	Berry RJ, Hall EJ, Forster DW, et al. Survival of mammalian cells exposed to X rays at ultra-high dose-rates. Br J Radiol, 1969, 42(494): 102-107.
7.	Epp ER, Weiss H, Djordjevic B, et al. The radiosensitivity of cultured mammalian cells exposed to single high intensity pulses of electrons in various concentrations of oxygen. Radiat Res, 1972, 52(2): 324-332.
8.	Weiss H, Epp ER, Heslin JM, et al. Oxygen depletion in cells irradiated at ultra-high dose-rates and at conventional dose-rates. Int J Radiat Biol Relat Stud Phys Chem Med, 1974, 26(1): 17-29.
9.	Michaels HB, Epp ER, Ling CC, et al. Oxygen Sensitization of CHO cells at ultrahigh dose rates: prelude to oxygen diffusion studies. Radiat Res, 1978, 76(3): 510-521.
10.	Ling CC, Gerweck LE, Zaider M, et al. Dose-rate effects in external beam radiotherapy redux. Radiother Oncol, 2010, 95(3): 261-268.
11.	Lohse I, Lang S, Hrbacek J, et al. Effect of high dose per pulse flattening filter-free beams on cancer cell survival. Radiother Oncol, 2011, 101(1): 226-232.
12.	Montay-Gruel P, Acharya MM, Petersson K, et al. Long-term neurocognitive benefits of FLASH radiotherapy driven by reduced reactive oxygen species. Proc Natl Acad Sci USA, 2019, 116(22): 10943-10951.
13.	Beyreuther E, Brand M, Hans S, et al. Feasibility of proton FLASH effect tested by zebrafish embryo irradiation. Radiother Oncol, 2019, 139: 46-50.
14.	Simmons DA, Lartey FM, Schüler E, et al. Reduced cognitive deficits after FLASH irradiation of whole mouse brain are associated with less hippocampal dendritic spine loss and neuroinflammation. Radiother Oncol, 2019, 139: 4-10.
15.	Buonanno M, Grilj V, Brenner DJ. Biological effects in normal cells exposed to FLASH dose rate protons. Radiother Oncol, 2019, 139: 51-55.
16.	Patriarca A, Fouillade C, Auger M, et al. Experimental set-up for FLASH proton irradiation of small animals using a clinical system. Int J Radiat Oncol Biol Phys, 2018, 102(3): 619-626.
17.	Vozenin MC, De Fornel P, Petersson K, et al. The advantage of FLASH radiotherapy confirmed in mini-pig and cat-cancer patients. Clin Cancer Res, 2019, 25(1): 35-42.
18.	Schüler E, Trovati S, King G, et al. Experimental platform for ultra-high dose rate FLASH irradiation of small animals using a clinical linear accelerator. Int J Radiat Oncol Biol Phys, 2017, 97(1): 195-203.
19.	Bourhis J, Sozzi WJ, Jorge PG, et al. Treatment of a first patient with FLASH-radiotherapy. Radiother Oncol, 2019, 139: 18-22.
20.	Ponette V, Le Péchoux C, Deniaud-Alexandre E, et al. Hyperfast, early cell response to ionizing radiation. Int J Radiat Biol, 2000, 76(9): 1233-1243.
21.	Shinohara K, Nakano H, Miyazaki N, et al. Effects of single-pulse (< or = 1 ps) X-rays from laser-produced plasmas on mammalian cells. J Radiat Res, 2004, 45(4): 509-514.
22.	Nias AH, Swallow AJ, Keene JP, et al. Survival of HeLa cells from 10 nanosecond pulses of electrons. Int J Radiat Biol Relat Stud Phys Chem Med, 1970, 17(6): 595-598.
23.	Epp ER. Response of cells to high-intensity pulsed radiation and possibilities for measuring oxygen diffusion times in cells. Trans N Y Acad Sci, 1970, 32(2): 253-261.
24.	Hall EJ. Radiation dose-rate: a factor of importance in radiobiology and radiotherapy. Br J Radiol, 1972, 45(530): 81-97.
25.	Ling CC. Time scale of radiation-induced oxygen depletion and decay kinetics of oxygen-dependent damage in cells irradiated at ultrahigh dose rates. Radiat Res, 1975, 63(3): 455-467.
26.	Spitz DR, Buettner GR, Limoli CL. Response to letter regarding "An integrated physico-chemical approach for explaining the differential impact of FLASH versus conventional dose rate irradiation on cancer and normal tissue responses". Radiother Oncol, 2019, 139: 64-65.
27.	Maxim PG, Keall P, Cai J. FLASH radiotherapy: newsflash or flash in the pan?. Med Phys, 2019, 46(10): 4287-4290.

1. Montay-Gruel P, Petersson K, Jaccard M, et al. Irradiation ina flash: unique sparing of memory in mice after whole brain irradiation with dose rates above 100 Gy/s. Radiother Oncol, 2017, 124(3): 365-369.
2. Favaudon V, Caplier L, Monceau V, et al. Ultrahigh dose-rate FLASH irradiation increases the differential response between normal and tumor tissue in mice. Sci Transl Med, 2014, 6(245): 245ra93.
3. Montay-Gruel P, Bouchet A, Jaccard M, et al. X-rays can trigger the FLASH effect: ultra-high dose-rate synchrotron light source prevents normal brain injury after whole brain irradiation in mice. Radiother Oncol, 2018, 129(3): 582-588.
4. Dewey DL, Boag JW. Modification of the oxygen effect when bacteria are given large pulses of radiation. Nature, 1959, 183(4673): 1450-1451.
5. Town CD. Radiobiology. Effect of high dose rates on survival of mammalian cells. Nature, 1967, 215(5103): 574-548.
6. Berry RJ, Hall EJ, Forster DW, et al. Survival of mammalian cells exposed to X rays at ultra-high dose-rates. Br J Radiol, 1969, 42(494): 102-107.
7. Epp ER, Weiss H, Djordjevic B, et al. The radiosensitivity of cultured mammalian cells exposed to single high intensity pulses of electrons in various concentrations of oxygen. Radiat Res, 1972, 52(2): 324-332.
8. Weiss H, Epp ER, Heslin JM, et al. Oxygen depletion in cells irradiated at ultra-high dose-rates and at conventional dose-rates. Int J Radiat Biol Relat Stud Phys Chem Med, 1974, 26(1): 17-29.
9. Michaels HB, Epp ER, Ling CC, et al. Oxygen Sensitization of CHO cells at ultrahigh dose rates: prelude to oxygen diffusion studies. Radiat Res, 1978, 76(3): 510-521.
10. Ling CC, Gerweck LE, Zaider M, et al. Dose-rate effects in external beam radiotherapy redux. Radiother Oncol, 2010, 95(3): 261-268.
11. Lohse I, Lang S, Hrbacek J, et al. Effect of high dose per pulse flattening filter-free beams on cancer cell survival. Radiother Oncol, 2011, 101(1): 226-232.
12. Montay-Gruel P, Acharya MM, Petersson K, et al. Long-term neurocognitive benefits of FLASH radiotherapy driven by reduced reactive oxygen species. Proc Natl Acad Sci USA, 2019, 116(22): 10943-10951.
13. Beyreuther E, Brand M, Hans S, et al. Feasibility of proton FLASH effect tested by zebrafish embryo irradiation. Radiother Oncol, 2019, 139: 46-50.
14. Simmons DA, Lartey FM, Schüler E, et al. Reduced cognitive deficits after FLASH irradiation of whole mouse brain are associated with less hippocampal dendritic spine loss and neuroinflammation. Radiother Oncol, 2019, 139: 4-10.
15. Buonanno M, Grilj V, Brenner DJ. Biological effects in normal cells exposed to FLASH dose rate protons. Radiother Oncol, 2019, 139: 51-55.
16. Patriarca A, Fouillade C, Auger M, et al. Experimental set-up for FLASH proton irradiation of small animals using a clinical system. Int J Radiat Oncol Biol Phys, 2018, 102(3): 619-626.
17. Vozenin MC, De Fornel P, Petersson K, et al. The advantage of FLASH radiotherapy confirmed in mini-pig and cat-cancer patients. Clin Cancer Res, 2019, 25(1): 35-42.
18. Schüler E, Trovati S, King G, et al. Experimental platform for ultra-high dose rate FLASH irradiation of small animals using a clinical linear accelerator. Int J Radiat Oncol Biol Phys, 2017, 97(1): 195-203.
19. Bourhis J, Sozzi WJ, Jorge PG, et al. Treatment of a first patient with FLASH-radiotherapy. Radiother Oncol, 2019, 139: 18-22.
20. Ponette V, Le Péchoux C, Deniaud-Alexandre E, et al. Hyperfast, early cell response to ionizing radiation. Int J Radiat Biol, 2000, 76(9): 1233-1243.
21. Shinohara K, Nakano H, Miyazaki N, et al. Effects of single-pulse (< or = 1 ps) X-rays from laser-produced plasmas on mammalian cells. J Radiat Res, 2004, 45(4): 509-514.
22. Nias AH, Swallow AJ, Keene JP, et al. Survival of HeLa cells from 10 nanosecond pulses of electrons. Int J Radiat Biol Relat Stud Phys Chem Med, 1970, 17(6): 595-598.
23. Epp ER. Response of cells to high-intensity pulsed radiation and possibilities for measuring oxygen diffusion times in cells. Trans N Y Acad Sci, 1970, 32(2): 253-261.
24. Hall EJ. Radiation dose-rate: a factor of importance in radiobiology and radiotherapy. Br J Radiol, 1972, 45(530): 81-97.
25. Ling CC. Time scale of radiation-induced oxygen depletion and decay kinetics of oxygen-dependent damage in cells irradiated at ultrahigh dose rates. Radiat Res, 1975, 63(3): 455-467.
26. Spitz DR, Buettner GR, Limoli CL. Response to letter regarding "An integrated physico-chemical approach for explaining the differential impact of FLASH versus conventional dose rate irradiation on cancer and normal tissue responses". Radiother Oncol, 2019, 139: 64-65.
27. Maxim PG, Keall P, Cai J. FLASH radiotherapy: newsflash or flash in the pan?. Med Phys, 2019, 46(10): 4287-4290.

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