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Flash放疗
赵维1, 田源2, 彭浩3
1斯坦福大学放射肿瘤系; 2迈胜医疗系统; 3武汉大学医学物理研究中心 430072
Flash radiotherapy
Wei Zhao1, Yuan Tian2, Hao Peng3
1Department of Radiation Oncology,Stanford University; 2Mevion Medical Systems; 3Research Center for Medical Physics,Wuhan University,Wuhan 430072,China
Abstract：Flash radiotherapy (Flash-RT) is a treatment modality that uses the normal tissue sparing regimen induced by ultra-high dose rate and ultra-fast irradiation. Compared to conventional dose rate radiotherapy,Flash-RT has the potential to provide the isoefficacy for tumors while achieving the remarkable normal tissue protection. Due to this unique feature,Flash-RT is attracting more and more attention from the radiotherapy community. An abundance of groups from both academia and industry are extensively studying the therapeutic ratio and underlying biological mechanisms. Here,we review the prior knowledge about Flash-RT and summarize the results that have been reported from various groups using both in vitro and animal studies with different experimental protocols. We also discuss possible biological mechanisms and the challenging of implementing Flash-RT,as well as its possible options for clinical applications.
[1] Delaney G,Jacob S,Featherstone C,el al. The role of radiotherapy in cancer treatment:estimating optimal utilization from a review of evidence-based clinical guidelines[J]. Cancer,2005,104(6):1129-1137. DOI:10.1002/cncr.21324. [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[J]. Sci Transl Med,2014,6(245):245-293. DOI:10.1126/scitranslmed.3008973. [3] Al-Hallaq H,Cao M,Kruse J,et al. Cured in a flash:reducing normal tissue toxicities using ultra-high-dose rates[J]. Int J Radiat Oncol Biol Phys,2019,104(2):257-260. DOI:10.1016/j.ijrobp.2019.01.093. [4] Maxim P,Keall P,Cai J. FLASH Radiotherapy:newsflash or flash in the pan?[J]. Med Phys,2019,In Press. DOI:10.1002/mp.13685. [5] Harrington K,Ultrahigh dose-rate radiotherapy:Next steps for FLASH-RT[J]. Clin Cancer Res,2019,25(1):3-5. DOI:10.1158/1078-0432. CCR-18-1796. [6] Hornsey S,Bewley D. Hypoxia in mouse intestine induced by electron irradiation at high dose-rates[J]. Int J Radiat Biol Relat Stud Phys Chem Med,1971,19(5):479-483. [7] Field S,Bewley D. Effects of dose-rate on the radiation response of rat skin[J]. Int J Radiat Biol Relat Stud Phys Chem Med,1974,26(3):259-267. [8] Montay-Gruel P,Petersson K,Jaccard M,et al. Irradiation in a flash:Unique sparing of memory in mice after whole brain irradiation with dose rates above 100 Gy/s[J]. Radiother Oncol,2017,124(3):365-369. DOI:10.1016/j.radonc.2017.05.003. [9] 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[J]. Radiother Oncol,2018,129(3):582-588. DOI:10.1016/j.radonc.2018.08.016. [10] Vozenin M,De Fornel P,Petersson K,et al. The advantage of flash radiotherapy confirmed in mini-pig and cat cancer patients[J]. Clin Cancer Res,2019,25(1):35-42. DOI:10.1158/1078-0432. CCR-17-3375. [11] Buonanno M,Grilj V,Brenner D. Biological effects in normal cells exposed to flash dose rate protons[J]. Radiother Oncol,2019,S0167-8140(19):30076-3. DOI:10.1016/j.radonc.2019.02.009. [12] Beyreuther E,Brand M,Hans S,et al. Feasibility of proton FLASH effect tested by zebrafish embryo irradiation[J]. Radiother Oncol,2019,S0167-8140(19):32964-0. DOI:10.1016/j.radonc.2019.06.024. [13] Gao J,Hu J,Guan X,et al. Salvage carbon-ion radiation therapy for locoregionally recurrent head and neck malignancies[J]. Sci Rep,2019,9(1):4259(1-9). DOI:10.1038/s41598-019-39241-y. [14] Town C. Effect of high dose rates on survival of mammalian cells[J]. Nature,1967,215(5103):847-848. [15] Berry R,Hall EJ,Forster DW,et al. Survival of mammalian cells exposed to x-rays at ultra-high dose-rates[J]. Br J Radiol,1969,42(494):102-107. [16] Montay-Gruel P,Acharya M,Petersson K,et al. Long-term neurocognitive benefits of flash radiotherapy driven by reduced reactive oxygen species[J]. Proc Natl Acad Sci USA,2019,116(22):10943-10951. DOI:10.1073/pnas.1901777116. [17] Laschinsky L,Karsch L,Le_mann E,et al. Radiobiological influence of megavoltage electron pulses of ultra-high pulse dose rate on normal tissue cells[J]. Radiat Environ Biophys,2016,55(3):381-391. DOI:10.1007/s00411-016-0652-7. [18] Le_mann M,Brauer-Krisch E,Hill M. Faster and safer? Flash ultrahigh dose rate in radiotherapy[J]. Br J Radiol, 2018,91(1082):20170628. DOI:10.1259/bjr.20170628. [19] Pratx G,Kapp D. A computational model of radiolytic oxygen depletion during FLASH irradiation and its effect on the oxygen enhancement ratio[J]. arXiv Preprint. DOI:arXiv:1905.06992. [20] Pratx G,Kapp D. Ultra-high-dose-rate FLASH irradiation may spare hypoxic stem cell niches in normal tissues[J]. Int J Radiat Oncol Biol Phys,2019,S0360-3016(19):30753-9. DOI:10.1016/j.ijrobp.2019.05.030. [21] Fernet V,Ponette E. Poly (adp-ribose) polymerase,a major determinant of early cell response to ionizing radiation[J]. Int J Radiat Biol,2000,76(12):1621-1629. DOI:https://doi.org/10.1080/09553000050201118. [22] Yovino S,Kleinberg L,Grossman SA,et al. The etiology of treatment-related lymphopenia in patients with malignant gliomas:modeling radiation dose to circulating lymphocytes explains clinical observations and suggests methods of modifying the impact of radiation on immune cells[J]. Cancer Invest,2013,31(2):140-144. DOI:10.3109/07357907.2012.762780. [23] Spitz DR,Buettner GR,Petronek MS,et al. An integrated physico-chemical approach for explaining the differential impact of flash versus conventional dose rate irradiation on cancer and normal tissue responses[J]. Radiother Oncol,2019,S0167-8140(19):30150-1. DOI:10.1016/j.radonc.2019.03.028 [24] Pajonk F,Vlashi E,McBride WH. Radiation resistance of cancer stem cells:the 4 R′s of radiobiology revisited[J]. Stem Cells,2010,28(4):639-648. DOI:10.1002/stem.318. [25] Bourhis J,Sozzi WJ,Jorge PG,et al. Treatment of a first patient with FLASH-radiotherapy[J]. Radiother Oncol,2019,S0167-8140(19):32959-7. DOI:10.1016/j.radonc.2019.06.019. [26] Maxim P,Tantawi S,Loo B,PHASER:a platform for clinical translation of FLASH cancer radiotherapy[J]. Radiother Oncol,2019,S0167-8140(19):30404-9. DOI:10.1016/j.radonc.2019.05.005. [27] Feuvret L,Bracci S,Calugaru V,et al. Efficacy and safety of adjuvant proton therapy combined with surgery for chondrosarcoma of the skull base:a retrospective, population-based study[J]. Int J Radiat Oncol Biol Phys, 2016,95(1):312-321. DOI:10.1016/j.ijrobp.2015.12.016. [28] Indelicato DJ,Merchant T,Laperriere N,et al. Consensus report from the stockholm pediatric proton therapy conference[J]. Int J Radiat Oncol Biol Phys,2016, 96(2):387-392. DOI:10.1016/j.ijrobp.2016.06.2446. [29] Almeida IP,Vilches-Freixas G,Cooley J,et al. Potential benefit of using an adaptive aperture in treating small lesions in the brain with proton therapy[C].57th annual meeting of the particle therapy cooperative group,2018:173. [30] Varian medical systems,Inc. Flash forward consortium[DB/OL][2019-03-18].https://www.varian.com/oncology/solutions/proton-therapy/flashforward-consortium. [31] IBA. Flash irradiation delivered in a clinical treatment room[DB/OL][2019-03-08].https://iba-worldwide.com/content/pt/proton-flash-irradiation-delivered-clinical-treatment-room. [32] Patriarca A,Fouillade C,Auger M,et al. Experimental set-up for flash proton irradiation of small animals using a clinical system[J]. Int J Radiat Oncol Biol Phys,2018, 102(3):619-626. DOI:10.1016/j.ijrobp.2018.06.403. [33] Loo B,Schuler E,Lartey F,et al. Delivery of ultra-rapid flash radiation therapy and demonstration of normal tissue sparing after abdominal irradiation of mice[J]. Int J Radiat Oncol Biol Phys,2017,98(2):E16-E16. DOI:https://doi.org/10.1016/j.ijrobp.2017.02.101. [34] 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[J]. Radiother Oncol,2019,S0167-8140(19):32942-1. DOI:10.1016/j.radonc.2019.06.006. [35] Girdhani S,Eric A,Alexander K,et al. FLASH:a novel paradigm changing tumor irradiation platform that enhances therapeutic ratio by reducing normal tissue toxicity and activating immune pathways[C]. AACR annual meeting,2019:LB-280. [36] ITN news. Netherlands proton therapy center delivers first clinical flash irradiation[DB/OL][2019-05-02].https://www.itnonline.com/content/netherlands-proton-therapy-center-delivers-first-clinical-flash-irradiation. [37] Lempart M,Blad B,Adrian G,et al. Modifying a clinical linear accelerator for delivery of ultra-high dose rate irradiation[J]. Radiother Oncol,2019,S0167-8140(19):30059-3. DOI:10.1016/j.radonc.2019.01.031. [38] Jorge PG,Jaccard M,Petersson K,et al. Dosimetric and preparation procedures for irradiating biological models with pulsed electron beam at ultra-high dose-rate[J]. Radiother Oncol,2019,S0167-8140(19):30403-7. DOI:10.1016/j.radonc.2019.05.004. [39] Hendry J,Moore J,Hodgson B,et al. The constant low oxygen concentration in all the target cells for mouse tail radionecrosis[J]. Radiat Res,1982,92(1):172-81.
2019, Vol. 28 
