Journal article
FLASH: New intersection of physics, chemistry, biology, and cancer medicine
Reviews of modern physics, Vol.96(3), 035002
09/2024
DOI: 10.1103/RevModPhys.96.035002
Abstract
Ultrahigh dose rate, FLASH radiotherapy has emerged as one of the most promising innovations over the past decade in the field of radiation oncology, with the potential to eradicate radiation resistant primary tumors and improve the therapeutic outcome for cancer patients. FLASH is based on delivering radiation doses at ultrahigh dose rates (UHDR; >40 Gy/s), more than 1000 times faster than irradiation at conventional dose rates (CONV). The experimental evidence demonstrating the differential effect of dose rate modulation on tumors and normal tissue is reviewed. Preclinical data consistently show that the antitumor efficacy of cytotoxic doses is not dependent on dose rate, but in normal tissues UHDR significantly reduces normal tissue toxicities compared to CONV, as observed in vivo. These observations define the FLASH effect. The FLASH effect has been reported to occur when using single or hypofractionated dose regimens in several experimental animal models (mice, rat, zebrafish, pig, and cats) and in multiple organs (lung, skin, gut, and brain) by numerous groups worldwide. Note that the FLASH effect has been demonstrated with electron, photon, and hadron (proton and heavier ion) beams. The current status and future technological development are reviewed, with an emphasis on critical beam parameters, future beam modalities, and prerequisites for safe clinical translation in terms of dosimetry, radioprotection, and treatment planning systems. Mechanistic investigations at the physicochemical and biological levels are presented, as are strategies to support and initiate clinical translation. This comprehensive review provides multidisciplinary radiation scientists with a road map of the technological, physical, chemical, biological, and clinical considerations that have made FLASH topical. These considerations are presented with a realistic and practical backdrop of the limitations and challenges that lie ahead.
Details
- Title: Subtitle
- FLASH: New intersection of physics, chemistry, biology, and cancer medicine
- Creators
- Marie-Catherine VozeninBilly W. LooSami TantawiPeter G. MaximDouglas R. SpitzClaude BailatCharles L. Limoli
- Resource Type
- Journal article
- Publication Details
- Reviews of modern physics, Vol.96(3), 035002
- DOI
- 10.1103/RevModPhys.96.035002
- ISSN
- 0034-6861
- eISSN
- 1539-0756
- Publisher
- AMER PHYSICAL SOC; COLLEGE PK
- Grant note
- Swiss National Science Foundation (SNSF): CRS II5_186369, IZSTZ0_198747/1 Swiss Cancer Research (Oncosuisse): KFS-4438-02-2018 NIH: PO1CA244091, R01CA254892, R44CA217607 National Institutes of Allergy and Infectious Diseases: R01CA233958, R01CA266673
We thank Dr. V. Favaudon, who initiated research on FLASH, for his contribution to the scientific discussion and his critical reading of the manuscript. We thank the biology team of the CHUV and UCI, especially H. Kacem, J. Ollivier, and B. Petit, and well as Drs. M. M. Acharya, Y. Alaghband B. Allen, J. E. Baulch, P. P. Montay-Gruel, and Ballesteros Zebadua for their past contributions to the FLASH project, and A. Almeida, O. G. G Drayson, and R. Kim for the help with figure preparation. We also thank Professors F. Bochud and J. Bourhis for their support, as well as Drs. T. Boehlen, T. Buchillier, L. Desorgher, P. Froidevaux, J. F. Germond, and V. Grilj for the fruitful scientific discussions. We thank the contributors to the FLASH radiation biology, medical physics, and accelerator-rf science program at Stanford Radiation Oncology and SLAC National Accelerator Laboratory, including E. Alemany, M. R Ashraf, M. Bazalova-Carter, K. Bush, K. M. Casey, F. Chavez, S. Chow, S. Dutt, M. Dworkin, J. T. Eggold, E. Engleman, E. E. Graves, V. Grover, B. Ha, N. Kapadia, R. B. Ko, A. C. Koong, F. M. Lartey, B. Lau, R. Lee, K. Levy, K. Liang, P. E. Loo, E. Nanni, R. Manjappa, S. Melemenidis, C. Nantista, S. Natarajan, H. Joshua No, G. Pratx, E. B. Rankin, S. Rokni, A. Rosenstrom, M. Santana, E. Schueler, M. Shumail, D. Simmons, L. Skinner, E. Snively, L. A. Soto, S. Strober, M. Surucu, A. Tremaine, V. Viswanathan, J. Wang, L. Wang, B. Whelan, Y. (Fred) Wu, and A. S. Yu. We are grateful for the support of the Stanford Department of Radiation Oncology and Dr. Q. T. Le. The studies were supported by a Sinergia grant from the Swiss National Science Foundation (SNSF) (Grant No. CRS II5_186369) (M.-C. V), a Spirit grant from SNSF Grant No. IZSTZ0_198747/1 (M.-C. V.), Swiss Cancer Research (Oncosuisse) Grant No. KFS-4438-02-2018 (M.-C. V.), NIH program Project Grant No. PO1CA244091 (M.-C. V., B. W. L., P. M., D. R. S., and C. L. L.), NIH Grant No. R01CA254892 (M.-C. V. and C. L. L.), National Institutes of Allergy and Infectious Diseases Grants No. R01CA233958 and No. R01CA266673 (B. W. L.), and NIH Grant No. R44CA217607 (B. W. L.). We gratefully acknowledge the support of the ISREC Foundation (2016-2020) - 2020) thanks to a donation from the Biltema Foundation (M.-C. V.), as well as the partnership of philanthropic donors to Stanford Radiation Oncology supporting the FLASH research program (B. W. L.).
- Language
- English
- Date published
- 09/2024
- Academic Unit
- Pathology; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center
- Record Identifier
- 9984719357202771
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