Annalisa Patriarca1, Charles Fouillade2, Michel Auger1, Frédéric Martin1, Frédéric Pouzoulet3, Catherine Nauraye1, Sophie Heinrich3, Vincent Favaudon4, Samuel Meyroneinc1, Rémi Dendale1, Alejandro Mazal1, Philip Poortmans1, Pierre Verrelle5, Ludovic De Marzi6. 1. Institut Curie, PSL Research University, Radiation Oncology Department, Paris, France. 2. Institut Curie, PSL Research University, Radiation Oncology Department, Paris, France; Institut Curie, PSL Research University, INSERM U1021/UMR3347, Orsay, France. 3. Institut Curie, PSL Research University, Translational Research Department, Experimental Radiotherapy Platform, Orsay, France. 4. Institut Curie, PSL Research University, INSERM U1021/UMR3347, Orsay, France. 5. Institut Curie, PSL Research University, Radiation Oncology Department, Paris, France; Institut Curie, PSL Research University, INSERM U1196/UMR9187, Orsay, France. 6. Institut Curie, PSL Research University, Radiation Oncology Department, Paris, France. Electronic address: ludovic.demarzi@curie.fr.
Abstract
PURPOSE: Recent in vivo investigations have shown that short pulses of electrons at very high dose rates (FLASH) are less harmful to healthy tissues but just as efficient as conventional dose-rate radiation to inhibit tumor growth. In view of the potential clinical value of FLASH and the availability of modern proton therapy infrastructures to achieve this goal, we herein describe a series of technological developments required to investigate the biology of FLASH irradiation using a commercially available clinical proton therapy system. METHODS AND MATERIALS: Numerical simulations and experimental dosimetric characterization of a modified clinical proton beamline, upstream from the isocenter, were performed with a Monte Carlo toolkit and different detectors. A single scattering system was optimized with a ridge filter and a high current monitoring system. In addition, a submillimetric set-up protocol based on image guidance using a digital camera and an animal positioning system was also developed. RESULTS: The dosimetric properties of the resulting beam and monitoring system were characterized; linearity with dose rate and homogeneity for a 12 × 12 mm2 field size were assessed. Dose rates exceeding 40 Gy/s at energies between 138 and 198 MeV were obtained, enabling uniform irradiation for radiobiology investigations of small animals in a modified clinical proton beam line. CONCLUSIONS: This approach will enable us to conduct FLASH proton therapy experiments on small animals, specifically for mouse lung irradiation. Dose rates exceeding 40 Gy/s were achieved, which was not possible with the conventional clinical mode of the existing beamline.
PURPOSE: Recent in vivo investigations have shown that short pulses of electrons at very high dose rates (FLASH) are less harmful to healthy tissues but just as efficient as conventional dose-rate radiation to inhibit tumor growth. In view of the potential clinical value of FLASH and the availability of modern proton therapy infrastructures to achieve this goal, we herein describe a series of technological developments required to investigate the biology of FLASH irradiation using a commercially available clinical proton therapy system. METHODS AND MATERIALS: Numerical simulations and experimental dosimetric characterization of a modified clinical proton beamline, upstream from the isocenter, were performed with a Monte Carlo toolkit and different detectors. A single scattering system was optimized with a ridge filter and a high current monitoring system. In addition, a submillimetric set-up protocol based on image guidance using a digital camera and an animal positioning system was also developed. RESULTS: The dosimetric properties of the resulting beam and monitoring system were characterized; linearity with dose rate and homogeneity for a 12 × 12 mm2 field size were assessed. Dose rates exceeding 40 Gy/s at energies between 138 and 198 MeV were obtained, enabling uniform irradiation for radiobiology investigations of small animals in a modified clinical proton beam line. CONCLUSIONS: This approach will enable us to conduct FLASH proton therapy experiments on small animals, specifically for mouse lung irradiation. Dose rates exceeding 40 Gy/s were achieved, which was not possible with the conventional clinical mode of the existing beamline.
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