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Impact of millimeter-scale target motion on the precision of spatially fractionated radiation therapy using proton minibeams.

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Τίτλος: Impact of millimeter-scale target motion on the precision of spatially fractionated radiation therapy using proton minibeams.
Συγγραφείς: Actis O; Center for Proton Therapy, Paul Scherrer Institute, Villigen PSI, Aargau, Switzerland., Fernandez-Palomo C; Institute of Anatomy, University of Bern, Bern, Switzerland., Trappetti V; Institute of Anatomy, University of Bern, Bern, Switzerland., Togno M; Center for Proton Therapy, Paul Scherrer Institute, Villigen PSI, Aargau, Switzerland., Pellicioli P; Institute of Anatomy, University of Bern, Bern, Switzerland., Leiser D; Center for Proton Therapy, Paul Scherrer Institute, Villigen PSI, Aargau, Switzerland., Meer D; Center for Proton Therapy, Paul Scherrer Institute, Villigen PSI, Aargau, Switzerland., Djonov V; Institute of Anatomy, University of Bern, Bern, Switzerland.
Πηγή: Medical physics [Med Phys] 2026 Sep; Vol. 53 (9), pp. e70638.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: John Wiley and Sons, Inc Country of Publication: United States NLM ID: 0425746 Publication Model: Print Cited Medium: Internet ISSN: 2473-4209 (Electronic) Linking ISSN: 00942405 NLM ISO Abbreviation: Med Phys Subsets: MEDLINE
Imprint Name(s): Publication: 2017- : Hoboken, NJ : John Wiley and Sons, Inc.
Original Publication: Lancaster, Pa., Published for the American Assn. of Physicists in Medicine by the American Institute of Physics.
Ιατρικοί όροι (MeSH): Proton Therapy*/instrumentation , Proton Therapy*/methods , Dose Fractionation, Radiation*, Chorioallantoic Membrane/radiation effects ; Animals ; Chick Embryo ; Movement
Περίληψη: Background: While pencil beam scanning (PBS) with motion mitigation such as re-scanning, breath hold, or gating is well established for treating moving targets in clinical practice, the precision for Spatially Fractionated Radiation Therapy (SFRT) using proton minibeams introduces presents a unique challenge. The sub-millimeter precision required for SFRT cannot be achieved with typical PBS spot sizes (millimeters), necessitating multi-slit beam collimation, which reduces the dose rate and reintroduces motion as a critical issue. In this study, we report on our experience with minibeam irradiations of chorioallantoic membranes (CAM) of chick embryos and discuss potential solutions to the motion problem.
Methods: The first experiment was conducted at a PBS gantry using 130 MeV protons and a 6 cm thick copper multi-slit collimator with 0.3 mm wide slits and 1 mm spacing. To achieve a target peak dose of 30 Gy, CAM samples were irradiated with more than 10 re-scans. Due to a 91% beam loss in the collimator, the total irradiation time extended to two min.
Results: Post-irradiation analysis using gafchromic film revealed smearing of the minibeam profiles, while biological tissue analysis uncovered unexpected and disrupted dose effects, likely caused by irregular CAM movement during irradiation. A subsequent experiment, incorporating additional setup optimizations such as reduced air gap and increased dose rate, shortened the irradiation time to below one min. This led to sharper dose profiles with negligible variation in valley dose and peak width, although a reduction in peak dose of 8%-13% was still observed. This variation is considered acceptable for our biological experiments.
Conclusions: For clinical applications, minibeam re-scanning is likely to be feasible only under ultra-high dose rate conditions (e.g., those required to induce the FLASH effect), where sufficiently short irradiation times minimize motion-induced dose degradation.
(© 2026 The Author(s). Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)
References: Anat Rec. 2001 Dec 1;264(4):317-24. (PMID: 11745087)
Phys Med Biol. 2017 Mar 7;62(5):1661-1675. (PMID: 28166055)
Med Phys. 2018 Jul 15;:. (PMID: 30009481)
Med Phys. 2012 Nov;39(11):6818-37. (PMID: 23127075)
Br J Radiol. 2019 Mar;92(1095):20180466. (PMID: 30359081)
Sci Rep. 2018 Nov 7;8(1):16479. (PMID: 30405188)
Int J Radiat Oncol Biol Phys. 2019 Jun 1;104(2):266-271. (PMID: 30703513)
Sci Rep. 2020 Jul 9;10(1):11368. (PMID: 32647361)
Int J Radiat Oncol Biol Phys. 2024 Oct 1;120(2):579-592. (PMID: 38621606)
Int J Radiat Oncol Biol Phys. 2016 May 1;95(1):234-241. (PMID: 26692028)
Cancers (Basel). 2021 Dec 22;14(1):. (PMID: 35008189)
Clin Transl Radiat Oncol. 2025 Feb 19;52:100932. (PMID: 40124645)
Contributed Indexing: Keywords: beam delivery; minibeams; proton therapy
Entry Date(s): Date Created: 20260819 Date Completed: 20260819 Latest Revision: 20260822
Update Code: 20260822
PubMed Central ID: PMC13486916
DOI: 10.1002/mp.70638
PMID: 42613851
Βάση Δεδομένων: MEDLINE
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  Data: Impact of millimeter-scale target motion on the precision of spatially fractionated radiation therapy using proton minibeams.
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  Data: <searchLink fieldCode="AU" term="%22Actis+O%22">Actis O</searchLink>; Center for Proton Therapy, Paul Scherrer Institute, Villigen PSI, Aargau, Switzerland.<br /><searchLink fieldCode="AU" term="%22Fernandez-Palomo+C%22">Fernandez-Palomo C</searchLink>; Institute of Anatomy, University of Bern, Bern, Switzerland.<br /><searchLink fieldCode="AU" term="%22Trappetti+V%22">Trappetti V</searchLink>; Institute of Anatomy, University of Bern, Bern, Switzerland.<br /><searchLink fieldCode="AU" term="%22Togno+M%22">Togno M</searchLink>; Center for Proton Therapy, Paul Scherrer Institute, Villigen PSI, Aargau, Switzerland.<br /><searchLink fieldCode="AU" term="%22Pellicioli+P%22">Pellicioli P</searchLink>; Institute of Anatomy, University of Bern, Bern, Switzerland.<br /><searchLink fieldCode="AU" term="%22Leiser+D%22">Leiser D</searchLink>; Center for Proton Therapy, Paul Scherrer Institute, Villigen PSI, Aargau, Switzerland.<br /><searchLink fieldCode="AU" term="%22Meer+D%22">Meer D</searchLink>; Center for Proton Therapy, Paul Scherrer Institute, Villigen PSI, Aargau, Switzerland.<br /><searchLink fieldCode="AU" term="%22Djonov+V%22">Djonov V</searchLink>; Institute of Anatomy, University of Bern, Bern, Switzerland.
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  Data: <searchLink fieldCode="MM" term="%22Proton+Therapy%22">Proton Therapy*</searchLink>/<searchLink fieldCode="MM" term="%22Proton+Therapy+instrumentation%22">instrumentation</searchLink> <br /><searchLink fieldCode="MM" term="%22Proton+Therapy%22">Proton Therapy*</searchLink>/<searchLink fieldCode="MM" term="%22Proton+Therapy+methods%22">methods</searchLink> <br /><searchLink fieldCode="MM" term="%22Dose+Fractionation%2C+Radiation%22">Dose Fractionation, Radiation*</searchLink><br /><searchLink fieldCode="MH" term="%22Chorioallantoic+Membrane%22">Chorioallantoic Membrane</searchLink>/<searchLink fieldCode="MH" term="%22Chorioallantoic+Membrane+radiation+effects%22">radiation effects</searchLink> ; <searchLink fieldCode="MH" term="%22Animals%22">Animals</searchLink> ; <searchLink fieldCode="MH" term="%22Chick+Embryo%22">Chick Embryo</searchLink> ; <searchLink fieldCode="MH" term="%22Movement%22">Movement</searchLink>
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  Data: Background: While pencil beam scanning (PBS) with motion mitigation such as re-scanning, breath hold, or gating is well established for treating moving targets in clinical practice, the precision for Spatially Fractionated Radiation Therapy (SFRT) using proton minibeams introduces presents a unique challenge. The sub-millimeter precision required for SFRT cannot be achieved with typical PBS spot sizes (millimeters), necessitating multi-slit beam collimation, which reduces the dose rate and reintroduces motion as a critical issue. In this study, we report on our experience with minibeam irradiations of chorioallantoic membranes (CAM) of chick embryos and discuss potential solutions to the motion problem.<br />Methods: The first experiment was conducted at a PBS gantry using 130 MeV protons and a 6 cm thick copper multi-slit collimator with 0.3 mm wide slits and 1 mm spacing. To achieve a target peak dose of 30 Gy, CAM samples were irradiated with more than 10 re-scans. Due to a 91% beam loss in the collimator, the total irradiation time extended to two min.<br />Results: Post-irradiation analysis using gafchromic film revealed smearing of the minibeam profiles, while biological tissue analysis uncovered unexpected and disrupted dose effects, likely caused by irregular CAM movement during irradiation. A subsequent experiment, incorporating additional setup optimizations such as reduced air gap and increased dose rate, shortened the irradiation time to below one min. This led to sharper dose profiles with negligible variation in valley dose and peak width, although a reduction in peak dose of 8%-13% was still observed. This variation is considered acceptable for our biological experiments.<br />Conclusions: For clinical applications, minibeam re-scanning is likely to be feasible only under ultra-high dose rate conditions (e.g., those required to induce the FLASH effect), where sufficiently short irradiation times minimize motion-induced dose degradation.<br /> (© 2026 The Author(s). Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)
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  Data: Anat Rec. 2001 Dec 1;264(4):317-24. (PMID: <searchLink fieldCode="PM" term="%2211745087%22">11745087)</searchLink><br />Phys Med Biol. 2017 Mar 7;62(5):1661-1675. (PMID: <searchLink fieldCode="PM" term="%2228166055%22">28166055)</searchLink><br />Med Phys. 2018 Jul 15;:. (PMID: <searchLink fieldCode="PM" term="%2230009481%22">30009481)</searchLink><br />Med Phys. 2012 Nov;39(11):6818-37. (PMID: <searchLink fieldCode="PM" term="%2223127075%22">23127075)</searchLink><br />Br J Radiol. 2019 Mar;92(1095):20180466. (PMID: <searchLink fieldCode="PM" term="%2230359081%22">30359081)</searchLink><br />Sci Rep. 2018 Nov 7;8(1):16479. (PMID: <searchLink fieldCode="PM" term="%2230405188%22">30405188)</searchLink><br />Int J Radiat Oncol Biol Phys. 2019 Jun 1;104(2):266-271. (PMID: <searchLink fieldCode="PM" term="%2230703513%22">30703513)</searchLink><br />Sci Rep. 2020 Jul 9;10(1):11368. (PMID: <searchLink fieldCode="PM" term="%2232647361%22">32647361)</searchLink><br />Int J Radiat Oncol Biol Phys. 2024 Oct 1;120(2):579-592. (PMID: <searchLink fieldCode="PM" term="%2238621606%22">38621606)</searchLink><br />Int J Radiat Oncol Biol Phys. 2016 May 1;95(1):234-241. (PMID: <searchLink fieldCode="PM" term="%2226692028%22">26692028)</searchLink><br />Cancers (Basel). 2021 Dec 22;14(1):. (PMID: <searchLink fieldCode="PM" term="%2235008189%22">35008189)</searchLink><br />Clin Transl Radiat Oncol. 2025 Feb 19;52:100932. (PMID: <searchLink fieldCode="PM" term="%2240124645%22">40124645)</searchLink>
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