In vivo validation and tissue sparing factor for acute damage of pencil beam scanning proton FLASH

Sørensen, Brita Singers; Sitarz, Mateusz; Ankjærgaard, Christina; Johansen, Jacob; Andersen, C.E.; Kanouta, E.; Overgaard, C.; Grau, Cai; Poulsen, P.R.

doi:10.1016/j.radonc.2021.12.022

Cited by 77 publications

(67 citation statements)

References 19 publications

(29 reference statements)

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“…It is worth pointing out that the instantaneous dose rate in a currently commercially available isochronous cyclotron‐based proton FLASH platform is typically about three to four orders of magnitude less than that of a linac‐based electron FLASH system 31 . Therefore, IC‐based dosimetry systems such as the ones investigated in this and other studies may still be a viable option 11,13,34 …”

Section: Discussionmentioning

confidence: 96%

“…31 Therefore, IC-based dosimetry systems such as the ones investigated in this and other studies may still be a viable option. 11,13,34 Strip detectors are often designed to gate the beam by monitoring the spot position and profile. To explore its potential applications in QA of proton beams, the spatial performance of the SICA has been compared with the Lynx detector in measurements of the spot positions and sizes, as shown in Figures 5 and 6.…”

Section: Discussionmentioning

confidence: 99%

“…Although FLASH‐RT delivered with electrons has produced the majority of preclinical results to date, 1,5–8 electron FLASH‐RT is limited in its eventual clinical translation to treat deep‐seated targets with sufficient conformity due to the properties intrinsic to electron interactions 4 . FLASH‐RT delivery using proton therapy has emerged as an attractive alternative because of its excellent dose conformity, its ability to treat deep‐seated targets, and the availability of existing treatment machines to deliver at UHDR 10–18 . Pencil beam scanning (PBS) is currently the most advanced and dominant technology of delivering proton RT that employs the dosimetric advantages of proton radiation.…”

Section: Introductionmentioning

confidence: 99%

“…They have been widely used as dose and beam position monitors in the treatment machine head and in various QA devices employed in current clinical practice 32,33 . In addition, a small number of IC‐based detectors have also been studied under high beam current conditions for FLASH‐RT using existing proton delivery systems up to a few hundred nanoamperes 10–13,27–30,34 . However, the experimental characterization and validation of quantities relevant for proton PBS FLASH‐RT remain lacking.…”

Section: Introductionmentioning

confidence: 99%

“…32,33 In addition, a small number of IC-based detectors have also been studied under high beam current conditions for FLASH-RT using existing proton delivery systems up to a few hundred nanoamperes. [10][11][12][13][27][28][29][30]34 However, the experimental characterization and validation of quantities relevant for proton PBS FLASH-RT remain lacking. As pointed out previously, proton PBS FLASH-RT requires monitoring beam spot position, profile, dwell time, and the delivered dose, at a high temporal resolution.…”

Section: Introductionmentioning

confidence: 99%

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A 2D strip ionization chamber array with high spatiotemporal resolution for proton pencil beam scanning FLASH radiotherapy

et al. 2022

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Purpose Experimental measurements of two‐dimensional (2D) dose rate distributions in proton pencil beam scanning (PBS) FLASH radiation therapy (RT) are currently lacking. In this study, we characterize a newly designed 2D strip‐segmented ionization chamber array (SICA) with high spatial and temporal resolution and demonstrate its applications in a modern proton PBS delivery system at both conventional and ultrahigh dose rates. Methods A dedicated research beamline of the Varian ProBeam system was employed to deliver a 250‐MeV proton PBS beam with nozzle currents up to 215 nA. In the research and clinical beamlines, the spatial, temporal, and dosimetric performances of the SICA were characterized and compared with measurements using parallel‐plate ion chambers (IBA PPC05 and PTW Advanced Markus chamber), a 2D scintillator camera (IBA Lynx), Gafchromic films (EBT‐XD), and a Faraday cup. A novel reconstruction approach was proposed to enable the measurement of 2D dose and dose rate distributions using such a strip‐type detector. Results The SICA demonstrated a position accuracy of 0.12 ± 0.02 mm at a 20‐kHz sampling rate (50 μs per event) and a linearity of R2 > 0.99 for both dose and dose rate with nozzle beam currents ranging from 1 to 215 nA. The 2D dose comparison to the film measurement resulted in a gamma passing rate of 99.8% (2 mm/2%). A measurement‐based proton PBS 2D FLASH dose rate distribution was compared to simulation results and showed a gamma passing rate of 97.3% (2 mm/2%). Conclusions The newly designed SICA demonstrated excellent spatial, temporal, and dosimetric performances and is well suited for commissioning, quality assurance, and a wide range of clinical applications in proton PBS clinical and FLASH‐RT.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

A 2D strip ionization chamber array with high spatiotemporal resolution for proton pencil beam scanning FLASH radiotherapy

et al. 2022

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A comprehensive pre‐clinical treatment quality assurance program using unique spot patterns for proton pencil beam scanning FLASH radiotherapy

Tsai,

Yang,

et al. 2024

J Applied Clin Med Phys

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BackgroundQuality assurance (QA) for ultra‐high dose rate (UHDR) irradiation is a crucial aspect in the emerging field of FLASH radiotherapy (FLASH‐RT). This innovative treatment approach delivers radiation at UHDR, demanding careful adoption of QA protocols and procedures. A comprehensive understanding of beam properties and dosimetry consistency is vital to ensure the safe and effective delivery of FLASH‐RT.PurposeTo develop a comprehensive pre‐treatment QA program for cyclotron‐based proton pencil beam scanning (PBS) FLASH‐RT. Establish appropriate tolerances for QA items based on this study's outcomes and TG‐224 recommendations.MethodsA 250 MeV proton spot pattern was designed and implemented using UHDR with a 215nA nozzle beam current. The QA pattern that covers a central uniform field area, various spot spacings, spot delivery modes and scanning directions, and enabling the assessment of absolute, relative and temporal dosimetry QA parameters. A strip ionization chamber array (SICA) and an Advanced Markus chamber were utilized in conjunction with a 2 cm polyethylene slab and a range (R80) verification wedge. The data have been monitored for over 3 months.ResultsThe relative dosimetries were compliant with TG‐224. The variations of temporal dosimetry for scanning speed, spot dwell time, and spot transition time were within ± 1 mm/ms, ± 0.2 ms, and ± 0.2 ms, respectively. While the beam‐to‐beam absolute output on the same day reached up to 2.14%, the day‐to‐day variation was as high as 9.69%. High correlation between the absolute dose and dose rate fluctuations were identified. The dose rate of the central 5 × 5 cm2 field exhibited variations within 5% of the baseline value (155 Gy/s) during an experimental session.ConclusionsA comprehensive QA program for FLASH‐RT was developed and effectively assesses the performance of a UHDR delivery system. Establishing tolerances to unify standards and offering direction for future advancements in the evolving FLASH‐RT field.

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Time structure of pencil beam scanning proton FLASH beams measured with scintillator detectors and compared with log files

et al. 2022

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Purpose Key factors in FLASH treatments are the ultra‐high dose rate (UHDR) and the time structure of the beam delivery. Measurement of the time structure in pencil beam scanning (PBS) proton FLASH treatments is challenging for many types of detectors since high temporal resolution is needed. In this study, a fast scintillator detector system was developed and used to measure the individual spot durations as well as the time when the beam moves between two positions (transition duration) during PBS proton FLASH and UHDR treatments. The spot durations were compared with machine log‐file recordings. Methods A detector system based on inorganic scintillating crystals was developed. The system consisted of four detector probes made of a sub‐millimeter ZnSe:O crystal that was coupled via an optical fiber to an optical reader with 50 kHz sampling rate. The detector system was used in two experiments, both performed with a PBS proton beam with 250 MeV beam energy and 215 nA requested nozzle beam current. The sampling rate enabled multiple measurements during each spot delivery and during the beam transition between spots. First, the detector was tested in a phantom experiment, where a total of 305 scan sequences were delivered to the four detectors. The number of spots delivered without beam interruption in a single scan sequence ranged from one to 35. The spot duration and transition duration were measured for each individual spot. Secondly, the detector system was used in vivo in preclinical experiments with FLASH irradiation of mouse legs placed in the entrance plateau of the beam. A single detector was placed 1 cm downstream of the irradiated mouse leg. The mouse dose ranged from 30.5 to 44.2 Gy and the field consisted of 35 spots. The spot durations as well as the mean dose rate (field dose divided by the measured field duration) for each mouse were determined using the detector and then compared with the corresponding log files. Results The phantom experiment showed that the logged total duration of an uninterrupted spot sequence was consistently shorter than the measured duration with a difference of −0.252 ms (95% confidence interval: [‐0.255, −0.249 ms]). This corresponded to 0.05%–0.07% of the spot sequence duration in the mice experiments. For individual spots, the mean ± 1SD difference between logged and measured spot duration was −0.39 ± 0.05 ms for the first spot in a sequence, 0.13 ± 0.04 ms for the last spot in a sequence, and −0.0017 ± 0.09 ms for the intermediate spots in a sequence. The measured spot transition durations were 0.20 ± 0.04 ms (5.1 mm horizontal steps) and 0.50 ± 0.04 ms (5.0 mm vertical steps). For the mouse experiments, the mean dose rate calculated from the measured field duration was 84.1–92.5 Gy/s. It agreed with log files with a root mean square difference of 0.02 Gy/s. Conclusions Fiber‐coupled scintillator detectors were designed with sufficient temporal resolution to measure the spot and transition duration during PBS proton UHDR deliveries. Their small volume makes the...

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In vivo validation and tissue sparing factor for acute damage of pencil beam scanning proton FLASH

Cited by 77 publications

References 19 publications

A 2D strip ionization chamber array with high spatiotemporal resolution for proton pencil beam scanning FLASH radiotherapy

A 2D strip ionization chamber array with high spatiotemporal resolution for proton pencil beam scanning FLASH radiotherapy

A comprehensive pre‐clinical treatment quality assurance program using unique spot patterns for proton pencil beam scanning FLASH radiotherapy

Time structure of pencil beam scanning proton FLASH beams measured with scintillator detectors and compared with log files

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