Current delivery limitations of proton PBS for FLASH

Zou, W.; Diffenderfer, Eric; Cengel, Keith A.; Kim, Michele M.; Avery, Steve; Konzer, J.; Cai, Yongliang; Boisseu, Paul; Ota, Kan; Yin, Lingshu; Wiersma, R; Carlson, David J.; Fan, Yi; Busch, Theresa M.; Koumenis, Constantinos; Lin, Alexander; Metz, James M.; Teo, Boon-Keng; Dong, Lei

doi:10.1016/j.radonc.2020.11.002

Cited by 45 publications

(48 citation statements)

References 44 publications

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“…For current proton PBS planning and treatment, multiple energy layers are used to generate spread-out Bragg peaks (SOBP) to cover the target volume. However, using SOBP becomes difficult for FLASH-RT to deliver ultra-high dose rate spots across an entire target volume with sufficiently high mean dose rates due to the inefficiency of beam transmission for lower energies beam [ 13 , 15 ]. Additionally, the typical energy/layer switch time is ~200 ms for energy degradation-based cyclotron systems [ 16 ] and on a scale of >1000 ms for synchrotron systems [ 17 ], which also prolongs the beam-on time.…”

Section: Introductionmentioning

confidence: 99%

Quantitative Assessment of 3D Dose Rate for Proton Pencil Beam Scanning FLASH Radiotherapy and Its Application for Lung Hypofractionation Treatment Planning

Kang

Wei

Choi

et al. 2021

Cancers

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To quantitatively assess target and organs-at-risk (OAR) dose rate based on three proposed proton PBS dose rate metrics and study FLASH intensity-modulated proton therapy (IMPT) treatment planning using transmission beams. An in-house FLASH planning platform was developed to optimize transmission (shoot-through) plans for nine consecutive lung cancer patients previously planned with proton SBRT. Dose and dose rate calculation codes were developed to quantify three types of dose rate calculation methods (dose-averaged dose rate (DADR), average dose rate (ADR), and dose-threshold dose rate (DTDR)) based on both phantom and patient treatment plans. Two different minimum MU/spot settings were used to optimize two different dose regimes, 34-Gy in one fraction and 45-Gy in three fractions. The OAR sparing and target coverage can be optimized with good uniformity (hotspot < 110% of prescription dose). ADR, accounting for the spot dwelling and scanning time, gives the lowest dose rate; DTDR, not considering this time but a dose-threshold, gives an intermediate dose rate, whereas DADR gives the highest dose rate without considering any time or dose-threshold. All three dose rates attenuate along the beam direction, and the highest dose rate regions often occur on the field edge for ADR and DTDR, whereas DADR has a better dose rate uniformity. The differences in dose rate metrics have led a large variation for OARs dose rate assessment, posing challenges to FLASH clinical implementation. This is the first attempt to study the impact of the dose rate models, and more investigations and evidence for the details of proton PBS FLASH parameters are needed to explore the correlation between FLASH efficacy and the dose rate metrics.

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Section: Introductionmentioning

confidence: 99%

Quantitative Assessment of 3D Dose Rate for Proton Pencil Beam Scanning FLASH Radiotherapy and Its Application for Lung Hypofractionation Treatment Planning

Kang

Wei

Choi

et al. 2021

Cancers

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“…These energy degraders cause a large decrease in efficiency, with beam losses up to 99% for 70 MeV protons [17], which greatly reduces the dose rate. Beam loss along with other challenges and unknowns have been discussed elsewhere [17][18][19]. Kourkafas et al recently reported the creation of a single scattering system with a rotating modulator wheel to create a proton SOBP at FLASH dose rates of approximately 75 Gy/s [20].…”

Section: Introductionmentioning

confidence: 99%

Comparison of FLASH Proton Entrance and the Spread-Out Bragg Peak Dose Regions in the Sparing of Mouse Intestinal Crypts and in a Pancreatic Tumor Model

Kim

Verginadis

Goia

et al. 2021

Cancers

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Ultra-high dose rate FLASH proton radiotherapy (F-PRT) has been shown to reduce normal tissue toxicity compared to standard dose rate proton radiotherapy (S-PRT) in experiments using the entrance portion of the proton depth dose profile, while proton therapy uses a spread-out Bragg peak (SOBP) with unknown effects on FLASH toxicity sparing. To investigate, the biological effects of F-PRT using an SOBP and the entrance region were compared to S-PRT in mouse intestine. In this study, 8–10-week-old C57BL/6J mice underwent 15 Gy (absorbed dose) whole abdomen irradiation in four groups: (1) SOBP F-PRT, (2) SOBP S-PRT, (3) entrance F-PRT, and (4) entrance S-PRT. Mice were injected with EdU 3.5 days after irradiation, and jejunum segments were harvested and preserved. EdU-positive proliferating cells and regenerated intestinal crypts were quantified. The SOBP had a modulation (width) of 2.5 cm from the proximal to distal 90%. Dose rates with a SOBP for F-PRT or S-PRT were 108.2 ± 8.3 Gy/s or 0.82 ± 0.14 Gy/s, respectively. In the entrance region, dose rates were 107.1 ± 15.2 Gy/s and 0.83 ± 0.19 Gy/s, respectively. Both entrance and SOBP F-PRT preserved a significantly higher number of EdU + /crypt cells and percentage of regenerated crypts compared to S-PRT. Moreover, tumor growth studies showed no difference between SOBP and entrance for either of the treatment modalities.

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“…The nozzle beam charge and profile were configured in Eclipse treatment planning system (Varian, Palo Alto, CA) 43 and the depth dose in water for the pencil beam was calculated. High cyclotron currents of 150 and 350 nA yield dose rates of 68.4 and 159.7 Gy/s, respectively, at the central axis Bragg Peak in water for 226.2 MeV pencil beams 44 …”

Section: Methodsmentioning

confidence: 99%

“…High cyclotron currents of 150 and 350 nA yield dose rates of 68.4 and 159.7 Gy/s, respectively, at the central axis Bragg Peak in water for 226.2 MeV pencil beams. 44 The cyclotron produces 2.4 ns micropulses at a high 106.2 MHz RF repetition rate. The speed of the IC is ultimately limited by ion transit times to the electrode in more than a few microseconds, 27 so that the 106.2 MHz RF rep rate is effectively averaged out.…”

Section: B Ion Recombinationmentioning

confidence: 99%

Characterization of a high‐resolution 2D transmission ion chamber for independent validation of proton pencil beam scanning of conventional and FLASH dose delivery

et al. 2021

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Introduction: Ultra-high dose rate (FLASH) radiotherapy has become a popular research topic with the potential to reduce normal tissue toxicities without losing the benefit of tumor control. The development of FLASH proton pencil beam scanning (PBS) delivery requires accurate dosimetry despite high beam currents with correspondingly high ionization densities in the monitoring chamber. In this study, we characterized a newly designed high-resolution position sensing transmission ionization chamber with a purpose-built multichannel electrometer for both conventional and FLASH dose rate proton radiotherapy. Methods: The dosimetry and positioning accuracies of the ion chamber were fully characterized with a clinical scanning beam. On the FLASH proton beamline, the cyclotron output current reached up to 350 nA with a maximum energy of 226.2 MeV, with 210 AE 3 nA nozzle pencil beam current. The ion recombination effect was characterized under various bias voltages up to 1000 V and different beam intensities. The charge collected by the transmission ion chamber was compared with the measurements from a Faraday cup. Results: Cross-calibrated with an Advanced Markus chamber (PTW, Freiburg, Germany) in a uniform PBS proton beam field at clinical beam setting, the ion chamber calibration was 38.0 and 36.7 GyEÁmm 2 /nC at 100 and 226.2 MeV, respectively. The ion recombination effect increased with larger cyclotron current at lower bias voltage while remaining ≤0.5 AE 0.5% with ≥200 V of bias voltage. Above 200 V, the normalized ion chamber readings demonstrated good linearity with the mass stopping power in air for both clinical and FLASH beam intensities. The spot positioning accuracy was measured to be 0.10 AE 0.08 mm in two orthogonal directions. Conclusion:We characterized a transmission ion chamber system under both conventional and FLASH beam current densities and demonstrated its suitability for use as a proton pencil beam dose and spot position delivery monitor under FLASH dose rate conditions.

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Current delivery limitations of proton PBS for FLASH

Cited by 45 publications

References 44 publications

Quantitative Assessment of 3D Dose Rate for Proton Pencil Beam Scanning FLASH Radiotherapy and Its Application for Lung Hypofractionation Treatment Planning

Quantitative Assessment of 3D Dose Rate for Proton Pencil Beam Scanning FLASH Radiotherapy and Its Application for Lung Hypofractionation Treatment Planning

Comparison of FLASH Proton Entrance and the Spread-Out Bragg Peak Dose Regions in the Sparing of Mouse Intestinal Crypts and in a Pancreatic Tumor Model

Characterization of a high‐resolution 2D transmission ion chamber for independent validation of proton pencil beam scanning of conventional and FLASH dose delivery

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