A Novel Proton Pencil Beam Scanning FLASH RT Delivery Method Enables Optimal OAR Sparing and Ultra-High Dose Rate Delivery: A Comprehensive Dosimetry Study for Lung Tumors

Wei, Shouyi; Lin, Haibo; Choi, J. Isabelle; Simone, Charles B.; Kang, Min Jueng

doi:10.3390/cancers13225790

Cited by 28 publications

(43 citation statements)

References 31 publications

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“…In recent years, the field of radiation therapy (RT) has witnessed a reemergence of tremendous interest in the delivery of RT at ultrahigh dose rates (UHDRs), typically greater than 40 Gy/s, beginning with the publication of Favaudon et al 1 . This interest is sparked by a large body of preclinical results that suggest that such UHDR delivery yields comparable tumor control while substantially reducing normal tissue toxicity in in vivo animal models 1–20 . This differential response to radiation delivered at UHDR between tumor and normal tissue widens the therapeutic window and is dubbed by the FLASH effect 1 .…”

Section: Introductionmentioning

confidence: 99%

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: Introductionmentioning

confidence: 99%

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

et al. 2022

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“…Also, transmission beams cannot spare the normal tissue at the distal edge of the target, which is validated by the comparison with conventional IMPT plans that place the Bragg peaks inside the targets. Although multiple-energy modulation as in conventional IMPT has not been available for FLASH-RT, using single-energy Bragg peak FLASH may provide a suitable solution to address the above issues, which we have evaluated by comparing the same dose metrics (23,39). Some previous in vivo and in vitro experiments (49)(50)(51) suggest that the FLASH effect may be triggered when a particular dose threshold is met; what is a clinically feasible dose fractionation is still not clear yet for liver cancers.…”

Section: Discussionmentioning

confidence: 99%

“…In proton FLASH-RT, transmission proton beams have been the most favorable choice of delivery owing to the sufficiently high beam current achievable with existing clinical systems. Recent efforts have reported combining transmission proton PBS with FLASH-RT, to translate the technology from bench to preclinic experiments, in aspects including proton systems (11)(12)(13)(14)(15), treatment planning (18)(19)(20)(21)(22)(23), and biological investigations (24,25). Proton PBS FLASH treatment planning plays a crucial role just as conventional treatment planning, but it faces new and unique challenges as the dose rate considerations must be included when evaluating the plan quality.…”

Section: Introductionmentioning

confidence: 99%

“…Currently, several treatment planning studies have applied proton PBS FLASH beams to the head and neck (H&N) (19,20,34) and lung cancers (18,22,23,35), with theoretical proton delivery parameters. van de Water et al (19) discussed the feasibility of achieving transmission FLASH with existing and theoretical machine settings, especially the beam current, with the dose rate quantified using the dose-averaged dose rate (DADR).…”

Section: Introductionmentioning

confidence: 99%

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FLASH Radiotherapy Using Single-Energy Proton PBS Transmission Beams for Hypofractionation Liver Cancer: Dose and Dose Rate Quantification

et al. 2022

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PurposeThis work aims to study the dose and ultra-high-dose rate characteristics of transmission proton pencil beam scanning (PBS) FLASH radiotherapy (RT) for hypofractionation liver cancer based on the parameters of a commercially available proton system operating under FLASH mode.Methods and MaterialsAn in-house treatment planning software (TPS) was developed to perform intensity-modulated proton therapy (IMPT) FLASH-RT planning. Single-energy transmission proton PBS plans of 4.5 Gy × 15 fractions were optimized for seven consecutive hepatocellular carcinoma patients, using 2 and 5 fields combined with 1) the minimum MU/spot chosen between 100 and 400, and minimum spot time (MST) of 2 ms, and 2) the minimum MU/spot of 100, and MST of 0.5 ms, based upon considerations in target uniformities, OAR dose constraints, and OAR FLASH dose rate coverage. Then, the 3D average dose rate distribution was calculated. The dose metrics for the mean dose of Liver-GTV and other major OARs were characterized to evaluate the dose quality for the different combinations of field numbers and minimum spot times compared to that of conventional IMPT plans. Dose rate quality was evaluated using 40 Gy/s volume coverage (V40Gy/s).ResultsAll plans achieved favorable and comparable target uniformities, and target uniformity improved as the number of fields increased. For OARs, no significant dose differences were observed between plans of different field numbers and the same MST. For plans using shorter MST and the same field numbers, better sparing was generally observed in most OARs and was statistically significant for the chest wall. However, the FLASH dose rate coverage V40Gy/s was increased by 20% for 2-field plans compared to 5-field plans in most OARs with 2-ms MST, which was less evident in the 0.5-ms cases. For 2-field plans, dose metrics and V40Gy/s of select OARs have large variations due to the beam angle selection and variable distances to the targets. The transmission plans generally yielded inferior dosimetric quality to the conventional IMPT plans.ConclusionThis is the first attempt to assess liver FLASH treatment planning and demonstrates that it is challenging for hypofractionation with smaller fractional doses (4.5 Gy/fraction). Using fewer fields can allow higher minimum MU/spot, resulting in higher OAR FLASH dose rate coverages while achieving similar plan quality compared to plans with more fields. Shorter MST can result in better plan quality and comparable or even better FLASH dose rate coverage.

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“…This challenge could potentially be overcome by the higher dose rates brought forth by newer accelerator technologies. With proton systems capable of delivering non-transmission ultra-high-dose rates or FLASH treatment ( 14 ), we envision that such 3DCM would be very valuable for SRS/SBRT treatment, with the patient motion-related error eliminated or minimized.…”

Section: Discussionmentioning

confidence: 99%

Conformal Dose Modulator for Proton Beam Therapy Part 1: A Simulation Study

et al. 2022

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PurposeConformal dose deliveries in proton therapy utilize either a passive scattering system with a modulator or a pencil beam scanning (PBS) system. Efforts have been made to achieve conformal dose delivery by scanning a single energy layer of pencil beams through a 3D conformal modulator (3DCM), which combines a spread-out Bragg peak (SOBP) modulator consisting of a micro-pyramid array and a range compensator. The current published approach of designing such 3DCM relies on forward calculation methods to determine the geometry of the modulator. This study presents an alternative designing algorithm that inversely generates the geometry of a 3DCM paired with a corresponding fluence map, customized to patient-specific clinical indications.MethodsCritical spacing governing the size and separation between neighboring micro-pyramids was first determined, under which the dose homogeneity at desired depths could be achieved. We designed an adaptive ring optimization method using a modified gradient descent algorithm to inversely calculate the geometry of the 3DCM. This method includes several stages that progressively optimize both target coverage and dose conformity. The output contains the geometry of the 3DCM and its corresponding proton fluence map. Monte Carlo (MC) simulation was used to validate the results.ResultsThe critical size and spacing of Lucite pyramids was determined to be 0.5 cm for a 184-MeV pristine proton beam. Using MATLAB (R2020a), the inverse designing algorithm generated an optimized 3DCM geometry and a fluence distribution achieving 100% target coverage with the 90% isodose surface and a corresponding conformity index of 1.057 on a spherical target. The resulting geometry was pruned to accommodate the MC simulation software and a currently accessible 3D printing service. The pruned geometry gave 95% target coverage by 90% isodose surface with a conformity index of 1.09 by ray-tracing dose computation. The MC simulation validated the 3DCM with 95% target coverage by 87% isodose surface and a conformity index of 1.12.ConclusionWe have demonstrated the feasibility of using a novel inverse optimization algorithm to generate 3DCM geometry and its corresponding proton beam fluence/intensity map, which could deliver highly conformal dose distribution with pencil beam scanning system using a single energy layer.

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A Novel Proton Pencil Beam Scanning FLASH RT Delivery Method Enables Optimal OAR Sparing and Ultra-High Dose Rate Delivery: A Comprehensive Dosimetry Study for Lung Tumors

Cited by 28 publications

References 31 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

FLASH Radiotherapy Using Single-Energy Proton PBS Transmission Beams for Hypofractionation Liver Cancer: Dose and Dose Rate Quantification

Conformal Dose Modulator for Proton Beam Therapy Part 1: A Simulation Study

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