Modifying a clinical linear accelerator for delivery of ultra-high dose rate irradiation

Lempart, Michael; Blad, Börje; Adrian, Gabriel; Bäck, Sven; Knöös, Tommy; Ceberg, Crister; Petersson, Kristoffer

doi:10.1016/j.radonc.2019.01.031

Cited by 139 publications

(174 citation statements)

References 13 publications

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“…As previously mentioned, most studies showing a FLASH effect has dedicated electron linear accelerators as the source of radiation (9,10,14,15,18,37). Recent studies have shown that clinical linear accelerators can be modified to deliver FLASH-RT with electrons, largely increasing the potential availability of FLASH-RT devices and facilitating the translation to clinical trials (66,67). However, an obvious limitation is the depth penetration with 4.5-20 MeV electron beams, only reaching to a few cm depths in tissue ( Table 3).…”

Section: Clinical Applications Of Flash-rtmentioning

confidence: 99%

Ultra-High Dose Rate (FLASH) Radiotherapy: Silver Bullet or Fool's Gold?

et al. 2020

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Radiotherapy is a cornerstone of both curative and palliative cancer care. However, radiotherapy is severely limited by radiation-induced toxicities. If these toxicities could be reduced, a greater dose of radiation could be given therefore facilitating a better tumor response. Initial pre-clinical studies have shown that irradiation at dose rates far exceeding those currently used in clinical contexts reduce radiation-induced toxicities whilst maintaining an equivalent tumor response. This is known as the FLASH effect. To date, a single patient has been subjected to FLASH radiotherapy for the treatment of subcutaneous T-cell lymphoma resulting in complete response and minimal toxicities. The mechanism responsible for reduced tissue toxicity following FLASH radiotherapy is yet to be elucidated, but the most prominent hypothesis so far proposed is that acute oxygen depletion occurs within the irradiated tissue. This review examines the tissue response to FLASH radiotherapy, critically evaluates the evidence supporting hypotheses surrounding the biological basis of the FLASH effect, and considers the potential for FLASH radiotherapy to be translated into clinical contexts.

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Section: Clinical Applications Of Flash-rtmentioning

confidence: 99%

Ultra-High Dose Rate (FLASH) Radiotherapy: Silver Bullet or Fool's Gold?

et al. 2020

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“…This configuration was different from previous work in the literature, which focused on reversible linac modifications where the linac was running in electron mode (smaller electron current) and measurements took place within the linac head. 22,23 The method chosen for this study removed the previous constraint of limited space within the linac head, allowing for flexibility in experimental designs for iRAI in this proof-of-concept study. However, the major downside of this modification is that it is currently irreversible.…”

Section: C Flash Electron Sourcementioning

confidence: 99%

An ionizing radiation acoustic imaging (iRAI) technique for real‐time dosimetric measurements for FLASH radiotherapy

et al. 2020

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Purpose: FLASH radiotherapy (FLASH-RT) is a novel irradiation modality with ultra-high dose rates (>40 Gy/s) that have shown tremendous promise for its ability to enhance normal tissue sparing while maintaining comparable tumor cell eradication toconventional radiotherapy (CONV-RT). Due to its extremely high dose rates, clinical translation of FLASH-RT is hampered by risky delivery and current limitations in dosimetric devices, which cannot accurately measure, in real time, dose at deeper tissue. This work aims to investigate ionizing radiation acoustic imaging (iRAI) as a promising image-guidance modality for real-time deep tissue dose measurements during FLASH-RT. The underlying hypothesis is that iRAI can enable mapping of dose deposition with respect to surrounding tissue with a single linear accelerator (linac) pulse precision in real time. In this work, the relationship between iRAI signal response and deposited dose was investigated as well as the feasibility of using a proof-of-concept dual-modality imaging system of ultrasound and iRAI for treatment beam co-localization with respect to underlying anatomy. Methods: Two experimental setups were used to study the feasibility of iRAI for FLASH-RT using 6 MeV electrons from a modified Varian Clinac. First, experiments were conducted using a single element focused transducer to take a series of point measurements in a gelatin phantom, which was compared with independent dose measurements using GAFchromic film. Secondly, an ultrasound and iRAI dual-modality imaging system utilizing a phased array transducer was used to take coregistered two-dimensional (2D) iRAI signal amplitude images as well as ultrasound B-mode images, to map the dose deposition with respect to surrounding anatomy in an ex vivo rabbit liver model with a single linac pulse precision. Results: Using a single element transducer, iRAI measurements showed a highly linear relationship between the iRAI signal amplitude and the linac dose per pulse (r 2 = 0.9998) with a repeatability precision of 1% and a dose resolution error <2.5% in a homogenous phantom when compared to GAFchromic film dose measurements. These phantom results were used to develop a calibration curve between the iRAI signal response and the delivered dose per pulse. Subsequently, a normalized depth dose curve was generated that agreed with film measurements with an RMSE of 0.0243, using correction factors to account for deviations in measurement conditions with respect to calibration. Experiments on the ex-vivo rabbit liver model demonstrated that a 2D iRAI image could be generated successfully from a single linac pulse, which was fused with the B-mode ultrasound image to provide information about the beam position with respect to surrounding anatomy in real time.

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“…11,12 It has also been suggested that the long-term neurocognitive benefits of FLASH radiotherapy might be driven by reduced reactive oxygen species (ROS) 14 and less hippocampal dendritic spine loss and neuroinflammation. 15 To date, FLASH irradiation has been realized using x rays generated in a synchrotron facility, 4 electrons generated by linear accelerators, [1][2][3]16,17 and protons using isochronous cyclotrons. [18][19][20] A summary of recent implementation of FLASH irradiation is provided in Table I.…”

Section: Introductionmentioning

confidence: 99%

Feasibility of proton FLASH irradiation using a synchrocyclotron for preclinical studies

et al. 2020

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It has been recently shown that radiotherapy at ultrahigh dose rates (>40 Gy/s, FLASH) has a potential advantage in sparing healthy organs compared to that at conventional dose rates. The purpose of this work is to show the feasibility of proton FLASH irradiation using a gantry-mounted synchrocyclotron as a first step toward implementing an experimental setup for preclinical studies. Methods: A clinical Mevion HYPERSCAN â synchrocyclotron was modified to deliver ultrahigh dose rates. Pulse widths of protons with 230 MeV energy were manipulated from 1 to 20 ls to deliver in conventional and ultrahigh dose rate. A boron carbide absorber was placed in the beam for range modulation. A Faraday cup was used to determine the number of protons per pulse at various dose rates. Dose rate was determined by the dose measured with a plane-parallel ionization chamber with respect to the actual delivery time. The integral depth dose (IDD) was measured with a Bragg ionization chamber. Monte Carlo simulation was performed in TOPAS as the secondary check for the measurements. Results: Maximum protons charge per pulse, measured with the Faraday cup, was 54.6 pC at 20 ls pulse width. The measured IDD agreed well with the Monte Carlo simulation. The average dose rate measured using the ionization chamber showed 101 Gy/s at the entrance and 216 Gy/s at the Bragg peak with a full width at half maximum field size of 1.2 cm. Conclusions: It is feasible to deliver protons at 100 and 200 Gy/s average dose rate at the plateau and the Bragg peak, respectively, in a small~1 cm 2 field using a gantry-mounted synchrocyclotron.

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Modifying a clinical linear accelerator for delivery of ultra-high dose rate irradiation

Cited by 139 publications

References 13 publications

Ultra-High Dose Rate (FLASH) Radiotherapy: Silver Bullet or Fool's Gold?

Ultra-High Dose Rate (FLASH) Radiotherapy: Silver Bullet or Fool's Gold?

An ionizing radiation acoustic imaging (iRAI) technique for real‐time dosimetric measurements for FLASH radiotherapy

Feasibility of proton FLASH irradiation using a synchrocyclotron for preclinical studies

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