Design, Implementation, and in Vivo Validation of a Novel Proton FLASH Radiation Therapy System

Diffenderfer, Eric; Verginadis, Ioannis I.; Kim, Michele M.; Shoniyozov, Khayrullo; Velalopoulou, Anastasia; Goia, Denisa; Putt, Mary; Hagan, Sarah; Avery, Stephen; Teo, K.; Zou, W.; Lin, Alexander; Swisher‐McClure, Samuel; Koch, Cameron J.; Kennedy, Ann R.; Minn, Andy J.; Maity, Amit; Busch, Theresa M.; Dong, Lei; Koumenis, Constantinos; Metz, James M.; Cengel, Keith A.

doi:10.1016/j.ijrobp.2019.10.049

Cited by 348 publications

(444 citation statements)

References 23 publications

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“…PBT may offer the best solution to be able to treat some deep-seated tumors, and there are several high-energy clinical PBT facilities already in place that can be modified to generate FLASH dose rates [63]. Furthermore, several innovative set-ups are already being tested using modified clinically available PBT beams [27,64]. However, implementation of FLASH PBT still has its technical limitations.…”

Section: Discussionmentioning

confidence: 99%

“…However in general, more recent in vivo studies investigating FLASH PBT have yielded much more positive findings by observing the FLASH effect, and associated tumor control compared to using conventional dose rates (summarized in Table 3). In an innovative study, a clinical 230 MeV proton accelerator using double-scattered protons under CT guidance was designed to deliver FLASH dose rates of 60-100 Gy/s and conventional dose rates of 0.5-1 Gy/s [27]. Here, 8-10-week-old C57BL/6J mice were subjected to whole abdominal irradiation with 15 Gy of either FLASH (78 Gy/s) or conventional dose-rate (0.9 Gy/s) protons and intestinal segments were harvested 3.5 days post-irradiation.…”

Section: Studies Investigating Flash Protonsmentioning

confidence: 99%

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FLASH Radiotherapy: Current Knowledge and Future Insights Using Proton-Beam Therapy

Hughes

Parsons

2020

IJMS

180

127

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FLASH radiotherapy is the delivery of ultra-high dose rate radiation several orders of magnitude higher than what is currently used in conventional clinical radiotherapy, and has the potential to revolutionize the future of cancer treatment. FLASH radiotherapy induces a phenomenon known as the FLASH effect, whereby the ultra-high dose rate radiation reduces the normal tissue toxicities commonly associated with conventional radiotherapy, while still maintaining local tumor control. The underlying mechanism(s) responsible for the FLASH effect are yet to be fully elucidated, but a prominent role for oxygen tension and reactive oxygen species production is the most current valid hypothesis. The FLASH effect has been confirmed in many studies in recent years, both in vitro and in vivo, with even the first patient with T-cell cutaneous lymphoma being treated using FLASH radiotherapy. However, most of the studies into FLASH radiotherapy have used electron beams that have low tissue penetration, which presents a limitation for translation into clinical practice. A promising alternate FLASH delivery method is via proton beam therapy, as the dose can be deposited deeper within the tissue. However, studies into FLASH protons are currently sparse. This review will summarize FLASH radiotherapy research conducted to date and the current theories explaining the FLASH effect, with an emphasis on the future potential for FLASH proton beam therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Studies Investigating Flash Protonsmentioning

confidence: 99%

FLASH Radiotherapy: Current Knowledge and Future Insights Using Proton-Beam Therapy

Hughes

Parsons

2020

IJMS

180

127

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“…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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“…Flash therapy, which delivers an ultra-high dose rate of more than 40 Gy/s and has a very short exposure time of [14][15][16].…”

Section: ) Flash Therapymentioning

confidence: 99%

Proton Therapy Review: Proton Therapy from a Medical

Lee

2020

Progress in Medical Physics

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With hope and concern, the first Korean proton therapy facility was introduced to the National Cancer Center (NCC) in 2007. It added a new chapter to the history of Korean radiation therapy. There have been challenging clinical trials using proton beam therapy, which has seen many impressive results in cancer treatment. Compared to the rapidly increasing number of proton therapy facilities in the world, only one more proton therapy center has been added since 2007 in Korea. The Samsung Medical Center installed a proton therapy facility in 2015. Most radiation oncology practitioners would agree that the physical properties of the proton beam provide a clear advantage in radiation treatment. But the expensive cost of proton therapy facilities is still one of the main reasons that hospitals are reluctant to introduce them in Korea. I herein introduce the history of proton therapy and the cutting edge technology used in proton therapy. In addition, I will cover the role of a medical physicist in proton therapy and the future prospects of proton therapy, based on personal experience in participating in proton therapy programs from the beginning at the NCC.

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Design, Implementation, and in Vivo Validation of a Novel Proton FLASH Radiation Therapy System

Cited by 348 publications

References 23 publications

FLASH Radiotherapy: Current Knowledge and Future Insights Using Proton-Beam Therapy

FLASH Radiotherapy: Current Knowledge and Future Insights Using Proton-Beam Therapy

Feasibility of proton FLASH irradiation using a synchrocyclotron for preclinical studies

Proton Therapy Review: Proton Therapy from a Medical

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