Electron FLASH Delivery at Treatment Room Isocenter for Efficient Reversible Conversion of a Clinical LINAC

Rahman, Mahbubur; Ashraf, Mudasir; Zhang, Rongxiao; Brůža, Petr; Dexter, Chad A.; Thompson, Lawrence H.; Cao, Xu; Williams, Benjamin B.; Hoopes, P. Jack; Pogue, Brian W.; Gladstone, David J.

doi:10.1016/j.ijrobp.2021.01.011

Cited by 61 publications

(64 citation statements)

References 40 publications

(27 reference statements)

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“…Most of the studies mentioned above, including the first human treatment, have been conducted in research environments intended for preclinical experiments, with accelerators that are not designed for medical use (1-5, 7-9, 12). However, it has recently been shown, by our group and others, that clinical linear accelerators can be modified to deliver the dose rates needed to observe a FLASH effect (13)(14)(15). Our group has modified an Elekta Precise linear accelerator (14) so that it can operate at dose rates of 400-500 Gy/s at a source-tosurface distance of 70 cm.…”

Section: Introductionmentioning

confidence: 99%

Establishment and Initial Experience of Clinical FLASH Radiotherapy in Canine Cancer Patients

Konradsson

Arendt

Jensen³

et al. 2021

Front. Oncol.

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FLASH radiotherapy has emerged as a treatment technique with great potential to increase the differential effect between normal tissue toxicity and tumor response compared to conventional radiotherapy. To evaluate the feasibility of FLASH radiotherapy in a relevant clinical setting, we have commenced a feasibility and safety study of FLASH radiotherapy in canine cancer patients with spontaneous superficial solid tumors or microscopic residual disease, using the electron beam of our modified clinical linear accelerator. The setup for FLASH radiotherapy was established using a short electron applicator with a nominal source-to-surface distance of 70 cm and custom-made Cerrobend blocks for collimation. The beam was characterized by measuring dose profiles and depth dose curves for various field sizes. Ten canine cancer patients were included in this initial study; seven patients with nine solid superficial tumors and three patients with microscopic disease. The administered dose ranged from 15 to 35 Gy. To ensure correct delivery of the prescribed dose, film measurements were performed prior to and during treatment, and a Farmer-type ion-chamber was used for monitoring. Treatments were found to be feasible, with partial response, complete response or stable disease recorded in 11/13 irradiated tumors. Adverse events observed at follow-up ranging from 3-6 months were mild and consisted of local alopecia, leukotricia, dry desquamation, mild erythema or swelling. One patient receiving a 35 Gy dose to the nasal planum, had a grade 3 skin adverse event. Dosimetric procedures, safety and an efficient clincal workflow for FLASH radiotherapy was established. The experience from this initial study will be used as a basis for a veterinary phase I/II clinical trial with more specific patient inclusion selection, and subsequently for human trials.

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Section: Introductionmentioning

confidence: 99%

Establishment and Initial Experience of Clinical FLASH Radiotherapy in Canine Cancer Patients

Konradsson

Arendt

Jensen³

et al. 2021

Front. Oncol.

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“…In our case, EBT‐XD Gafchromic Film was calibrated using the clinical energy and dose rate under reference conditions in the 0–40 Gy range. EBT Gafchromic film has previously shown to be insensitive to high dose rates below ~10 6 –10 9 Gy/s 22–24 and has been successfully used for FLASH‐RT electron dosimetry 13,25–27 …”

Section: Methodsmentioning

confidence: 99%

“…EBT Gafchromic film has previously shown to be insensitive to high dose rates below ~10 6 -10 9 Gy/s [22][23][24] and has been successfully used for FLASH-RT electron dosimetry. 13,[25][26][27] Following the tuning of the RF driver, the measured current increased from 3.35 pC/s (conventional 16 MeV mode) to 692 pC/s (FLASH-RT 16 MeV mode), a dose rate enhancement ratio of 206.7-delivering 2067 Gy/ min, or 34.5 Gy/s, under reference conditions. Given an estimated bremsstrahlung efficiency of 4.0% from commissioning data (confirmed by published values 28 ) this translates to a dose rate of ~82.7 Gy/min at isocenter arising from bremsstrahlung photons alone as summarized in Figure 1.…”

Section: Conversion Of a Linac To Flash-rt Dose Ratesmentioning

confidence: 99%

Radiation shielding and safety implications following linac conversion to an electron FLASH‐RT unit

et al. 2021

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Purpose Due to their finite range, electrons are typically ignored when calculating shielding requirements in megavoltage energy linear accelerator vaults. However, the assumption that 16 MeV electrons need not be considered does not hold when operated at FLASH‐RT dose rates (~200× clinical dose rate), where dose rate from bremsstrahlung photons is an order of magnitude higher than that from an 18 MV beam for which shielding was designed. We investigate the shielding and radiation protection impact of converting a Varian 21EX linac to FLASH‐RT dose rates. Methods We performed a radiation survey in all occupied areas using a Fluke Biomedical Inovision 451P survey meter and a Wide Energy Neutron Detection Instrument (Wendi)‐2 FHT 762 neutron detector. The dose rate from activated linac components following a 1.8‐min FLASH‐RT delivery was also measured. Results When operated at a gantry angle of 180° such as during biology experiments, the 16 MeV FLASH‐RT electrons deliver ~10 µSv/h in the controlled areas and 780 µSv/h in the uncontrolled areas, which is above the 20 µSv in any 1‐h USNRC limit. However, to exceed 20 µSv, the unit must be operated continuously for 92 s, which corresponds in this bunker and FLASH‐RT beam to a 3180 Gy workload at isocenter, which would be unfeasible to deliver within that timeframe due to experimental logistics. While beam steering and dosimetry activities can require workloads of that magnitude, during these activities, the gantry is positioned at 0° and the dose rate in the uncontrolled area becomes undetectable. Likewise, neutron activation of linac components can reach 25 µSv/h near the isocenter following FLASH‐RT delivery, but dissipates within minutes, and total doses within an hour are below 20 µSv. Conclusion Bremsstrahlung photons created by a 16 MeV FLASH‐RT electron beam resulted in consequential dose rates in controlled and uncontrolled areas, and from activated linac components in the vault. While our linac vault shielding proved sufficient, other investigators would be prudent to confirm the adequacy of their radiation safety program, particularly if operating in vaults designed for 6 MV.

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“…Electrons are the most commonly used radiation source at the moment for Flash radiobiology experiments, and the first patient receiving a Flash treatment was irradiated with a 5.6 MeV electron beam 4 . It has also been demonstrated that linacs used in clinical practice can be modified to deliver ultrahigh‐dose rate with electrons 12,13 …”

Section: Beam Production and Deliverymentioning

confidence: 99%

Treatment planning for Flash radiotherapy: General aspects and applications to proton beams

et al. 2022

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The increased radioresistence of healthy tissues when irradiated at very high dose rates (known as the Flash effect) is a radiobiological mechanism that is currently investigated to increase the therapeutic ratio of radiotherapy treatments. To maximize the benefits of the clinical application of Flash, a patient‐specific balance between different properties of the dose distribution should be found, that is, Flash needs to be one of the variables considered in treatment planning. We investigated the Flash potential of three proton therapy planning and beam delivery techniques, each on a different anatomical region. Based on a set of beam delivery parameters, on hypotheses on the dose and dose rate thresholds needed for the Flash effect to occur, and on two definitions of Flash dose rate, we generated exemplary illustrations of the capabilities of current proton therapy equipment to generate Flash dose distributions. All techniques investigated could both produce dose distributions comparable with a conventional proton plan and reach the Flash regime, to an extent that was strongly dependent on the dose per fraction and the Flash dose threshold. The beam current, Flash dose rate threshold, and dose rate definition typically had a more moderate effect on the amount of Flash dose in normal tissue. A systematic estimation of the impact of Flash on different patient anatomies and treatment protocols is possible only if Flash‐specific treatment planning features become readily available. Planning evaluation tools such as a voxel‐based dose delivery time structure, and the inclusion in the optimization cost function of parameters directly associated with Flash (e.g., beam current, spot delivery sequence, and scanning speed), are needed to generate treatment plans that are taking full advantage of the potential benefits of the Flash effect.

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Electron FLASH Delivery at Treatment Room Isocenter for Efficient Reversible Conversion of a Clinical LINAC

Cited by 61 publications

References 40 publications

Establishment and Initial Experience of Clinical FLASH Radiotherapy in Canine Cancer Patients

Establishment and Initial Experience of Clinical FLASH Radiotherapy in Canine Cancer Patients

Radiation shielding and safety implications following linac conversion to an electron FLASH‐RT unit

Treatment planning for Flash radiotherapy: General aspects and applications to proton beams

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