Background and Aims

PEPITES* is a brand new operational prototype of an ultra-thin (<10 μm water-equivalent thickness), radiation-resistant beam profiler capable of continuous operation on mid-energy (O(100 MeV)) charged particle accelerators.

Methods

Designed to provide a minimal beam perturbation, PEPITES uses secondary electron emission (SEE) for the signal because it requires only a minimal thickness of material (10 nm). The lateral beam profile is sampled using segmented electrodes, constructed by thin film methods. Gold strips, as thin as the electrical conductivity allows (~ 50 nm), are deposited on an as thin as possible insulating substrate. When crossing the gold, the beam ejects the electrons by SEE, the current thus formed in each strip allows the sampling.

Results

The signal is very linear and offers a large dynamic without any saturation effect, so the device can be used to measure the properties of beams used for Flash-RT modalities. Characterized at ARRONAX with 68 MeV proton beams up to 100 nA and at medical energies at CPO-Orsay, the system has been subjected to doses of up to 10⁹ Gy with high rate (O(10 μA)) without showing significant degradation and electrodes remained intact after receiving the equivalent of over than 1000 6 MeV electron flash treatments.

Conclusions

A demonstrator with a new ASIC 32-channel electronics is installed at ARRONAX in a dedicated chamber and is used routinely with conventional beams. The performances of the system and its behavior over time will thus be characterized. Moreover, first measurements with Flash-RT 68 MeV proton beams have been done and will be presented.

*LLR, ARRONAX cyclotron and CEA

**Orsay Protontherapy Center (Institut Curie)

This study is supported by three programs of the Agence Nationale de la Recherche, ANR-17-CE31-0015 and ANR- 11-EQPX-0004

Background and Aims

To present the optimization of an irradiation setup suitable to investigate the FLASH effect in high-energy proton beams, and to characterize the dosimetric properties (absolute and relative dose) of the irradiation beam in view of in vivo pre-clinical experiments.

Methods

An experimental setup consisting of a scattered single pencil beam and a copper collimator (17 mm aperture) was optimized (in TOPAS simulations and measurements) to achieve uniform dose/dose rate coverage after the applicator. Absolute dosimetry was performed with EBT3 films and a PTW microDiamond cross-calibrated in a proton beam (PSI), and with passive dosimeters (TLD, alanine) from IRA (CHUV) calibrated in a Co-60 reference beam. A scintillator screen was also used for relative dose measurements.

Results

A robust and reproducible irradiation setup capable to deliver protons at ultra-high dose rates was implemented and characterized at PSI Gantry 1. The thickness of the collimator, as well as its distance from the irradiation nozzle, were optimized to achieve dose rates > 100 Gy/s. Indeed, the dose rate at the exit of the applicator is increased (> 25%) by scattered protons compared to the dose rate in the un-collimated beam. The average dose measured by the PSI’s and IRA’s detectors was in agreement within ± 2%. In the optimized scenario, the surface lateral dose uniformity was found to be within ± 5% over the collimator’s aperture.

Conclusions

A single pencil proton beam can be scattered and collimated to achieve ultra-high dose rates in a 17 mm large uniform field. Dosimetric agreement could be established in a controlled bilateral comparison with active and passive detectors. This study serves as basis for a larger investigation which aims at comparing the FLASH effect in different irradiation beams with in vivo biological models.

Background and Aims

Lately the research on FLASH effect pushed both the understanding of its scientific basis and the related accelerator technologies. This effort renewed the interest for electron beam, not only at low energy, as currently used for skin tumors or IORT, but also for Very High Energy Electron.

VHEE beams were suggested in the past as an alternative for deep seated tumors, but their complexity and cost kept them away from the clinical implementation. However, the recent developments in the field of compact electron acceleration at high intensity represent a promising perspective.

Methods

The SAFEST project aims to build a VHEE LINAC with FLASH capability, meant both for preclinical research and as prototype of a clinical device. The machine design is based on a conventional C-band LINAC with high gradient accelerating structure. The size (few meters) and the cost of the machine is compatible with clinical use.

SAFEST will be a flexible machine (70<Ebeam<130 MeV) with possibility of using both flat (100 cm²) or pencil beam field, with repetition frequency>100 Hz, and instantaneous dose rate >10⁶ Gy/pulse. The low magnetic rigidity of the beam allows for a small and fast active scanning system. Two experimental rooms are foreseen for preclinical and radiobiology studies.

To optimize the machine design and to estimate the expected clinical performances a dedicated TPS for VHEE, based on MC dose kernel, has been developed

Results

DVH for tumor and organs at risk has been obtained for different deep seated tumors. The SAFEST beam outperforms IMRT photon treatment, even using the same number of fields and without the possible enhancement due to FLASH delivery

Conclusions

The SAFEST approach represents a valid and realistic alternative to standard RT even at standard dose rate delivery. Furthermore, FLASH effect capability of such a beam opens new perspective in the RT of deep seated tumors

Background and Aims

Background: This study is the first direct comparison of two converted clinical LINACs producing ultra-high dose rate (UHDR) electron beams with the same conversion methods.

Aim: Quantify the differences in the spatial and temporal properties of the beams to assess potential clinical impacts for FLASH radiotherapy.

Methods

Materials: UHDR electron beams were produced on Varian Trilogy and 2100C/D linear accelerators by retracting the target, setting the carousel to an empty port and running in 10MV photon mode. Lateral profiles were measured by radiochromic film in solid water phantom at 2 cm depth with an open 40x40cm² field. Percent-depth-dose (PDD) were measured along the central axis with film placed at varying depths. The per-pulse-output was recorded with a photomultiplier tube that amplified the Cherenkov emission signal from an optical fiber placed outside the beam, with film providing cumulative absolute dosimetry for the delivery.

Results

Results: Spatial beam characteristics were similar between the two machines, with the Trilogy showing slightly wider profiles along inline and crossline directions. The mean dose-per-pulse on the Trilogy was 29% higher than the 2100C/D at 0.96Gy/pulse (mean dose rate of 347Gy/s vs. 268Gy/s). Temporally, the Trilogy exhibited greater stability of the output (interquartile range of 0.02 vs. 0.25Gy/pulse). The 2100C/D showed low-dose outliers in output, and variability during the initial 20 pulses, while the Trilogy output was nearly stable from the first pulse.

Conclusions

Conclusions: While both LINAC’s achieve UHDR in a large field, stability across initial pulses with high dose rates from the start are key to ensure the quality, repeatability, and safety of UHDR deliveries. The Trilogy demonstrated superiority in stability throughout the delivery and favorable for the clinical translation of FLASH-RT as the entire treatment may consist of only a few pulses. Verification of beam stability in these experimental systems is strongly advised prior to use.

Background and Aims

FLASH effects have been observed at the conditions of ultra-high dose rates and high doses (>7Gy) of radiation. The high-dose threshold contradicts the prevailing practice of conformal treatment to lower normal tissue dose. GRID radiotherapy spatially modulate the delivery of high-dose radiation to large targets without enhancing toxicity associated with a large field treatment. We hypothesize that the local-regional nature of the FLASH and GRID effects can be exploited for clinical translations. Here, we investigate the feasibility of a novel preclinical x-ray irradiation system for temporal and spatial modulation of orthovoltage x-ray pencil beams.

Methods

The proposed system employs two commercially available 150kVp x-ray sources with rotating anode technology in a parallel-opposed arrangement to support x-ray pencil beams at FLASH dose-rates. Dosimetric characterization of the x-ray pencil beam at various sizes (1-5 mm) was performed by measuring beam output and profiles from a single source using calibrated Gafchromic EBT3 films in a 20-mm thick solid water phantom. Pencil beams from parallel-opposed sources were then simulated by the summation of single source data in the idealized alignment.

Results

FLASH doses rates can be achieved in-phantom for pencil beam sizes larger than 1.0mm at reasonable distances from focal spot. For example, maximum dose rates of 54.7 and 37.3Gy/s can be delivered to the phantom center placed at 61mm SSD by 2- and 1-mm pencil beams, respectively. A peak-to-valley dose ratio (PVDR) of 92:1 can be achieved by 2-mm pencil beams with 3-mm edge-to-edge spacing. Variable PVDRs can be delivered by combining open field with pencil beam irradiations.

Conclusions

It is feasible to modulate radiation in space (GRID) and time (FLASH) using our proposed x-ray irradiation system, appropriate for preclinical radiation research. The system allows comprehensive laboratory investigations on the potential translational combination of FLASH with GRID irradiation to spare normal tissues and eradicate the tumor.