Background and Aims

To enable ultra-high dose rate irradiations (e.g. necessary for FLASH RT) with a Varian ProBeam system, a new beam monitoring system for proton pencil beam scanning has been successfully designed, tested and put to use for first applications.

Methods

The new beam monitor system is based on established air-filled ionization chamber technology and includes two independent dose monitors as well as position monitors for the lateral x and y directions as needed for modern pencil beam scanning applications.

Results

Precise handling of ultra-high dose rate scanned proton pencil beams was demonstrated for up to 350 nA proton beam current in the treatment room nozzle with measured recombination losses in the dose monitors well below 1%.

Conclusions

A first installed new beam monitoring solution enables fully integrated use of ultra-high dose rate beams and is in use for the first clinical proton FLASH trial (FAST-01) and part of Varian's FLEX research kit for non-clinical use. A further optimized solution will in the future enable fast switching between conventional and ultra-high dose rate modes without the necessity of hardware changes.

This work has received funding from the European Union’s H2020 Research and Innovation Programme, under Grant Agreement No. 730983.

Background and Aims

Development of proton therapy is strongly driven by in-vivo experiments, which are, however, subject to increasingly strict ethical and technical requirements. Proton irradiation of small animals demands for versatile experimental setups and intelligent protocols. To realize precise positioning and treatment, on-site imaging with proton radiography was integrated into an existing beam setup for mouse brain sub-volume irradiation at University Proton Therapy Dresden.

Methods

A flat panel detector was installed on proton beam axis behind mouse position. Transmission radiographic images were acquired at high energy (200 MeV) with a single-scattered proton beam. Image quality was optimized regarding resolution, contrast and minimal dose deposition in the animal. The hippocampus as target region for current mouse irradiation experiments was determined by registration of mouse brain atlas data with pre-treatment off-site CT scans and x-ray images.

Results

The developed workflow allows precise brain irradiation with lateral target positioning accuracy <0.2 mm. Imaging with dose depositions <20 mGy in mice was achieved. For accurate irradiation, the designated target volume (right hippocampus) was aligned with the collimated treatment beam by registering the radiography image with off-site x-ray images with custom-made software (Figure 1). Immunohistochemically staining of DNA damage on histological whole-brain tissue sections validated successful positioning and irradiation (Figure 2).

Conclusions

Proton radiography enables effective high-precision lateral alignment of proton beam and target volume in mouse irradiation experiments with limited dose exposure.

This work was supported by EU-Horizon2020 grant 730983 (INSPIRE).

Figure 1. Workflow with x-ray image and radiography overlay for accurate positioning

Figure 2. Tissue section after irradiation

Background and Aims

Seven proton therapy centers collaborating within INSPIRE project participated in the mailed dosimetry audit of proton therapy treatment units utilizing spot scanning beams organized by EURADOS WG9 'Radiation dosimetry in radiotherapy'.

Methods

Prototype assembly for positioning the detectors in the water phantom has been developed and tested during simultaneous irradiation at IFJ PAN in Krakow and PTC in Prague in June 2020. Alanine, radiophotoluminescent and thermoluminescent detectors from five European institutes have been irradiated with 10 x 10 cm² single layer field and 10 x 10 x 10 cm³ plan.

Results

Very good agreement between the two centers has been obtained for alanine, RPL and TL detectors. Based on the results of the initial experimental campaign, the assembly for detector positioning has been modified. As a next step, one assembly for each participating center has been produced including the corresponding number of water-proof detector holders. In the frame of INSPIRE join research activity, audit manuals, detectors and holder assemblies were distributed to participating centers. Audit irradiations took place in all centers during March-April 2021.

Conclusions

The obtained results provide an indication of dosimetric agreement between centers and bases for definition of standardization procedures in dosimetry of active scanning proton beams. After a successful initial experience, mailed audit of scanning proton beams may become a part of clinical routine helping in standardization of active proton beam dosimetry.

This work was partially supported from the European Union's H2020 Research and Innovation Programme, under Grant Agreement No: 730983 (INSPIRE project).

Background and Aims

We present the current status and outcomes of the joint radiobiological experiment performed at eight European proton therapy centers or research institutes. The study aims to spot the potential differences in the in vitro proton RBE values measured by different groups sharing a similar setup and identify its causes.

Methods

A phantom and a protocol for sample preparation and post-processing are shared among the participants to ensure minimal differences in the biological part of the experimental procedure. In this phantom, V79 cells grow on the polyester slides that can be inserted at different depths, which enables their simultaneous irradiation at multiple positions within the radiation field. The setup is irradiated with proton beams with two SOBP configurations (6 cm, 6 Gy, and 4 cm, 8 Gy), followed by the reference photon irradiation (LINAC or x-ray), and the biological effect is evaluated using a colony-forming assay.

Results

The study is still ongoing, and the spread of data for measured cell survival is yet to be evaluated. However, some non-obvious differences in the experimental procedures and setups are already revealed, e.g. post-processing timing or varying dose distributions in the beam plateau/fall-off regions.

Conclusions

As an outcome of the experiment, we plan to summarize the details of the experimental procedure for biological experiments with proton beams, differing between the centers across Europe. Accounting for these details would help to harmonize future studies in the field.

This work was supported by EU Horizon2020 grant 730983 (INSPIRE).

Background and Aims

In PT, the highest dose rate is achieved at 250MeV. Such beams shoot through the patient at the expense of conformity. Morever, healthy-tissue fraction doses above the FLASH theshold of 8-10Gy require single beams per fraction, compromising conformity of equivalent dose (EQD2). We investigate for which FLASH enhancement ratio (FER), this is outweighed by the FLASH effect in lung SBPT.

Methods

Assuming a/b=10Gy for the target, isoeffective plans to 54Gy/3, 65.5Gy/5, 73.7Gy/7 and 80.0Gy/9 were optimized for 12 patients in in-house developed software. CTV delineations were available. A 5mm CTV-PTV margin was applied. Only small PTVs (range: 4.4-10.1cc) were included. Equiangular co-planar arrangements of 244MeV shoot-through beams, avoiding serial OARs, were used. To enable single-beam per fraction delivery, the beam number was equal to the fraction number. Dose was prescribed per beam: D_95%,PTV = 100%D_pres/#beams. A constant FER was assumed and applied to healthy-tissue voxel fraction doses: d_j → d_j/FER for all voxels j. Voxel EQD2s for FLASH-enhanced single-beam per fraction delivery and conventional multi-beam treatments were calculated. The conformity index (CI) of EQD2, with a/b=3Gy for healthy tissue, i.e., CI=V_EQD2,pres/V_PTV, was evaluated.

Results

Median CIs were 7.1 (range: 4.7-8.2), 5.7 (3.9-6.7), 5.2 (3.6-5.9) and 4.6 (3.4-5.5) for conventional 3, 5, 7 and 9 beam treatments. CIs for FLASH-enhanced treatment are shown in Fig. 1. Break-even FERs were 1.33 (1.30-1.36), 1.23 (1.22-1.24), 1.18 (1.15-1.20) and 1.15 (1.10-1.15) with 3, 5, 7 and 9 beams.

Conclusions

If the FLASH enhancement ratio exceeds 1.3, FLASH outweighs EQD2 conformity loss in single-beam per fraction shoot-through lung SBPT.

Background and Aims

FLASH radiotherapy requires the development of new detectors to be able to cope with ultra-high-pulse-dose-rates (UHDpulse) beams. This work aims to test customized Timepix3 detectors to identify the most suitable sensor and settings to be used for the characterization of stray radiation produced in UHDpulse proton beams (PB).

Methods

Dose rates (DR) exceeding 160Gy/s were delivered by a pencil proton beam of 220MeV energy at the University Proton Therapy Dresden, Germany. For data collection two customized semiconductor pixel detectors, Timepix3 ASIC chip, with electronics placed on a flexible cable (50mm distance from the sensor, Fig. 1) were immersed, in turns, inside a water-phantom. The detectors were moved laterally at different depth during irradiation.

Figure 1. Experimental setup with Minipix-Timepix3-Flex detector placed in a waterproof cadge.

Results

The Minipix-Timepix3-Flex detector (Fig. 1) provides ns timing resolution at the pixel level together with quantum-imaging sensitivity with 100% detection efficiency for heavy-charged particles. The integrated per-pixel deposited energy, number of registered events, and DR were measured (Fig. 2).

Figure 2. The plots show the spatial distribution of integrated deposited energy at 50mm (left) and 100mm (right) behind Bragg Peak for a 2ms proton pulse measured with Minipix-Timepix3 with 100µm (top) and 650µm (bottom) thick silicon sensor.

Conclusions

A detector equipped with a thinner silicon sensor, 100µm, is more suitable for UHDpulse PB measurements due to the reduced amplitude of the signal and pixel size, allowing to register higher event rates.

Acknowledgements: This work was supported by the 18HLT04UHDpulse project founded by EMPIR-programme and EU INSPIRE (730983) project.