Background and Aims

The FLASH effect occurs in tissue when therapeutic radiation dose is delivered at ultra-high dose-rates (UHDR), greater than 40 Gy/s. At these dose-rates, the probability of sparing healthy tissue is greatly enhanced whilst damage to cancerous tissue remains devastating. In the clinic, accurate determination of absorbed-dose delivered to the target region at UHDR is challenging due to inefficient collection of charge within ionisation chambers (IC), and over-response of radiochromic film (RCF).

National Physical Laboratory (NPL), scientists re-purposed a simple portable graphite calorimeter (SPGC), for use with UHDR particle beams.

Methods

Measurements were carried out using a clinical 250 MeV scanned-proton beam system adapted to deliver FLASH proton radiotherapy beams and compared with the NPL primary-standard level graphite proton calorimeter, IC, RCF and alanine pellets, all in terms of dose-to-water.

Results

Preliminary analysis indicates agreement between the SPGC and primary-standard level calorimeter is within the overall combined measurement uncertainties of 1.5%, k=1. Calculation of calorimeter perturbation factors using Monte Carlo simulations are ongoing, as well as analysis of RCF, IC and alanine data.

Conclusions

This presentation will explain the measurement protocol carried out, present the results obtained and the associated levels of measurement uncertainty to show how a simple, portable calorimeter can be an effective tool in the clinic to accurately determine absorbed-dose delivered to the target at a significantly lower value of measurement uncertainty than current IC measurement protocols, typically >2%, k=1, or to determine correction factors for IC and RCF measurements in the clinic.

This project was funded by EMPIR 18HLT04UHDpulse

Background and Aims

In the process of establishing calorimetry as a primary standard for Very High Energy Electrons (VHEEs), measurements were performed in an ultra-high-dose-rate (UHDR) VHEE beam using the CLEAR facility at CERN. VHEEs with energies up-to 200 MeV could provide various benefits over standard clinical energy electron beams including increased conformity, deep-seated and complex tumour treatment as well as beam scanning and focusing.

Methods

The National Physical Laboratory graphite calorimeter, designed for Intensity Modulated Radiotherapy (IMRT), measured dose-to-graphite up-to approximately 5 Gy/pulse with dose-to-water calculated by application of a preliminary graphite-to-water conversion factor determined using the Geant4 Monte Carlo code. The CLEAR beamline allowed for investigation of both clinical dose-rate and UHDR regimes through tuning of the number of electron bunches per-pulse and the charge-per-bunch.

Results

As a result, the instantaneous dose-rate ranged between 5x10⁶ Gy/s and 3.1x10⁸ Gy/s whilst pulse widths ranged from 666 ps (1 bunch-per-pulse) to 133.2 ns (200 bunches-per-pulse). The dose-per-pulse ranging from 0.03 Gy/pulse to 5.26 Gy/pulse was found to increase linearly with increasing charge-per-pulse with R²=0.98 .

Conclusions

These calorimetry measurements allowed for absolute determination of ionisation chamber correction factors applicable to clinical dosimetry protocols. Moreover, a full uncertainty budget including calorimeter vacuum gap correction and perturbation factors is currently being developed such that the translation of UHDR VHEE beams to the clinical setting can be accelerated.

This project 18HLT04 UHDpulse has received funding from the EMPIR programme co-financed by the Participating States and from the European Union’s Horizon 2020 research and innovation programme.

Background and Aims

Despite FLASH radiotherapy is attracting an increasing interest in the last few years, a clear explanation of the FLASH effect still needs to be addressed. In this context, the project aims to investigate the FLASH effect correlating radiobiological measurements with modeling and simulations, with the goal to explore current hypotheses of oxygen depletion and tissue immune-response.

Methods

An experimental setup has been designed for irradiating 2D cell culture under controlled oxygen levels. The biological response will be matched by simulation of radical production and interactions using Monte Carlo approaches. Additionally, we are evaluating to use Organ-On-A-Chip technology to investigate the tissue immune-response to ultra-high dose-rate. Currently, there are very few data in the literature for what concerns the use of Organ-On-A-Chip for radiobiological purposes. The Organ-On-A-Chip microchamber allows different cells of the same tissue to be seeded separated by a porous membrane allowing the cells to interact between them as would happen in a real tissue. Liver, lung and brain models have been developed and successfully used for drug studies.

Results

These preliminary data will provide better understanding of the response of Organ-on-a-chips to radiation with the possibility to evaluate the relative effectiveness of different radiation exposure modalities at tissue level. Following the irradiation, the Organ-On-A-Chip can be processed using conventional radiobiological assays (immunofluorescence staining for DNA damages, live/dead staining, staining of ROS…) and possibly histology techniques.

Conclusions

The controlled environment of these chips makes them an interesting and promising subject of investigation for addressing the FLASH effect, particularly regarding the immune-response hypothesis.

Background and Aims

Advancement in accelerator technology has led to the development of systems capable of generating particle beams with ultra-high dose rates per pulse, facilitating investigations of radiation therapy modalities characterized by dose deliveries exceeding several hundred Gy/s. The FLASH effect is induced at rates greater than 40 Gy/s, subsequently reducing undesired healthy tissue damage, whilst maintaining comparable tumour control to conventional techniques. Further, laser-driven acceleration of charged particle beams produced with compact “plasma accelerators” are characterized by even higher dose rates per pulse (up to 10⁹ Gy/s) at quasi-instantaneous irradiations.

Methods

Despite this, dosimetry of these beams has proven to be technically challenging, requiring the development of novel strategies to replace already established methods for conventional radiotherapy. As such, a small portable graphite calorimeter has been developed and modified at National Physical Laboratory (NPL) to conduct absolute dose measurements of high dose rate per pulse proton beams.

Results

Proof of principle measurement of the absorbed dose of laser-driven proton beams have been carried out with this device, representing the first ever based on calorimetry techniques. Energetic proton beams of up to 40 MeV were produced using the VULCAN petawatt laser system of the Central Laser Facility of the Rutherford Appleton Laboratory. Doses per pulse of up to 3 Gy were measured, with negligible electromagnetic pulse (EMP) contribution to the signal.

Conclusions

This project 18HLT04 UHDpulse has received funding from the EMPIR programme co-financed by the Participating States and from the European Union’s Horizon 2020 research and innovation programme.