Outcomes for industrial and other user communities

This project will impact Europe’s health care sector, such as radiotherapy clinics treating cancer patients working on the clinical implementation of FLASH radiotherapy, as well as innovations in the medical device industry via manufacturers of radiotherapy facilities and dosimetry equipment. FLASH radiotherapy is expected to be widely adopted once manufacturers of irradiation facilities are able to provide high intensity beams in upgraded or new facilities and after clinics have commissioned these facilities. By using FLASH radiotherapy the time of the pure irradiation will be reduced from approximately one minute per field to less than one second in some cases. Apart from the significant savings in time this potentially leads to improved patient treatments and healthcare. The project’s recommendations for reference dosimetry for clinical FLASH proton and electron beams will also allow medical physicists in radiotherapy clinics to measure the dose under reference conditions and consequently calibrate the beam monitor. This is an important step in the commissioning of FLASH radiotherapy facilities, and clinics preparing for the clinical introduction of FLASH radiotherapy and manufacturers of FLASH facilities, are either part of this consortium or will be part of the project’s stakeholder committee, thus support rapid uptake of the project’s outputs.

This project will provide the necessary metrology to enable reliable and traceable dosimetry for medical physicist and clinicians in FLASH facilities. To support this the consortium brings NMIs and academia together with clinical participants (AU, HPTC and PSI) with much of the experimental work conducted at clinical beam lines. The project will improve the existing measurement infrastructure for dosimetry in FLASH radiotherapy within Europe by extending the operational range of primary standards to high dose-rates and by developing (i) software for the simulation of recombination effects, (ii) data sets of recombination corrections k_s and k_Q correction factors, (iii) reference dosimetry methodology for scanning UHDR proton beams and for UHDPP electron beams, and (iv) characterised clinical like reference fields for UHDPP electron beams. This will allow manufacturers of detectors for dosimetry in radiotherapy beams to assure the quality of their products for application in UHDR scanning proton and UHDPP electron beam facilities. Further to this, the involvement of several manufacturers in the project’s stakeholder committee will provide much needed end user feedback and help to ensure that these facilities and capabilities meet their needs and with better utilisation (including for new and other detectors than those investigated in this project).

In addition, the project will engage with healthcare sector and other user communities via social media, stakeholder symposiums and a webinar. The project will also disseminate its outcomes to them through the scientific councils of AAPM (chief stakeholder for the project), the ESTRO dissemination network and via the Varian Flash Forward Consortium (FFC) https://www.varian.com/en-gb/about-varian/research/flashforward- consortium. The Varian FFC includes a range of institutions and has the goal to establish preclinical study designs, develop technical solutions, and share research protocols to advance clinical translation of FLASH therapy. The project’s inputs to AAPM, ESTRO and the Varian FFC will help to transfer of the project’s developments to the wider European radiotherapy community.

Outcomes for the metrology and scientific communities

The European metrology community is currently leading globally in the field of dosimetry for advanced radiotherapy. This project will further this lead by improving the capabilities of European NMIs active in this field. The project will develop primary standards to ensure traceability of dosimetry in FLASH beams to the SI. In conventional radiotherapy, primary standards such as water and graphite calorimeters are most widely used to disseminate the quantity of D_w. To ensure the traceability of dosimetry to the SI, the primary standards are subject to regular verifications, before acceptance as national primary standard, which are carried out by the BIPM through international key comparisons such as BIPM.RI(I)-K6 for MV photon beams. However, these primary standards and their comparisons have only been designed for conventional dose-rate radiotherapy beams. This project will address this issue and conduct a comparison of the project’s portable primary standards for scanning UHDR proton beams at a clinical facility. In order to gain recognition as primary standards for measurements of D_w in UHDR proton beams, the project’s comparison will be registered with the BIPM Key Comparison Database (KCDB). This will be the first ever comparison attempting to ensure traceability of dosimetry for UHDR proton beams. The comparison results will be approved and shared with CCRI(I), so that NMIs who are not part of the consortium can use the project’s standards for UHDR proton beams in the near future.

The traceability route prescribed in CoPs for most conventional proton- beams and in most cases for conventional electron beams is based on a ⁶⁰Co calibration. Due to the high dose rate and high DPP of FLASH beams it is unclear whether this traceability route remains applicable for this application. The recommendations for reference dosimetry in FLASH beam will provide guidance on traceability routes for reference dosimetry in FLASH radiotherapy. Using these recommendations NMIs will be able to plan the development of services for calibration of secondary standards for FLASH radiotherapy.

This project will enable NMIs to extend their existing electron accelerators to clinical-like reference fields similar to those in clinical UHDPP electron accelerators. Current accurate dosimetry CoPs recommend an upper limit on recombination corrections (for example IAEA TRS-398 uses 3 %). However, for the UHDR and UHDPP conditions in FLASH radiotherapy facilities this might not be possible in all circumstances. The simulation of recombination effects is a relatively new research topic. Therefore, the project will extend existing models to more realistic situations and compare the simulation results with experimental results. The project’s in-depth investigations by measurements and simulations will lead to a better understanding of recombination effects in ionisation chambers which could lead to improved methods for the determination of k_s by simulations and to a relaxation of current upper limits. The project will develop model software for the simulation of recombination effects, which will be shared publicly as opensource software in order to allow stakeholders from other scientific communities to benefit from it.

Finally, the project will disseminate its outcomes to the metrology and scientific communities through peer-reviewed journal papers, presentations at conferences and via the EURAMET EMN for Radiation Protection and European Particle Therapy Network.

Outcomes for relevant standards

Documentary standards and CoPs for reference dosimetry in radiotherapy have been issued by the IAEA, IEC, DIN, AAPM, the Institute of Physics and Engineering in Medicine (IPEM) and the Netherlands Commission on Radiation Dosimetry (NCS). The IAEA TRS‑398 is used globally for dosimetry for conventional radiotherapy. Additionally, DIN, IPEM, NCS, AAPM have issued CoPs with slightly different approaches, that are extensively used by medical physicists. However, these CoPs are not applicable in FLASH radiotherapy and specific CoPs for reference dosimetry for FLASH radiotherapy do not currently exist.

AAPM TG 359 is working on recommendations for FLASH radiotherapy, and IEC 62C WG3 is in the process of updating the standard IEC 60731 “Medical electrical equipment – Dosimeters with ionisation chambers as used in radiotherapy”. DIN has also recently started a working group with the aim to develop a CoP on reference dosimetry for FLASH radiotherapy facilities. Therefore, these committees and working groups are highly relevant for this project and the consortium will use its existing contacts with them to disseminate recommendations for reference dosimetry for scanning UHDR proton and UHDPP electron beams.

Longer‑term economic, social and environmental impacts

More than 1 M cancer patients are treated with radiotherapy annually in the EU. FLASH radiotherapy offers future, huge potential benefits to patients by significantly reducing side‑effects (e.g. a 40 % reduction in normal‑tissue toxicity) while still suppressing tumour growth. This perfectly fits with the long‑term 2030 vision of ESTRO: ‘Radiation oncology. Optimal health for all together‘. However, to support the longer‑term roll out and clinical implementation of FLASH radiotherapy it is vital to have reference dosimetry based on CoPs. The outcomes of this project will provide this reference dosimetry for scanning UHDR proton beams and UHDPP electron beams and hence facilitate patient care across the EU with significantly improved oncology care and quality of life.

As FLASH radiotherapy produces significantly less normal tissue damage, it should be possible to use a smaller number of high dose FLASH radiotherapy treatments for patients in the future, thus saving both time and money and enhancing patient care and reducing side effects. This should reduce the cost of treatment for each patient and more fully offset Europe’s € 3bn investment in proton therapy. The clinical use of FLASH radiotherapy requires novel secondary standards for which their suitability for application remains to be investigated. The standardisation of accurate radiation dosimetry for FLASH beams is a prerequisite for successful clinical application of these beams in cancer therapy. Therefore, the uptake of the project’s results in new CoPs for FLASH radiotherapy should support and stimulate scientific advances and economic growth in both FLASH radiotherapy and associated secondary standards.