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EMPIR project helps deliver new tool in the fight against cancer

Image showing a box being ticked next to the words Proton Therapy
Patient approval for proton therapy

FLASH radiotherapy is a new form of cancer treatment promising to minimise damage caused to healthy tissue but requiring metrology for its safe use

One in two people will develop cancer in their lifetime. Around half of those affected by this disease receive treatment in the form of ionising radiation – traditionally using as x-rays or γ-rays. More recently, a new way of delivering radiation treatment has emerged that could be effective against currently hard to treat tumours – FLASH radiotherapy.

FLASH radiotherapy involves delivering radiation doses – using proton, electron, X-ray beams or heavy particles – in very short time scales (a fraction of a second) at ultra-high dose rates. This promises to be equally effective at killing cancer cells but, can significantly spare healthy neighbouring tissue.

 

Any radiation treatment requires a precise knowledge of the radiation dose delivered – and, so far, this has proven to be difficult for FLASH therapy. The current ‘gold standard’ for dosimetry for most radiation modalities, are ionisation chamber measurements. The ultra-high dose rates, used in FLASH therapy, are several orders of magnitude higher than those currently employed in conventional radiotherapy treatments, resulting in significant ‘recombination’ events in these types of detectors. This results in large correction factors, which cannot be easily evaluated.  Subsequently, this leads to high measurement uncertainties.

One potential method to obtain FLASH therapy dosages is the use of calorimeters. In these instruments, energy from the radiation beam is absorbed by a material – such as graphite – which raises the temperature of the material that is directly proportional to the absorbed dose. The use of these instruments in conventional radiotherapy treatments has been limited due to their complexity. FLASH therapy, with its ‘burst’ of ultra-high dose-rate radiation, causes the temperature in calorimeters to rise very rapidly, hence limiting heat transfer effects within the system, making them an ideal candidate for measuring the dose delivered. However, these types of dosimeters also require the application of correction factors to ensure their accuracy.

During EMPIR project Metrology for advanced radiotherapy using particle beams with ultra-high pulse dose rates (18HLT04, UHDpulse) a portable, primary-standard proton calorimeter developed by NPL, the National Metrology Institute of the UK, was used to characterise the ultra-high dose rate proton beam at Cincinnati Children’s Hospital Medical Center (USA), an international leader in developing new cancer treatments for children and young adults. The graphite-based calorimeter was compared to conventional ionisation chambers,  predecessing the first ever clinical trial for FLASH proton therapy involving ten patients with bone cancer.

NPL scientists obtained beam-dependent correction factors for their calorimeter under FLASH proton irradiation conditions using Monte Carlo simulations and accurately measured clinically relevant absorbed dose to water for the primary standard instrument. The results indicated that the NPL primary standard graphite calorimeter is able to obtain radiation dose measurements with 0.9 % uncertainty – comparable to primary standard uncertainties in conventional radiotherapy.  This work has since been published in the journal Nature’s Scientific Reports.

The development of a portable standard for FLASH therapy, such as NPL’s graphite calorimeter, will not only improve the accuracy and consistency of the dose delivered to patients – but also opens the way to safe implementation of clinical trials for this new form of cancer treatment.

The coordinator of the EMPIR  UHDpulse project, Andreas Schuller (PTB) said about the work:

 “This work is a building block enabling the development of future dosimetry protocols for FLASH RT as well as safe, accurate and consistent delivery for this new treatment modality to clinical practice. The NPL’s support of the world’s first in-human clinical trial (FAST-01) for proton ultra-high dose rate (UHDR) FLASH radiotherapy was critical for the FDA approval and provided the hospital with the confidence to commence clinical implementation of this new technology. The FAST-02 trial is currently underway”.

This EMPIR project is co-funded by the European Union's Horizon 2020 research and innovation programme and the EMPIR Participating States.


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