Algorithmic development of proton radiography for image-guided proton radiotherapy of lung cancer.

Informations projet

MSPrad

N° de convention de subvention: 101023220

DOI

10.3030/101023220

Projet clôturé

Date de signature de la CE 12 Avril 2021

Date de début 1 Septembre 2021

Date de fin 31 Août 2023

Financé au titre de

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coût total

€ 224 933,76

Contribution de l’UE

€ 224 933,76

Coordonné par

UNIVERSITY COLLEGE LONDON
United Kingdom

Periodic Reporting for period 1 - MSPrad (Algorithmic development of proton radiography for image-guided proton radiotherapy of lung cancer.)

Période du rapport: 2021-09-01 au 2023-08-31

Résumé du contexte et des objectifs généraux du projet

The purpose of this project was to improve a lung cancer patient’s outcome following proton beam radiotherapy (PBT) treatment, by exploiting a new instrument – the proton radiography imager. Lung cancer has unmet needs; it is common (48,500 diagnosed every year) and difficult to treat (5-year survival rate is 16.4%). In 2018, it was the most common cause of cancer death in the UK, costing £2.4 billion/year to the economy. PBT is available in the UK since 2021. It has the potential to improve cancer survival odds because it has clinical benefits over traditional radiotherapy. PBT is used to treat cancer by delivering a strong dose of radiation to the tumour, while avoiding damage to healthy tissues; meaning the treatment is less toxic to patients. However, this method is not as effective for lung cancer because the tumour moves as the patient breathes, making it difficult to hit the target accurately. A solution to help PBT reach its potential is to adapt the treatment by following the tumour with real-time imaging. The aim of this project is to develop a first-of-its-kind proton imager for lung cancer treatment. The instrument aims to generate patient images called proton radiographs to guide PBT towards targeting tumours while sparing healthy tissue. Preliminary studies show that image guided PBT may improve the two-year survival rate by 17% with respect to current practices; it is therefore an important project for society.

The overall objectives of the current action were to set down the theoretical and experimental bases to demonstrate the potential of this imaging device. This included developing an image reconstruction methodology for this type of device, demonstrating the potential of the technology and reconstruction method through computer simulations, then building a prototype device, and characterising image quality achievable with it.

A reconstruction method was developed, and it was demonstrated that it consistently provides the best image quality amongst existing methodologies for fast proton imaging. This was achieved first through Monte Carlo simulations. Then, a prototype device was built, and it was demonstrated, through experimental datasets acquired at 3 healthcare centres – University College London Hospitals (UCLH), Mayo Clinic Arizona and the Marburg Ion Therapy Centre – that high image quality can be achieved with images that can be produced in real time.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

An image reconstruction framework for integrated mode proton radiography that combines 2D information from lateral cameras and a reprojection kernel derived from the Fermi-Eyges theory was developed. It was extensively validated through Monte Carlo simulations to demonstrate high image quality (contrast, resolution, quantitative accuracy). This has been disseminated at two international conferences (European Society for Radiotherapy and Oncology (ESTRO) 2022 Annual Meeting, The third ion imaging workshop in 2022).
In the meanwhile, an experimental setup was built at UCLH; its potential was demonstrated first at the PBT at University College London Hospitals and at Mayo Clinic Arizona, where state of the art imaging capabilities for an integrated mode imaging device were obtained. This has been disseminated to two international conferences: the ESTRO 2023 Annual Meeting as well as the Particle Therapy Co-Operative (PTCOG) 2023 annual meeting; a scientific publication on this topic is under review as of September 2023.
Following demonstration of imaging capabilities, the device was used to produce real time imaging of simple moving objects, towards a demonstration of real-time tracking. Most of this work has been performed since mid-2023 at UCLH and the Marburg Ion therapy Centre. The latter allowed us to also evaluate the performance with carbon ion beams rather than just protons. We demonstrated highly accurate tracking abilities and characterised motion artifacts that arise with proton imaging. These results are being disseminated at various international (the fourth ion imaging workshop) and national (the proton physics research and implementation group (PPRIG) 2023 annual meeting), and aim to further show those results at the PTCOG 2024 annual meeting.

The figure attached to the report shows a schematic of the device (a), the actual built device (b), raw data images (c), high quantitative accuracy to characterise proton beams (d), high spatial localisation accuracy (e), and selected examples of scanned objects with previous state of art (distal) and the current method (lateral), in figures (f) and (g).

The current action led to the successful obtention of various research grants at University College London. A UCL global engagement fund for north America was obtained to perform measurements in 2022 at Mayo Clinic Arizona and demonstrate cross-centre usage of our device. Furthermore, a UCL Devices & Diagnostics TIN Pilot Data Scheme was obtained to allow the purchase of more performant equipment for the built device. This was also followed by dissemination activities on the project on UCL’s website. A 2023 UCL Fellowship Incubator Scheme was also obtained to fund measurements at the Marburg Ion Therapy Centre. Finally, the work done over the past two years under the Marie-Slokodowska-Curie Individual Fellowship led to a successful application to a National Institute for Health and Care Research (NIHR) invention for innovation product development award (£561229) to further develop proton radiography for adaptive radiography and image guidance.

Over the course of the action, our group co-organised the 3rd ion imaging workshop in Munich in 2022, and are now the main organisers of the 4th ion imaging workshop that is held in London in October 2023, which helps solidifies UCL and UCLH’s position as leaders in image guidance for proton imaging.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

This action, through the development and theoretical/experimental validation of a device and image reconstruction methods, led to one of the first demonstrations of real-time (sub-second) imaging capabilities with a proton beam, and was also expanded to carbon ion beams, and establishes proton radiographic imaging as an imaging modality available towards real-time treatment adaptation. As the technology has been demonstrated with both protons and carbon ions, it increases the number of patients that can be reached, as carbon ion treatment facilities are also under development.

Overall, this project was a crucial step towards improving the overall survival of lung cancer patients, which can lead to a reduction of the economic burden in the UK – and European Union - related to the occurrence of lung cancer. Furthermore, potential applications for treatment adaptation were identified for head and neck cancer, further improving the pool of cancer patients that can benefit of this technology.

Throughout the course of the project, it was also identified that the proton imaging device can be used as a quality assurance (QA) tool for clinical medical physicists. This has the potential of accelerating the QA workflow in proton radiotherapy departments, and help clinical scientists focus on patient care.
Furthermore, with the NIHR grant introduced in the last section, the device will be further developed with a patient public involvement (PPI) approach in mind – a group of patients is currently being formed, who will provide feedback and patient advice on the development of the device.

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