Proton beam therapy
Particle accelerator technologies originally designed for particle physics experiments are being optimised and applied to improve proton beam therapy treatment for cancer patients.
Cancer is now the second most common cause of death worldwide, with the disease accounting for 9.6 million lives last year, according to the World Health Organisation. Radiotherapy, widely heralded by clinicians as an increasingly promising cancer therapy technique, combines X-rays and electrons with proton or ion beams to create a unique treatment that is highly effective at targeting tumours.
Proton beam therapy, a form of radiotherapy that emerged as a result of R&D efforts into fundamental particle physics experiments, such as the ones underway at Conseil Européen pour la Recherche Nucléaire (CERN) in Geneva, uses a beam of high-energy protons for the treatment of specific types of tumours. Although progress has been made in the use of proton beams for cancer treatment, further R&D into the optimisation of the underpinning accelerator technologies and advanced imaging systems is required to maximise its effectiveness.
Proton beam therapy
American Physicist Robert R Wilson introduced the idea of using heavy charged particles in cancer therapy. In his paper Radiological Use of Fast Protons, published in Radiology, 1946, Wilson pointed out the distinct difference in depth dose profile between photons and heavy charged particles. While photons deposit their energy along the beam path in an exponentially decreasing manner, heavy charged particles like protons and ions show little interaction when they first enter the target and deposit the dominant portion of their energy only close to the end of their range. This leads to an inverse dose profile, exhibiting a well-defined peak of energy deposition, known as the Bragg Peak. The depth of the Bragg Peak in the target can be selected precisely by choosing the initial energy of the particles. This allows for a significant reduction of dose delivered outside the primary target volume and leads to substantial sparing of normal tissue and nearby organs at risk.
By March 2013, around 110,000 people had received cancer treatment with particle beams, the vast majority having been treated with protons and around 15,000 patients with heavier ions such as helium, carbon, neon and argon. By modulating the energy and direction of a proton beam, clinicians can deliver a homogeneous dose of radiation over a 3D tumour volume and prevent damage to the healthy surrounding tissue, nearby vital organs or critical body parts such as the spinal cord. The beam can also be extremely well controlled to follow the outline of a tumour. This level of precision makes the technology uniquely suited to delicate applications such as the treatment of eye cancers or brain tumours.
In 2018, the first of two new NHS-funded high energy proton beam therapy facilities opened in the UK. The Christie proton beam therapy centre in Manchester treated its first patient just before Christmas. The building work for a second NHS centre located in London is almost complete, with proton beam therapy treatment set to begin in early 2020. Together, these two facilities will treat up to 750 patients every year and will complement other facilities such as the Clatterbridge Centre NHS Foundation Trust in Merseyside, which has been treating patients with eye cancer using low-energy proton beam therapy since 1989.
Optimising medical accelerators
Although there have been a number of recent advances in proton beam therapy, more research is needed to maximise its effectiveness. This was the idea behind an international collaborative research network into the optimisation of medical accelerators (OMA), which I proposed with international partners in 2015. The project has received almost €4mln of funding from the EU and has been developing methods to improve ion beam therapy.
OMA is a network of more than 30 partner organisations, comprising universities, research centres, ion beam treatment facilities and industrial companies based all across Europe. The network aims to address technological challenges in key areas such as the design and optimisation of ion beam therapy facilities, numerical simulations for the development of advanced treatment schemes, and in beam and patient imaging techniques. The project centres around 15 early stage research fellows who are working on dedicated research projects at their host institution and in collaboration with other OMA partners to maximise the benefits of ion beam therapy.
There are a number of interesting challenges to address. For example, it would be highly desirable to reduce both the size and cost of the accelerator that delivers the beam to the patient, while simultaneously improving the machine’s performance. To achieve this, we need to expand our horizons beyond the current generation of available technologies. Among the approaches being explored in the OMA network are new types of accelerating structures and beam delivery systems, simulation tools and beam diagnostics for monitoring beam parameters in real-time without impacting on the treatment beam.
Applying LHC to oncology
University of Liverpool OMA Fellow, Jacinta Yap, who is part of my research group, is working at the Cockcroft Institute in Warrington, UK, on a project that is using a sensor technology originally designed for, and still used on, the Large Hadron Collider at CERN – the world’s largest and most powerful particle accelerator. In collaboration with others in the group and collaborators at the Clatterbridge Cancer Centre, she is applying this Vertex Locator (VELO) sensor to radiotherapy.
The VELO detector was designed by colleagues in the University of Liverpool Institute of Physics High Energy Particle Physics Group at CERN. Imagine a CD and slice it lengthwise down the centre – the detector looks visually similar, consisting of two modules that make up each half of the disc. At the centre, there is a hole between the halves, which allows a beam of particles to pass through without any degrading effects.
The detector’s sensitive regions are sensors comprised of thousands of tiny silicon strips. Any particles that come into contact will deposit a minute amount of charge, which is then measured and recorded. In the LHC, the detectors are positioned inside the beam pipe close to the high energy proton beam, allowing it to pass through without disturbance. This enables the sensors to resolve interactions and the paths of particles originating from proton collisions, to be reconstructed and studied by particle physicists at CERN.
By adapting and repurposing the detectors for medical beamlines, Yap and the researchers are able to measure the halo of particles surrounding the beam as it passes through the detector’s sensors. Relating this to the primary beam, it is possible to obtain important information about the delivery of the beam, ensuring that it reaches the patient safely and as planned. This requires an understanding of its motion from the accelerator, as it travels along the beamline and through the components which modify it so it is suitable for medical treatment. Yap has been carrying out simulation studies that help to understand the behaviour of the system at the Clatterbridge facility in greater detail.
For treating patients, the detectors are used to measure the particle outliers around the beam, correlate this information to the total expected beam and then ultimately calculate the dose which would be delivered to the patient. This is the final amount of radiation needed for a successful outcome of the treatment and is prescribed by the team of medical professionals. This team would assess the patient, identify the best course of treatment and develop a treatment plan, ensuring that the correct amount of radiation could be delivered to the target site.
Through measuring beam characteristics, this non-interceptive method of monitoring the delivery in real-time will allow for more precise treatment. It can help reduce time during machine setup and quality assurance measurements, enabling more people to receive treatment and reduce overall cost.
To further optimise proton beam therapy, R&D within OMA has focused on the development of patient imaging techniques, where patient motion is monitored in real time and can take breathing motion into account during irradiation. Fellows have also carried out studies into improving biological and physical simulation models using Monte Carlo methods. These Monte Carlo codes allow us to build a better understanding of what is happening by modelling the radiation and the physics processes, to study the beam and its interactions with cells. This is relevant for treatment, where improvements to the data used and how they are used by the codes can optimise treatment plans and the treatment itself.
The Fellows have also carried out research at major clinical facilities across Europe, such as the ion beam centres Fondazione Centro Nazionale Adroterapia Oncologic (CNAO) in Pavia, Italy, and MedAustron in Vienna, Austria. They have developed improvements for the machine control system which enables more precise control of the treatment beam, as well as better beam extraction methods, so the treatment can be delivered with even higher precision to the patient.
All of these studies are directly connected to wider R&D efforts into the improvement of accelerators for fundamental science applications. They show how closely medical applications are connected with more general accelerator R&D. Proton beam therapy is one example of how technology originally developed for fundamental studies benefits society beyond scientific discoveries. Particle accelerators are used more widely to image, characterise and treat materials and surfaces for a whole range of applications. They allow material scientists to better understand the behaviour of existing materials and engineer better materials for applications that improve our daily lives.
Research within the OMA network covers a range of areas R&D that had never previously been addressed. By bringing together cancer experts, accelerator designers, instrumentation and imaging specialists, and leading researchers in Monte Carlo simulations, the network helps to refine beam control, reliability and accelerator delivery techniques, with attention to external instrumentation and hadron tomography development for enhanced patient safety and reduced diagnostic radiation dose. The project tackles an interdisciplinary R&D programme that highlights the importance of international collaboration, knowledge and researcher exchange.
Professor Carsten Welsch is University of Liverpool, UK, Head of the Department of Physics.