Fighting Cancer with Protons

As a physicist, the things I learned at university were mostly along the lines of Maxwell’s equations, special relativity, Fourier transforms, quantum mechanics, and numerical methods. Five years ago I certainly didn’t envision myself working in cancer science, let alone be applying some of what I learned at university to cancer research. 

 

Although I’ve barely stepped foot in a lab, don’t have a white lab coat, and I haven’t looked down a microscope since GCSE biology, I’m now confident I can call myself a cancer researcher. Of course, it helps to be working in a multi-disciplinary group, with a team of supervisors made up of expert biologists, engineers, chemists and clinicians.  

 

But as I’ve learned, physics also provides a crucial role in cancer science in many forms. For me, the link between my physics background and passion for cancer research came in the form of the proton.  

 

The proton was discovered in Manchester just over 100 years ago, so it’s only fitting that this is also the city which drew me to research its use in cancer research via radiation therapy. 

 

How is radiation used to treat cancer?  

 

Alongside surgery and chemotherapy, radiotherapy is one of the most common formof cancer treatments1. Although it only accounts for about 5% of the NHS England cancer budget, radiotherapy is used in around 40% of cancer cures2. 

 

Conventional radiotherapy generally uses a beam of X-rays, which enters the body, deposits energy via ionisations and kills cancerous tissue by damaging its DNA. The aim of radiotherapy is to destroy the cancer, while minimising damage to surrounding healthy tissue. 

 

Techniques such as intensity-modulated radiotherapy (IMRT), which uses multiple X-ray beams at various intensities to conform the dose to the tumour, have been developed to achieve this. Although a low dose of radiation in normal tissue is very likely to be inconsequential to the patient, it can lead to side effects and a slightly heightened risk of second cancers developing 

 

 

What is proton therapy?  

 

X-ray radiotherapy is a constantly advancing field with significant ongoing research3. But what particularly drew me to the field of cancer research was radiotherapy using protons.  

 

The proton is the positively charged subatomic particle found in the nucleus of every atom. Decades after its discovery in Manchester in 1919, its use in radiotherapy was first proposed in 1946Patients were treated using protons in labs over the next few decades, but it wasn’t until the 1990s that protons started to be used in hospital-based treatments.  

 

In 2018, The Christie in Manchester became home to the first high-energy NHS proton beam therapy centre in the UK4 

Image: AboutManchester.co.uk 

 

How are protons different from X-rays?  

 

The main difference between protons and X-rays is that X-rays are waves while protons are particles with mass. A beam of X-rays will penetrate through the whole body and come out the other side, depositing energy in an exponential way.  

 

Protons on the other hand can be made to stop in the tumour. This is where the physics comes in – the law for swift charge particles traversing matter (the Bethe formula) dictates that a proton’s energy loss is inversely proportional to the square of its velocity: 

So as the proton slows down in the body, the square of its velocity decreases very quickly and the energy loss suddenly gets very big – it therefore deposits a significant proportion of its energy near the point where it stops. If we can time that right, we can make sure all that energy goes into the tumour.

The shape of the proton’s energy distribution is known as the Bragg peak. Because of this sharp peak in energy, there is reduced radiation dose in the healthy tissue and very little exit dose, which can mean fewer side effects for patients.  

 

Tumours are generally quite a bit wider than a single proton Bragg peak though, so multiple proton energies can be used to create a spread-out Bragg peakor a technique called pencil beam scanning to scan over the target area5. 

 

From the physics, protons appear to have huge advantage over X-rays for treating cancer. It’s important to note though that while protons certainly have their benefits, in practice, X-ray based treatments often offer the more suitable form of therapy4. 

 

Proton Therapy Research at Manchester 

 

Although proton therapy is a well-established treatment technique, there are a number of scientific challenges to address for it to achieve its full potential. The PRECISE Group at Manchester has its own dedicated research facility6 within The Christie’s Proton Beam Therapy Centre aimed at addressing some of these challenges7

Image: AboutManchester.co.uk 

 

 

The multi-disciplinary nature of the group means research can cover the physics of the proton beam and its energy deposition, the chemistry of the reactions that take place as the proton interacts with the body, through to the biological effect of the proton radiation and the potential for clinical translation. We aim to understand the effect of proton radiation at every stage, so we can find ways of making better.  

 

Look out for our Show and Tell as part of the GM Cancer Virtual Cancer Week8 where you can see inside our research room and hear more about some of our key areas of research. 

 

 

FLASH Radiotherapy  

 

The topic that I’m particularly interested in is FLASH radiotherapyPre-clinical studies have shown that when radiation is delivered very quickly at very high dose rates, normal tissue is significantly spared compared to delivery at conventional rates, while damage to the tumour remains the same9. The sparing effect of this ultra-high-dose-rate (or ‘FLASH’) radiation has been shown in a number of biological systems, but the reason it happens still hasn’t quite been figured out.  

 

One key hypothesis involves hypoxia – oxygen plays a key role in radiotherapy, and a lack of it generally results in a state of resistance to radiotherapyIt’s suggested that FLASH radiation causes oxygen to be depleted in cells at a rate that is too fast for cells to be re-supplied with oxygen diffusing from the blood. The normal tissue therefore becomes more resistant to the radiation.  

 

My research involves developing a mathematical model of FLASH radiation interacting with oxygen in cells – this is where the skills from my physics background really come into play. We can use this model to understand oxygen depletion from FLASH radiation more fully, and determine the conditions under which sparing effect might take place10. 

 

Computational or mathematical models are a great tool to determine specific biological studies we should be doing and identify key experimental parameters. Consequently, findings from experiments at each stage can be fed back into models to validate simulations and develop them further.  

 

Creating this positive feedback loop between computational simulations and experimental data is a big part of research in the PRECISE group. Not only is this the best way to research and develop cutting-edge treatment techniques, it brings together experts across a number of disciplines, so a physicist like me can feel part of something that will truly benefit cancer treatment for patients. 

 

~This article was written by Beth Rothwell on behalf of the LIVE with Scientists team. All views belong solely to the author. ~ 

 

References: 

 

  1. Cancer Research UK. Cancer diagnosis and treatment statistics. Available at: https://www.cancerresearchuk.org/health-professional/cancer-statistics/treatment  

  1. Cullen et al. Recommendations for achieving a world-class radiotherapy service in the UK.Technical Report 2014. 

  1. Garibaldi et al. Recent advances in radiation oncology. Ecancer Medical Science. 2017; 11:785.  

  1. The Christie NHS Foundation Trust. Proton Beam Therapy. Available at: https://www.christie.nhs.uk/patients-and-visitors/services/protons 

  1. Proton Therapy UK. How proton therapy works. Available at: 
    https://ukprotontherapy.co.uk/about-proton-therapy/how-proton-therapy-works/ 

  1. The Christie charity, Proton beam research. Available at: https://www.christie.nhs.uk/the-christie-charity/why-we-need-your-help/how-youve-helped/proton-beam-research 

  1. University of Manchester, Faculty of Biology, Medicine & Health. Proton Therapy Research. Available at: https://www.bmh.manchester.ac.uk/research/domains/cancer/proton/ 

  1. Greater Manchester Cancer, Virtual Cancer Week 2021. Available at: https://gmcancer.org.uk/vcw/ 

  1. Vozenin et al. Biological benefits of ultra-high dose rate FLASH radiotherapy: sleeping beauty awoken. Clin Oncol. 2019; 31: 407-415.  

  1. Rothwell at el. Determining the parameter space for effective oxygen depletion for FLASH radiation therapyPhys Med Biol. 2021;66:055020