Radiotherapy in a FLASH
Proton therapy and the PRECISE group
27% of patients in the UK will receive radiotherapy as part of their cancer treatment, but it has associated side-effects through the damage of healthy cells surrounding the tumour site.
One of the latest innovations in radiotherapy being investigated at The University of Manchester, is the phenomenon of FLASH radiotherapy. FLASH delivers radiation at an ultra-high dose rate over a very short time span. It has been shown to spare healthy tissues while still killing the tumour. However, a greater understanding of how FLASH radiotherapy works is needed before its translation into the clinical setting.
We speak to Beth Rothwell about proton beam therapy and her PhD working within the PRECISE group.
We aim to research ways of improving proton therapy for patients and minimise the associated side-effects. FLASH radiotherapy is a key example of how we could benefit patient outcomes.
Postgraduate Researcher at The University of Manchester
FLASH is thought to cause oxygen depletion in healthy cells at a rate too fast for these cells to be re-supplied with oxygen from the blood. Tissues that have low levels of oxygen are generally more resistant to radiation and so it is hypothesised that this transient lack of oxygen means normal tissue is spared.
Beth’s research involves the development of a model to look at how oxygen reacts in cells post radiation. This information can then be translated into biological experiments and inform future practice.
Although she works in cancer research, Beth is a physicist by background. During her degree at the University of Birmingham, Beth discovered her love for medical physics, focusing her third-year research project on particle therapy for treating cancer.
“I never really thought about using physics in healthcare that much and using physics to treat cancer was a completely new concept to me. It’s how I discovered proton therapy and decided it was a subject I’d like to do a PhD in,” Beth said.
Following her graduation, Beth began her PhD in Proton Therapy at the end of 2018 at The University of Manchester – home to the first NHS high energy proton centre in the UK with a dedicated proton research facility.
“I was lucky enough to get to chat to Professor Karen Kirkby who is the Chair for Proton Therapy Physics and meet some of the research group, the PRECISE group. I learned about some of the amazing research they do so I decided I wanted to be a part of it and I guess here I am,” she continued.
Investigating the biological effects of protons
Beth’s PhD began with the broad aim of improving the biological effect of protons, applying mathematical modelling techniques to cancer radiobiology. At the inception of her PhD, an emerging topic within the field of radiotherapy was FLASH. Preclinical studies just a few years before had shown when radiation was delivered at high speeds with very high dose rates, normal tissue was significantly spared compared to delivery at conventional dose rates while tumoral damage remained the same.
She decided to focus her research on improving proton therapy and understanding how and why FLASH happens to optimise the mechanism for patient benefits.
As a physicist, some of the tools we are equipped with in our undergraduate studies are computer programming and mathematical modelling. The aim of my PhD is to use modelling as a tool to determine what we call the parameter space of FLASH radiotherapy.
Currently, it is largely unknown what causes this FLASH effect and there are lots of factors that could be contributing. Carrying out biological experiments is an important requirement to ascertain what these factors are.
“We can use mathematical models like the one that I’m developing in my PhD to explore these factors. We want to carry out and identify key experimental parameters and then we can back translate these findings from experiments into our models. This will mean we can validate simulations and create a positive feedback loop between computational simulations and experimental data,” she continued.
These findings can then be translated clinically to develop hypotheses that can be applied in the clinical setting to improve patient outcomes.
Interdisciplinary team science
When asked how it feels to be a physicist in cancer research, Beth replied: “I think as a physicist, there are skills that I can bring to cancer research and skills I’ve seen other physicists bring in terms of computational skills, mathematical skills, and looking at biological processes from a very fundamental approach.”
“Our group, PRECISE, epitomises the “Team Science” approach. We have physicists and engineers working alongside those from the life and clinical sciences and we even have a Health Economist as part of the team. We also work very closely with the clinical proton teams at The Christie,” she continued.
I like being able to know how this research will use physics to actually help people in a very realistic and clear way. I think every form of discipline has its own value, and working together in multidisciplinary environments is the best way to get the most out of this research.
Advice for prospective physics researchers
“Definitely be prepared for a learning curve. Be ready to learn new subjects and an entirely new vocabulary. You have to come in with a completely open mind and create a network of people from various disciplines so you can draw in expertise from all different fields,” she answered.
Beth described her experience of working in Manchester through the collaboration between the MCRC, the University of Manchester and The Christie: “There is a real collaborative nature present in the cancer research team and what I have experienced has been really wonderful.”
In her third year of her four-year PhD, Beth is currently exploring options for the future.
“I would definitely like to see what happens with FLASH research and how it may be translated clinically in amongst current clinical treatments,” Beth said.
“I’m particularly interested in the use of mathematical and computational tools for research. I’d love to take on a role where I can encourage the skills of physicists, mathematicians, computer scientists in all different disciplines of research and create these kinds of multidisciplinary environments that have really benefited my work,” she concluded.