Cambridge researchers jointly lead UK’s first proton beam therapy for breast cancer patients

The first UK trial to test the benefits of proton beam therapy for some breast cancer patients will be jointly led by Cambridge researchers.

Proton beam therapy uses charged particles instead of X-rays to target radiotherapy beams more precisely but it is expensive and only available in certain locations in the country.

The PARABLE trial will compare it to standard radiotherapy for patients who are at greater risk of long-term heart problems after radiotherapy treatment.

It will help to determine whether proton beam therapy could deliver sufficient doses of radiotherapy to breast tissue, while minimising the off-target radiation delivered to the heart.

More than 30,000 people with breast cancer receive radiotherapy following surgery. Standard breast cancer radiotherapy uses high energy X-rays to kill cancer cells, which lowers the risk of cancer coming back and increases survival rates. It is very effective for the vast majority of people, with the benefits far outweighing the small side effects.

But there is a very small risk of radiotherapy leading to heart problems much later in life. This affects fewer than one per cent of people treated overall, but the risk may be greater for some breast radiotherapy patients.

This is typically those patients that require radiotherapy on breast tissue and lymph nodes located close to the heart and/or because they have an increased underlying risk
of developing heart problems later in life.

Prof Charlotte Coles, professor of breast cancer clinical oncology at the University of Cambridge and consultant oncologist at Addenbrooke’s Hospital and chief investigator of the PARABLE trial, said: “Although only a very small group of people are affected by a higher risk of heart problems later in life, it can still be a serious issue. Most patients treated with radiotherapy have decades of healthy life ahead of them and we need to do everything we can to avoid possible future heart problems related to treatment.

“Standard breast radiotherapy is really effective for most people with very few side effects, but there is a small group of patients for whom proton beam therapy may be a better option.”

Twenty-two sites across the country will be involved in the trial, which will enrol 192 people.

Those allocated to receive proton beam therapy will be treated at The Christie NHS Foundation Trust in Manchester or University College London Hospitals NHS Foundation Trust, and accommodation will be provided for those travelling far from home.

The trial is being led by researchers at the University of Cambridge, Institute of Cancer Research, London, and the Royal Marsden NHS Foundation Trust and managed by the Cancer Research UK-funded Clinical Trials and Statistics Unit at the Institute of Cancer Research (ICR).

The researchers hope it will enable doctors to deliver the required dose of radiotherapy where it is needed, while minimising the dose delivered to the heart and without increasing the risk of early side effects, which can include skin redness and changes in breast appearance.

The average radiotherapy dose that the heart is likely to receive can be predicted from the planning scan. Together with the patient’s age and medical history, the potential lifetime risk of heart problems can be estimated.

Prof Judith Bliss, director of the Cancer Research UK-funded Clinical Trials and Statistics Unit at the Institute of Cancer Research, London, which is managing the trial, said: “The PARABLE trial will measure the average dose of radiotherapy delivered to the heart to predict long-term heart damage. Using this early predictor will allow us to uncover the potential benefits of using proton beam therapy for long-term heart health in years rather than decades.”

Those patients predicted to have at least a two per cent or more potential lifetime risk of heart problems from radiotherapy will be invited to take part – a category that includes about 500 out of every 30,000 people who receive radiotherapy for breast cancer.

Those entering the trial will either receive standard radiotherapy or proton beam therapy.

Measuring the radiation dose delivered to the heart will be used as an early predictor of possible later heart problems to avoid the long wait for results to be available.

Questionnaires will also be completed by those in the trial to assess side-effects, including skin reactions, breast pain and swelling, and other symptoms which are particularly important for patients.

Dr Anna Kirby, consultant clinical oncologist at the Royal Marsden NHS Foundation Trust, breast cancer radiotherapy team lead at the Institute of Cancer Research, London, and radiotherapy lead for the PARABLE trial, said: “We have already learnt a huge amount about how to optimise and standardise current breast cancer radiotherapy practices alongside optimising proton beam therapy approaches. We hope that the PARABLE trial will help us to further personalise radiotherapy treatments and ensure that people can access the radiotherapy approach that is best for them, regardless of where they live.”

While proton beam therapy has been used in other countries to treat breast cancer, the number of participants in these trials are small.

There are no reported trials directly comparing proton beam therapy with standard radiotherapy.

The trial is being funded by a National Institute for Health and Care Research and Medical Research Council partnership and the NHS proton centres – UCLH and The Christie – provided expert guidance on the trial protocol development.

School caterer joins trial

Some patients have already been recruited to the trial.

School caterer Kim Jones, 44, from Ely, was diagnosed with breast cancer in February 2022 after noticing thickening of the skin and painful twinges in her left breast.

She was referred by her GP for urgent scans at the breast clinic, and after having mammograms, ultrasounds and biopsies, the diagnosis was confirmed.

Kim was referred to Addenbrooke's Hospital, where she had chemotherapy followed by a mastectomy and lymph node removal.

She has joined the PARABLE trial and her proton beam therapy began at The Christie on 24 October.

Kims, who is married to Mark, with whom she has two boys, Dylan, 11, and Elwood, 11, said: "I was told I might be suitable to participate in the PARABLE trial as it would potentially benefit patients with a high risk of long-term heart complications. As I already had an issue with my heart, the trial seemed like a great idea.

"When I was told that I'd been accepted onto the trial, I felt very lucky to have the opportunity to get this treatment. Clinical trials are incredibly important as they are the best way to evaluate which treatments work the best.

"The proton beam therapy centre at The Christie is bright and spacious and feels very relaxing. My experience of being treated at The Christie so far has been superb. The staff are wonderful and seem to have thought of everything. Their care is second to none, and I feel completely safe in their hands."

After the proton beam therapy, Kim will have further chemotherapy and hormone therapy at Addenbrooke's.