The first head-to-head comparative trial of proton beam therapy as a breast cancer treatment has launched in the UK.
While standard radiotherapy is very effective for the vast majority of people with breast cancer, there is a very small risk of it leading to heart problems later in life – overall less than 1% of the more than 30,000 people annually who receive radiotherapy following surgery for breast cancer.
Although proton beam therapy has been used in other countries to treat breast cancer, trials have been small and direct comparisons of proton beam therapy with standard radiotherapy are lacking. Currently the NHS says there is "not enough evidence" to make proton beam therapy generally available to treat breast cancer.
Proton Beam Targets Tissues More Precisely
The phase III, multi-centre, randomised PARABLE trial aims to assess whether proton beam therapy can deliver adequate radiotherapy doses to breast tissue while minimising off-target radiation to the heart.
Proton beam therapy can target radiotherapy beams more precisely as its physical properties result in reduced dose being deposited in the normal tissue beyond the tumour, tumour bed, or lymph nodes (target tissues), unlike standard radiotherapy where there is dose extension beyond the target tissues.
The trial will randomise 192 patients at greater risk of radiotherapy-induced heart toxicity after radiotherapy to either proton beam therapy or tailored radiotherapy. People allocated to receive proton beam therapy will be treated at either University College London Hospitals NHS Foundation Trust or The Christie NHS Foundation Trust in Manchester, with accommodation provided for those needing to travel far from home. Patients will receive treatment for 3 weeks and will be followed up for 5 years.
Patients will be recruited from a planned 22 sites managed by the ICR across the UK over a 2.5 year period. The trial is a synergetic enterprise between researchers at the University of Cambridge, the Institute of Cancer Research (ICR), London, and the Royal Marsden NHS Foundation Trust. It will be managed by the Clinical Trials and Statistics Unit at the ICR.
Some Patients at Higher Risk of Later Cardiac Effects
Announcing the trial, the ICR pointed out that the risk of later life heart problems due to breast radiotherapy may be higher than 1% for a very small group of people. Professor Judith Bliss, chair of the UK Breast Intergroup and director of the ICR Clinical Trials and Statistics Unit, explained:"Radiotherapy is a very effective part of treatment for breast cancer that helps to lower the risk of cancer returning and has been shown to improve survival. However, effectively delivering standard radiotherapy can be difficult when the patient's breast tissue and lymph nodes are located close to their heart, or they are already at risk of heart problems.
"We're delighted to launch the PARABLE trial to put proton beam therapy to the test and determine whether it has benefits over standard radiotherapy in a group of people who may need more targeted treatment.
"The PARABLE trial will measure 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."
For the trial, those who are predicted to have at least a 2% potential lifetime risk of heart problems from radiotherapy will be invited to take part. Around 500 in every 30,000 people who receive radiotherapy for breast cancer fall into this category. As proton beam therapy uses charged particles instead of x-rays to target tumours more precisely, the team hope that it will allow delivery of the required dose of radiotherapy while minimising radiation to the heart, and without increasing the risk of early side effects such as skin redness and changes in breast appearance. Study participants will be asked to complete questionnaires detailing side-effects including skin reactions, breast pain and swelling.
'Monumental Collaborative Effort' for Trial Launch
Dr Anna Kirby, consultant clinical oncologist at the Royal Marsden NHS Foundation Trust, breast cancer radiotherapy team lead at the ICR, and radiotherapy lead for the PARABLE trial, said:"It has been a monumental collaborative effort between patient advocates and professionals working in breast cancer radiotherapy research throughout the UK and beyond to develop, secure funding for, and now launch this trial.
"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."
Professor David Sebag-Montefiore, academic clinical oncologist at the University of Leeds and former chair of the National Cancer Research Institute (NCRI) Clinical and Translational Radiotherapy Research Working Group (CTRad) which supported the development of PARABLE, said: "There is untapped potential in proton beam therapy, potentially reducing the risks of side-effects following cancer treatment. It is critically important that we conduct well-designed clinical trials to determine when proton beam therapy can be beneficial for people with breast cancer. We are really pleased that the groundwork and mentorship provided by CTRad has led to the successful funding of such an important clinical trial."
Funding: The Clinical Trials and Statistics Unit at the ICR is funded by Cancer Research UK. The trial itself is funded by the National Institute for Health and Care Research and the Medical Research Council.