̽��ֱ�� of Cambridge - Institute of Cancer Research

First UK proton beam therapy trial for breast cancer launches

cjb250 — Wed, 04 Jan 2023 09:17:27 +0000

̽��ֱ��trial will compare proton beam therapy – which can target radiotherapy beams more precisely – with 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 can help to deliver adequate doses of radiotherapy to breast tissue, while minimising off-target radiation delivered to the heart.

̽��ֱ��trial will enrol 192 people across a planned 22 sites in the UK. People allocated to receive proton beam therapy will be treated at either ̽��ֱ��Christie NHS Foundation Trust in Manchester or ̽��ֱ�� College London Hospitals NHS Foundation Trust, with accommodation provided for those who are travelling far from home.

̽��ֱ��PARABLE trial is being led by researchers at the ̽��ֱ�� 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 ̽��ֱ��Institute of Cancer Research (ICR). It is funded by a National Institute for Health and Care Research and Medical Research Council partnership. ̽��ֱ��NHS proton centres – UCLH and ̽��ֱ��Christie – also provided expert guidance on the trial protocol development.

Every year in the UK over 30,000 people with breast cancer receive radiotherapy following surgery as part of their treatment. Standard breast cancer radiotherapy uses high energy x-rays to kill cancer cells. As well as lowering the risk of cancer coming back, radiotherapy can increase survival rates.

Standard breast cancer radiotherapy is very effective for the vast majority of people and the benefits far outweigh small side effects. However, there can be a very small risk of radiotherapy leading to heart problems much later in life (less than one per cent of people treated). ̽��ֱ��risk of heart problems later in life due to breast radiotherapy maybe be higher than one per cent for a very small group of people. This is usually because their breast tissue and the lymph nodes which require radiotherapy treatment are located close to the heart, and/or because they have an increased underlying risk of developing heart problems later in life.

Professor Charlotte Coles, Professor of Breast Cancer Clinical Oncology at the ̽��ֱ�� of Cambridge, 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.”

Proton beam therapy uses charged particles instead of X-rays to target tumours more precisely. Researchers hope it will allow doctors to deliver the required dose of radiotherapy where it’s needed, while minimising the dose of radiation delivered to the heart, and without increasing the risk of early side effects such as skin redness and changes in breast appearance.

̽��ֱ��average radiotherapy dose that the heart is likely to receive from the radiotherapy planning scan can be estimated and together with age and other medical history, this information is used to predict the potential small lifetime risk of heart problems.

Professor Judith Bliss, Director of the Cancer Research UK-funded Clinical Trials and Statistics Unit at ̽��ֱ��Institute of Cancer Research, London, which is managing the PARABLE trial, said: “ ̽��ֱ��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.”

People who are 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. Around 500 out of every 30,000 people who receive radiotherapy for breast cancer fall into this category. People who enter the trial will either receive standard radiotherapy or proton beam therapy.

̽��ֱ��trial will measure radiation dose delivered to the heart as an early predictor of possible heart problems, to avoid the need for lengthy follow up for many years before results are available.

People in the trial will also record their experiences using questionnaires so that researchers can assess side-effects including skin reactions, breast pain and swelling, and other symptoms which are particularly important for patients.

Proton beam therapy has been used in other countries to treat breast cancer, but numbers of participants in these trials are small and there have been no reported trials that directly compare proton beam therapy with standard radiotherapy.

̽��ֱ��researchers stress the importance of evaluating the benefits of proton beam therapy – which is expensive and only available in certain locations across the UK – thoroughly in a clinical trial.

Dr Anna Kirby, Consultant Clinical Oncologist at the Royal Marsden NHS Foundation Trust, Breast Cancer Radiotherapy Team Lead at ̽��ֱ��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.

Adapted from a press release from ̽��ֱ��Institute of Cancer Research

Cambridge researchers are jointly leading the first UK trial to test the benefits of proton beam therapy for certain patients with breast cancer.

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

Charlotte Coles

FatCamera (Getty Images)

An Asian woman in her 60s embraces her mid-30s daughter who is battling cancer - stock photo

Kim Jones: Patient story

Kim Jones, 44, a school caterer from Ely, was diagnosed with breast cancer in February 2022 after noticing some thickening of the skin and painful twinges in her left breast. Her GP referred her for urgent scans at the breast clinic, and after having mammograms, ultrasounds and biopsies, the diagnosis was confirmed.

Kim was then referred to Addenbrooke's Hospital in Cambridge, where she had chemotherapy followed by a mastectomy and lymph node removal. Following acceptance to the PARABLE trial, Kim's proton beam therapy commenced at ̽��ֱ��Christie on 24 October.

Kim 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."

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

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

Kim is married to Mark, and they have two boys, Dylan, age 14, and Elwood, age 11. She enjoys walking, reading, live music and spending time with her family.

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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Prostate cancer risk prediction algorithm could help target testing at men at greatest risk

cjb250 — Fri, 09 Dec 2022 21:00:39 +0000

CanRisk-Prostate, developed by researchers at the ̽��ֱ�� of Cambridge and ̽��ֱ��Institute of Cancer Research, London, will be incorporated into the group’s CanRisk web tool, which has now recorded almost 1.2 million risk predictions. ̽��ֱ��free tool is already used by healthcare professionals worldwide to help predict the risk of developing breast and ovarian cancers.

Prostate cancer is the most common type of cancer in men. According to Cancer Research UK, over 52,000 men are diagnosed with the disease each year and there are more than 12,000 deaths. Over three-quarters (78%) of men diagnosed with prostate cancer survive for over 10 years, but this proportion has barely changed over the past decade in the UK.

Testing for prostate cancer involves a blood test that looks for a protein known as a prostate-specific antigen (PSA) that is made only by the prostate gland; however, it is not always accurate. According to the NHS website, around three in four men with a raised PSA level will not have cancer. Further tests, such as tissue biopsies or MRI scans, are therefore required to confirm a diagnosis.

Professor Antonis Antoniou from the Department of Public Health and Primary Care at the ̽��ֱ�� of Cambridge said: “Prostate cancer is the most common cancer in men in the UK, but population-wide screening based on PSA isn’t an option: these tests are often falsely positive, which means that many men would then be biopsied unnecessarily. Also, many prostate tumours identified by PSA tests are slow-growing and would not have been life-threatening. ̽��ֱ��treatment of these tumours may do more harm than good.

“What we need is a way of identifying those men who are at greatest risk, allowing us to target screening and diagnostic tests where they are most needed, while also reducing the harms for those men who have low risk of the disease. This is what CanRisk-Prostate aims to do. For the first time, it combines information on the genetic makeup and prostate cancer family history, the main risk factors for the disease, to provide personalised cancer risks.”

Prostate cancer is one of the most genetically determined of common cancers. Inherited faulty versions of the BRCA2, HOXB13 and possibly BRCA1 genes are associated with moderate-to-high risk of prostate cancer, though such faults are rare in the population. In addition, there are several hundred more common genetic variants that each confer a lower risk, but in aggregate they act like ‘volume control’ that moderate or increase the prostate cancer risk.

Writing in the Journal of Clinical Oncology, the researchers – supported by Cancer Research UK – describe the development of the first comprehensive prostate cancer model using genetic and cancer family history data from almost 17,000 families affected by prostate cancer. It uses data on rare genetic faults in moderate-to-high-risk genes and a risk score based on 268 common low-risk variants, together with detailed cancer family history, to predict the future risks.

One in six men (16%) will develop prostate cancer by the time they are 85 years old. Using the model, the team found that the predicted risk was higher for men who had a father diagnosed with prostate cancer – 27% if the father was diagnosed at an older age (80 years) but as high as 42% if the father was diagnosed at a young age (50 years).

̽��ֱ��risks were considerably higher for men with genetic faults. For example, 54% of men who carry an alteration in the BRCA2 gene would develop prostate cancer – however, among men with BRCA2 gene faults, the risks were substantially lower if they also had a small number of the low-risk variants, but much higher if they also had a large number of the low-risk variants.

In practice, say the researchers, clinicians will be able to use any combination of cancer family history, rare and common genetic variants to provide a personalised risk.

To validate their model, the team ran the risk model on an independent cohort of over 170,000 men recruited to UK Biobank, a biomedical database and research resource containing anonymised genetic, lifestyle and health information from half a million UK participants. All of these men were free from prostate cancer when they were recruited to the study, but more than 7,600 developed prostate cancer within the subsequent ten years.

When validating their model, the researchers found that 86% of the UK Biobank participants who developed cancer were in the half of men with the highest predicted risks, which suggests that it may be possible to target screening and diagnostic tests to the subgroup of the population at highest risk, among whom the majority of the cancers will occur.

Dr Tommy Nyberg from the MRC Biostatistics Unit at Cambridge said: “We’ve created the most comprehensive tool to date for predicting a man’s risk of developing prostate cancer. We hope this will help clinicians and genetic counsellors assess their clients’ risk and provide the appropriate follow-up.

“Over the next 12 months, we aim to build this tool into the widely used CanRisk tool, which will facilitate the risk-based clinical management of men seen in family cancer clinics and enable risk-adapted early detection approaches to the population at large.”

Professor Ros Eeles from ̽��ֱ��Institute of Cancer Research, London and co-author on the study said: “This is an important step forward as it will enable clinicians to have conversations with men about their individual risk of prostate cancer based on the most accurate computer model to date. This will help them in making decisions about screening.”

So far, the data used to develop CanRisk-Prostate has been from men of European ancestry. ̽��ֱ��team hope to be able to include data from men of other ethnicities as further research is undertaken.

̽��ֱ�� ̽��ֱ�� of Cambridge recently launched the Early Cancer Institute with the aim of detecting cancer early enough to cure it. It is the first physical institute in the UK dedicated to early cancer. A new Cambridge Cancer Research Hospital is also planned for the near future, bringing together clinical and research expertise in a new, world-class hospital, designed in partnership with patients.

There is also an Early Detection and Diagnosis centre at ̽��ֱ��Institute of Cancer Research and ̽��ֱ��Royal Marsden NHS Foundation Trust where a prostate risk clinic has been established to translate these findings into targeted screening programmes.

̽��ֱ��research was supported by the Cancer Research UK-funded CanRisk programme. Additional support for CanRisk-Prostate was provided by Prostate Cancer UK, ̽��ֱ��Institute of Cancer Research, Everyman Campaign, National Cancer Research Network UK, National Cancer Research Institute, NIHR Cambridge Biomedical Research Centre and the NIHR Biomedical Research Centre at ̽��ֱ��Institute of Cancer Research and ̽��ֱ��Royal Marsden NHS Foundation Trust.

Reference
Nyberg, T et al. CanRisk-Prostate: a comprehensive, externally validated risk model for the prediction of future prostate cancer. Journal of Clinical Oncology; 9 Dec 2022; DOI: 10.1200/JCO.22.01453

Cambridge scientists have created a comprehensive tool for predicting an individual’s risk of developing prostate cancer, which they say could help ensure that those men at greatest risk will receive the appropriate testing while reducing unnecessary – and potentially invasive – testing for those at very low risk.

What we need is a way of identifying those men who are at greatest risk, allowing us to target screening and diagnostic tests where they are most needed, while also reducing the harms for those men who have low risk of the disease. This is what CanRisk-Prostate aims to do

Antonis Antoniou

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