Single-dose radiotherapy for breast cancer

Single-dose radiotherapy for breast cancer confirmed to be suitable for most patients: Results from further analysis of the large international TARGIT-A trial led from University College London brings more good news for patients diagnosed with breast cancer. Four important questions have been answered by this new analysis.

The new paper can be accessed at https://doi.org/10.1038/s41416-021-01440-8

Previously:

TARGIT-IORT is a pioneering breast cancer therapy developed by UCL clinicians, which requires just one shot of radiotherapy. With TARGIT-IORT therapy, eight out of every ten patients have no need for any further post-operative radiotherapy treatments. In August 2020, the findings of the large international TARGIT-A randomised trial, were published in the BMJ (https://www.bmj.com/content/370/bmj.m2836.full.pdf), and confirmed the long-term effectiveness of Targeted Intraoperative Radiotherapy (TARGIT-IORT): a breast cancer treatment which is increasingly available throughout the world. At long-term follow up (average 8.6 years, maximum 18.9 years), TARGIT-IORT has been proven to be as effective as the long course of post-operative radiotherapy in terms of controlling breast cancer. It also substantially reduced deaths from other causes such as cardiovascular causes, lung problems and other cancers.

TARGIT-IORT is delivered immediately after lumpectomy (tumour removal), via a small ball-shaped device placed inside the breast, directly where the cancer had been. The single-dose treatment lasts for around 20 to 30 minutes and replaces the need for extra hospital visits, benefiting the patient. Previous studies have shown that TARGIT-IORT has fewer radiation-related side effects compared with conventional whole breast radiotherapy, with less pain, superior cosmetic outcome and a better quality of life. The TARGIT-IORT technique was developed by clinical academics, Professors Vaidya, Tobias and Baum, in 1998 in collaboration with the manufacturers.

Conventional external beam radiotherapy (EBRT) is delivered from outside the body via a radiotherapy machine (linear accelerator), and consists of a daily treatment session (known as fractions) to the whole breast, over a period between three to six weeks. Each of these treatments is given over a few minutes, but requires 15 to 30 hospital visits, which could be a significant distance from where the patient lives.

The TARGIT-A trial: To establish TARGIT-IORT’s long-term effectiveness, 2,298 women aged 45 or over with invasive ductal carcinoma (breast cancer) and a tumour of up to 3.5cm in size, were randomly assigned to receive either TARGIT-IORT or the traditional EBRT. This large clinical trial, designed and run from UCL, involved 32 hospitals and medical centres in ten countries: the UK, France, Germany, Italy, Norway, Poland, Switzerland, United States, Canada and Australia. The trial started in March 2000, which has enabled researchers to publish these long-term results.

New findings:

The new findings show that breast cancer outcomes were just the same with TARGIT-IORT and EBRT irrespective of the tumour subgroup. In fact, if the cancer was grade 1 or 2, there was an overall survival advantage with TARGIT-IORT.

Lead author, Professor Jayant Vaidya, (Professor of Surgery and Oncology, UCL Surgery & Interventional Science), said: “With TARGIT-IORT, women can have their surgery and radiation treatment for breast cancer all at the same time. This reduces the amount of time spent in hospital and enables women to recover more quickly, meaning they can get back to their lives more quickly.

“These new results, make it clear that the TARGIT-IORT is effective in all tumour subgroups of invasive duct cancer. Our new online tool can help clinicians make a decision about additional radiotherapy for each individual patient. The data suggest the strong possibility of an abscopal effect of TARGIT-IORT during lumpectomy. This is an important finding and should fuel further research, opening doors to new treatments.”

Professor Michael Baum (Emeritus Professor of Surgery, UCL Surgery & Interventional Science), said: “These results are the highest level of evidence proving not only the effectiveness of TARGIT-IORT but confirming that it avoids deaths from other causes. The new data is biologically very interesting and the new tools will make its application in routine clinical practice much easier. I am pleased that it will benefit thousands of breast cancer patients around the world.”

Professor Jeffrey S Tobias (Professor of Clinical Oncology, UCL & UCLH) said: “With TARGIT-IORT, the majority of patients presenting with early localised breast cancer will never need any further radiotherapy. They will avoid all the side effects

of whole breast radiotherapy. Very few patients (1- 2%) will develop a local recurrence (i.e., in the breast itself). Our new analysis shows that even if they do, it will not detract from an excellent prognosis – a rather different state of affairs from the more serious outlook if this were to happen after EBRT. ”

Four important questions answered by the detailed analysis:

1) Which patients can have TARGIT-IORT, and 2) who needs additional EBRT?

Further analysis of the TARGIT-A trial published today in the British Journal of Cancer in Aug 20201 found that local control of breast cancer was just as good with TARGIT-IORT and EBRT for all tumour subgroups (size, grade, ER, PgR, HER2, lymph node status).

In fact, for patients with grade 1 or 2 cancers, TARGIT-IORT improved overall survival by 4.4% (p=0.036) A web-based decision-aid https://targit.org.uk/addrt is now available and it can help individualise treatment for each patient.

3) Do all local recurrences after surgery have the same adverse implications?

The TARGIT-A trial had already found that the chance of a patient remaining free of local recurrence with TARGIT-IORT or EBRT were just the same. The new analysis confirmed the well-known poor prognosis (much higher risk of distant disease and death) of patients who develop a local recurrence after conventional whole breast radiotherapy. The good news was that those few patients who get a local recurrence after TARGIT-IORT, fare extremely well – their risk of distant disease or death is the same as those patients who don’t have a local recurrence.

4) Are deaths reduced by avoiding EBRT as well as by giving TARGIT-IORT?

In addition to avoiding scattered radiation from EBRT that can damage nearby vital organs such as the heart and the lungs, giving TARGIT-IORT during lumpectomy seems to have its own beneficial absopal (mean distant, away from the surgical site) and immunomodulatory effect. This is because the TARGIT-IORT seems to protect against deaths from cardiovascular causes, lung problems and other cancers in a drug-like manner, even when EBRT is given. This new finding is corroborated by similar results at other parts of the body, opening the door to a new therapeutic avenue.

45,000 patients in 260 centres in 38 countries have already received TARGIT-IORT (https://doi.org/10.14324/000.wp.10121050). Many more patients should now be offered this effective, convenient, safer, cosmetically superior and less expensive treatment that is much preferred by patients.

Funding for the trial was provided by the National Institute for Health Research (NIHR) Health Technology Assessment programme, UCL Comprehensive Biomedical Research Centre, and Cancer Research UK. Read the blog post at https://cancercommunity.nature.com/posts/invasive-ductal-breast-cancer-targeted-intraoperative-radiotherapy-during-lumpectomy-is-better-for-patients-than-whole-breast-radiotherapy-whatever-the-tumour-subtype

Further reading: https://targit.org.uk/publications.

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