Breast Cancer RT during Surgery May Assuage Treatment

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Two recent studies reveal how a “one-stop” concentrated radiotherapy administered during lumpectomy may give some patients with early stage breast cancer a feasible option to existing treatments. Researchers say the method shows promise, however they reason that further research is required to identify which patients will be the benefactors of this new alternative.

Most women with breast cancer who receive lumpectomy or partial mastectomy also receive a dose of radiation distributed to the whole of the affected breast.

This sort of treatment, known as external beam radiotherapy (EBRT), diminishes the risk of cancer recurring, however it is not a simple treatment and can have serious side effects. It also takes weeks and requires frequent attendance for it to achieve results. This is why some women prefer to have full mastectomy.

Met by an insufficient state of affairs, researchers have been exploring whether a single dose of radiation, administered during or soon after surgery and specifically targeted at the site of the tumor, might provide a viable alternative.

The two studies, one published in The Lancet and the other in The Lancet Oncology, detail the results of two trials (TARGIT-A and ELIOT), each assessing a different manner of delivering such targeted radiation.

In the TARGIT-A trial, a large international team of researchers compared TARGIT with a traditional EBRT course. The TARGIT method employed a small X-ray machine to administer targeted radiation to the tumor site once only during lumpectomy or about a month later, while the EBRT course consisted of daily doses of radiotherapy for between 3 and 6 weeks.

Spanning all 12 years of the trial, over 1,700 women experienced TARGIT, and another similar-sized group experienced standard EBRT at over 30 centers.

From both groups of women, the difference in the 5-year risk of recurring cancer fell under 2.5%, highlighting that a single TARGIT treatment was no less effective than EBRT in controlling cancer.

Additionally, the overall rate of death (number of patients who died within the 5-year period) was 3.9% with TARGIT and 5.3% with EBRT, mostly because of considerably fewer deaths due to other cancers and cardiovascular conditions.

When the researchers limited their analysis to only include comparison of TARGIT given during surgery against EBRT, the local recurrence of breast cancer and deaths due to breast cancer were the same in both groups, yet deaths from other causes were considerably lower in the TARGIT group than the EBRT group (1.3% versus 4.4%, respectively).

One of the study leaders, Prof. Jayant Vaidya of University College London, UK, said the most significant advantage of TARGIT for women with breast cancer is they can have their complete radiotherapy treatment in conjunction with lumpectomy, with lower toxicity to the breast, the heart and other organs.

"Our research supports the use of TARGIT concurrent with lumpectomy, provided patients are selected carefully, and should allow patients and their clinicians to make a more informed choice about individualizing their treatment, saving time, money, breasts and lives,” she said.

In The ELIOT trial, published in The Lancet Oncology, a group of researchers in Italy tested a slightly different targeted radiotherapy. Unlike TARGIT where X-rays are used, ELIOT, which is an abbreviation for electron intraoperative radiotherapy, emits electron radiation to the tumor site.

The participants were tallied to just over 1,300 women attending the European Institute of Oncology in Milan for early breast cancer treatment, half of whom underwent ELIOT during lumpectomy surgery, and the other half, the controls, underwent traditional EBRT following lumpectomy.

The results revealed that cancer recurrence in the affected breast was notably higher in the ELIOT group than in the controls. This was the case regardless of whether the researchers classed recurrence as either to the tumor site or anywhere in the affected breast.

However, in spite of all this, the overall survival at 5 years did not greatly differ between the ELIOT and control group; 34 deaths as opposed to 31 deaths respectively. Moreover, there was no considerable difference in deaths caused by breast cancer or by any other causes.

For this study, the researchers also analyzed the tumors of women whose cancer returned and discovered tumor size (over 2 cm) and estrogen-receptor negative (ER-negative) were among the factors most likely to be responsible for recurrence.

"For women who receive intraoperative radiotherapy, identifying the features most commonly associated with recurrence of cancer in the breast that has been operated on will allow us to identify the patients most likely to benefit from subsequent external radiotherapy,” said study leader Prof. Umberto Veronesi, of the European Institute of Oncology in Milan.

“While the rates of local recurrence were much higher in the women who received ELIOT, for some women, the benefits of not having to undergo weeks of radiotherapy outweigh a higher risk of the cancer returning,” he explained.

He also notes that it is encouraging to see no real differences between the ELIOT and standard treatment group in terms of deaths; and concludes that such improvements should work to improve the quality of life for patients, in addition to helping physicians make better use of all the available medical information to help identify the patients most likely to benefit from the treatment.

In an accompanying comment on both studies, Prof. David Azria and Dr. Claire Lemanski, of the Institut du Cancer Montpellier in France, believe further research is required in order to discover which patients are least likely to suffer breast cancer recurrence following radiation therapy at the time of surgery.

"The new data from TARGIT-A and ELIOT reinforce our conviction that intraoperative radiotherapy during breast-conserving surgery is a reliable alternative to conventional postoperative fractionated irradiation, but only in a carefully selected population at very low risk of local recurrence,” they said.

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