Two new studies published in leading journals this week show how a "one-stop" targeted radiotherapy given during lumpectomy may offer some patients with early-stage breast cancer a viable alternative to current treatments. Experts say the approach looks promising but more research is needed to identify which patients are most likely to benefit.

Most women with breast cancer who undergo lumpectomy or partial mastectomy also undergo a course of radiation delivered to the whole of the affected breast.

While such treatment - called external beam radiotherapy, EBRT - reduces the risk of cancer coming back, it is not an easy undertaking and can cause unpleasant side effects. It takes weeks and requires regular attendance at centers that are not always easy to get to.

Such a prospect is sometimes the reason some women have a full mastectomy.

Faced with this rather unsatisfactory state of affairs, researchers have been investigating whether a single dose of radiation, given during or soon after surgery and specifically targeted at the site of the tumor, might offer a workable alternative.

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

The TARGIT-A trial

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

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

Across both groups of women, the difference in the 5-year risk of the cancer returning in the breast was under 2.5%, indicating that a single TARGIT treatment was no less effective than EBRT in controlling cancer.

Also, 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, mainly because of significantly fewer deaths due to other cancers and cardiovascular conditions.

When the researchers restricted their analysis to include only 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, but deaths from other causes were significantly 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, says the most important benefit of TARGIT for women with breast cancer is they can have their complete radiotherapy treatment at the same time as their lumpectomy, with lower toxicity to the breast, the heart and other organs, adding that:

"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."

The ELIOT trial

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 stands for electron intraoperative radiotherapy, emits electron radiation to the tumor site.

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

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

However, despite this, the overall survival at 5 years did not differ significantly between the ELIOT and control group (34 deaths versus 31 deaths respectively). And there were no significant differences in deaths due to breast cancer or to any other causes.

In this study, the researchers also analyzed the tumors of women whose cancer returned and found tumor size (over 2 cm) and estrogen-receptor negative (ER-negative) were among the features most likely to be linked to recurrence.

Study leader Prof. Umberto Veronesi, of the European Institute of Oncology in Milan, says:

"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."

He goes on to explain that 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 says it is also encouraging that after 5 years, deaths in the ELIOT and standard treatment groups were no different.

Prof. Veronesi concludes that advances like the one they tested should help improve quality of life for patients, and he hopes their findings will help clinicians make better use of all the available medical information to help identify the patients most likely to benefit from the treatment.

Experts say more research needed

In an accompanying comment on both studies, Prof. David Azria and Dr. Claire Lemanski, of the Institut du Cancer Montpellier in France, say more research is now needed to find out which patients are least likely to experience a return of their breast cancer after receiving radiation therapy at the time of surgery, adding:

"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."