Single Radiotherapy Session for Breast Cancer an Option to Daily Postop Treatments

Two new studies revealed that targeted radiotherapy delivered to women undergoing surgery for early breast cancer could offer an effective alternative to current procedures.

Most women who undergo partial mastectomy (lumpectomy) surgery for breast cancer also complete a course of radiotherapy delivered to the whole of the affected breast. EBRT has been shown to cut the risk of cancer recurring in the breast, but can cause disagreeable side effects, and requires women to attend radiotherapy centers for 20–30 days after surgery, which can cause problems for women who live far away from radiotherapy centers, especially those in very rural or remote areas. In some cases, women who are qualified for lumpectomy may end up undergoing full mastectomy, simply because they cannot meet the demands of ensuing radiotherapy treatment required by partial tissue removal.

Women who undergo lumpectomy are at risk of the cancer recurring, typically either at, or near, the site of the original tumor if they do not choose to have radiotherapy treatment. This has led several groups of researchers to assess whether a single dose of radiation, specifically targeted to the tumor area, and delivered during or right after surgery, might offer a practical alternative treatment to reduce the risk of recurrence. Two articles published November 11, 2013, in the Lancet and the Lancet Oncology revealed new findings from two trials evaluating two different methods of delivering targeted radiation in this way.

In the Lancet article, an international team of researchers led by Prof. Michael Baum and Prof. Jayant Vaidya, from the University College London (UK), explored the performance of TARGIT (where radiation is delivered to the tumor site using a miniature X-ray emitting device) compared with a standard EBRT course of daily doses for three to six weeks. Over 12 years, 1,721 women received the study treatment (TARGIT), compared to a control group of 1,730 women who received standard EBRT treatment. The TARGIT technique was originally developed by Prof. Michael Baum, Prof. Jayant Vaidya, and Prof. Jeffrey Tobias, and has been assessed in 33 different centers since 1998.

The 3,451 patients who participated in the final analysis were comprised from two separate strata, equivalent to two trials run in parallel. The first included 2,298 patients, 1,140 of whom received TARGIT at the same time of the initial surgery. These participants were compared with 1,158 patients receiving conventional EBRT. However, after receiving requests from some clinicians, they extended the trial to include 1,143 women, 562 of whom were allocated EBRT, and 581 of whom were assigned to receive TARGIT as a second procedure a median of 37 days after surgery (postpathology stratum).

The trial was intended to portray real-life practice as far as possible, so women who had received TARGIT at the time of surgery but were subsequently shown to carry high-risk features for recurrence also received EBRT. Overall, about 80% patients in the TARGIT group completed their surgery and radiotherapy under a single anesthetic agent, without needing any additional EBRT.

The researchers specified at the outset that if the difference in five-year local recurrence between the two treatments was less than 2.5% then TARGIT should be considered “non-inferior” (as good as) standard radiotherapy. Across all trial participants, the difference in five-year risk for cancer coming back in the breast (local recurrence) was within the originally set limit of 2.5%, meaning that a single TARGIT treatment was “non-inferior” to EBRT in controlling cancer. Furthermore, the overall mortality was 3.9% with TARGIT and 5.3% with EBRT, due to significantly fewer deaths from cardiovascular causes and other cancers. When TARGIT was given at the same time as lumpectomy, as the researchers originally planned, the local recurrence and breast cancer deaths were similar in the TARGIT and EBRT groups, and deaths from other causes were significantly reduced with TARGIT (1.3% for TARGIT vs. 4.4% for EBRT).

Researchers who authored the Lancet Oncology article led by Prof. Umberto Veronesi of the European Institute of Oncology (Milan, Italy; www.ieo.it), reported findings from a trial of a slightly different way of delivering targeted radiation using a device that generates electron radiation to the tumor site (electron intraoperative radiotherapy [ELIOT]). Six hundred and fifty-one women attending the European Institute of Oncology in Milan, Italy for early breast cancer treatment received ELIOT during lumpectomy surgery, and a control group of 654 women received standard EBRT after lumpectomy.

The researchers differentiated between true local recurrence of breast cancer, and recurrence of cancer in the same breast that had been operated on (ipsilateral recurrence). In both instances, after five years, recurrence was significantly higher in the ELIOT group than the control group: 21 women (2.5%) in the ELIOT group experienced local recurrence, rising to 35 women (4.4%) when any ipsilateral recurrence was included, compared to just four women (0.4%) in the control group who experienced any recurrence.

Overall survival at five years, in spite of the different rates of breast cancer recurrence, did not differ significantly between the ELIOT and control groups (34 deaths in ELIOT vs. 31 deaths in the control group); there were no substantial disparities between the number of deaths caused by breast cancer, or due to any other cause.

For the patients in the ELIOT group, the researchers examined the characteristics of tumors where relapse occurred, allowing them to identify several features tied to recurrence, including large tumor (> 2 cm), and estrogen-receptor negative (ER-negative).

Prof. David Azria and Dr. Claire Lemanski of the Institut du Cancer Montpellier (France), writing in an editorial comment on both studies, suggested that although it is clear that additional study will be needed to identify the patients least apt to experience recurrence of cancer after undergoing surgery and intraoperative radiotherapy, “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.”

Related Links:
University College London
European Institute of Oncology