For patients with breast cancer, intraoperative radiotherapy given at the time of lumpectomy was found to be “non-inferior” in five-year follow-up to the use of conventional postoperative whole-breast external-beam radiotherapy (EBRT) and had equivalent breast cancer-specific mortality but fewer non-cancer deaths. The results from that study, the randomized TARGIT-A trial conducted in Europe, North America, and Australia, are now available online ahead of print in The Lancet (doi.org/10.1016/S0140-673661950-9).
In an interview, the lead author, Jayant S. Vaidya, PhD, Professor of Surgery and Oncology at University College London, said he and his colleagues decided to use a “risk-adapted” strategy—meaning that about 15 percent of the patients allocated to receive TARGIT were also given supplementary external-beam radiation when high-risk features were revealed during surgery, rather than keeping strictly to the allocated protocol.
“Local control of breast cancer and breast cancer mortality are similar to those of whole breast radiotherapy, and there are significantly fewer deaths from other causes such as cardiovascular disease and other cancers,” he said.
The team concluded that TARGIT was a safe and effective alternative to post-surgery radiotherapy and that it could benefit patients by removing the need for repeat radiotherapy sessions and also reduce treatment costs.
For the study, a total of 3,451 patients with breast cancer were randomized at 33 centers in 11 countries to receive either single-dose TARGIT directly to the tissues immediately surrounding the tumor—using a spherical applicator for 20 to 30 minutes—or a standard surgical course of EBRT. In patients randomized before lumpectomy, TARGIT was given concurrently with surgery; while among patients randomized after their operation the wound was re-opened to administer TARGIT. In both situations the outcomes were substantially the same.
The study met the pre-specified primary outcome criterion for non-inferiority requiring any absolute difference in local recurrence to be less than 2.5 percent among the 1,222 patients followed out to a median of five years. The findings were that local recurrence in the conserved breast was 3.3 percent for TARGIT versus 1.3 percent for EBRT.
Vaidya said the advantage of using the targeted approach was that each patient's treatment was complete when she left the operating room: “We close the wound, and that's the end of it,” he explained.
The breast cancer mortality rate was 2.6 percent in patients receiving TARGIT and 1.9 percent among women treated with EBRT. But in the case of non-breast cancer deaths, TARGIT was significantly better: only 1.4 percent of these patients died as compared with 3.5 percent of patients receiving external radiotherapy. Overall mortality was also better for patients receiving TARGIT than in patients treated with EBRT—3.9 percent compared with 5.3 percent.
The coauthor of an accompanying editorial (doi:10.1016/S0140-673662304-1), David Azria, MD, PhD, from Val d'Aurelle Cancer Center in Montpellier, France, said the data confirm that TARGIT is a good option, but only in patients at low risk of recurrence: “The key message is to have an excellent selection of patients,” he said in an interview.
“All trials confirm that patients have to present with small tumors—less than two centimeters—patients have to be older than age 60, the grade of the tumor has to be low—grade I, sometimes grade II—and have positive hormonal expression. These are the four most important criteria.”
The senior author of the study, Michael Baum, MB, ChB, FRCS, Professor Emeritus of Surgery and Visiting Professor of Medical Humanities at University College London, said he thought that risk-adapted intraoperative radiotherapy was a welcome new addition—especially in busy radiotherapy centers where it could help efficiency and in resource-poor settings where multiple outpatient visits for radiotherapy are impractical.
“For women who meet the entry criteria as described in the TARGIT trial—and understanding that a minority of 15 percent may then need additional ‘top-up’ treatment—we can confidently say that this approach is no worse than whole breast irradiation. And when it comes to toxicity, tolerability, and cosmetic outcome it's a little better,” he said.
Vaidya concluded: “TARGIT's most important benefit is that it is so much more convenient for patients—they don't have to keep traveling for six weeks. For a busy cancer doctor it can free up resources for treating other cancers. It can also save money for a busy health care system.”
In a video interview with Peter Goodwin on the iPad edition of this issue, investigators Jayant S. Vaidya, PhD, and Michael Baum, MB, ChB, FRCS, elaborate on their findings and the clinical implications.
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