Intraoperative RT Misses 'TARGIT' But Emerges Strong

Neil Osterweil

December 07, 2012

SAN ANTONIO, Texas — Targeted intraoperative radiotherapy (TARGIT) for early breast cancer was associated with slightly more same-breast recurrences but fewer deaths not related to breast cancer than standard external-beam radiotherapy (EBRT). This finding comes from the TARGIT-A trial.

Jayant Sharad Vaidya, MD, a consultant surgeon at University College London, United Kingdom, presented the trial results here at the 35th Annual San Antonio Breast Cancer Symposium.

There were 2.01% more same-breast recurrences, the primary end point, in patients treated with TARGIT than in those treated with EBRT (P = .042).

For the secondary end point of mortality, TARGIT was associated with a trend toward lower overall mortality (absolute difference, –1.4%; P = .01) and there were significantly fewer deaths from causes other than breast cancer (absolute difference, –2.1%; P = .009).

There were 88 deaths during the 5 years of follow-up — 36 related to breast cancer and 52 not related to breast cancer. With TARGIT, there was no significant difference in overall mortality (hazard ratio [HR], 0.70; P = .099) or breast cancer deaths (HR, 0.96; P = .56). However, the 5-year risk for death from causes other than breast cancer was lower with TARGIT than with EBRT (1.4% vs 3.5%; HR, 0.47; = .009).

"We believe that these data will significantly improve the...individualization of local treatment for breast cancer," Dr. Vaidya said.

The documented adverse effects of ionizing radiation might have led to the excess deaths with EBRT, Matthew P. Goetz, MD, associate professor of oncology and pharmacology at the Mayo Clinic in Rochester, Minnesota, told Medscape Medical News.

"We know from data that radiation can increase the risk of nonbreast-cancer-related deaths, and clearly there are data [related to] cardiac deaths. It was not surprising to see that; what was surprising was to see it in a relatively small study, and relatively early on," Dr. Goetz said.

The study demonstrates that it is possible to treat relatively low-risk patients without significantly increasing their risk for death from cardiovascular or other noncancer causes, he explained.

Dr. Goetz moderated the session at which the data were presented, but was not involved in the study.

The TARGIT technique involves a mobile electron generator and accelerator that can be wheeled into an operating room. The radiation is delivered by a spherical-tip applicator that is inserted into the surgical wound. It delivers 20 Gy to the tumor bed and 5 Gy at a distance of 5 mm to give a uniform dose to the tissues at highest risk.

Risk-Adapted Strategy

Investigators from 33 centers in Australia, Europe, and the United States enrolled 3451 women older than 45 years with unifocal invasive ductal carcinoma (most tumors were smaller than 3.5 cm). The women were randomized to receive either standard fractionated EBRT or risk-adapted radiotherapy with a single dose of TARGIT.

With the risk-adapted strategy, women who received TARGIT and were found postoperatively to have high-risk factors were strongly encouraged to receive additional EBRT. About 15% of women received both forms of radiation.

There were 34 cases of ipsilateral breast recurrence; these occurred slightly but significantly more often in the TARGIT group. Nonetheless, the absolute difference of 2.01% fell within the prespecified boundary for noninferiority of TARGIT (2.5%), Dr. Vaidya said.

Prespecified subgroups consisted of patients randomized to TARGIT before lumpectomy who received radiation and surgery in a single session, and those randomized after lumpectomy who received TARGIT in a separate procedure (delayed TARGIT). The investigators looked at progesterone-receptor (PgR) status as a surrogate for hormone sensitivity.

Most of the difference in ipsilateral breast recurrence was accounted for by PgR-negative patients (studies have suggested they are less sensitive to radiation) and by patients in the delayed TARGIT group.

An independent assessor determined that the decrease in deaths not related to breast cancer with TARGIT was driven by the few cardiovascular events and the few deaths from other cancers.

Dr. Vaidya said that the preferred option is to use TARGIT concurrently with lumpectomy in PgR-positive patients, with the subsequent addition of EBRT if prognostic factors not detected before surgery are present. Those factors include previously undetected lobular cancers, positive tumor margins, and the presence of extensive intraductal components.

The study was supported by the UK National Health Service. Dr. Vaidya and Dr. Goetz have disclosed no relevant financial relationships.

35th Annual San Antonio Breast Cancer Symposium (SABCS): Abstract S4-2. Presented December 6, 2012.