The Lynx Group

Intraoperative Radiotherapy Fares Well Against EBRT

March 2013, Highlights

Low-dose intraoperative radiation therapy has proved comparable with whole-breast irradiation for preventing breast cancer recurrence, according to the preliminary results of the large randomized Targeted Intraoperative Radiotherapy (TARGIT-A) trial.

After a median follow-up of 29 months, the estimated 5-year absolute difference in relapses is 2.0% in favor of whole-breast irradiation. Although this numerically favors whole-breast irradiation, the difference is still within the 2.5% margin established for noninferiority.

In addition, a trend toward lower mortality has emerged in the intraoperative radiotherapy arm, driven by significantly lower non–breast cancer mortality, reported Jayant S. Vaidya, MBBS, MS, DNB, PhD, FRCS, a leader in breast surgery and oncology and a Consultant Surgeon at the Whittington, Royal Free, and University College London hospitals.

“The locoregional recurrence is mainly driven by ipsilateral breast recurrence, and it is not seen in the largest subgroup of prepathology, PgR [progesterone receptor]-positive cases,” said Dr Vaidya. “Similarly, all recurrence is driven by ipsilateral breast recurrence, and there is no difference in the largest subgroup of prepathology PgR-positive patients. We saw no difference in the rate of distant recurrence.”

Dr Vaidya noted that primary breast cancer often develops in a multicentric manner, but recurrence is most often ipsilateral. As a result, focusing radiation therapy on the primary tumor site is a logical strategy, giving rise to the TARGIT-A protocol, which was developed at University College London.

The rationale for the approach is further supported by evidence from 2008 that irradiation of the wound bed inhibits proliferation, motility, and invasiveness that can be stimulated by wound fluid.

Using a portable radiation therapy machine, clinicians deliver an approximate 20-Gy dose directly to the wound bed after surgical excision. Patients with high-risk features receive supplemental external beam radiation therapy (EBRT).

The TARGIT-A Trial

Dr Vaidya reported findings from the ongoing TARGIT-A randomized trial comparing intraoperative radiotherapy and EBRT. The study population consists of 2020 women (aged ≥45 years) with unifocal early invasive breast cancer (preferably <3.5 cm). All patients had a median follow-up of 4 years (5 years for 1222 patients).

Preliminary results showed a 2.05 hazard ratio (HR) for recurrence for TARGIT versus for EBRT (P = .042).

A planned analysis of data stratified by hormone receptor status showed that the difference in recurrence rate owed primarily to the increased loco­regional recurrence in patients with PgR-negative tumors and to delayed delivery of TARGIT (necessitating reopening of the wound cavity).

An analysis limited to the women with the PgR-positive tumors who received TARGIT as planned produced a between-group difference of 0.18% compared with the EBRT group.

In addition to recurrences, 88 deaths have occurred in the 2 treatment groups. The overall analysis yielded an HR of 0.70 in favor of TARGIT, representing a trend toward lower mortality. The estimated 5-year non–breast cancer mortality was 1.4% for the TARGIT group versus 3.5% in the EBRT group, which translated into a 53% reduction in the hazard in favor of TARGIT.

With regard to applying TARGIT in clinical practice, Dr Vaidya emphasized careful patient selection.

“Patients should fulfill the eligibility criteria for the TARGIT-A trial,” Dr Vaidya said. “The preferred treatment option is concurrent TARGIT [at the time of surgery] in progesterone receptor–positive patients. Add external beam radiotherapy if adverse prognostic factors are present.”

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