From the Journals

One-off blast of RT, rather than weeks, for early breast cancer


Controversy of Earlier Results

Vaidya and colleagues comment that these new results confirm earlier findings from this trial. They were initially presented in 2012 by Vaidya at the San Antonio Breast Cancer Symposium and subsequently published in The Lancet, as previously reported by Medscape Medical News. Those earlier results showed a trend toward lower overall mortality with TARGIT (absolute difference, -1.3%; P = .01) and significantly fewer deaths from causes other than breast cancer (absolute difference, -2.1%; P = .009).

However, TARGIT was associated with slightly more same-breast recurrences at that time (3.3% vs 1.3%; P = 0.42), even though this was still within the 2.5% margin for non-inferiority.

The new longer-term results show a similar pattern.

It was this risk of same-breast recurrences that sparked the heated debate over the findings, as some breast cancer experts argued that this needs to be weighed against various potential benefits of IORT for patients: greater convenience, potentially improved mortality, and lower costs.

The extent of that “vigorous debate” was highlighted in 2015 in the International Journal of Radiation Oncology, Biology, Physics, (the Red Journal), in which editor-in-chief Anthony Zietman, MD, shared numerous letters to the editor, written in response to two editorials, that contained “passionately and articulately expressed” views from “senior investigators and breast cancer physicians from around the globe.”

At the same time, in 2015, another approach to IORT was reported at the American Society for Radiation Oncology (ASTRO) annual meeting and simultaneously published online in The Lancet. This was accelerated partial-breast irradiation (APBI) delivered directly to the tumor bed using multicatheter brachytherapy at the time of lumpectomy in women with early breast cancer. The results showed outcomes that were comparable with whole-breast irradiation, but with fewer side effects.

Those findings prompted a 2016 update to the ASTRO consensus statement on APBI to note that APBI after lumpectomy may be suitable for more women with early-stage breast cancer, including younger patients and those with ductal carcinoma in situ.

In comments to Medscape Medical News, Jimenez noted that several recent studies have shown efficacy for various IORT approaches. There have been two phase 3 non-inferiority studies, namely the NSABP B-39 and the RAPID trial, that evaluate the use of APBI in lieu of whole-breast radiation. There have also been two trials as well as the evaluation of a 5-day ultrahypofractionated whole-breast radiation course per the UK Fast and Fast-Forward trials, compared with several weeks of whole-breast radiation.

“Collectively, these studies lend support for fewer and/or more targeted radiotherapy treatments for our patients and have the potential to reduce patient burden and limit healthcare costs,” Jimenez told Medscape Medical News.

Indeed, the TARGIT-A researchers write that their long-term findings “have shown that risk-adapted single-dose TARGIT-IORT given during lumpectomy can effectively replace the mandatory use of several weeks of daily postoperative whole-breast radiotherapy in patients with breast cancer undergoing breast conservation.”

Given the numerous benefits to patients that this approach provides, the choice should ultimately rest with the patient, the authors conclude.

An extended follow-up of the trial (TARGIT-Ex) is ongoing, as is the TARGIT-B(oost) trial looking at TARGIT-IORT as a tumor bed boost with EBRT boost in younger women and those with higher-risk disease.

The TARGIT-A trial was sponsored by University College London Hospitals (UCLH) Comprehensive Biomedical Research Centre and funded by UCLH Charities, the National Institute for Health Research Health Technology Assessment program, Ninewells Cancer Campaign, the National Health and Medical Research Council, and the German Federal Ministry of Education and Research. The authors reported numerous disclosures, as detailed in the publication.

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