TARGIT-IORT in early breast cancer—real world evidence for a risk-adapted approach

Since the first publication of the TARGIT-A trial results (1) demonstrating very low recurrence rates and local control outcomes similar to external beam radiotherapy (EBRT), targeted intraoperative radiotherapy (TARGIT-IORT) has become a standard option in the treatment of early breast cancer. According to a survey published in 2022, almost 45,000 patients with breast cancer have been treated with TARGIT-IORT in 260 centers in 35 countries all over the world (2). TARGIT-IORT is used either as an anticipated intraoperative boost combined with EBRT in primary surgery (3) or after neoadjuvant therapy (4) or as a definitive intraoperative radiotherapy (IORT) replacing EBRT within the framework of breast conserving therapy (1).

Tan and colleagues reported real world evidence from Australia regarding the use of IORT using a 50-kV X-ray brachytherapy device delivering 20 Gray to the surface of the applicator as definitive radiotherapy in a risk-adapted approach. Whereas the question of whether different ways of application of intraoperative radiation really yield different results is far from being answered, the technique used by the authors is—although a brachytherapy approach—physically very similar to the TARGIT-IORT using the Intrabeam™ used by the TARGIT-A investigators. However, it has to be acknowledged that the Xoft™ device used by Tan et al. has not been used in prospective clinical trials.

What is more important regarding the question of comparability of the data reported by Tan and colleagues and the TARGIT-A trial is the risk-adapted approach. As in TARGIT-A, the authors planned IORT in patients with early breast cancer being candidates for breast conserving surgery based on risk factors known before surgery. If postoperative pathology revealed additional risk factors or a higher risk than anticipated—positive margins, node positivity, presence of lymphovascular invasion, higher grade or larger tumor size than previously thought—patients were scheduled for EBRT. In a 4 year follow up this strategy led to a local recurrence rate of 0.99% and a distant recurrence rate of 0.99% in a population of 101 patients (5). These data are indicating a very low risk of recurrence in this population and are in line (in fact even numerically lower) with the longer-term follow-up of the TARGIT-A trial (6) and with other real-world data published in the recent past (7).

Other trials investigating IORT, such as the ELIOT trial, have reported an up to ten-fold higher recurrence rate for IORT compared to EBRT (8). Although the excellent database has led to an inclusion of IORT in national and international guidelines (9), this striking difference has inhibited a global and general adoption of the technique. A closer look reveals a fundamental difference between the approaches that completely explains the different results. The radiation techniques used in the ELIOT trial (8) and in the TARGIT-A trial (1) are very different, but probably that is not what really makes the difference. Whereas the TARGIT-A trial as well as the study of Tan et al. and many other real-world datasets have used a risk-adapted approach, the ELIOT trial was designed as a strict 1:1 randomization irrespective of a postoperative risk assessment. The strict 1:1 design led to a reduced local control in the IORT arm, whereas the risk-adapted approach described above yielded a comparable local control compared to EBRT. This is completely in line with the paradigm that a one-size-fits-all approach is probably never a good idea in oncology. De-escalation strategies require a wise patient selection process in order to balance the primum nil nocere between efficacy and side effects. Keeping that in mind, it is not surprising that the risk-adapted indication of IORT—supplemented by EBRT if needed—as introduced by Vaidya and colleagues in the TARGIT-A trial is superior to a simple “IORT or EBRT” as practiced in the ELIOT trial.

The authors of “Retrospective analysis of intra-operative radiotherapy (IORT) in early breast cancer—an Australian institution experience” are to be congratulated, of course because of their excellent data but most of all because of the wisdom of choosing the risk-adapted approach as one of the first series with the Xoft™ device.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Translational Breast Cancer Research. The article has undergone external peer review.

Peer Review File: Available at https://tbcr.amegroups.com/article/view/10.21037/tbcr-25-25/prf

Funding: None.

Conflicts of Interest: The author has completed the ICMJE uniform disclosure form (available at https://tbcr.amegroups.com/article/view/10.21037/tbcr-25-25/coif). H.C.K. reports receiving payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Pfizer, Novartis, Roche, Genomic Health/Exact Sciences, Amgen, AstraZeneca, Riemser, Carl Zeiss Meditec, TEVA, Theraclion, Janssen-Cilag, GSK, LIV Pharma, Lilly, Daiichi Sankyo, Gilead, and Zuellig; support for attending meetings and/or travel from Carl Zeiss Meditec, LIV Pharma, Novartis, Amgen, Pfizer, Daiichi Sankyo, Tesaro, Gilead, AstraZeneca, Zuellig, and Stemline; participating on a Data Safety Monitoring Board or Advisory Board for Pfizer, Novartis, SurgVision, Carl Zeiss Meditec, Amgen, Onkowissen, MSD, Gilead, Daiichi Sankyo, Seagen, Genomic Health/Exact Sciences, Agendia, and Lilly; and holding stock from Theraclion SA. The author has no other conflicts to declare.

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References

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