Letters Regarding the TARGIT-A Trial: The Editor's Introduction

Abstract

The first articles in the print edition of the International Journal of Radiation Oncology, Biology, Physics (the Red Journal) are usually its feature articles or editorials. It is unusual for us to choose to lead with correspondence. We have in this edition, however, broken with custom, and for good reason. All the correspondence we feature revolves around a single subject: the use of intraoperative radiation therapy in early-stage breast cancer. An early report from the TARGIT-A trial was published in The Lancet in 2014 and has, since that time, provoked vigorous debate (1Vaidya J.S. Wenz F. Bulsara M. et al.Risk-adapted targeted intraoperative radiotherapy versus whole-breast radiotherapy for breast cancer: 5-year results for local control and overall survival from the TARGIT-A randomised trial.Lancet. 2014; 383: 603-613Abstract Full Text Full Text PDF PubMed Scopus (612) Google Scholar). This debate was heightened by a recent exchange of editorials in this journal (2Hepel J. Wazer D.E. A flawed study should not define a new standard of care.Int J Radiat Oncol Biol Phys. 2015; 91: 255-257Abstract Full Text Full Text PDF PubMed Scopus (29) Google Scholar, 3Vaidya J.S. Bulsara M. Wenz F. et al.Pride, prejudice, or science: Attitudes towards the results of the TARGIT-A trial of targeted intraoperative radiation therapy for breast cancer.Int J Radiat Oncol Biol Phys. 2015; 92: 491-497Abstract Full Text Full Text PDF PubMed Scopus (49) Google Scholar). What we publish here are the unselected letters arising from that exchange. They come from senior investigators and breast cancer physicians from around the globe and are all passionately and articulately expressed. In the recent history of the Red Journal we have not seen such an exchange of polar opposite views, and we believe this results from the existential nature of the original TARGIT-A trial report. After decades of careful and progressive investigation into fractionated radiation therapy, women have been moved from a dark past of radical mastectomies into the modern era of breast conservation. TARGIT-A applauds that outcome but suggests there may be another way to achieve it. Many careers have been built around fractionated radiation therapy for breast cancer, and it comprises a substantial proportion of the practice of the average contemporary radiation oncologist. Depending on your perspective, intraoperative radiation therapy is thus either a very serious threat or a quantum leap forward. Data will ultimately resolve this debate as TARGIT-A matures and other studies are published, but for now it is, as you will read, “red hot.” The letters draw on 3 themes. The first is a scientific discussion of methodology that focuses on the advantages and pitfalls of noninferiority studies and the importance of mature follow-up. The second regards trial governance: how trials are organized, monitored, and overseen. The third is the interpretation of the data. It is in this latter category that the value, or otherwise, of intraoperative radiation therapy is in the eye of the beholder. There are some subjects for which the stakes are so high that scientific discourse can cross a line into irresolvable ideological or quasi-religious debate, and it is in this third category that we come closest to this. “My God is better than your God” is an irresolvable argument. In medicine, however, data and a common desire to benefit our patients should act as a compass to guide resolution. As you will read, both sides powerfully invoke the breast cancer patient to illuminate their case, and it will take a moral philosopher to separate them. We have chosen to highlight this correspondence in a fashion unprecedented for the Red Journal, to show how difficult it can be to interpret data from randomized studies. Those of you who have taken a side on this issue may have your positions challenged. Those of you who have not considered this issue would do well to do so. It is one substantial aspect of our practice that may, or may not, change dramatically in the very near future. The discussion also casts a very revealing light on our own behaviors and attitudes as physicians and scientists.