TARGITed.

Top Line: What’s all the fuss about the updated results of intra-operative radiation (IORT) in TARGIT-A?

The Commentary: If you read the recent publications of 5-year outcomes from the TARGIT-A trial, you might have wondered, “why aren’t more people doing this?” And if you read some of the recent commentary (here, here, here, and here), you probably thought, “that escalated quickly.” TARGIT-A has a troubled past that may have unfortunately tainted everyone’s view of the true merits of the trial. As a reminder, TARGIT-A randomized women to intra-operative radiation therapy versus standard external beam radiation. Roughly two-thirds were randomized at the time of lumpectomy (pre-pathology) while the rest were randomized after lumpectomy (post-pathology). Things turned sour when, with just 2.4 years median follow-up, the authors concluded—some say prematurely—that 5-year local recurrence was non-inferior with IORT. With that same short follow-up, they also touted a reduced risk of non-breast cancer mortality. These results were met with significant international statistical criticism, which included a letter from the former chair of the data monitoring committee. The most recent results with actual 5-year follow-up showed non-inferior local recurrence with IORT in the pre-pathology cohort (2.1 with IORT vs 0.9%), while the results from the post-pathology arm showed that IORT was not non-inferior (4 vs 1%).

TBL: Despite showing a relatively low rate of recurrence with IORT, TARGIT-A shows how the loss of perceived objectivity by the academic community can permanently affect the interpretation of trial results. | Shah, Bentzen, Fastener, and Vaidya, JAMA Oncol 2020