Same-Day Breast Cancer Surgery and TARGIT-IORT: Better than Selective Omission of Radiotherapy?

Abstract

Results of the TARGIT-R (retrospective) multi-institutional study on intraoperative radiation therapy (IORT) have been eagerly awaited and are now published in this issue of Annals of Surgical Oncology. 1 In this case series comprising 667 patients, IORT was delivered using the Intrabeam system (low-kilovoltage X-rays; Carl Zeiss, Oberkochen, Germany) between 2007 and 2013 at 12 North American institutions with active breast cancer programs. The aim of this study was to provide real-world evidence on outcomes of Intrabeam IORT in order to supplement the results of the TARGIT-A randomized clinical trial. Results of the TARGIT-A trial have generated considerable controversy, given small but possibly significant differences in local control between IORT versus whole-breast radiation and concerns that IORT target volumes were too small and IORT radiation doses were too low. 4 The need for real-world evidence regarding the effectiveness of IORT was underscored by the 2017 update to the American Society for Radiation Oncology (ASTRO) guideline on partial breast irradiation, which recommended that Intrabeam IORT should be used within the context of a prospective registry or clinical trial. 5 The authors of the TARGIT-R trial are therefore to be commended for heeding this call and for providing this important evidence to help foster a greater understanding regarding the real-world effectiveness of Intrabeam within current practice in the US. The current report includes 667 patients, and it is notable that it includes only 71% of the originally reported patient cohort. 6 Of greatest interest in the current manuscript is the subgroup of 477 patients treated with primary IORT, defined as IORT delivered at the time of segmental mastectomy without additional whole-breast irradiation. In this cohort, median age was 68 years, 94% of tumors were estrogen receptor-positive, 3% were lymph node-positive, and only 15% of tumors were high-grade. Due to these overall favorable characteristics, one would assume that the anticipated risks of in-breast tumor recurrence (IBTR) within 5 years would generally be similar to other clinical trials that enrolled a low-risk patient population. For example, both the PRIME II and CALGB 9343 trials enrolled low-risk patient populations and reported a 5-year IBTR risk of 4% in patients treated with endocrine therapy alone, compared with 1% in patients treated with endocrine therapy and whole-breast irradiation. ,8 Based on the results of these clinical trials, coupled with the low-risk nature of the population treated with primary IORT on the TARGITR study, we expected that the risk of IBTR in the TARGITR study would be\\ 4% and approach 1% at 5 years. However, to our surprise, the 5-year risk of IBTR in the primary IORT cohort of TARGIT-R was 8% (95% confidence interval 5.0–10.3%; n = 42 of 477 patients). Even when the authors selected subsets of the primary IORT cohort limited to patients who met criteria established by modern partial breast irradiation guidelines, 5-year IBTR rates ranged from 7.0 to 9.1%, suggesting that more stringent selection criteria would be unlikely to meaningfully reduce the 5-year risk of IBTR following primary IORT reported herein. The authors also noted that noncompliance with endocrine therapy was associated with a higher IBTR risk (hazard ratio 3.67), which is consistent with the conventional wisdom that adjuvant endocrine Society of Surgical Oncology 2021