Intraoperative Radiation Therapy in Breast Cancer: Still Not Ready for Prime Time.

Breast conserving therapy remains one of the most important advances in cancer management in the past century, with multiple trials demonstrating its equivalence to mastectomy with respect to long term cancer outcomes. Unfortunately, studies have documented that adjuvant radiation therapy, a critical component of breast conserving therapy, remains under utilized. Data suggest that treatment duration (5–6.5 weeks) can frequently be attributed to this finding. In light of this and secondary to the increasing costs associated with breast cancer radiation therapy, shortened courses of radiation therapy have been explored including both hypofractionated whole breast irradiation (WBI) and accelerated partial breast irradiation (APBI) that shorten treatment duration to three and one week, respectively. Prospective randomized trials evaluating these techniques have been promising, demonstrating equivalence to traditional WBI with respect to clinical outcomes, toxicities, and breast cosmesis. Intraoperative radiation therapy (IORT) represents an alternative to these techniques that delivers treatment at the time of surgery as a single fraction of radiation (in the majority of cases). Increasingly, IORT is being offered to women with early-stage breast cancer as the definitive radiation therapy modality following breast conserving surgery. What is concerning is that these patients are being offered this, as yet, unproven therapy off-protocol with insufficient data to support its safety and efficacy compared with WBI or alternative techniques (APBI or hypofractionated WBI). This is unfortunate as radiation therapy in breast cancer represents an area of research that has undergone progress in the past five decades through systematic evidence-based treatment paradigm evolution; breast conserving therapy was verified via multiple randomized trials demonstrating comparable outcomes to mastectomy, and postmastectomy radiation therapy similarly demonstrated a survival benefit in several trials before wide-scale incorporation into treatment paradigms. Therefore, the rapid introduction of IORT is concerning as these steps have not been taken prior to wide-scale utilization, leading to a potential for higher rates of local recurrence or increased toxicity. It should be noted that two large randomized trials have been performed to evaluate the role of IORT in early-stage breast cancer compared with WBI, the current standard of care. The targeted intraoperative radiotherapy (TARGIT) trial was a randomized noninferiority trial that included 3,451 women enrolled in 10 countries between 2000 and 2012. Patients were randomized to IORT (delivered at the same time as surgery or as a separate procedure) or WBI; however, 21 % of the prepathology IORT patients received WBI because of predefined factors including lobular carcinoma in situ, extensive intraductal component, lymphovascular space invasion, node positivity, or other factors specific to each institution. IORT was delivered using a 50-kv X-ray source to deliver 20 Gy to the surface of the excision cavity (5 Gy at 1 cm). While initial data with short follow-up (median follow-up \2 years) and limited events (n = 11) was promising, a recent update found that IORT, even with WBI supplementation in one-fifth of the Society of Surgical Oncology 2013