While certainly very convenient for patients, delivery of the entire course of therapy in a single dose raises concerns regarding accuracy of the RT delivery, tumor control, and normal tissue toxicity. When IORT is delivered after the tumor has been excised and normal breast tissue re-approximated, it is theoretically more difficult to define the target volume for the radiation oncology team.This uncertainty may be compensated by irradiating a wider margin of surrounding breast tissue. With the authors’ technique of irradiating the tumor in situ,²⁵ they precisely calculated the target volume by preoperative ultrasound, which allowed them to select the appropriate cone size and electron energy, as well as the incision site and cone angle, for each tumor individually prior to skin incision.The skin is then retracted to expose the undisturbed tumor bed and tumor and a smaller margin of surrounding breast tissue are treated.However, a potential drawback to the authors’ approach is the smaller treatment volume.The optimal dose for IORT is not known. Veronesi et al. found 21Gy to be welltolerated after a dose-escalation study. However, a single dose of 15Gy is estimated to be biologically equivalent to standard dose and fractionation (25 treatments of 50Gy) for breast cancer.^26–29

The lower dose and smaller volume may result in better cosmesis, but it may also result in increased risk of local recurrence, an issue that the authors are studying. For this reason, they have carefully chosen criteria, including age, that must be satisfied for delivery of IORT as sole treatment; disease not meeting these restrictions requires additional EBRT per protocol. With short-term follow-up, the initial analysis of toxicity and feasibility of the authors’ in situ IORT indicates that the technique is well-tolerated to date. The authors have had two cases of acute toxicity in 18 patients, one WB mastitis and one delayed wound healing. In either case, it is not certain that IORT was related to the complication. To date, the authors have seen no grade 3 or 4 subcutaneous toxicity in the 20 patients with >90 day follow-up.

In conclusion, the early results of single-fraction IORT, delivered either prior to or following partial mastectomy, seem encouraging. Acute toxicity and cosmetic result does not appear to be adversely affected by delivering RT at the same time as performing a partial mastectomy. While longer follow-up is awaited to determine actual tumor-bed recurrence rates, optimizing target volume and delivery and continued attention to acute and chronic toxicity must be primary goals for investigators. If successful, IORT could dramatically increase the number of women who choose breast-preserving therapy because of the convenience of surgical resection and tumor-bed RT in a single visit.