The rationale for the use of segmental radiation therapy in place of whole-breast irradiation is based on the finding that approximately 85% of breast relapses are confined to the same quadrant of the breast as the primary tumor (1). Tumoral foci are usually near the primary tumor, and residual microscopic disease occurring in the same quadrant as the resection is often the cause of local disease recurrence. Phase I and II trials have demonstrated that single-dose intraoperative radiotherapy (IORT) for localized breast cancers can be applied without increasing the normal rate of complications after surgery. Other studies with brachytherapy with longer follow-up demonstrated that partial radiation therapy can be performed safely with good local control and good cosmesis in selected patients.

The ability to deliver a single therapeutic dose of radiation to the tumor bed during surgery or within 5 days after surgery, thereby avoiding the standard 5- to 6-week external-beam treatment, may benefit patients through alleviating psychological distress, allowing earlier return to normal life, and reducing related expenses, including the cost of the procedure and other indirectly associated expenses.

Shortening the course of radiotherapy from the standard 6-week regimen to a single-dose intraoperative technique lowers costs and allows more convenience for patients. It also increases compliance to 100% and eliminates the attrition rate during standard radiotherapy because of side effects or logistical difficulties in traveling to the radiation facility (1). It may allow more breast conservation in rural geographic areas where radiation facilities or transportation are not readily available and where many women must undergo mastectomy because of these secondary issues.

Precisely targeting therapy to the lumpectomy cavity with IORT also directs radiation to the site most likely to need therapy and spares the brachial plexus, heart, and lungs. It avoids an incorrectly directed boost of standard radiotherapy because of lack of clips or seroma to define the lumpectomy cavity accurately. Benda et al. (2) showed discrepancies between radiation oncologists in planning cavity boosts, with variation in targets of more than 1 cm. Radiation to the skin is also reduced by shielding and may be associated with improved cosmesis and possibly elimination of radiation-induced angiosarcoma.

When radiation is delayed because of timing around chemotherapy, there is evidence to suggest increased local failure (3). Although data are conflicting, irradiating immediately renders arguments for or against giving chemotherapy first moot.

Partial radiation therapy has been tested in several clinical phase I and II studies and is currently under investigation for phase III in a major nationwide National Surgical Adjuvant Breast and Bowel Project – Radiation Therapy Oncology Group (NSABP-RTOG) study randomizing breast cancer patients submitted to conservative surgery to receive conventional whole-breast external-beam radiation therapy or partial radiation therapy in the form of three-dimensional (3D) conformal external beam, brachytherapy with MammoSite or brachytherapy with iridium implants. Other trials in Europe such as the Electron Intraoperative radioTherapy (ELIOT) trial and TARGeted Intraoperative radioTherapy (TARGIT) trial are studying the delivery of partial radiation therapy during surgery, immediately after quadrantectomy, or lumpectomy.

As part of the TARGIT trial, criteria for IORT are defined as age greater than 40 years and unicentric invasive breast cancer less than 3 cm in size treatable by lumpectomy (5). The European Institute of Oncology trial limits participants to patients older than 48 years with unifocal small invasive cancer (maximum tumor diameter 2.5 cm).

Because IORT is still considered an experimental treatment for breast cancer, it has been limited outside of trials in use to older patients with early-stage cancer or patients who are not candidates for standard whole-breast irradiation, such as those previously irradiated or those with severe comorbidities (6). It has also been evaluated as a boost dose with standard radiotherapy to the whole breast, although when this is decided on as the course of treatment, a longer interval of 5 to 6 weeks between IORT and standard radiotherapy seems to be associated with reduced morbidity compared with intervals shorter than 4 weeks (7). Another use of IORT is as a dose to the nipple–areolar complex after nipple-sparing mastectomy. A total of 800 patients receiving IORT were compared with 200 receiving standard radiotherapy to the nipple–areolar complex with no significant difference in outcome, even when a group with close margins was evaluated (8).

Patients with bilateral breast cancer, multifocal or multicentric breast cancer, clinically positive lymph node metastasis, or extensive ductal carcinoma in situ (DCIS) are not candidates for IORT. Exclusion criteria for standard radiation also apply, such as collagen vascular disease and pregnancy, although a preliminary dose analysis of potential fetal radiation exposure in Milan showed negligible delivery to the fetus (9).