In order to reduce treatment costs and increase utility of radiotherapy, hypofractionated whole breast irradiation (HWBI) and accelerated partial breast irradiation (APBI) were developed. HWBI decreases the duration of whole breast radiation therapy to 3–4 weeks. However, patients are still faced with quality-of-life difficulties associated with multiple repeat visits over a long time period. APBI is radically different in that only the surgical bed, rather than the whole breast, is targeted for irradiation. Treating smaller volumes allows safe delivery of higher doses of radiation per treatment, obtaining the same biologic effectiveness in only 1–5 days [9–13]. Early results of several large prospective phase III trials comparing APBI with whole breast irradiation demonstrated similar outcomes, supporting the hypothesis that for select patients [9, 14, 15], whole breast irradiation may not be necessary. In NSABP B-39, the largest phase III trial comparing whole breast radiation and APBI, APBI can be delivered using invasive approaches via various brachytherapy applications or 3D conformal RT (3D-CRT). On this study, more than 70 % of patients randomized to APBI are treated using 3D-CRT as compared with brachytherapy, even though 3D-CRT treats a volume approximately 5× larger than the brachytherapy techniques [16]. This larger volume irradiated leads to a concern that 3D-CRT could result in a higher rate of subcutaneous fibrosis [17] and unacceptable cosmesis [18, 19], as volume is one of the most important predictors of morbidity [20]. Yet many patients choose to receive 3D-CRT instead of brachytherapy because of the distinct advantage of being completely noninvasive.

Over the last 30 years, advances in immobilization, computer-based treatment planning and delivery, and image guidance have revolutionized the ways in which small tumors are treated with RT. Stereotactic radiosurgery (SRS) was introduced in 1968 as a tool for noninvasive neurosurgery but was not widely adopted until 3D imaging became available. The pinpoint accuracy and high dose concentration achievable with SRS allow safe delivery of “ablative” doses of radiation. SRS has been a success story for patients with brain metastases by improving local control, quality of life, and survival [21]. Its success has hinged on minimizing the volume of normal tissue receiving a “significant” dose of radiation while maximizing dose to the tumor.

SRS outside the brain, called stereotactic body RT (SBRT), has been more challenging [22]. Unlike intracranial targets that do not move in reference to a rigid stereotactic head frame, targets located outside the brain cannot be perfectly immobilized and the organ/tumor motion requires the physician to add a margin to ensure appropriate dose coverage of the target volume. The planning target volume (PTV) is defined by an additional margin to account for tumor motion and setup uncertainties. This added margin increases the volume of tissue irradiated, which theoretically increases the risk of side effects [23]. Over the last 15 years, solutions have allowed SBRT to treat tumors outside the brain [24, 25]. In fact, in lung cancer, the results [26, 27] have been so impressive that investigators are currently challenging the paradigm of surgery as the standard of care for patients with small lung cancers [28].

SBRT of breast cancer has been addressed in only two published reports [29, 30]. These studies have severe limitations because of poor immobilization and lack of adequate image guidance, allowing only subtherapeutic doses of radiation and possible marginal misses because of set up uncertainty. One of the major challenges of SBRT for breast cancer is that the breast is pliable. These challenges have been solved in the brain, thorax, and abdomen with commercially available immobilization devices. In addition in the breast, surrounding structures have placed limitations on beam delivery. These technical obstacles have been solved through an NIH-SBIR grant mechanism (4R44CA132254-02) at the University of Maryland by Yu et al. [31] with the inception of GammaPod™ technology, commercialized by the Xcision Medical System, LLC (Xcision). A detailed description of the GammaPod™ device and underlying technology will be provided in subsequent sections.

The GammaPod™ device has several advantages over current technologies capable of SBRT, including but not limited to (1) the vacuum assisted breast immobilization device has improved accuracy and reproducibility. In addition, the patient is treated in the prone position, similar to positioning for stereotactic breast biopsy or MR imaging of the breast, thus minimizing the effect of breathing motion. Subsequently, the margin required for PTV can be decreased from 1.0 to 0.3 cm, potentially reducing the volume radiated by threefold [32]. (2) This device uses 36 noncoplanar Co-60 sources that rotate during treatment to form 36 noncoplanar arcs, producing a dose distribution similar to that of the GammaKnife™ for intracranial targets [33]. (3) This system allows differential dosing of target volumes [34] (dose painting; similar to that in intensity modulated RT techniques), which cannot be accomplished with any invasive APBI approaches. This allows higher doses to the gross tumor with lower “subclinical doses” to ablate microscopic foci, which can lie 1.0–1.5 cm beyond the index lesion [35, 36].

GammaPod™ offers the opportunity to deliver curative doses of radiation using SBRT more precisely than current surgical standards, thereby minimizing the amount of breast tissue ablated and improving cosmesis. If this treatment is as effective as it has proven for lung cancer, SBRT could lead to a paradigm shift similar to that seen in lung cancer, with completely noninvasive treatment of early breast cancer with only a few high dose “ablative” treatments delivered over the course of less than 1 week.

In preparation for developing a clinical trial using SBRT with ablative doses of RT, we investigated the role of preoperative 3D-CRT APBI as a method to reduce morbidity and allow greater utility of APBI. We have demonstrated that using a preoperative target volume dramatically decreases the PTV by a mean average value of 56 % when compared with the standard postoperative target [32]. In a subsequent publication, we reported that preoperative 3D-CRT APBI showed significant clinical advantages by decreasing dose to all surrounding normal tissues and substantially increasing (by 60 %) the number of patients eligible for APBI using 3D-CRT [37]. Based on these dosimetric advantages, we are currently testing this hypothesis on a prospective trial at the University of Maryland. This trial uses the same treatment guidelines (i.e., clinical treatment volume and PTV expansions) and dose fractionation (38.5 Gy delivered in ten equal fractions over 5 days) as NSABP B-39, with the only difference being the sequence of surgery and RT. Based on early data from the first 25 patients treated on study, a complete pathologic response was achieved.

These pathologic findings have been quite exciting for two reasons. First, only a low “adjuvant” dose of radiation was administered, and, second and more important, a response was actually seen. These tumors are slow growing and can take a long time to respond. Prostate cancer, which has similar growth patterns, takes years to show histologic resolution of tumor following radiotherapy. Therefore, we believe that small, early stage breast cancer, SBRT may replace lumpectomy and postoperative RT. With the less aggressive, slower growing tumors in the breast, it is likely that SBRT will approach or surpass the efficacy of 90 %+ local control rates seen in SBRT for lung cancer. Although clearly many studies will be necessary to prove this hypothesis, in order for SBRT to be realized as a standalone treatment, a noninvasive measure of success is key which will require functional imaging such as MRI or PET. If successful and implemented clinically in the future, select patients will receive SBRT alone. The geometric accuracy will likely improve cosmesis by causing minimal-to-no volume loss, eliminate surgical scarring, improve quality of life issues currently associated with prolonged treatment periods, and enhance overall outcomes.

The GammaPod™ device comprises three major components: the gamma irradiation unit housing the Cobalt-60 radioactive sources and collimation structure, a breast immobilization unit to facilitate stereotactic localization and prone patient support and a continuous trajectory patient positioning assembly.