Purpose Diffusion of accelerated partial breast irradiation (APBI) into clinical practice is limited by the need for specialized equipment and training. Skin markers and an intra-tumor biopsy marker were utilized for verification during treatment. Results MRI imaging was critical for target delineation as not all breast tumors were reliably identified on CT scan. Breast shape differences were consistently seen between CT LMK-235 and MRI but did not impede image registration or tumor identification. Target volumes were markedly smaller than historical post-operative volumes and normal tissue constraints were easily met. A biopsy marker within the breast proved sufficient for set up localization. Conclusions This single fraction linear-accelerator based ABPI approach can be easily incorporated at most treatment centers. In vivo targeting may improve accuracy and can reduce the dose to normal tissues. Keywords: radiotherapy breast cancer partial breast preoperative Introduction Breast conservation lumpectomy followed by adjuvant radiotherapy has been LMK-235 standard of care for treatment of breast cancer since the early 1990’s 1 2 In the twenty years since our understanding of the complexity and variability of breast tumor biology has evolved significantly 3. In response there has been a paradigm shift in utilization of systemic therapy most notably with development and widespread adoption of the Oncotype DX test for early stage ER positive tumors4. In contrast change in breast radiotherapy practice in the US has been limited with the most standard regimen still approximately 5-6 weeks of whole breast treatment 5. The most mature research efforts to date focus on reducing duration of radiation treatment. 10 year data from multiple randomized clinical trials now support non-inferiority of a 3 week whole breast radiation course compared to the standard 5 LMK-235 week course 6 7 Ongoing efforts to further improve convenience and reduce toxicity focus on rapid treatment of the tumor bed plus a small margin of normal tissue over 1 to 5 days. Accelerated Partial Breast Irradiation (APBI) is the subject of multiple ongoing or recently completed randomized trials 8-10. Early data from these and prior phase I/II studies show comparable efficacy to whole breast radiation in low-risk early-stage patients. Intracavitary and external beam radiotherapy the two most common APBI approaches are widely available and relatively easily applied. However treatment is still intensive requiring 10 treatments delivered 6 hours apart over five days. Furthermore data are accumulating that toxicity outcomes appear to be driven by technique. In particular soft tissue fibrosis and cosmetic outcomes may be LMK-235 suboptimal with external beam techniques possibly related to large volumes of tissue treated to high doses in the post-operative setting 11 12 Single fraction intra-operative APBI allows women to complete radiotherapy while under anesthesia for breast surgery. This method is more convenient and treats a smaller breast volume than external beam APBI. Rabbit polyclonal to ALX4. Results reported to date from randomized Italian and European trials show excellent local control and minimal toxicity 9 10 However in addition to potential concerns about dose coverage many centers do not have the means to incorporate the costly equipment or necessary flexibility in operative scheduling. In contrast most radiation facilities can perform stereotactic radiosurgery high precision rapid linear accelerator based external beam irradiation. Highly conformal stereotactic radiosurgery is ideal to minimize volume of uninvolved breast tissue and skin receiving high-dose during APBI two advantages of intra-operative therapy that likely contribute to acceptable outcomes seen in trials. In fact treatment of the intact tumor pre-operatively allows for an even smaller and potentially more accurate target volume than LMK-235 IORT. Our prior work evaluating the dosimetric feasibility of this approach demonstrated a greater than 14% absolute reduction in volume of breast receiving prescription dose and a nearly 40% absolute reduction in volume receiving half prescription dose 13. We report here implementation aspects of our phase I dose-escalation trial evaluating preoperative single fraction breast radiotherapy for treatment of early stage breast cancer in highly selected women with favorable tumor biology. Methods Patient selection Women ages 55 or older with clinically node negative unifocal 2. 0 LMK-235 cm or less biopsy proven low/intermediate grade ductal carcinoma in-situ or invasive carcinoma were.