Abstract Background: Randomized trials in selected early stage breast cancer patients with up to 10 year follow-up have proven that Accelerated Partial Breast Irradiation (APBI) given via High Dose Rate (HDR) implant bid in 5 days is equivalent to whole breast External Radiation Therapy (XRT) given qd in 5-6 weeks in regard to breast tumor local recurrence (LR) [1-2]. However, complications with APBI implant in a Medicare database review have been significant, with 3.95% of women requiring Mastectomy, 16.2% developing infections, and another 16.3% experiencing non-infection complications including rib fractures, fat necrosis, and breast pain [3]. Recently APBI using non-invasive Intensity Modulated Radiation Therapy (IMRT) or Stereotactic Body Radiation Therapy (SBRT) given qd in 5 fractions has been shown in another randomized trial with 5 year follow-up to be equivalent to qd XRT in 6 weeks, with respect to LR [4]. IMRT/SBRT was superior in regard to acute effects, late effects, and cosmesis. Objectives: In the randomized clinical trial of APBI IMRT/SBRT, the Clinical Target Volume (CTV) was defined by the injection of individual fiducial markers bordering the surgical cavity. At our institution, we have used the Biozorb fiducial system to localize the CTV for SBRT. We sought to confirm the APBI SBRT/IMRT results with a simpler fiducial system. Materials and Methods: Between 2017 and 2019, 86 patients have undergone SBRT targeted to a Biozorb defined CTV with the walls of the surgical cavity sewn to the Biozorb device. Eligible patients were older than age 40, had tumor sizes ≤ 3 cm, negative surgical margins, and negative sentinel node dissections. SBRT dose was 30 Gy given in 5 fractions. Dose Constraints were as follows: V-30 Gy < 105%, Ipsilateral Breast V-15 Gy < 50%, Ipsilateral Lung V-10 Gy < 20%, Contralateral Lung V-5 Gy < 10%, Heart V-3 Gy < 20%, Contralateral Breast Dmax < 2 Gy and Skin Dmax < 27 Gy. The Planning Target Volume (PTV) ranged from 27 to 355 cc with a median of 80 cc. PTV = CTV + 1-2 cm. Results: Follow-up ranged from 1-24 months with a median of 12 months. LR has been 0% (0/86). There were no skin reactions. One patient developed pain around the Biozorb site. This resolved within 2 days on a short course of steroids. Cosmetic results as rated by the Surgeon, Radiation Oncologist, and Nurse, were rated excellent in 100% (86/86) of cases. Conclusions:Non-invasive APBI with SBRT given qd over 5 days targeted to Biozorb has resulted in LR, complications, and cosmetic results which compare favorably to invasive APBI given bid with HDR implant. At last follow-up, there have been no LR, skin reactions, or complications. Cosmesis has been excellent in 100% of patients. Refernces:1. Polgar C, Fodor J, Major T, et al. Breast-conserving therapy with partial or whole breast irradiation: Ten-year results of the Budapest randomized trial. Radiother Oncol 2013; 108[2]: 197-202. 2. Strnad V, Ott O, Hildebrandt G, et al. 5-year results of accelerated partial breast irradiation using sole interstitial multicatheter brachytherapy versus whole-breast irradiation with boost after breast-conserving surgery for low-risk invasive and in-situ carcinoma of the female breast: a randomised, phase 3, non-inferiority trial. Lancet 2016; 387[10015]: 229-38. 3. Smith G, Xu Y, Bucholz T, et al. Association between treatment with brachytherapy vs whole-breast irradiation and subsequent mastectomy, complications, and survival among older women with invasive breast cancer. JAMA 2012; 307[17]: 1827-37. 4. Livi L, Meattini I, Marrazzo L, et al. Accelerated partial breast irradiation using intensity-modulated radiotherapy versus whole breast irradiation: 5-year survival analysis of a phase 3 randomised controlled trial. Eur J Cancer, 2015; 51 [4]: 451-63. Citation Format: Rufus Mark, Valerie Gorman, Steven McCullough. Five day accelerated partial breast irradiation (APBI) using stereotactic body radiation therapy (SBRT) in stage 0-II breast cancer: A report of 86 patients with up to 2 year follow-up [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-13-08.