2715 - Preliminary Results of a Phase I Trial Using Preoperative Stereotactic Ablative Breast Radiotherapy (SABER) for Selected Early-Stage Breast Cancer

I. C. Ogobuiro¹, S. B. Kesmodel², J. Net³, I. M. Reis⁴, and C. Takita⁵; ¹Department of Radiation Oncology, University of Miami, Sylvester Comprehensive Cancer Center, Miami, FL, ²Surgical Oncology Division, University of Miami, Sylvester Comprehensive Cancer Center, Miami, FL, ³Radiology Department, University of Miami, Sylvester Comprehensive Cancer Center, Miami, FL, ⁴Department of Public Health Sciences and Sylvester Biostatistics/Bioinformatics Shared Resources (BBSR), University of Miami, Sylvester Comprehensive Cancer Center, Miami, FL, ⁵Department of Radiation Oncology, University of Miami/Sylvester Comprehensive Cancer Center, Miami, FL

Purpose/Objective(s): The feasibility and outcomes associated with preoperative partial breast irradiation, targeting the reduction of target volume and treatment duration, remains unknown. Thus, we proposed a phase 1 study testing preoperative stereotactic ablative breast radiotherapy (SABER) in a selected subset of early-stage breast cancer patients. Aims include to determine the recommended phase 2 dose (RP2D), assess feasibility and toxicity, primary estimation of complete pathologic response rate, and cosmetic outcome. Materials/

Methods: Patients 50 or older, with a diagnosis of cT1N0M0, ER/PR+, HER2-negative invasive breast cancer were included. Oncotype testing, along with pre- and post-radiotherapy (RT) multiparametric (mp) breast MRI, was conducted. SABER total dose of 40Gy was administered in 5 fractions over non-consecutive days spanning 2 weeks. Radiographic response was evaluated using RECIST criteria. All patients underwent lumpectomy and sentinel node biopsy, 4-6 weeks post-RT, and resected tumors were assessed for pathologic response. Cosmetic evaluation was performed before radiation, after radiation but prior to surgery, and after surgery. Patient-reported outcomes using BCTOS were evaluated at scheduled intervals.
Results: This is the preliminary results of the first dose-cohort of patients treated in our phase 1 trial. From 8/2020-11/2023, ten patients were screened, but 4 became ineligible due to tumor size >T1 by MRI (2 patients), Oncotype testing was not performed (1 patient), and in one patient time between biopsy and SABER was >3 months. The first cohort for the clinical trial comprised of 6 White patients, 83% Hispanics, with a median age of 55.5 years. Clinical stage was T1a (16.5%), T1b (16.5%), T1c (67%), N0 (100%), M0 (100%) invasive ductal carcinoma. All tumors were ER/PR+/HER2-, grade 1 (67%), grade 2 (33%). The median Oncotype score was 13. All patients received SABER as planned. Evaluation of SABER response was performed with pre- and post-SABER mp-MRI using RECIST criteria and compared with pathologic response. RECIST response was concordant in only 2/6 patients (33%). 2 patients that had pCR (33%) were stable disease (SD) by RECIST assessment; 2 others had pathologic SD and partial response (PR), were evaluated as CR by RECIST. With a median follow-up of 18 (3-24) months, all patients achieved 100% excellent cosmesis post-SABER. 4 patients had grade 1 fatigue, 1 patient had acute radiation dermatitis grade 1 and grade 2 breast pain, that resolved. There were no grade 3 or 4 AE’s.
Conclusion: Preliminary findings suggest that preoperative SABER at a dose of 40Gy in 5 fractions is feasible, with acceptable toxicity and yields excellent cosmetic outcomes. MRI does not appear to be a good predictor of residual disease or response after preoperative RT, compared to the strong correlation between MRI findings and residual disease following neoadjuvant systemic therapy. Further prospective studies are needed to assess tumor response after pre-operative ablative RT.