Abstract P3-19-03: Preliminary results of a feasibility study assessing radiation response with MRI/CT directed preoperative accelerated partial breast irradiation in the prone position for hormone responsive early stage breast cancer
Authors: Beyer Sasha , Smith Tamara , Sekhon Ashley , Bazan Jose , Jhawar Sachin , Healy Erin , Wei Lai , Yildiz Vedat , Mohamed Mohamed , Knopp Michael , White Julia 
Published: March 2022

Abstract
BACKGROUND: Accelerated partial breast irradiation (APBI) has emerged as an alternative to whole breast irradiation (WBI) following lumpectomy for select patients. However, the challenges to post-operative APBI include targeting inaccuracy and the inability to measure tumor response to radiation. We hypothesized that preoperative APBI (pAPBI) could reliably target the tumor using MRI-guidance that is acquired prone in combination with our established prone breast radiation delivery. We developed methodology for prone CT simulation to establish radiation position, MRI acquisition in treatment position, registration of MRI-CT data for treatment planning, and treatment delivery with daily cone-beam CT using the same immobilization platform. This study aimed to assess the reproducibility, toxicity and local control associated with MRI/CT-directed prone pAPBI. METHODS: This was a prospective, single arm study enrolling patients &gt;50 yo with clinical (c) Stage IA ER+/PR+/HER2- breast cancer intending lumpectomy. Axillary US and MRI imaging to confirm clinical node negative disease was required. A planning CT in the prone position was followed by MRI using the same prone immobilization platform. Rigid registration of MRI-CT data was used for radiation planning. pAPBI of 3850 cGy was delivered in 10 fractions BID with the same prone immobilization technique. Another MRI was obtained 4 weeks post-APBI to assess tumor response. The intensity, kinetics and volume of the lesion on MRI was quantitatively assessed and an experienced reader evaluated MRI volume and kinetic changes in the tumor post-APBI. Lumpectomy was performed 4-6 weeks after APBI. Simon 2 stage design required assessment after accrual of 19 patients for assessment of feasibility. RESULTS: Nineteen cStage IA ER+/PR+/HER2- breast cancer patients with a median age of 65 (range 51-78) were enrolled on the study, completed APBI, lumpectomy, and adjuvant AI. Median follow up was 3.4 years. Mean clinical tumor size was 1.1 cm ± 0.4 and mean path tumor size was 0.94 cm ± 0.6. There was complete pathologic response in 10.5% (n=2) and an additional 36.8% (n=7) were downstaged from clinical stage (measured by mammogram/US) to pathologic stage, resulting in a total response of 47.4% (n=9). Six (31.6%) patients had stable disease after APBI. Four (21.0%) were upstaged from clinical stage to pathological stage. Tumor response detected by MRI significantly correlated with tumor response based on clinical to pathologic stage (p=0.03). Cosmesis was rated as excellent/good in 89.5% (n=17) patients post-APBI. Cosmesis worsened to fair in 2 patients post-APBI, one of which required adjuvant WBI after focal triple negative breast cancer was detected on pathology. Three patients had positive macrometastatic lymph nodes on final pathology despite clinically negative nodes on imaging. One in-breast recurrence outside the RT field was detected by MRI at 14 months, resulting in a locoregional recurrence rate of 5.4% at 3.4 years. Another patient developed metastases at 20 months. CONCLUSIONS: Using the same prone platform, all patients successfully underwent CT simulation, MRI acquisition, and completed pAPBI. Nearly half of enrolled patients had a measurable tumor response to pAPBI based on MRI and pathologic response, confirming the accuracy and reproducibility of defining tumor targets with our MRI/CT-directed pAPBI approach. While this methodology for prone pAPBI resulted in good cosmesis and local control and remains a promising approach for select patients, the challenge of excluding patients with subclinical lymph node positive disease remains. Correlative studies will determine whether Ki-67 and OncotypeDx pre- and post-APBI can help predict response to pAPBI.
Citation Format: Sasha Beyer, Tamara Smith, Ashley Sekhon, Jose Bazan, Sachin Jhawar, Erin Healy, Lai Wei, Vedat Yildiz, Mohamed Mohamed, Michael Knopp, Julia White. Preliminary results of a feasibility study assessing radiation response with MRI/CT directed preoperative accelerated partial breast irradiation in the prone position for hormone responsive early stage breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-19-03.