Abstract OT2-12-02: Feasibility study to evaluate performance of the LUM imaging system for intraoperative detection of residual tumor in patients with breast cancer receiving neoadjuvant therapy
Authors: Smith Kate P , Ferrer Jorge , Webster Alexandra , Kelly Bridget , Schlossberg Brian , Chang Manna , Smith Barbara 
Published: March 2022

Abstract
Background: Microscopically tumor-free lumpectomy margins are the goal for breast conserving surgery. With current tools, 15% to 25% of lumpectomies have positive margins and require a second surgical procedure increasing cost and patient discomfort. In addition, current lumpectomy margin assessment techniques show poor performance in predicting residual disease at re-excision, with a PPV of only 35%. Better detection tools are needed to guide the removal of cancer missed during the initial lumpectomy and reduce second operations. The LUM015 imaging agent is injected intravenously before surgery and its fluorescence signal is activated by proteases in tumor cells and the invasive front. The LUM Imaging System visualizes the activated LUM015 in the lumpectomy cavity via a hand-held detector and proprietary tumor detection software. This system was previously tested in multiple single-site studies and a prospective 234 patient multi-site study that demonstrated successful detection of residual cancer in the lumpectomy cavity. Initial studies excluded the ~20% of breast cancer patients receiving neoadjuvant therapy. Patchy tumor cell death with preoperative therapy can leave small, multifocal deposits of tumor invisible on pre-operative imaging and not palpable or visible during surgery. In this study, we are evaluating the LUM Imaging System in this patient population. Trial Design and Specific Aims: A prospective, multi-center study was designed to evaluate the potential impact of neoadjuvant therapy on tumor detection algorithms, which will be refined if needed. The first cohort of 10 patients will address this objective. A second cohort will further evaluate the feasibility, safety and efficacy of the LUM Imaging System in this patient population. 114 neoadjuvant therapy patients with invasive breast cancer and/or ductal carcinoma in situ will enroll at 6 US medical centers. After excision of the main lumpectomy specimen, patients are randomized 3:1 to device or control arms. In the device arm, the cavity is imaged and margins with LUM015 positive signal are excised. In the control arm, the surgeon records images within the cavity but no LUM015-directed margins are excised. Final comprehensive shave margins are removed in both arms to evaluate extent of residual disease after the use of the LUM Imaging System or after standard lumpectomy resection. Eligibility Criteria: This study seeks to enroll women, over the age of 18 and primary invasive breast cancer (IBC), ductal carcinoma in situ (DCIS) or a combination of IBC/DCIS undergoing a lumpectomy for their breast malignancy who have received any form of neoadjuvant treatment prior to undergoing surgery. Exclusions include patients allergic to polyethylene glycol or contrast agents. Use of blue node mapping dyes before imaging with the LUM015 is not allowed. Accrual and Study Progress: Cohort 1 has completed enrollment and interim analysis. No new risks specific to this patient population were identified and the fluorescence signals measured were within the expected range resulting in no initial changes to the tumor detection algorithm. Four patients have enrolled into cohort 2. This trial is registered as NCT04440982. This study is funded by NIH grant R01CA212138 awarded to Dr. Barbara Smith.
Citation Format: Kate P Smith, Jorge Ferrer, Alexandra Webster, Bridget Kelly, Brian Schlossberg, Manna Chang, Barbara Smith. Feasibility study to evaluate performance of the LUM imaging system for intraoperative detection of residual tumor in patients with breast cancer receiving neoadjuvant therapy [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 OT2-12-02.