Abstract PS1-21: Molecular fluorescence-guided surgery using Beva800 for the assessment of tumor margins during breast conserving surgery of patients with primary breast cancer (MARGIN-II)
Authors: Kolberg Hans-Christian , Röhm Carmen , Stachs Angrit , Schütz Florian , Blohmer Jens-Uwe , Wetzig Sarah , Hartmann Steffi , Heil Jörg , Hahn Markus 
Published: February 2021

Introduction:The goal of breast conserving surgery (BCS) for early breast cancer (EBC) is to remove the tumor and a surrounding rim of normal tissue, while preserving as much of the normal breast tissue as possible. Incomplete resections are associated with higher rates of surgical re-excision. Repeat surgeries are not only a burden to patients physically but also psychologically and can delay recommended adjuvant therapies. Accurate determination of tumor margins during surgery is therefore critical for successful outcome. Breast cancer tissue produces significantly higher amounts of VEGF-A than healthy tissue. VEGF-A stimulates tumor angiogenesis and is therefore an excellent target for molecular imaging techniques. The fluorescence imaging agent bevacizumab-IRDye800CW (Beva800) is a conjugate of bevacizumab (a humanized antibody targeting human VEGF) and IRDye800CW (a near-infrared fluorescence dye) which binds specifically to VEGF-A. Beva800 provides a potentially highly efficacious approach to imaging specimen and cavity margins during BCS. Herein we present a phase II study that combined Beva800 with the SurgVision Explorer Air camera for intraoperative margin assessment during BCS for EBC.Methods:MARGIN II is a multicenter open-label single arm prospective clinical trial aimed at evaluating Beva800 for assessment of tumor margins in women with EBC scheduled for BCS. The study was a within-patient comparison of positive tumor margin rates using BCS standard of care compared to intraoperative assessment with 4.5 mg Beva800 and fluorescence imaging with the SurgVision Explorer Air camera. Patients undergoing neoadjuvant chemotherapy were excluded. All patients received a single intra-venous bolus injection of 4.5 mg of Beva800 three days before surgery. The fluorescent signal was visualized during surgery using NIR fluorescence imaging (700-1000 nm). This wavelength window typically has very low tissue auto-fluorescence (filtering out background noise) and greater tissue penetration depth due to reduced haemoglobin absorption. Standard of care assessment was defined as visual inspection, palpation and, in cases of pre-operative wire marking, specimen sonography or mammography. Beva800 efficacy was determined as the number of patients in which a pathology-confirmed positive margin was identified by fluorescence guided surgery using Beva800 but not by standard of care BCS. The results per patient were divided into two clusters: results after standard of care BCS and results after fluorescence guided surgery, according to their margin status at pathology. The need for re-operation because of involved margins within 30 days after the first BCS and the safety of 4.5 mg Beva800 was assessed.Results:The recruitment goal of 40 patients in 5 centers has almost been reached and results of the final analysis will be presented at the meeting.Conclusion:Molecular fluorescence-guided surgery using Beva800 has the potential to change the practice of breast conserving surgery by avoiding unnecessary re-operations. This would lead to fewer interventions, a reduced burden on patients through repeat surgery and reduced delay of adjuvant therapies.

Citation Format: Hans-Christian Kolberg, Carmen Röhm, Angrit Stachs, Florian Schütz, Jens-Uwe Blohmer, Sarah Wetzig, Steffi Hartmann, Jörg Heil, Markus Hahn. Molecular fluorescence-guided surgery using Beva800 for the assessment of tumor margins during breast conserving surgery of patients with primary breast cancer (MARGIN-II) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-21.