Abstract
BACKGROUND: Current intraoperative margin assessment techniques lack the accuracy needed for clinical practice. Indocyanine green fluorescence imaging (ICG-FI) offers a useful technique for detection of tumoral tissue, including breast cancer (BC). There is a great inconsistency in the literature regarding the use of ICG for BC fluorescence imaging mainly concerning ICG dosing and the timing of administration. This study aims to determine the dose and timing of intravenous (IV) ICG administration that provides the optimal diagnostic accuracy for ICG-FI margin assessment during breast-conserving surgery (BCS). METHODS: This study (BREASTIFLU-1) is a phase II cross-sectional diagnostic accuracy study. It is a five-arm, single-center, prospective, randomized, observational-interventional, open-label study that will include patients with histologically proven early-stage (cT1-T2, cN0-N1) BC who are planned to undergo BCS. Two preoperative timeframes will be used for the administration of five different IV ICG doses in single-dose patient arms. In the intraoperative arms, patients will receive 0.125 mg/kg or 0.25 mg/kg ICG administered IV at induction anesthesia. In the preoperative arms, patients will receive 0.5 mg/kg, 1 mg/kg, or 2 mg/kg ICG administered 24 h before surgery. The primary endpoint is accuracy of the ICG-FI technique for the detection of positive surgical margins. Secondary endpoints include the following: comparison of ICG-FI technique accuracy at different doses and timings, characterization of breast tumor fluorescence, and evaluation of fluorescence intensity of axillary lymph nodes. The trial aims to include 227 patients. Participant recruitment is expected to be complete at the beginning of 2026, and results for the primary outcome are expected to be available in 2026. DISCUSSION: BREASTIFLU-1 is the first initiative to compare an intraoperative dose of ICG to preoperative ICG administration and is aligned with efforts to standardize the ICG-FI technique. Determining the best dose and timing for IV ICG injection is a crucial step toward using ICG-FI in practice. ICG-FI may provide a relatively easy and quick method to use for reducing the rate of positive margins after BCS. TRIAL REGISTRATION: This trial was registered on February 15, 2023 at Clinical Trials Information System EU2023-504024-26-00 and on September 10, 2023 at ClinicalTrials.gov NCT06227338.