Abstract PO5-22-09: Positive pegulicianine fluorescence rate in the lumpectomy cavity correlates with tumor distance to margins in excised tissue
Authors: Wapnir Irene , Hwang E Shelley , Hunt Kelly , Carr David , Blumencranz Peter , Chang Manna , Smith Kate , Ferrer Jorge , Smith Barbara 
Published: May 2024

Abstract
Title: Positive pegulicianine fluorescence rate in the lumpectomy cavity correlates with tumor distance to margins in excised tissue
Background: A randomized, two-arm pivotal study of pegulicianine fluorescence guided surgery (pFGS) at 14 US sites was conducted using the Lumicell Direct Visualization System (DVS) to identify residual cancer in the lumpectomy cavity after the standard of care (SoC) tumor excision. We reported that the Lumicell DVS detects residual cancer in the lumpectomy cavity, including in orientations pathologically negative on the SoC specimen. In addition, 15% (9 of 62) of patients with positive SoC margins were converted to final negative margins by taking Lumicell DVS directed cavity margins, avoiding a second unnecessary surgery. Interestingly, 8 of these 9 patients had no tumor found in the Lumicell DVS guided specimens. We hypothesize that fluorescence decreases as the distance from the tumor boundary increases. We analyzed data from the pivotal study (NCT03686215) to assess correlation of pegulicianine signal with tumor-to-margin distance, and its potential clinical value.
Methods: The pivotal study enrolled 406 patients undergoing breast conserving surgery (BCS) for stage 0-III breast cancers. Patients received an IV injection of pegulicianine 2-6 hours prior to surgery. After the standard of care lumpectomy was completed, additional Lumicell DVS-guided cavity margins were excised at sites of positive pegulicianine fluorescence signal in the lumpectomy cavity walls using a hand-held imaging device and patient-calibrated cancer detection software. The positive fluorescence rate, that is, the rate at which the Lumicell DVS indicates areas suspected to contain cancer, was calculated as the ratio of orientations with positive pegulicianine signal to the total number of orientations with (1) negative margins, (2) positive margins and (3) positive margins with ink on tumor, on the initial SoC lumpectomy specimen. Calculations were made on a per-margin basis. Positive margins were defined as ink on tumor for invasive cancer and tumor less than 2 mm from the margin for ductal carcinoma in situ (DCIS) alone.
Results: Results are presented in Table 1. We found a statistically significant higher positive fluorescence rate in orientations with positive margins (p=0.044). The positive fluorescence rate was even higher (21.1%) when only considering cases with ink on tumor (a subset of the positive margin group).
Discussion: By design, pegulicianine is activated by enzymes within the tumor and in stromal cells at the invasive front surrounding the tumor. Thus, when tumor is closer to the edge of the lumpectomy specimen, the rate of positive pegulicianine fluorescence in the cavity increases, being highest when there is tumor present at the inked margin. This feature of pegulicianine fluorescence guides the surgeon to resect more tissue in these areas in order to achieve a negative margin of the required width. The conversion of positive margins after the SoC lumpectomy to appropriately wide final negative margins prevents a second surgery, even when there is no tumor in the DVS guided margins. These findings have strengthened our understanding of the utility of this technology.
Table 1 Positive cavity wall fluorescence rate for SoC lumpectomy positive margins, SoC lumpectomy negative margins and SoC lumpectomy ink on tumor margins
Citation Format: Irene Wapnir, E Shelley Hwang, Kelly Hunt, David Carr, Peter Blumencranz, Manna Chang, Kate Smith, Jorge Ferrer, Barbara Smith. Positive pegulicianine fluorescence rate in the lumpectomy cavity correlates with tumor distance to margins in excised tissue [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-22-09.