Clinical Impact of Intraoperative Margin Assessment in Breast-Conserving Surgery With a Novel Pegulicianine Fluorescence-Guided System: A Nonrandomized Controlled Trial

Abstract

Importance: Positive margins following breast-conserving surgery (BCS) are often identified on standard pathology evaluation. Intraoperative assessment of the lumpectomy cavity has the potential to reduce residual disease or reexcision rate following standard of care BCS in real time.

Objective: To collect safety and initial efficacy data on the novel pegulicianine fluorescence-guided system (pFGS) when used to identify residual cancer in the tumor bed of female patients undergoing BCS.

Design, setting, and participants: This prospective single-arm open-label study was conducted as a nonrandomized multicenter controlled trial at 16 academic or community breast centers across the US. Female patients 18 years and older with newly diagnosed primary invasive breast cancer or ductal carcinoma in situ DCIS undergoing BCS were included, excluding those with previous breast cancer surgery and a history of dye allergies. Of 283 consecutive eligible patients recruited, 234 received a pegulicianine injection and were included in the safety analysis; of these, 230 were included in the efficacy analysis. Patients were enrolled between February 6, 2018, and April 10, 2020, and monitored for a 30-day follow-up period. Data were analyzed from April 10, 2020, to August 5, 2021.

Interventions: Participants received an injection of a novel imaging agent (pegulicianine) a mean (SD) of 3.2 (0.9) hours prior to surgery at a dose of 1 mg/kg. After completing standard of care (SOC) excision, pFGS was used to scan the lumpectomy cavity to guide the removal of additional shave margins.

Main outcomes and measures: Adverse events and sensitivity, specificity, and reexcision rate.

Results: Of 234 female patients enrolled (median [IQR] age, 62.0 [55.0-69.0] years), 230 completed the trial and 1 patient with a history of allergy to contrast agents had an anaphylactic reaction and recovered without sequelae. Correlation of pFGS with final margin status on a per-margin analysis showed a marked improvement in sensitivity over standard pathology assessment of the main lumpectomy specimen (69.4% vs 38.2%, respectively). On a per-patient level, the false-negative rate of pFGS was 23.7% (9 of 38), and sensitivity was 76.3% (29 of 38). Among 32 patients who underwent excision of pFGS-guided shaves, pFGS averted the need for reexcision in 6 (19%).

Conclusions and relevance: In this pilot feasibility study, the safety profile of pegulicianine was consistent with other imaging agents used in BCS, and was associated with a reduced need for second surgery in patients who underwent intraoperative additional excision of pFGS-guided shaves. These findings support further development and clinical performance assessment of pFGS in a prospective randomized trial.

Trial registration: ClinicalTrials.gov Identifier: NCT03321929.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Hwang reported grants from Lumicell during the conduct of the study and grants from Lumicell outside the submitted work. Dr Carr reported personal fees from Lumicell during the conduct of the study. Dr Chagpar reported grants from Lumicell during the conduct of the study and personal fees from Protean Biodiagnostics, Sanofi Aventis, Guardant Health, Puma Diagnostics, and Athenex outside the submitted work. Dr Dekhne reported grants from Lumicell during the conduct of the study. Dr Dodge reported grants from Penn State during the conduct of the study. Dr Hunt reported grants from Lumicell during the conduct of the study as well as personal fees from Armada Health and research funding from Cairn Surgical and Eli Lilly, paid to their institution, outside the submitted work. Dr Lesnikoski reported grants from Lumicell to Baptist MD Anderson during the conduct of the study. Dr Wapnir reported the National Institutes of Health subaward from Lumicell during the conduct of the study and National Institutes of Health subawards from Lumicell and Massachusetts General Hospital outside the submitted work. No other disclosures were reported.

Figures

Figure 1.. Pegulicianine Fluorescence–Guided System (pFGS) Tumor Detection Device and Protocol

A, The Lumicell device was installed at each site with all components mounted on a mobile tower. On-site hands-on training was conducted for the surgeons, operating room staff, and study team prior to study activation. A, The Lumicell study monitor was present either in person or virtually for each procedure to oversee device use and data collection. B, Study schema for intraoperative use of the Lumicell device. Up to 2 additional shave margins were allowed per margin orientation. C, Intraoperative images demonstrating a red signal indicating pFGS uptake. Additional shave margins were excised in the inferior and inferior lateral orientations with resultant elimination of signal. IV indicates intravenously.

Figure 2.. CONSORT Diagram

pFGS indicates pegulicianine fluorescence–guided system.