Feasibility Study of a Novel Protease-Activated Fluorescent Imaging System for Real-Time, Intraoperative Detection of Residual Breast Cancer in Breast Conserving Surgery

Ann Surg Oncol. 2020 Jun;27(6):1854-1861. doi: 10.1245/s10434-019-08158-1. Epub 2020 Jan 2.

Abstract

Background: Obtaining tumor-free margins is critical to prevent recurrence after lumpectomy for breast cancer. Unfortunately, current approaches leave positive margins that require second surgeries in 20-40% of patients. We assessed the LUM Imaging System for real-time, intraoperative detection of residual tumor.

Methods: Breast lumpectomy cavity walls and excised specimens were assessed with the LUM Imaging System after 1 mg/kg intravenous LUM015, a protease-activatable fluorescent agent. Fluorescence at potential sites of residual tumor in lumpectomy cavity walls was evaluated intraoperatively with a sterile hand-held probe, with real-time predictive results displayed on a monitor intraoperatively, and later correlated with histopathology.

Results: In vivo lumpectomy cavities and excised specimens were imaged after LUM015 injection in 45 women undergoing breast cancer surgery. Invasive ductal and lobular cancers and intraductal cancer (DCIS) were included. A total of 570 cavity margin surfaces in 40 patients were used for algorithm development. Image analysis and display took approximately 1 s per 2.6-cm-diameter circular margin surface. All breast cancer subtypes could be distinguished from adjacent normal tissue. For all imaged cavity surfaces, sensitivity for tumor detection was 84%. Among 8 patients with positive margins after standard surgery, sensitivity for residual tumor detection was 100%; 2 of 8 were spared second surgeries because additional tissue was excised at sites of LUM015 signal. Specificity was 73%, with some benign tissues showing elevated fluorescent signal.

Conclusions: The LUM015 agent and LUM Imaging System allow rapid identification of residual tumor in the lumpectomy cavity of breast cancer patients and may reduce rates of positive margins.

MeSH terms

  • Adult
  • Aged
  • Breast Neoplasms / pathology
  • Breast Neoplasms / surgery*
  • Carcinoma, Ductal, Breast / pathology
  • Carcinoma, Ductal, Breast / surgery
  • Carcinoma, Lobular / pathology
  • Carcinoma, Lobular / surgery
  • Diagnostic Imaging
  • Feasibility Studies
  • Female
  • Fluorescent Dyes / chemistry
  • Follow-Up Studies
  • Humans
  • Intraoperative Care*
  • Mastectomy, Segmental / methods*
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Recurrence, Local / diagnosis*
  • Neoplasm Recurrence, Local / surgery
  • Neoplasm, Residual / diagnosis*
  • Neoplasm, Residual / surgery
  • Peptide Hydrolases / metabolism*
  • Prognosis
  • Retrospective Studies

Substances

  • Fluorescent Dyes
  • Peptide Hydrolases