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

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.

• Authors: Barbara L Smith, Conor R Lanahan, Michelle C Specht, Bridget N Kelly, Carson Brown, David B Strasfeld, Jorge M Ferrer, Upahvan Rai, Rong Tang, Travis Rice-Stitt, Anna Biernacka, Elena F Brachtel, Michele A Gadd
• Journal: Annals of surgical oncology (Ann Surg Oncol) Vol. 27 Issue 6 Pg. 1854-1861 (Jun 2020) ISSN: 1534-4681 [Electronic] United States
• PMID: 31898104 (Publication Type: Journal Article)

Chemical References

• Fluorescent Dyes
• Peptide Hydrolases

Topics

• Adult
• Aged
• Breast Neoplasms (pathology, surgery)
• Carcinoma, Ductal, Breast (pathology, surgery)
• Carcinoma, Lobular (pathology, 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, surgery)
• Neoplasm, Residual (diagnosis, surgery)
• Peptide Hydrolases (metabolism)
• Prognosis
• Retrospective Studies