Real-time, intraoperative detection of residual breast cancer in lumpectomy cavity walls using a novel cathepsin-activated fluorescent imaging system

Breast Cancer Res Treat. 2018 Sep;171(2):413-420. doi: 10.1007/s10549-018-4845-4. Epub 2018 Jun 9.

Abstract

Purpose: Obtaining tumor-free surgical margins is critical to prevent recurrence in breast-conserving surgery but it remains challenging. We assessed the LUM Imaging System for real-time, intraoperative detection of residual tumor.

Methods: Lumpectomy cavity walls and excised specimens of breast cancer lumpectomy patients were assessed with the LUM Imaging System (Lumicell, Inc., Wellesley MA) with and without intravenous LUM015, a cathepsin-activatable fluorescent agent. Fluorescence at potential sites of residual tumor was evaluated with a sterile hand-held probe, displayed on a monitor and correlated with histopathology.

Results: Background autofluorescence was assessed in excised specimens from 9 patients who did not receive LUM015. In vivo lumpectomy cavities and excised specimens were then imaged in 15 women undergoing breast cancer surgery who received no LUM015, 0.5, or 1 mg/kg LUM015 (5 women per dose). Among these, 11 patients had invasive carcinoma with ductal carcinoma in situ (DCIS) and 4 had only DCIS. Image acquisition took 1 s for each 2.6-cm-diameter surface. No significant background normal breast fluorescence was identified. Elevated fluorescent signal was seen from invasive cancers and DCIS. Mean tumor-to-normal signal ratios were 4.70 ± 1.23 at 0.5 mg/kg and 4.22 ± 0.9 at 1.0 mg/kg (p = 0.54). Tumor was distinguished from normal tissue in pre-and postmenopausal women and readings were not affected by breast density. Some benign tissues produced fluorescent signal with LUM015.

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

Keywords: Breast cancer; Image-guided surgery; Intraoperative tumor detection; Lumpectomy surgery.

MeSH terms

  • Adult
  • Aged
  • Biopsy
  • Breast Neoplasms / diagnosis*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / surgery*
  • Cathepsins*
  • Female
  • Humans
  • Immunohistochemistry
  • Intraoperative Period
  • Mastectomy, Segmental* / methods
  • Middle Aged
  • Neoplasm, Residual / diagnostic imaging*
  • Neoplasm, Residual / metabolism
  • Neoplasm, Residual / pathology*
  • Optical Imaging* / methods
  • Surgery, Computer-Assisted

Substances

  • Cathepsins