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

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.

Figure 1:

LUM Imaging System images of transected tumors with and without LUM015 injection: (a) Transected lumpectomy specimen from Patient 5, IDC and DCIS, no LUM015 with tumor:normal signal ratio of 1.9 (b) Transected tumor specimen from Patient 8, IDC and DCIS, 0.5mg/kg LUM015 with tumor:normal signal ratio of 4.8. Images are plotted on linear brightness scales for which the minimum pixel value is black and the maximum pixel value is white. Scale bars = 1 cm.

Figure 2:

(a-b) Fluorescent image captured from transected ex vivo resected IDC mass from Patient 8. Pathology slide taken from same resected mass; the oval hole within the mass is a processing artifact (c-d) Fluorescent image captured from transected ex vivo resected DCIS specimen in Patient 7. Pathology highlights evidence of 3 mm area of DCIS (e-f) Ex vivo imaging of medial margin from patient 7. Two small fluorescent features appear, enlarged in the inset. Two foci of DCIS appear in the corresponding pathology slide. (g-h) Lumpectomy transection LUM Image and corresponding H&E stained slide from patient 6. Pathology report defined lesion as invasive mammary carcinoma with mixed ductal and lobular features with DCIS within the invasive carcinoma.

Figure 3:

Ex vivo specimen and in vivo lumpectomy cavity wall fluorescent signal correlated with histopathology. In vivo data not available for patients 6 and 9.