Page 147 - Fluorescence-guided cancer surgery

Imaging FRα positive ovarian and breast cancer 145
In breast cancer, up to 20% of patients have positive resection margins after resection of the primary tumor3. Visualizing tumor cells during surgery could lower the risk of an incomplete resection as identi cation of a positive margin can result in direct resection of residual tumor tissue. Although this will probably not in uence overall survival, as patient with positive resection margins are currently treated with a re-resection or more intensive radiotherapy, signi cantly lower healthcare costs and burden to the patient could result. To investigate this concept, both FRα positive breast cancer patients treated with BCS and breast ablation were included in the current feasibility study. However, for future applicability of uorescence imaging in breast cancer surgery, the most added value is to be expected in BCS. Moreover, a signi cant number of patients with breast carcinoma is pre-treated with neoadjuvant systemic chemotherapy to reduce the primary tumor to facilitate BCS instead of radical mastectomy40. Although pre-treatment with systemic therapy does not result in an increased number of positive resection margins41, recognition of vital tumor tissue can be challenging. As FRα status is not changed by chemotherapy27;42, uorescence imaging could be of added value in these challenging cases.
In literature, FRα positive breast cancer lesions are described in up to 30% of patient43-45. In our series however, only 11% of the obtained biopsies stained positive for FRα. No explanation was found for this lower expression level. A high number of normal breast tissue stained weak positive for FRα, mainly located at the apical surface of epithelial cells and at myoepithelial cells. This nding has been described previously43;45, and does not necessarily cause a pitfall for FRα as target for uorescence guided surgery, because the myoepithelium is not accessible for blood carried contrast agents.
Several limitations of the described technique and contrast agent were caused by the optical properties of the contrast agent. EC17 uoresces at 488nm, which does not allow identi cation of lesions located beneath the surface. In 3 patients with ovarian cancer, the greater omentum was suspected for malignancy, but only showed uorescence after dissection of the tissue and this clearly showed the low tissue penetration of the photons emitted by EC17. We identi ed 23% false-positive lesions in the patients with ovarian cancer. The non-malignant lesions that uoresced in this study were in particular collagen-containing structures, from which it is known that they can show auto uorescence in the visible light spectrum14;46.