Page 149 - Fluorescence-guided cancer surgery

Imaging FRα positive ovarian and breast cancer 147
METHODS
Investigational agent
EC17 (molecular formula: C42H36N10Na2O10S; On Target Laboratories LLC, West Lafayette, USA) consists of a folate analogue conjugated to 5- uorescein isothiocyanate (FITC), which is exited between the wavelengths of 465 and 490nm and uoresces at wavelengths of 520-530 nm. Before administration, the frozen vials containing 5 mg/mL EC17 in 3 mL water for injection were thawed and diluted in 10 mL sterile saline. Patients received 0.1 mg/kg EC17 intravenously over 10 minutes, 2-3 hours before surgery.
Patients
Patients suspected of early stage epithelial ovarian cancer presenting at the department of Gynecology of the Leiden University Medical Center (LUMC) between February 2014 and September 2014 scheduled to undergo staging surgery or of advanced epithelial ovarian cancer scheduled to undergo cytoreductive surgery, were included in this study. All patients gave written informed consent.
For breast cancer, patients presenting at the department of Surgery of the LUMC between May 2014 and February 2015 planned for, either breast conserving surgery (BCS) or breast ablation, were eligible for participation. After selection, preoperatively obtained biopsies of potentially eligible patients were stained for FRα expression using immunohistochemistry (IHC). FRα expression was assessed by using a membranous scoring method with a scale ranging from 0 to 3+, as described by O’Shannessy et al.49 A score of 0 corresponded to absence of staining; 1+ equaled faint staining on luminal borders; 2+ equaled moderate staining on apical and sometimes lateral borders and 3+ indicated strong circumferential staining. The tumor was considered positive when more than 10% of malignant cells were positively stained (>0). Assessment of the stained biopsies was performed by a pathologist (VTHBMS or TB), and after presence of FRα positive tumor cells was con rmed, patients were eligible for EC17 administration. All patients gave written informed consent.
Exclusion criteria were age<18, pregnancy (excluded by pregnancy test in woman of childbearing potential), renal impairment (de ned as eGFR<50 mL/ min/1.73m2), impaired liver function (de ned as evidenced by greater than 3x the upper limit of normal (ULN) for ALT, AST, or total bilirubin), or a history of anaphylactic reaction to EC17, insect bites or uorescein.