Page 150 - Fluorescence-guided cancer surgery

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Chapter 9
Clinical Trial
The study was approved by the Medical Ethics Committee of the LUMC and was performed in accordance with the laws and regulations of the Netherlands. Suitability of selected patients was further assessed by a medical screening consisting of a medical history, physical examination including vital signs, weight, 12-lead ECG, and routine laboratory assessments.
Before administration of EC17, two iv cannulas were inserted. One iv cannula was used for study drug administration and the cannula in the contralateral arm for PK sampling (Supplementary Methods, online available). After administration, safety assessments (blood pressure, pulse, peripheral oxygen saturation and temperature) and blood collection for pharmacokinetics were performed regularly from just prior to administration up to the end of surgery. A stopping rule was de ned in the protocol. In case of treatment-related serious adverse events or results suggesting futility to continue, the trial would be halted or stopped.
Surgical procedure in ovarian cancer patients
All surgical procedures were performed by laparotomy through a midline abdominal incision. After opening of the abdominal cavity, the surgical eld was searched for the primary tumor and metastases visible by the naked eye or palpation. Thereafter, the Artemis imaging system (see below for details) was used to identify uorescent signals. When a uorescent signal was observed, the operating surgeon performed a biopsy or resection of the uorescent tissue. In case of non- uorescence, only lesions macroscopically suspect for malignancy were resected. Resected specimens were marked as clinically suspect or not clinically suspect and as uorescent or non- uorescent. All resected lesions were examined by a pathologist for tumor status. In addition, an immunohistochemical (IHC) staining for FRα expression and uorescence microscopy (Leica DM5500B uorescence microscope) were performed to assess concordance of uorescence with tumor and FRα presence and to evaluate binding sites of EC17 (Supplementary Methods, online available).
To assess the number of malignant lesions that were identi ed by the naked eye and/or uorescence imaging, stills from intraoperative obtained videos were analyzed by three dedicated gynecologic oncologists, experienced in ovarian cancer surgery. A total of 5 di erent images were analyzed. Each image was analyzed 3 times (normal, horizontally and vertically ipped), leading to a