Background: Almost a third of the resections in patients with colorectal liver metastases (CRLM) undergoing curative surgery, end up being tumor-margin positive (≤1 mm margin). Near-infrared fluorescent (NIRF) imaging using the fluorescent contrast agent indocyanine green (ICG) has been studied for many different applications. When administered in a relatively low dose (10 mg) 24 hours prior to surgery, ICG accumulated in hepatocytes surrounding the CRLM. This results in the formation of a characteristic fluorescent 'rim' surrounding CRLM when located at the periphery of the liver. By resecting the metastasis with the entire surrounding fluorescent rim, in real-time guided by NIRF imaging, the surgeon can effectively acquire margin-negative (>1 mm) resections. This pilot study aims to describe the surgical technique for using near-infrared fluorescence imaging to assess tumor-margins in vivo in patients with CRLM undergoing laparoscopic or robot-assisted resections.Methods: Out of our institutional database we selected 16 CRLM based on margin-status (R0; n=8, R1; n=8), which were resected by a minimally-invasive approach using ICG-fluorescence. NIRF images acquired during surgery, from both the resection specimen and the wound bed, were analysed for fluorescent signal.We hypothesized that a protruding fluorescent rim at the parenchymal side of the resection specimen could indicate a too close proximity to the tumor and could be predictive for a tumor-positive surgical margin. NIRF images were correlated to final histopathological assessment of the resection margin.Results: All lesions with a NIRF positive resection plane in vivo were reported as having a tumor-positive margin. Lesions that showcased no protruding rim in the wound bed in vivo were diagnosed as having a tumor-negative margin in 88% of cases. A 5-step surgical workflow is described to document the NIRF signal was used assess the resection margin in vivo for future clinical studies.
Conclusions:The pilot study shows that image-guided surgery using real-time ICG-fluorescence has the potential to aid surgeons in achieving a tumor-negative margin in minimally invasive liver metastasectomies.The national multi-centre MIMIC-Trial will prospectively study the effect of this technique on surgical tumor-margins (Dutch Trial Register number NL7674).
Background
Carcinoembryonic antigen is overexpressed in colorectal cancer (CRC), making it an optimal target for fluorescence imaging. A phase I/II study was designed to determine the optimal imaging dose of SGM-101 for intraoperative fluorescence imaging of primary and recurrent CRC.
Methods
Patients were included and received a single dose of SGM-101 at least 24 h before surgery. Patients who received routine anticancer therapy (i.e., radiotherapy or chemotherapy) also were eligible. A dedicated near-infrared imaging system was used for real-time fluorescence imaging during surgery. Safety assessments were performed and SGM-101 efficacy was evaluated per dose level to determine the most optimal imaging dose.
Results
Thirty-seven patients with CRC were included in the analysis. Fluorescence was visible in all primary and recurrent tumors. In seven patients, no fluorescence was seen; all were confirmed as pathological complete responses after neoadjuvant therapy. Two tumors showed false-positive fluorescence. In the 37 patients, a total of 97 lesions were excised. The highest mean intraoperative tumor-to-background ratio (TBR) of 1.9 (p = 0.019) was seen in the 10-mg dose. This dose showed a sensitivity of 96%, specificity of 63%, and negative predictive value of 94%. Nine patients (24%) had a surgical plan alteration based on fluorescence, with additional malignant lesions detected in six patients.
Conclusions
The optimal imaging dose was established at 10 mg 4 days before surgery. The results accentuate the potential of SGM-101 and designated a promising base for the multinational phase III study, which enrolled the first patients in June 2019.
This multicentre pilot study investigated the role of peroperative carcinoembryonic antigen (CEA)‐specific fluorescence imaging during cytoreductive surgery–hyperthermic intraperitoneal chemotherapy surgery in peritoneal metastasized colorectal cancer. A correct change in peritoneal carcinomatosis index (PCI) owing to fluorescence imaging was seen in four of the 14 included patients. The use of SGM‐101 in patients with peritoneally metastasized colorectal carcinoma is feasible, and allows intraoperative detection of tumour deposits and alteration of the PCI.
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