Intraoperative optical imaging of peritoneal carcinomatosis of colorectal origin using a VEGF targeted fluorescent tracer – Results of the Hi-Light study, a first in human imaging study
Presented by Niels J. Harlaar, M.D. Ph.D., University of Groningen
Optimal cytoreduction in addition to a Hyperthermic IntraPEritoneal Chemotherapy (HIPEC) procedure is of essential value in the curative treatment of peritoneal carcinomatosis of colorectal origin. Currently, the maximum size of detection of peritoneal lesions with tactile and visual inspection is only several millimeters. Smaller lesions may go undetected. As tactile and visual inspection do not distinguish between benign and malignant lesions, unnecessary resections of organs may result. More accurate detection of small metastases could enable a way to distinguish between benign and malignant lesions improving the efficacy of hyperthermic chemotherapy, preventing over- and under-treatment.
Peritoneal metastases of colorectal origin were detected using bevacizumab-IRDye800CW, a near-infrared fluorescent tracer targeting VEGF-A, in combination with an intraoperative camera system. After exposure of the abdominal cavity, two surgeons independently calculated the PCI (peritoneal cancer index). Initially based on palpation and visual inspection, followed by imaging using the fluorescence platform. Biopsies were taken from fluorescent and non-fluorescent areas for ex vivo analysis by H&E staining and fluorescence microscopy.
In this Proof-of-Concept study currently, seven patients have been included and analyzed. A total of 87 lesions were imaged and histologically analyzed. In 31 out of 58 fluorescent lesions (54%) cancerous cells were found during histological analysis. All 23 non-fluorescent lesions were cancer negative. Additionally, in two patients the method detected cancer tissue that was initially missed by inspection and palpation. In one patient this concerned a positive resection margin and in the second case a para-aortal lymph node metastasis was found (figure). Most false positive lesions appeared to be foreign inclusion bodies such as suturing material from previous surgery. In spite of the relatively high false positive rate, the PCI decreases with 1 up to 6 points using this technique. The ex vivo fluorescence analyses of paraffin embedded tissue slices of tumor and non-tumor lesions showed a mean tumor to normal ratio of 7,2 (SD 2,2).
Intraoperative near-infrared fluorescence imaging of peritoneal carcinomatosis during the HIPEC procedure is technically feasible. The high sensitivity (100%) gives the surgeon potentially a real-time tool for intraoperative decision-making. This indicates that this technique could prevent both undertreatment and overtreatment. Undertreatment coud be prevented by more complete detection of malignant lesions, Overtreatment could be prevented by intraoperative identification of non-malignant lesions that do not require resection. A less extensive but just surgical procedure will reduce morbidity, but possibly increase survival. We state that these preliminary results are promising for a subsequent phase II study.