First in-human intraoperative optical imaging of peritoneal carcinomatosis of colorectal origin using the VEGF-targeted near-infrared fluorescent tracerbevacizumab-IRDye800CW: a feasibility study. HI-LIGHT study, NL45588-042-13

Jongh, S.J. de (2015) First in-human intraoperative optical imaging of peritoneal carcinomatosis of colorectal origin using the VEGF-targeted near-infrared fluorescent tracerbevacizumab-IRDye800CW: a feasibility study. HI-LIGHT study, NL45588-042-13. thesis, Medicine.

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Abstract

Introduction Optimal cytoreduction (CRS) in addition to Hyperthermic IntraPEritoneal Chemotherapy (HIPEC) is essential for the curative treatment of peritoneal carcinomatosis (PC) of colorectal origin. Currently, differentiation between benign and malignant lesions can be very difficult and the diagnostic accuracy profile of tactile and visual inspection remains unknown. Better tumor detection could lead to improved radical cytoreduction. In this study we used nearinfrared fluorescence (NIRF) imaging to enhance surgical vision. Methods Patients scheduled for CRS and HIPEC were included in this feasibility study (n=7). The NIRF tracer bevacizumab-IRDye800CW targeting VEGF-A was administered intravenously two days prior to surgery. After exposure of the abdominal cavity, two surgeons independently calculated the peritoneal cancer index (PCI) first by inspection and palpation, subsequently using the NIR intraoperative camera system. Biopsies were taken from fluorescent and non-fluorescent areas for ex-vivo validation and correlation of fluorescence. Results No (serious) adverse events related to tracer administration occurred in any of the seven patients. In total 87 peritoneal lesions were imaged and histologically analyzed. In 31 out of 58 fluorescent lesions cancerous cells were detected during histopathological analysis. All 23 non-fluorescent lesions were cancer negative, indicating a sensitivity of 100%. Additionally, in two patients this method detected cancerous tissue that was otherwise missed by inspection and palpation alone. In one patient this concerned a positive resection margin and in another patient a para-aortal lymph node metastasis was detected. Despite the relatively high false positive rate (47%), the PCI decreased 2.9 points on average per patient. Most false positive lesions appeared to be highly fibrotic and vascularized lesions or foreign inclusion bodies such as suturing material from previous surgery. Fluorescence was strongly correlated with vital tumor tissue ex-vivo at a microscopic level, with a tumor-to-normal ratio of 6,92 ± 2,47 (mean ± sd). Conclusion Intraoperative NIRF-imaging of PC during CRS is technically feasible and safe. This highly sensitive technique can lead to a more optimal cytoreduction by leaving suspicious lesions that are not fluorescent in situ. Moreover, stage migration might occur due to better patient selection, possibly enabling more patients to benefit from the curative CRS and HIPEC procedure. Therefore, this technique has to potential to prevent both over and under treatment. Additionally, NIRF-imaging enables the evaluation of possible positive resection margins, which might be of use in the treatment of locally advanced rectal cancer. We state that these preliminary results are promising for a subsequent phase II study.

Item Type:	Thesis (Thesis)
Supervisor name:	Supervisor and Dam, Prof. dr. Gooitzen M. van and Co-supervisors and Harlaar, Drs. Niels J. and Koller, Drs. Marjory and University Medical Centre Groningen (UMCG) and Surgery – Surgical Oncology and Image and Fluorescence-guided Surgery and Working Group
Faculty:	Medical Sciences
Date Deposited:	25 Jun 2020 10:43
Last Modified:	25 Jun 2020 10:43
URI:	https://umcg.studenttheses.ub.rug.nl/id/eprint/495

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