Image Guided Surgery in Sinonasal Inverted Papilloma by Targeting Vascular Endothelial Growth Factor

Rationale: During surgical resection, it is very challenging to discriminate between sinonasal inverted papilloma (SNIP) and surrounding tissue, as SNIP is associated with inducement of granulomatous inflammation of the environment. As a result, the surgeon has to perform a thorough resection in order to remove the complete inverted papilloma, which is associated with substantial morbidity. Clearly, there is need for an instrument that is able to guide the surgeon to discriminate between SNIP and surrounding tissue. Molecular imaging techniques using targeted optical contrast agents is a promising technique to accommodate this need. Vascular Endothelial Growth Factor (VEGF) is overexpressed in SNIP compared to normal epithelium of the sinonasal area and has been used effectively in molecular imaging.

Objectives: The main objective is to study if the conjugate bevacizumab-IRDye800CW accumulates more in sinonasal inverted papilloma than in normal sinonasal mucosa.

Study design: The current study is a non-randomized, non-blinded, prospective, single center, pilot dose-escalation study. A minimum of five and a maximum of eight patients with SNIP will be included. Five patients will be administered with 10 mg bevacizumab-IRDye800CW. An interim analysis is performed after inclusion of the first three patients to determine if a tumor-to-background ratio (TBR) of ≥2 is obtained by either intraoperative fluorescence in vivo measurements or by ex vivo back-table fluorescence imaging. If a TBR of ≥2 is found, inclusion is continued to five patients. If not, the dose is adjusted to 25 mg. Again, a similar interim analysis is performed after inclusion of the first three patients to determine the TBR.

Study population: All included patients will meet the in- and exclusion criteria and have a biopsy confirmed diagnosis of primary or recurrent sinonasal inverted papilloma and are scheduled to undergo surgical resection.

Patient related study procedures: Patients will - after written informed consent - receive an intravenous injection of the fluorescent tracer. The dose will be either 10 mg or 25 mg. Two to four days later, the peroperative fluorescence imaging and multidiameter single fiber reflectance and single fiber fluorescence (MDSFR/SFF) spectroscopy will be performed of the tumor and woundbed.