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Christine Law, Ashley Minuk, Isabella Irrcher, James Farmer, Vladimir Kratky; Identification of vascular endothelial growth factor protein in eyelid basal cell carcinomas: A potential novel, non-surgical therapy. Invest. Ophthalmol. Vis. Sci. 2014;55(13):851.
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The gold-standard treatment for eyelid basal cell carcinomas (BCCs) is complete excision. Due to limited eyelid surface area, excisions may lead to extensive surgical reconstruction. Anti-vascular endothelial growth factor (VEGF) agents have been commonly used as targeted therapy of other systemic cancers. No research has quantified skin BCC VEGF levels relative to their pathologic subtype. We investigated the potential role of VEGF as a non-surgical treatment target by quantifying VEGF levels in eyelid BCCs, and testing the safety of bevacizumab eyelid injections in an animal model.
All patients with biopsy-proven BCCs undergoing lesion excision from April to October 2013 were included. A 2.5mm punch biopsy was obtained from both the BCC and uninvolved skin away from the lesion. All BCC lesions were sent to pathology for final histopathologic diagnosis. The punch biopsy samples were processed for tissue VEGF levels through a commercially available VEGF enzyme-linked immunosorbent assay. To assess safety, bevacizumab was injected subcutaneously into the left eyelid of New Zealand white rabbits. Each right rabbit eyelid received volume-matched saline control. Eyelid punch biopsies for histological examination of inflammation were obtained pre-injection, at week 1 and 5 post-injection. Adverse events were recorded, and photographs taken weekly to assess eyelids for gross clinical changes.
A total of 14 patients with pathology-proven BCCs were included. Histopathologic types included infiltrative (8/14), nodular (5/14), and micronodular (1/14). BCC versus uninvolved skin VEGF levels were not different as a whole (1219 pg/mL vs. 974 pg/mL; P=0.400). However, according to their histopathologic type, infiltrative BCCs displayed significantly higher VEGF levels compared to non-cancerous skin (1334 pg/mL vs. 343 pg/mL; P=0.001). Nodular BCC VEGF levels were not elevated (949 pg/mL vs. 1709 pg/mL; P=0.204). No adverse events, significant inflammation, or gross clinical change of rabbit eyelids were seen at any time point after bevacizumab injection.
We show (1) eyelid infiltrative BCCs, the most aggressive of our subtypes, are VEGF-positive tumors, and (2) bevacizumab eyelid injections are safe through our animal model. Thus anti-VEGF therapy may offer a novel, targeted, non-surgical treatment option for infiltrative BCCs.
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