Growth of Uveal Melanoma following Intravitreal Bevacizumab

Abstract

Purpose: Typically treatment of large melanomas (by Collaborative Ocular Melanoma Study criteria) is restricted to enucleation, due to size constraints for plaque brachytherapy. Because primary and metastatic uveal melanoma cells are inhibited by bevacizumab (an anti-vascular endothelial growth factor), this prospective study evaluated the impact of intravitreal bevacizumab on large uveal melanomas that were destined for enucleation. Size reduction by bevacizumab would potentially salvage these eyes by making them eligible for treatment with plaque brachytherapy. Procedures: Two patients with large uveal melanoma were each treated with one intravitreous injection of bevacizumab (1.25 mg/0.05 mL). Results: Both tumors displayed paradoxical growth 1 week following the injection, with confirmed growth 1 week later (increase from baseline of 1.1 mm in one eye and 3.1 mm in the other eye). Both eyes were enucleated and monosomy 3 and vasculogenic mimicry patterns were identified in both tumors. At 9 years follow-up, both patients were alive and metastasis free. Conclusion: These patients demonstrate that neoadjuvant intravitreous bevacizumab does not decrease the size of large uveal melanomas and may, in fact, result in their paradoxical growth. This observation supports a cautious approach in the use of intravitreous bevacizumab for uveal melanoma, particularly in the neoadjuvant setting.

TRPM8 Activation via 3-Iodothyronamine Blunts VEGF-Induced Transactivation of TRPV1 in Human Uveal Melanoma Cells

“…As a matter of fact, such treatment is reported to even promote expansion of melanoma cells in vitro (Dithmer et al, 2017 ). Furthermore, neoadjuvant intravitreous injection of this VEGF trap failed to shrink large size melanoma and is even counter indicated in these cases because it may instead even promote melanoma growth (Francis et al, 2017 ).…”

Treatment response to intravitreal bevacizumab in small pigmented choroidal lesions with subretinal fluid

“…We were concerned, as such tumor growth could be a possible adverse effect of bevacizumab. Recently, similar cases of paradoxical enlargement were reported in patients with uveal melanoma after IVB [32]. They used IVB as a neoadjuvant concept for treating uveal melanoma, but observed that the tumor size increased rather than decreased, and the study was terminated early.…”

Vasculogenic mimicry as a poor diagnostic and prognostic indicator in patients with malignant‎ melanoma: A ‎systematic review and meta-analysis

“…Recently, in vivo and in vitro studies showed that twistrelated protein 1 (Twist1), neurogenic locus notch homolog protein 4 (Notch4), hypoxia inducible factor (HIF)-1a , EPH receptor A2 (EphA2), matrix metalloproteinase (MMP)-1, 2, -9, -14, and vascular endothelial (VE)-cadherin are potential therapeutic targets and prognostic indicators in VM+ tumor samples [22,56]. Moreover, these studies suggest that VM+ tumor samples were resistant to common antiangiogenic drugs, such as apatinib, bevacizumab, and sunitinib [23,34,57]. The high ratio of neovascularization in VM+ tumor promotes angiogenesis, metastasis, and tumor growth along with extensive hypoxia and necrosis as well as induced recruitment of various pro-angiogenic factors, such as bone marrow-derived CD45 + myeloid cells, pericyte progenitor cells, and mature F4/80 + tumor-associated macrophages [58,59].…”