Impact of uveal melanoma thickness on post‐plaque radiotherapy outcomes in the prophylactic anti‐vascular endothelial growth factor era in 1131 patients

Abstract

Importance The impact of tumour thickness on radiation complications following plaque radiotherapy for uveal melanoma in the anti‐vascular endothelial growth factor (VEGF) era remains unknown. Background To evaluate treatment outcomes following plaque radiotherapy and prophylactic intravitreal bevacizumab for uveal melanoma based on initial tumour thickness. Design This was a retrospective, interventional case series. Participants Patients with uveal melanoma were included in this study. Methods A review of medical records was conducted of patients with uveal melanoma treated with plaque radiotherapy and prophylactic intravitreal bevacizumab from 7 July 2000 to 2 November 2018. Main outcomes measures Radiation‐related outcomes of cystoid macular oedema (CME), radiation maculopathy, papillopathy, retinopathy, iris neovascularization (NVI) and neovascular glaucoma (NVG) were compared based on tumour thickness (small [<3.0 mm] vs medium [3.1‐8.0 mm] vs large [>8.0 mm]). Results Of 1131 eyes, 341 (30%) had small, 633 (56%) medium and 157 (14%) large melanoma. Comparison (small vs medium vs large) at 4 years following radiotherapy revealed large melanoma with greater Kaplan‐Meier estimated risk of CME (37% vs 37% vs 63%, P < .001), earlier onset of CME (33 vs 26 vs 19 months, P < .001) and greater development of NVI (<1% vs 2% vs 13%, P < .001) and NVG (1% vs 2% vs 12%, P < .001). Radiation‐induced maculopathy, papillopathy and retinopathy were not associated with tumour thickness. Conclusions and relevance Compared with small and medium uveal melanoma, large uveal melanoma demonstrated greater 48‐month risk for CME, shorter time to CME onset and greater development of NVI and NVG following plaque radiotherapy and prophylactic intravitreal bevacizumab.

Uveal melanoma in 2020: Does size still matter?

“…For patients with large tumours, globe‐sparing treatment with radiation may be preferred over enucleation in the hopes of maintaining some useful vision. However, even with the use of prophylactic anti‐VEGF therapies following radiation treatment, larger, thicker tumours in the study by Yang et al 15 were still associated with a higher risk of radiation complications and were more likely to require enucleation (small vs medium vs large 1% vs 1% vs 4% P<.001) at an earlier time point (small vs medium vs large 69 months vs 27 months vs 41 months P=.03) compared to patients with smaller tumours.…”

“…Since then, multiple studies have examined the use of anti‐vascular endothelial growth factor (VEGF) intravitreal agents in an attempt to prevent post‐radiation cystoid macular oedema (CMO) and associated visual loss following radiotherapy of uveal melanoma 12‐14 . Yang et al, 15 in this issue, of Clinical and Experimental Ophthalmology examined the impact of uveal melanoma thickness following plaque radiotherapy on radiation outcomes in the anti‐VEGF era. They reported that, even with the use of prophylactic anti‐VEGF treatment, tumour thickness remained an important risk factor for radiation complications, with larger melanoma demonstrating greater Kaplan‐Meier estimated risk of OCT‐evident CMO ( P < .001), earlier onset of CMO ( P < .001) and greater development of neovascularisation of the iris ( P < .001) and neovascular glaucoma ( P < .001) 15 .…”

“…Yang et al, 15 in this issue, of Clinical and Experimental Ophthalmology examined the impact of uveal melanoma thickness following plaque radiotherapy on radiation outcomes in the anti‐VEGF era. They reported that, even with the use of prophylactic anti‐VEGF treatment, tumour thickness remained an important risk factor for radiation complications, with larger melanoma demonstrating greater Kaplan‐Meier estimated risk of OCT‐evident CMO ( P < .001), earlier onset of CMO ( P < .001) and greater development of neovascularisation of the iris ( P < .001) and neovascular glaucoma ( P < .001) 15 . In contrast to results from studies prior to the use of prophylactic anti‐VEGF previously mentioned, 10 tumour thickness was not a predictor for visual outcome.…”

“…Multimodal imaging has allowed us to more accurately identify small uveal melanoma and high‐risk lesions, with the risk of growth to melanoma increasing with each millimetre increase in naevus thickness 5 . The use of prophylactic anti‐VEGF treatments might offer an improved visual prognosis, especially for thicker tumours, although thickness remains a significant risk factor for radiation complications and enucleation 15 . Finally, while uveal melanoma size as described in the AJCC staging classification is an important prognostic factor, the newly described TCGA classification might be more accurate and useful in predicting the risk of metastatic disease 21 .…”

Powerful predictors

“…The group led by Shields worked with a large data set from 1131 patients to show that uveal melanoma thickness impacted the likelihood of complications from radiation retinopathy, including cystoid macular oedema, iris neovascularisation and neovascular glaucoma. 12 In another large study focused on uveal melanoma, Jabbarli et al sought predictors for scleral necrosis after brachytherapy across a group of 3960 patients. 13 Multiple risk factors were identified by case-control proportional hazard analysis, including tumour margin anterior to the equator, extraocular tumour extension, scleral contact dose, conjunctival dehiscence, superior rectus muscle disinsertion and use of glaucoma medication.…”