Retrospective analysis of secondary enucleation for uveal melanoma after plaque radiotherapy

Abstract

Background Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Plaque brachytherapy (PRT) is widely accepted as an effective globe-conserving treatment modality for UM. However, local treatment failure and complications lead to the enucleation of irradiated eyes. We conducted this study to explore the causes and long-term prognosis for UM patients who accepted secondary enucleation after plaque radiotherapy. Methods This was a retrospective cohort study. Data of patients who underwent secondary enucleation for UM after plaque radiotherapy, from July 2007 to July 2019, at Beijing Tongren Hospital were analyzed. Kaplan–Meier analysis was performed to assess the probability of indications, metastasis, and metastasis-related death. Cox regression analysis was used to analyze associations of the prognostic factors. Results Eight hundred and eighty patients were clinically diagnosed with uveal melanoma and initially treated by iodine-125 plaque radiotherapy, 132 of whom underwent secondary enucleation and pathological examination in the same hospital. Fifty-two (39.4%) eyes were enucleated simply because of uncontrollable neovascular glaucoma (NVG). Forty-four (33.3%) patients suffered from tumor recurrence. Tumor non-response occurred in 18 (13.6%) cases. Ten (7.6%) eyes received enucleation entirely due to other types of glaucoma. Failure to preserve the eyes for other reasons occurred in eight (6.1%) patients. At a median follow-up of 58.1 [IQR: 40.9–90.5] months, the systemic spread was detected in 45 (34.1%) patients, and 38 of them died. On multivariate analysis, tumor largest basal diameter (HR 1.15 [95% CI: 1.01, 1.31]), tumor non-response (HR 7.22 [95% CI: 2.63, 19.82]), and recurrence (HR 3.29 [95% CI: 1.54, 7.07]) were risk factors for metastasis. Increased age (HR 1.54 [95% CI: 1.07, 2.23]), tumor non-response (HR 7.91 [95% CI: 2.79, 22.48]), and recurrence (HR 3.08 [95% CI: 1.13, 7.23]) were risk factors for metastasis-related death. Conclusions NVG was the major reason for secondary enucleation for Chinese UM patients after PRT. Tumor non-response and recurrence were associated with a significantly higher risk of long-term metastasis and metastasis-related death.

Radiotherapy in Uveal Melanoma: A Review of Ocular Complications

“…Several parameters may contribute to the development or progression of NVG. Tumor thickness [47,59,93,95], higher tumor apical height [109], posterior tumors (located between posterior pole and equator) [47], peripapillary location [47,59,95,123], mushroom configuration [95], volume of posterior segment receiving more that 20Gy [93], Bruch's membrane rupture [93], higher grade of radiation retinopathy [121], initial retinal detachment [59], and local recurrence [59] are predictive factors reported in the literature.…”

“…The main adverse events of sub-tenon triamcinolone are ocular hypertension, cataract (30% to 45%), and prolapse of orbital fat [33,108]. Intravitreal anti-VEGF injection involves the risk of endophthalmitis and the theoretical risk of cardiovascular complications [87,108,109]. Radiation maculopathy is vastly suppressed by intravitreal anti-VEGF therapy, mainly through the use of bevacizumab, ranibizumab, and aflibercept [33,36,87,96,107,108].…”

“…Neovascular glaucoma (NVG), a form of secondary glaucoma, manifests as a result of the neovascularization of the iris and the anterior chamber angle [52]. NVG is the major reason for secondary enucleation, and it may occur after all forms of radiotherapy for uveal melanoma [45,47,48,89,99,102,109]. It is believed that the pathogenesis of radiationinduced NVG is based on the release of proangiogenic factors from direct radiation damage to tumor endothelial cells.…”