Supplementary Material for: Predictors of Local Recurrence and Progression-Free Survival in Iodine-125 brachytherapy-treated Uveal Melanomas: A modern institutional study

Introduction: Iodine-125 brachytherapy is an effective eye-sparing treatment for uveal melanoma. Previous work has shown that uveal melanomas cluster into distinct molecular classes based on gene expression profiles—discriminating low-grade from high-grade tumors. Our objective was to identify clinical and molecular predictors of local recurrence (LR) and progression-free survival (PFS). Methods: We constructed a retrospective database of uveal melanoma patients from the University of Miami’s electronic medical records that were treated between 8/1/2012-5/1/2019, with either COMS-style or Eye Physics plaque. Data on tumor characteristics, pre-treatment retinal complications, post-plaque treatments, LR and PFS were collected. Univariate and multivariate Cox models for cumulative incidence of LR and PFS were conducted using SAS version 9.4. Results: We identified 262 patients, with a median follow-up time of 33.5 months. 19 patients (7.3%) had local recurrence and 56 patients (21.4%) were classified as PFS. We found that ocular melanocytosis (HR = 5.55, p < 0.001) had the greatest impact on PFS. Genetic expression profile did not predict local recurrence outcomes (HR = 0.51, p = 0.297). Conclusion: These findings help physicians identify predictors for short-term brachytherapy outcomes allowing better shared decision making with patients pre-operatively when deciding between brachytherapy vs. enucleation. Patients stratified to higher risk groups based on pre-operative characteristics such as ocular melanocytosis should be monitored more closely. Future studies must validate these findings using a prospective cohort study.

引言：碘-125近距离放射治疗（Iodine-125 brachytherapy）是葡萄膜黑色素瘤（uveal melanoma）的有效眼保全治疗手段。既往研究显示，葡萄膜黑色素瘤可基于基因表达谱划分为不同的分子亚型，以此区分低级别与高级别肿瘤。本研究旨在明确局部复发（local recurrence, LR）与无进展生存期（progression-free survival, PFS）的临床及分子预测因素。

方法：本研究从迈阿密大学电子病历系统中构建了2012年8月1日至2019年5月1日期间接受治疗的葡萄膜黑色素瘤患者回顾性数据库，所有患者均接受了COMS型或Eye Physics型放射性敷贴器治疗。研究收集了患者的肿瘤特征、治疗前视网膜并发症、敷贴治疗后干预措施、局部复发及无进展生存期相关数据。采用SAS 9.4统计软件构建了针对局部复发与无进展生存期累积发生率的单因素及多因素Cox比例风险回归模型。

结果：本研究共纳入262例患者，中位随访时间为33.5个月。其中19例（7.3%）患者发生局部复发，56例（21.4%）患者达到无进展生存终点。研究发现，眼黑素细胞增多症（ocular melanocytosis）对无进展生存期的影响最为显著（风险比=5.55，P<0.001）；而基因表达谱无法预测局部复发结局（风险比=0.51，P=0.297）。

结论：本研究结果有助于临床医生明确近距离放射治疗短期结局的预测因素，从而在术前为患者提供更充分的共同决策支持，协助其在近距离放射治疗与眼球摘除术之间做出选择。对于根据术前特征（如眼黑素细胞增多症）被划分为高风险组的患者，应予以更密切的随访监测。未来需开展前瞻性队列研究以验证本研究结果。