King's Ophthalmology Research Unit (KORU), Department of Ophthalmology, King's College Hospital, London, UK; Faculty of Life Sciences and Medicine, King's College London, London, UK.
King's Ophthalmology Research Unit (KORU), Department of Ophthalmology, King's College Hospital, London, UK; Faculty of Life Sciences and Medicine, King's College London, London, UK.
Lancet. 2024 Jul 6;404(10447):44-54. doi: 10.1016/S0140-6736(24)00687-1. Epub 2024 Jun 11.
Neovascular age-related macular degeneration (nAMD) is a leading cause of blindness. The first-line therapy is anti-vascular endothelial growth factor (anti-VEGF) agents delivered by intravitreal injection. Ionising radiation mitigates key pathogenic processes underlying nAMD, and therefore has therapeutic potential. STAR aimed to assess whether stereotactic radiotherapy (SRT) reduces the number of anti-VEGF injections required, without sacrificing visual acuity.
This pivotal, randomised, double-masked, sham-controlled trial enrolled participants with pretreated chronic active nAMD from 30 UK hospitals. Participants were randomly allocated in a 2:1 ratio to 16-Gray (Gy) SRT delivered using a robotically controlled device or sham SRT, stratified by treatment centre. Eligible participants were aged 50 years or older and had chronic active nAMD, with at least three previous anti-VEGF injections, including at least one in the last 4 months. Participants and all trial and image reading centre staff were masked to treatment allocation, except one unmasked statistician. The primary outcome was the number of intravitreal ranibizumab injections required over 2 years, tested for superiority (fewer injections). The main secondary outcome was Early Treatment Diabetic Retinopathy Study visual acuity at two years, tested for non-inferiority (five-letter margin). The primary analysis used the intention-to-treat principle, and safety was analysed per-protocol on participants with available data. The study is registered with ClinicalTrials.gov (NCT02243878) and is closed for recruitment.
411 participants enrolled between Jan 1, 2015, and Dec 27, 2019, and 274 were randomly allocated to the 16-Gy SRT group and 137 to the sham SRT group. 240 (58%) of all participants were female, and 171 (42%) of all participants were male. 241 participants in the 16-Gy SRT group and 118 participants in the sham group were included in the final analysis, and 409 patients were treated and formed the safety population, of whom two patients allocated to sham treatment erroneously received 16-Gy SRT. The SRT group received a mean of 10·7 injections (SD 6·3) over 2 years versus 13·3 injections (5·8) with sham, a reduction of 2·9 injections after adjusting for treatment centre (95% CI -4·2 to -1·6, p<0·0001). The SRT group best-corrected visual acuity change was non-inferior to sham (adjusted mean letter loss difference between groups, -1·7 letters [95% CI -4·2 to 0·8]). Adverse event rates were similar across groups, but reading centre-detected microvascular abnormalities occurred in 77 SRT-treated eyes (35%) and 13 (12%) sham-treated eyes. Overall, eyes with microvascular abnormalities tended to have better best-corrected visual acuity than those without. Fewer ranibizumab injections offset the cost of SRT, saving a mean of £565 per participant (95% CI -332 to 1483).
SRT can reduce ranibizumab treatment burden without compromising vision.
Medical Research Council and National Institute for Health and Care Research Efficacy and Mechanism Evaluation Programme.
新生血管性年龄相关性黄斑变性（nAMD）是导致失明的主要原因。一线治疗方法是玻璃体内注射抗血管内皮生长因子（anti-VEGF）药物。电离辐射减轻了 nAMD 主要发病机制，因此具有治疗潜力。STAR 旨在评估立体定向放射治疗（SRT）是否可以减少所需的抗 VEGF 注射次数，同时不牺牲视力。
这项关键性、随机、双盲、假对照试验招募了来自英国 30 家医院的经预处理的慢性活动性 nAMD 患者。参与者按照 2:1 的比例随机分配到 16 格雷（Gy）SRT 组或假 SRT 组，按治疗中心分层。合格的参与者年龄在 50 岁或以上，患有慢性活动性 nAMD，至少接受过三次抗 VEGF 注射，其中至少有一次在过去 4 个月内。参与者和所有试验和图像阅读中心工作人员对治疗分配均进行了双盲，但有一名未蒙面的统计学家除外。主要结局是两年内所需的玻璃体内雷珠单抗注射次数，检验是否有优势（注射次数更少）。主要次要结局是两年时早期治疗糖尿病视网膜病变研究视力，检验是否有非劣效性（5 个字母差距）。主要分析采用意向治疗原则，对有可用数据的参与者进行方案预设的安全性分析。该研究在 ClinicalTrials.gov 注册（NCT02243878），现已关闭招募。
2015 年 1 月 1 日至 2019 年 12 月 27 日期间，共有 411 名参与者登记，其中 274 名随机分配到 16-Gy SRT 组，137 名随机分配到假 SRT 组。所有参与者中，240 名（58%）为女性，171 名（42%）为男性。16-Gy SRT 组的 241 名参与者和假 SRT 组的 118 名参与者被纳入最终分析，409 名患者接受了治疗并形成了安全性人群，其中两名被分配到假治疗的患者错误地接受了 16-Gy SRT。SRT 组在两年内平均接受了 10.7 次注射（6.3 次），而假 SRT 组接受了 13.3 次注射（5.8 次），调整治疗中心后减少了 2.9 次注射（95%CI -4.2 至 -1.6，p<0.0001）。SRT 组最佳矫正视力变化不劣于假 SRT（组间调整后的平均字母损失差异为 -1.7 个字母[95%CI -4.2 至 0.8]）。各组的不良事件发生率相似，但在接受 SRT 治疗的眼睛中发现了 77 只（35%）和假治疗的眼睛中发现了 13 只（12%）阅读中心检测到的微血管异常。总的来说，有微血管异常的眼睛的最佳矫正视力往往比没有的好。减少雷珠单抗注射次数抵消了 SRT 的成本，每位参与者平均节省 565 英镑（95%CI -332 至 1483）。
SRT 可以减少雷珠单抗的治疗负担，同时不影响视力。
英国医学研究理事会和国家卫生与保健研究所疗效与机制评价计划。
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