Abstract：
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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).
CONCLUSIONS: SRT can reduce ranibizumab treatment burden without compromising vision.
BACKGROUND: Medical Research Council and National Institute for Health and Care Research Efficacy and Mechanism Evaluation Programme.
METHODS: 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.
RESULTS: 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).
CONCLUSIONS: SRT can reduce ranibizumab treatment burden without compromising vision.
BACKGROUND: Medical Research Council and National Institute for Health and Care Research Efficacy and Mechanism Evaluation Programme.
摘要：
背景：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。一线疗法是通过玻璃体内注射递送的抗血管内皮生长因子(抗VEGF)剂。电离辐射减轻了nAMD潜在的关键致病过程，因此具有治疗潜力。STAR旨在评估立体定向放疗（SRT）是否减少了所需的抗VEGF注射次数，而不牺牲视力。
方法：这个关键，随机化，双面蒙面,假对照试验纳入了来自英国30家医院的接受慢性活动性nAMD预处理的参与者.参与者以2：1的比例随机分配给使用机器人控制设备或假SRT交付的16灰色（Gy）SRT，由治疗中心分层。符合条件的参与者年龄在50岁或以上，患有慢性活动性nAMD，至少三次之前的抗VEGF注射，包括过去4个月中的至少一个。参与者以及所有试验和图像阅读中心的工作人员都被掩盖了治疗分配，除了一个未蒙面的统计学家.主要结果是2年内所需的玻璃体内雷珠单抗注射次数。测试的优越性（较少的注射）。主要次要结果是早期治疗糖尿病视网膜病变研究两年时的视力，测试非劣效性(五字母边缘)。初步分析使用了意向治疗原则，并根据方案对参与者的可用数据进行安全性分析.该研究已在ClinicalTrials.gov（NCT02243878）注册，并因招募而关闭。
结果：在2015年1月1日至2019年12月27日之间招募的411名参与者被随机分配到16GySRT组，137名被随机分配到假SRT组。所有参与者中有240人（58%）是女性，所有参与者中有171名(42%)为男性。16-GySRT组的241名参与者和假手术组的118名参与者被纳入最终分析，409名患者接受了治疗，形成了安全人群，其中两名被分配到假治疗的患者错误地接受了16GySRT。SRT组在2年内平均接受10·7次注射（SD6·3），而假手术组平均接受13·3次注射（5·8），调整治疗中心后，注射量减少2·9（95%CI-4·2至-1·6，p<0·0001）。SRT组最佳矫正视力变化不劣于假手术(组间调整后的平均字母丢失差异，-1·7个字母[95%CI-4·2至0·8])。各组不良事件发生率相似，但是阅读中心检测到的微血管异常发生在77只接受SRT治疗的眼(35%)和13只接受假治疗的眼(12%).总的来说,有微血管异常的眼睛往往比没有的眼睛具有更好的最佳矫正视力。更少的雷珠单抗注射抵消了SRT的成本，每位参与者平均节省565英镑(95%CI-332至1483)。
结论：SRT可在不损害视力的情况下降低雷珠单抗治疗负担。
背景：医学研究委员会和国家卫生与护理研究所的疗效和机制评估计划。
方法：这个关键，随机化，双面蒙面,假对照试验纳入了来自英国30家医院的接受慢性活动性nAMD预处理的参与者.参与者以2：1的比例随机分配给使用机器人控制设备或假SRT交付的16灰色（Gy）SRT，由治疗中心分层。符合条件的参与者年龄在50岁或以上，患有慢性活动性nAMD，至少三次之前的抗VEGF注射，包括过去4个月中的至少一个。参与者以及所有试验和图像阅读中心的工作人员都被掩盖了治疗分配，除了一个未蒙面的统计学家.主要结果是2年内所需的玻璃体内雷珠单抗注射次数。测试的优越性（较少的注射）。主要次要结果是早期治疗糖尿病视网膜病变研究两年时的视力，测试非劣效性(五字母边缘)。初步分析使用了意向治疗原则，并根据方案对参与者的可用数据进行安全性分析.该研究已在ClinicalTrials.gov（NCT02243878）注册，并因招募而关闭。
结果：在2015年1月1日至2019年12月27日之间招募的411名参与者被随机分配到16GySRT组，137名被随机分配到假SRT组。所有参与者中有240人（58%）是女性，所有参与者中有171名(42%)为男性。16-GySRT组的241名参与者和假手术组的118名参与者被纳入最终分析，409名患者接受了治疗，形成了安全人群，其中两名被分配到假治疗的患者错误地接受了16GySRT。SRT组在2年内平均接受10·7次注射（SD6·3），而假手术组平均接受13·3次注射（5·8），调整治疗中心后，注射量减少2·9（95%CI-4·2至-1·6，p<0·0001）。SRT组最佳矫正视力变化不劣于假手术(组间调整后的平均字母丢失差异，-1·7个字母[95%CI-4·2至0·8])。各组不良事件发生率相似，但是阅读中心检测到的微血管异常发生在77只接受SRT治疗的眼(35%)和13只接受假治疗的眼(12%).总的来说,有微血管异常的眼睛往往比没有的眼睛具有更好的最佳矫正视力。更少的雷珠单抗注射抵消了SRT的成本，每位参与者平均节省565英镑(95%CI-332至1483)。
结论：SRT可在不损害视力的情况下降低雷珠单抗治疗负担。
背景：医学研究委员会和国家卫生与护理研究所的疗效和机制评估计划。
