高危视网膜母细胞瘤化疗3周期与6周期对比：一项随机临床试验
Three vs 6 Cycles of Chemotherapy for High-Risk Retinoblastoma: A Randomized Clinical Trial.
作者信息
Ye Huijing, Xue Kang, Zhang Ping, Chen Rongxin, Zhai Xiaowen, Ling Li, Xiao Wei, Tang Lijuan, Wang Hongsheng, Mao Yuxiang, Ai Siming, Bi Yingwen, Liu Qing, Zou Yusha, Qian Jiang, Yang Huasheng
机构信息
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, China.
Department of Ophthalmology and Shanghai Key Laboratory of Visual Impairment and Restoration, Eye, Ear, Nose, and Throat Hospital of Fudan University, Shanghai, China.
出版信息
JAMA. 2024 Nov 19;332(19):1634-1641. doi: 10.1001/jama.2024.19981.
IMPORTANCE
Adjuvant therapy is an important and effective treatment for retinoblastoma. However, there is a lack of head-to-head clinical trials comparing 3 vs 6 cycles of CEV chemotherapy (carboplatin, etoposide, and vincristine) for enucleated unilateral retinoblastoma with high-risk pathological features.
OBJECTIVE
To assess whether 3 cycles of CEV chemotherapy is noninferior to 6 cycles for enucleated unilateral retinoblastoma with high-risk pathological features.
DESIGN, SETTING, AND PARTICIPANTS: This double-center, randomized, open-label, noninferiority trial was conducted at 2 premier eye centers in China and included 187 patients who had undergone enucleation for unilateral retinoblastoma with high-risk pathological features (massive choroidal infiltration, retrolaminar optic nerve invasion, or scleral infiltration) between August 2013 and March 2024. The final date of follow-up was March 21, 2024.
INTERVENTIONS
Patients were randomly assigned to receive either 3 (n = 94) or 6 (n = 93) cycles of CEV chemotherapy regimen after enucleation.
MAIN OUTCOMES AND MEASURES
The primary end point was disease-free survival, with a noninferiority margin of 12%. Secondary end points encompassed overall survival, safety, economic burden, and the quality of life of children.
RESULTS
All 187 patients (median [IQR] age, 25.0 [20.0-37.0] months; 83 [44.4%] female) completed the trial. Median (IQR) follow-up was 79.0 (65.5-102.5) months. Five-year disease-free survival was 90.4% for the 3-cycle group vs 89.2% for the 6-cycle group (difference, 1.2% [95% CI, -7.5% to 9.8%]), which met the noninferiority criterion (P = .003 for noninferiority). The 6-cycle group experienced a higher frequency of adverse events, greater reduction in quality of life scores, and increased costs compared with the 3-cycle group.
CONCLUSIONS AND RELEVANCE
Among patients with unilateral pathologic high-risk retinoblastoma, 3 cycles of CEV chemotherapy resulted in 5-year disease-free survival that was noninferior to 6 cycles of CEV chemotherapy.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT01906814.
重要性
辅助治疗是视网膜母细胞瘤的一种重要且有效的治疗方法。然而，对于具有高危病理特征的单侧视网膜母细胞瘤眼球摘除术后，缺乏关于3个周期与6个周期的CEV化疗（卡铂、依托泊苷和长春新碱）的头对头临床试验。
目的
评估对于具有高危病理特征的单侧视网膜母细胞瘤眼球摘除术后，3个周期的CEV化疗是否不劣于6个周期的CEV化疗。
设计、地点和参与者：这项双中心、随机、开放标签、非劣效性试验在中国的2个顶级眼科中心进行，纳入了187例在2013年8月至2024年3月期间因单侧视网膜母细胞瘤伴高危病理特征（大量脉络膜浸润、视神经管后段侵犯或巩膜浸润）而接受眼球摘除术的患者。最终随访日期为2024年3月21日。
干预措施
患者在眼球摘除术后被随机分配接受3个周期（n = 94）或6个周期（n = 93）的CEV化疗方案。
主要结局和衡量指标
主要终点是无病生存期，非劣效界值为12%。次要终点包括总生存期、安全性、经济负担以及儿童的生活质量。
结果
所有187例患者（中位年龄[四分位间距]，25.0[20.0 - 37.0]个月；83例[44.4%]为女性）完成了试验。中位（四分位间距）随访时间为79.0（65.5 - 102.5）个月。3周期组的5年无病生存率为90.4%，6周期组为89.2%（差异为1.2%[95%置信区间，-7.5%至9.8%]），达到了非劣效标准（非劣效性P = 0.003）。与3周期组相比，6周期组不良事件发生率更高，生活质量评分下降幅度更大，且成本增加。
结论及相关性
在单侧病理高危视网膜母细胞瘤患者中，3个周期的CEV化疗导致的5年无病生存期不劣于6个周期的CEV化疗。
试验注册
ClinicalTrials.gov标识符：NCT01906814。
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