近日，中山大学中山眼科中心杨华胜教授团队研究了3个和6个周期化疗治疗视网膜母细胞瘤的患者预后。2024年10月21日，《美国医学会杂志》发表了这一成果。

辅助治疗是视网膜母细胞瘤的一种重要而有效的治疗方法。然而，缺乏对具有高危病理特征的单侧视网膜母细胞瘤剜除术进行3个周期与6个周期CEV化疗（卡铂、依托泊苷和长春新碱）的直接临床试验。

为了评估对于具有高危病理特征的单侧视网膜母细胞瘤，3个周期的CEV化疗是否不劣于6个周期，研究组在中国2个主要眼科中心进行了一项双中心、随机、开放标签、非劣效性试验，包括187名患者，他们在2013年8月至2024年3月期间接受了单侧视网膜母细胞瘤剜除术，且具有高危病理特征（大量脉络膜浸润、层后视神经浸润或巩膜浸润）。

随访的最后日期是2024年3月21日。干预措施为患者在眼球摘除后被随机分配接受3个（n=94）或6个（n=93）周期的CEV化疗方案。主要终点是无病生存率，非劣效边缘为12%。次要终点包括儿童的总体生存、安全、经济负担和生活质量。

所有187名患儿（中位[IQR]年龄，25.0[20.0-37.0]个月；83名[44.4%]女性）完成了试验。中位随访（IQR）为79.0（65.5-102.5）个月。3个周期组的5年无病生存率为90.4%，而6个周期组为89.2%（差异为1.2%[95%CI，-7.5%至9.8%]），符合非劣效性标准（非劣效P=0.003）。与3周期组相比，6周期组发生不良事件的频率更高，生活质量评分下降幅度更大，成本也更高。

研究结果表明，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5年无病生存率不低于6个周期的CE化疗。

附：英文原文

Title: Three vs 6 Cycles of Chemotherapy for High-Risk Retinoblastoma: A Randomized Clinical Trial

Author: Huijing Ye, Kang Xue, Ping Zhang, Rongxin Chen, Xiaowen Zhai, Li Ling, Wei Xiao, Lijuan Tang, Hongsheng Wang, Yuxiang Mao, Siming Ai, Yingwen Bi, Qing Liu, Yusha Zou, Jiang Qian, Huasheng Yang

Issue&Volume: 2024-10-21

Abstract:

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.

DOI: 10.1001/jama.2024.19981

Source: https://jamanetwork.com/journals/jama/fullarticle/2825162