Abstract：
Patients with large uveal melanomas are at major risk of liver metastases. Some patients are reluctant to undergo the standard treatment (ie, immediate enucleation). Proton therapy yields 5-year local control rates and eyeball retention of >85% and ≈20% in large uveal melanomas. Patients with T3/T4 uveal melanomas refusing enucleation were randomized between standard 4 to 13 Gy-fraction or moderately hypofractionated 8 to 6.5 Gy-fraction proton therapy. The main endpoint was the 2-year local recurrence-free survival without enucleation.
A single-masked 1:2 randomized phase 2 trial was conducted between 2015 and 2017 with planned endoresection and distance to the posterior pole as strata. Local events were defined as local relapse, or enucleation due to complications or relapse.
The 32 patients, with a mean age of 64 years, had T3/4 (N = 17/15), M1 (N = 2) uveal melanomas, of mean tumor diameter and thickness of 16.5 mm and 9.1 mm, and of posterior location in 56.5%. Median follow-up was 56.7 months. The 2-year local recurrence-free survival rate without enucleation was 79% (95% confidence interval, 65%-96%), similar in both arms. There were 9 enucleations, 3 at relapse and 6 for toxicities. Twelve patients had distant metastases. The 2-year-overall survival was 72% (95% confidence interval, 58%-89%). At baseline, visual acuity by average logarithm value of the minimum angle of resolution was 0.68 and 0.70 in the standard and experimental arms, and at last follow-up 2 and 1.7, with mean differences of 1.44 and 1.01, respectively (P = .39).
An 8-times 6.5 Gy scheme is feasible without deteriorating local control and with similar toxicity rates in patients with large uveal melanomas. Larger studies incorporating adjuvant treatments are warranted.
A single-masked 1:2 randomized phase 2 trial was conducted between 2015 and 2017 with planned endoresection and distance to the posterior pole as strata. Local events were defined as local relapse, or enucleation due to complications or relapse.
The 32 patients, with a mean age of 64 years, had T3/4 (N = 17/15), M1 (N = 2) uveal melanomas, of mean tumor diameter and thickness of 16.5 mm and 9.1 mm, and of posterior location in 56.5%. Median follow-up was 56.7 months. The 2-year local recurrence-free survival rate without enucleation was 79% (95% confidence interval, 65%-96%), similar in both arms. There were 9 enucleations, 3 at relapse and 6 for toxicities. Twelve patients had distant metastases. The 2-year-overall survival was 72% (95% confidence interval, 58%-89%). At baseline, visual acuity by average logarithm value of the minimum angle of resolution was 0.68 and 0.70 in the standard and experimental arms, and at last follow-up 2 and 1.7, with mean differences of 1.44 and 1.01, respectively (P = .39).
An 8-times 6.5 Gy scheme is feasible without deteriorating local control and with similar toxicity rates in patients with large uveal melanomas. Larger studies incorporating adjuvant treatments are warranted.
摘要：
目的：患有大型葡萄膜黑素瘤的患者存在肝转移的主要风险。一些患者不愿意接受标准治疗(即，立即摘除)。在大型葡萄膜黑色素瘤中，质子治疗可产生5年局部控制率和>85％和≈20％的眼球保留率。拒绝摘除的T3/T4葡萄膜黑色素瘤患者被随机分为标准4至13Gy分数或中度低分数8至6.5Gy分数质子治疗。主要终点是无眼球摘除的2年无局部复发生存期。
方法：在2015年至2017年之间进行了一项单盲1:2随机2期试验，计划进行内切除，并以与后极的距离为地层。局部事件定义为局部复发，或由于并发症或复发而摘除。
结果：32例患者，平均年龄64岁，有T3/4（N=17/15），M1（N=2）葡萄膜黑色素瘤，平均肿瘤直径和厚度为16.5毫米和9.1毫米，后部位置占56.5%。中位随访时间为56.7个月。无摘除术的2年无局部复发生存率为79%(95%置信区间,65%-96%），双臂相似。有9次摘除,复发时3例，毒性6例。12例患者有远处转移。2年总生存率为72%(95%置信区间，58%-89%）。在基线,在标准臂和实验臂中，最小分辨率角度的平均对数值的视力分别为0.68和0.70，最后随访2和1.7，平均差异分别为1.44和1.01（P=0.39）。
结论：对于患有大型葡萄膜黑素瘤的患者，8倍6.5Gy方案是可行的，而不会恶化局部控制，并且毒性发生率相似。有必要进行更大规模的纳入辅助治疗的研究。
方法：在2015年至2017年之间进行了一项单盲1:2随机2期试验，计划进行内切除，并以与后极的距离为地层。局部事件定义为局部复发，或由于并发症或复发而摘除。
结果：32例患者，平均年龄64岁，有T3/4（N=17/15），M1（N=2）葡萄膜黑色素瘤，平均肿瘤直径和厚度为16.5毫米和9.1毫米，后部位置占56.5%。中位随访时间为56.7个月。无摘除术的2年无局部复发生存率为79%(95%置信区间,65%-96%），双臂相似。有9次摘除,复发时3例，毒性6例。12例患者有远处转移。2年总生存率为72%(95%置信区间，58%-89%）。在基线,在标准臂和实验臂中，最小分辨率角度的平均对数值的视力分别为0.68和0.70，最后随访2和1.7，平均差异分别为1.44和1.01（P=0.39）。
结论：对于患有大型葡萄膜黑素瘤的患者，8倍6.5Gy方案是可行的，而不会恶化局部控制，并且毒性发生率相似。有必要进行更大规模的纳入辅助治疗的研究。
